Lecture on Stereochemistry: Configurational Isomers

yellow class let&#39;s review configurational isomers where we ask the question do the two molecules so let&#39;s just start let&#39;s draw let&#39;s draw a molecule here okay ch3 so we have two molecules here um foreign we have two molecules here molecule a and molecule B and we want to know what is the relationship between these two first thing we do do they have the same molecular formulas yes they do do they have the same or different connectivity the connectivity is all the same so but now we know that they have the same molecular formulas same connectivity okay so they have but they differ in the orientation of the molecules in space so we know that they are stereoisomers of one another but what kind of stereoisomers are they diastereomers or enantiomers now let&#39;s just rehash the definition of enantiomers enantiomers are two molecules right that the same molecular formula that they are mirror images of one another do you see how this is molecule a molecule B when you look at them you could envision that there&#39;s a mirror there and they are mirror images of one another even though they&#39;re two separate molecules we are asking the question what&#39;s the relationship between these two so we see that there&#39;s a mirror plane or a mirror image sorry but when you take this molecule and try to Super superimpose it it&#39;s non-superimposable it does not superimpose so by definition an enantiomer are molecules that are mirror images of one another that are not superimposable so these two molecules right here are enantiomers of one another diastereomers on the other hand you have the same molecular formula same connectivity but what is different the orientation in space so if we had a molecule that looked like this versus this we can see same connectivity same molecular formula but but these groups are different in are in different spatial orientations so they&#39;re stereisomers of one another because there&#39;s no free rotation around this double bond but when we take it does this molecule and this molecule are they mirror images of one another no they&#39;re not they&#39;re not mere images because look at that if I wanted to draw the mirror image of this molecule what would that mirror image look like let&#39;s see here it would look like that&#39;s what the mirror image of this one would look like do you see how this pink one and this blue one they don&#39;t look alike so between these two molecules they are not mirror images of one another and look if I took this molecule could I superimpose it on this one no so that a definition the definition for a diastereomer is when you&#39;re looking at one molecule and a second molecule and you can see that they are not mirror images of one another and they&#39;re not superimposable so that makes them diastereomers but what but we have to have the same connectivity and the same molecular formula that just follows the definitions from following this flowchart as you continue up that flow chart all right so let&#39;s take a look at diastereomers a little bit more now there&#39;s some really cool features here and one feature amongst uh enantiomers when you look at two molecules that are enantiomers of one another they&#39;re going to have the same physical properties so they&#39;re going to have the same boiling point the same melting point and and when you get into the lab they&#39;ll have similar uh or they&#39;ll have the same physical properties when you want to separate them if I call them chromatography diastereomers on the other hand have different physical properties so they will have when you compare these two molecules they&#39;re going to have different boiling points different melting points Isn&#39;t that cool so that&#39;s a key thing to remember when it comes to physical properties enantiomers have the same physical properties diastereomers have different physical properties now let&#39;s delve in and look at diastereomers a little bit more because they are very very important all right let&#39;s take a look at this molecule when you look at it how many stereocenters do you see that one and that one so we have two stereocenters now look at what that can actually do to us to us here we could have it come out as a wedge for both of them like this and when we figure out the r and s we can see that we have an R here and an S there but these stereocenters could have very well have been drawn like this both as dashes all right and if they were drawn that way then they would have been the opposite like that what&#39;s the relationship between these two molecules if I call that molecule a and molecule B what&#39;s the relationship between those two if you look really really hard you will see that if you take this molecule here and flip it 180 degrees you will see that they are mirror images of one another so if I take molecule B and rotate it 180 degrees so I&#39;ll call it B Prime because I&#39;m just taking molecule B and rotating it it looks like it looks like this that&#39;s a wedge do you see how B Prime here and a there are mirror images of one another but if I try to take b or B Prime and put it on top and superimpose you&#39;ll see that they&#39;re non-superimposable so by definition that makes these two compounds enantiomers of one another okay so those are enantiomers right there now but now we can have different combinations of these stereocenters I could make it this one a wedge and this one a dash so what&#39;s the stereo Center here here that would be a r and that&#39;s an R like that but then I could have had a different another combination and I&#39;ll drop below here I could have had that one as a dash and this one as a wedge so what&#39;s that going to do for us that&#39;s going to make that an s and that an s look at that so what&#39;s the relationship between these two green ones hopefully you can see that they are mirror images of one another so that makes them enantiomers and let&#39;s give them letter designations we&#39;ll say that&#39;s uh molecule C and molecule d and you can&#39;t see that I&#39;ll put it right there so molecule d huh so now I could say okay those are enantiomers those are enantiomers but what&#39;s the relationship between molecule a and moleculed C what&#39;s the relationship between those two well what you have to do is draw the molecules out so all draw a molecule a here as shown like this so that&#39;s molecule a then I&#39;ll draw molecule C so let&#39;s molecule C now what&#39;s the relationship between a and C what I try to do is I try to take one of them typically for summary it&#39;s it doesn&#39;t matter but I always go to the right one I take this right molecule and I flip it and rotate it to find a mirror image so what I&#39;m going to do is take C and I&#39;m just going to flip it 180 degrees and so when I flip it 180 degrees it&#39;s going to look like this h and my methyl so I just took that molecule and flipped it 180. so you saw how it went from a wedge to a dash and a wedge or a dash to a wedge okay now I look and why did I flip it 180 degrees because I wanted these substituents like a a mirror image and I see that the methyls are wedges and wedges so those are mirroring but that&#39;s a wedge that&#39;s a Dash It&#39;s Not Mirror so the whole molecule is not a mirror image so when I look at a and C I&#39;m like okay they&#39;re not mirror images so I have a little check box here and I have the question are they mirror images and are they superimposable okay and I see that they are not mirror images so x no are they superimposable no so that is a diastereomer by definition a diastereomers are two molecules that are not mirror images and not superimposable but when I do that same analysis for A and B and I have my little check boxes here mirror and superimposable I look at a and b and I&#39;m like okay they are mirror images check are they superimposable no so that makes them enantiomers because that&#39;s the definition enantiomers are mirror images but are not superimposable so what do you think is the relationship between B and C B and C what is the relationship what do you think the relationship is between a and d that is those are questions I want you to figure out and you can we can talk about them during class if or you could show me what you&#39;ve got and we can discuss it okay but based off of the exercise that I just did you should be able to figure that out but look at the craziness of this you have one molecule that I could have drawn that we started off drawing like this we started off with it looking like this right but we got four different stereoisomers and this is the cool thing slash crazy thing difficult thing about organic chemistry and Pharmacy and medical school is let&#39;s just say this is all hypothetical but the hypothetical principles that I&#39;m sharing apply is what if you wanted to design this molecule as a drug to cure an illness but when you synthesize it you make four isomers and what if only isomer a cured the disease and isomers b c and d kill you or have a negative effect like birth defects so you have to synthesize only this one but if you ever have a trace amount of b c and d then you&#39;re going to have negative effects so this stereoisomers are very very important in Pharmacy and in the medical field is because some enantiomers some diastereomers can kill you cause side effects or have no effect and that&#39;s one of the challenges that we face when we&#39;re designing and synthesizing drugs the different stereoisomers yeah and the reason why it&#39;s that&#39;s the case why not all four of these could um help with the disease is because in biology you have what&#39;s called what you have molecules that are called enzymes and enzymes they recognize molecules based off of their shape they&#39;re three-dimensional shape and the shape of a is going to be different than b c and d and so the molecule the enzyme may only recognize that shape and not those so biology and chemistry coming together is a really fun fun concept and you&#39;ll get more of that when you take biochemistry all right so there&#39;s a formula that we can look can use by looking at a molecule and using this formula 2 to the n that equal sign will tell us how many isomers we would expect so when we would look at this molecule and we&#39;re like how many isomers stereoisomers can we have remember the answer it was four so when you look at a molecule you identify how many stereocenters there are and there&#39;s two so two to the n equals 4. now this equation says it is the maximum amount okay the maximum amount of stereoisomers running out of board space there now let&#39;s just tack on another stereocenter how many stereocenter or stereoisomers would we expect 2 to the 3 is what eight I&#39;m not going to draw all eight of these out but that would be a good exercise to look at that if you like but the idea here is that this equation is going to tell you the maximum amount of stereoisomers it can be less depending on the molecule and the reason why it can be less than this number that you calculate is because you will find that some compounds are going to be miso all right you have miso compounds and we will talk about those later but what that means okay but miso compounds is going to um reduce this number okay so we&#39;ll talk about meso compounds in a bit but I just need you to understand that this formula gives you the maximum it can be less another interesting thing about this is look how complex the chemistry can be if you just have three stereocenters in your molecule you can have eight different steroisomers and what if that molecule you&#39;re trying to make is only an active drug in one of those eight isomers so it&#39;s going to be really really difficult to synthesize just one of those isomers so that is one problem what if the other seven isomers hurt you so you got to figure out so all these problems so this is one reason why Pharmaceuticals are so expensive is because they have stereocenters and it just complicates um synthesizing these drugs now organic chemists are getting better and better every day on figuring out how to make the isomer of interest and make that one only instead of a mixture of these so and we&#39;ll talk more about that and if you want to learn more about um synthesizing molecules with just one serial isomer then that&#39;s a graduate level concept but it&#39;s a lot of fun all right so let&#39;s see what do we want to do next here so let&#39;s take a molecule okay and make a statement here that is cyclohexane which I did not draw very well okay what we can say is if a molecule let&#39;s look at this one down here if a molecule has one stereocenter okay it will always be chiral we can make that bold statement one stereocenter it&#39;s chiral but if you take a compound like here our dice substituted cyclohexane ring this molecule has two stereocenters let&#39;s make those look like stars when it has two stereocenters it is not a guarantee that the molecule is chiral it may be chiral and it may not and what I&#39;m going to discuss now is how can I tell how can I tell when I look at a compound if it has two stereocenters if it&#39;s chiral or not and the way that we do that is does it have a plane asymmetry or does it have a axis of rotation okay so what we&#39;re going to look at is rotational symmetry and we&#39;re going to look at playing a symmetry arguments here so let&#39;s take a look at this molecule right here and we&#39;ll draw our methyl group like this we see that there are two stereocenters so what is it is it a chiral or not well if you can find a plane of symmetry anywhere in the molecule okay or any plane if you find any plane of symmetry in the molecule the molecule will be a chiral so look at this if I took this molecule and draw drew a plane right through the middle all right so I&#39;m taking a plane and going right through the molecule what do we see this half right there is the exact same half over there do you see how they match perfectly if I took this plane of symmetry I could sandwich the two halves together so whenever you have a plane of symmetry found in your molecule it&#39;s always going to be a chiral even though there are two stereocenters plane of symmetry is always going to give you a a chiral molecule now what if we take a look at the isomer of that what if we looked at a molecule that looks like this all right now when I&#39;m looking here is there a plane of symmetry right here all right is this half matched this half exactly no it does not this half has a dash and this half has a wedge so there&#39;s no plane of symmetry here would there be a plane of symmetry right here so let&#39;s get rid of this line here all right is there a plane of symmetry well that has all hydrogens and then this side has the methyl group so no there&#39;s no plane of symmetry there so there&#39;s no plane of symmetry we do know those are stereocenters but what does this guy have here this molecule has a rotational symmetry all right now a rotational symmetry is if you can take a molecule and rotate it and it looks exactly the same way as before you rotated it all right so what I&#39;m trying to say is if you look at this molecule here okay and what we&#39;re going to do is take this molecule and rotate it 180 degrees all right all right what you have to do is you play this little trick in your mind if I take this molecule close my eyes and rotate it 180 degrees and then I open up my eyes and if it looks exactly the same then I know we have a rotational symmetry so if I numbered if I could number these okay I&#39;ll put a one there and a 2 there and I&#39;m just putting these one and two here just to keep track of it but when we open our eyes and look at the molecule we do not see these ones in these twos okay if they&#39;re not there so if I take this molecule close my eyes flip it 180 degrees what am I going to see I&#39;m going to see that we&#39;ll see that&#39;s number one that&#39;s number two but remember these ones and twos are just there to um help us guide us to not see where the carbons are going but the principle is if you took this molecule close your eyes and flipped it over and then you saw this do you see how there&#39;s no difference between the two so that is a rotational symmetry there now this rotational symmetry here is very different than a plane of symmetry this molecule here yes it has a rotational symmetry but this molecule is still chiral all right it is still chiral okay let&#39;s summarize this and so the reason why I showed you these two uh different types of symmetries because they&#39;re different so what we&#39;ve learned is that if a molecule has a plane of symmetry if you find any plane with symmetry then the molecule is always going to be a chiral if you find a molecule has rotational symmetry that is irrelevant if it&#39;s chiral or not I just showed you that there&#39;s just a different form of symmetry going on here okay so rotational symmetry does not tell you if it&#39;s chiral or not it&#39;s irrelevant okay just know that there is a thing called rotational symmetry you&#39;ll be able you&#39;ll be using that more in orgo too it&#39;s just to introduce the concept okay now there&#39;s a third point that you need to understand and I&#39;m going to read it to you it says a compound that lacks a plane of symmetry will most likely be chiral although there are rare exceptions which can mostly be ignored for our purposes okay so a compound that lacks the plane of symmetry more often than not is going to be uh chiral so if we take a look at this molecule right here yes it has rotational symmetry but there is absolutely no plane asymmetry and since there&#39;s no plane of symmetry with a really high chance we can say it&#39;s going to be chiral there are exceptions and we&#39;re just going to ignore those exceptions okay no but so that&#39;s what you can basically it&#39;s just all around this if there&#39;s a plane of symmetry a chiral no plane asymmetry chiral more often than not okay sorry okay we&#39;re not going to look at any exceptions there so let&#39;s take this molecule here and figure out how many stereoisomers we would expect for this compound so how do we proceed well we have to find the stereocenters and we see two right there so 2 to the 2 equals 4 and that is the maximum amount of stereoisomers we would detect so let&#39;s start drawing them out okay we could see one where we have a da a wedge and a Dash like that we could have a second molecule where the o h here is a dash and now it&#39;s a wedge here what&#39;s the relationship between these two they&#39;re not superimposable but they are mirror images so so those two would be enantiomers of one another we could draw another one where both our wedges right and then we could then draw them both as dashes so 2 to the 2 or 2 to the n 2 to the N is the formula we see that we have four one two three four so when we analyze these things we can see these are enantiomers of one another A and B are enantiomers but then when we look at these two right here look at what happens what if I took this molecule right here and flipped it 180 degrees can you see that if I took this molecule and flipped it 180 degrees what would it look like it would match this guy so in reality this isomer and this isomer are not isomers of one another they are identical molecules so how many are we actually going to get how many stereoisomers we&#39;re only going to get three well that is the max but what is the actual number that&#39;s going to be three stereoisomers and the reason why do we only have three is because these two are identical they&#39;re the same molecule so we can just erase that okay now when we take a look at this compound here we can call that c compound C has a special name called a meso compound and meso compounds are molecules that have to at least two stereocenters and they have what a plane of symmetry so that makes the meso compound a chiral so meso compounds let&#39;s just say it one more time what makes a meso compound meso well it&#39;s a molecule with at least two stereocenters and it has a plane of symmetry which makes it a chiral so that&#39;s what you have to look out for when I give you a molecule and I say how many serial isomers are present you could say in a free response question there is a maximum of four but if I ask the question and I&#39;m saying how many draw them all you&#39;re going to find out that there&#39;s only three in this particular example so you&#39;ve got to watch out for those meso compounds what we have now is to take and look at molecules in a different way we&#39;ve looked at zigzag structures we&#39;ve looked at Newman and now we have what&#39;s called a fissure projection and Fisher projections will take a molecule right here the zigzag and convert it into this right here this is a fissure projection and the way I keep Fischer projections and Newman projections separate and distinct is official projection does look like fish bones that&#39;s what I&#39;m visualizing and Fischer projections are typically used when you&#39;re looking at sugars so this molecule right here is a sugar and Dr Fisher here just wanted a quicker and easier way to look at sugars this way okay so what we want to learn how to do is go from a zigzag to a fissure and then a fissure to a zigzag now in order to do that we need to take back up a little bit and understand what A Fischer projection is so if I have a molecule that looks like this ethyl group a hydrogen and a ch3 group we can see that it&#39;s also that&#39;s Central carbon right there it is a carbon okay so that&#39;s the Fischer projection what the Fischer projection is telling us okay is that we have that Central carbon and the horizontal lines okay are representing wedges h o h and the vertical lines are representing dashes that bit of information is super super important you have to remember these horizontal lines are wedges okay now why is that so important to understand is because look at this molecule here what is the stereochemistry sorry what is the um configuration is it an r or an s well when we look at it we can prioritize things that&#39;s going to be Priority One two and three and then priority four right so what would the what is the configuration well we go one two so we&#39;re going clockwise one two three so that would be an R because they&#39;re going clock guys right whoa whoa four is the lowest priority and it is what a wedge what have we always said the lowest priority has to be facing in the back it has to be a dash and so what&#39;s the trick when we see the lowest priority as a wedge we just take the opposite of what we&#39;ve calculated so one two three clockwise so that should be an R but our lowest priority is a wedge so we have to take the opposite so that is a s but you can do that in the Fischer projection one two three four you can still do it but you have to realize what the Fischer projection is those are wedges so one two three so R but that&#39;s a way so we have to take the opposite so that would be a s that is the important thing one of the important things to remember about Fischer projections is that&#39;s what it&#39;s showing us so what I recommend you to do is you could take this molecule here and draw it or I want you to go and make a model of it just like this all right and when you make that model you&#39;ll be able to see that Fischer projections can look like this okay you can actually take a molecule like this okay and you can grab it and spin it in such a way that you can make it look like this so you can take that molecule and Orient it in such a way to make it look like this that you have two groups pointing out at you and then two groups pointing away from you so you can make take a very simple molecule like methane and you can position up just like that highly encourage you to get a model system and do that so now what we&#39;re going to do is now take these simple principles and apply it to a sugar which is a little bit more complicated because it has what it has six carbons there and it&#39;s going to have how many stereocenters when we take a look at this molecule here we see one two three four so we have four stereocenters so if we number this zigzag one two three four five six whenever we have a zigzag you&#39;re going to find the aldehyde or the carboxylic acid or a ketone and those are typically found on either end it doesn&#39;t matter which end it&#39;s just you need to find the end where that aldehyde or carboxylic acid or just let&#39;s say carbonyl compound carbonyl functional group you&#39;re going to find that and you&#39;re going to just number hey there&#39;s six carbons and you&#39;re going to place that carbonyl at the very top of your fissure projection so that&#39;s going to be one two three four five and six now this is very very important because carbons two three four and five they are what stereocenters and if you take this o h and this hydrogen swap it you have now made a different sugar you cannot swap these they&#39;re not interchangeable that sugar is defined by the stereochemistry and so when you come over to the Fischer projection the stereochemistry here has to match has to be perfectly matched so how do you go from the zigzag and looking at Carbon too how do I know the oh is on my left and not the right and then vice versa when you look at Carbon 4 how do you know okay look so now that&#39;s what we&#39;re going to do next is I&#39;m going to show you the tricks that I use to figure out the stereochemistry on the Fisher projection the first thing that you&#39;re going to do is I&#39;m going to take this molecule and just redraw it by rotating it 90 degrees okay so just to save time I&#39;m going to pause the video but rotate this 90 degrees and redraw it so I&#39;ve taken this molecule and I&#39;ve just rotated it 90 degrees and you see that if we number the carbons again the stereochemistry has not changed you can see in carbon two it&#39;s a wedged hydroxyl wedged hydroxyl okay everything has to match if I made a mistake then you call me out on it but double checking carbon 3 is dashed o h okay carbon four is dashed oh carbon 5 is dastilates okay so everything matches now how you do this how do you figure out the answer here well here&#39;s how you do it remember that these horizontal lines means that they&#39;re wedges they&#39;re sticking out at us and in order to see that we have to look at this vertical molecule here and approach it from the carbon that is pointed right so you see how Carbon 2 is pointing this way okay so what we have to do is approach that point so I&#39;ve got to move my box here so we need to approach it from this side so I&#39;m going to see my pointer finger I&#39;m basically going to take my eyeball and look at that carbon carbon two my eyeball is right here I&#39;m looking at that point now when I&#39;m looking at that point I&#39;m now going to use my handlebar analogy and I see that the o h is a wedge so that&#39;s sticking out of the board so that&#39;s going to be my left hand and then the hydrogen is a dash so that&#39;s in the board so that&#39;s in my right hand I&#39;m going to grab them like handlebars and then I&#39;m going to ride my bike over and then turn and paste it right onto the board you see how the hydrogen was in my right hand and the oh was in my left they match now if we do that same approach now with carbon 3 now it would be a mistake to take my eyeball and look at Carbon 3 this way why because we&#39;re trying to find the point on that Apex on that carbon so that is not the approach that we have to take we have to approach our eyeball from this direction now looking at Carbon three I see that the o h is in the board so in my left hand and then the hydrogen is out of the board in my right hand and then I take it go to carbon three boom hydrogen to my right oh to my left and then it&#39;s just do it all over again let&#39;s take a look at Carbon four so we have a wedged hydrogen so that&#39;s over here in my left hand the dashed oh is in the board so that&#39;s in my right hand take it drive it over boom Oh hydrogen and you just keep doing that all right so what so that&#39;s how you go from zigzag to Fisher now you I also want you to be able to go from the fissure to the zigzag and so what you&#39;re going to do is just the exact opposite okay the exact opposite of what I&#39;ve just showed you and so we&#39;ll get practice we&#39;ll get some practice problems to look at that what&#39;s another thing that we can do with Fischer projections here we can look at these look at those stereocenters and figure out if they&#39;re RS figure out the configuration now we can use this as a reference here let&#39;s figure out the stereocenter here at Carbon two so we had to prioritize things so that&#39;s going to be let&#39;s do a different color here what&#39;s this what&#39;s the configuration at Carbon 2. so that&#39;s one I&#39;m prioritizing in pink so that would be three and four okay so we&#39;re prioritizing things so we&#39;re going one two three so we&#39;re going in the counterclockwise Direction the lowest priority is a dash so that&#39;s perfect so one two three counterclockwise so that makes that a s so that means this carbon has to be an S it has to be if we prioritize we can prioritize right on the Fischer projection that&#39;s one because we&#39;re looking at this carbon that&#39;s two and then all of this down here is three and that would be priority four okay now we look at it we count it one two three we&#39;re going clockwise one two three so that&#39;s an R no hold on what did we say about Fischer projections those are wedges so we have to say that okay yes this is the numbering scheme one two three clockwise but we have to remember that the H and o h are wedges so that makes the lowest priority a wedge so we just have to take the opposite so that would be an s okay so we keep doing that and you so you could do that for every single stereocenter and you should be able to do that okay let&#39;s see what time do we have here Let&#39;s see we have a few moments well class I think that&#39;s going to be a good stopping point so let me just give you some words of advice here everything that we&#39;re learning in these this chapter here is very visual and it can be difficult for some people to see it in their head and so what you can do is get your model kit draw build these molecules and make those connections to what the molecule looks like on a on a board or a piece of paper to what it actually looks like in three dimensions and building those models takes time but I promise you the time that you invest in building these models will pay out handsome rewards like good good stuff can come from it um and then as always if you ever need help don&#39;t wait till the last minute these concepts are very difficult to cram in right before an exam you have to get help with well in advance okay so I&#39;ll leave you with that if you need any help reach out to the Tas reach out to me we&#39;re more than happy to

yellow class let&amp;#39;s review configurational isomers where we ask the question do the two molecules so let&amp;#39;s just start let&amp;#39;s draw let&amp;#39;s draw a molecule here okay ch3 so we have two molecules here um foreign we have two molecules here molecule a and molecule B and we want to know what is the relationship between these two first thing we do do they have the same molecular formulas yes they do do they have the same or different connectivity the connectivity is all the same so but now we know that they have the same molecular formulas same connectivity okay so they have but they differ in the orientation of the molecules in space so we know that they are stereoisomers of one another but what kind of stereoisomers are they diastereomers or enantiomers now let&amp;#39;s just rehash the definition of enantiomers enantiomers are two molecules right that the same molecular formula that they are mirror images of one another do you see how this is molecule a molecule B when you look at them you could envision that there&amp;#39;s a mirror there and they are mirror images of one another even though they&amp;#39;re two separate molecules we are asking the question what&amp;#39;s the relationship between these two so we see that there&amp;#39;s a mirror plane or a mirror image sorry but when you take this molecule and try to Super superimpose it it&amp;#39;s non-superimposable it does not superimpose so by definition an enantiomer are molecules that are mirror images of one another that are not superimposable so these two molecules right here are enantiomers of one another diastereomers on the other hand you have the same molecular formula same connectivity but what is different the orientation in space so if we had a molecule that looked like this versus this we can see same connectivity same molecular formula but but these groups are different in are in different spatial orientations so they&amp;#39;re stereisomers of one another because there&amp;#39;s no free rotation around this double bond but when we take it does this molecule and this molecule are they mirror images of one another no they&amp;#39;re not they&amp;#39;re not mere images because look at that if I wanted to draw the mirror image of this molecule what would that mirror image look like let&amp;#39;s see here it would look like that&amp;#39;s what the mirror image of this one would look like do you see how this pink one and this blue one they don&amp;#39;t look alike so between these two molecules they are not mirror images of one another and look if I took this molecule could I superimpose it on this one no so that a definition the definition for a diastereomer is when you&amp;#39;re looking at one molecule and a second molecule and you can see that they are not mirror images of one another and they&amp;#39;re not superimposable so that makes them diastereomers but what but we have to have the same connectivity and the same molecular formula that just follows the definitions from following this flowchart as you continue up that flow chart all right so let&amp;#39;s take a look at diastereomers a little bit more now there&amp;#39;s some really cool features here and one feature amongst uh enantiomers when you look at two molecules that are enantiomers of one another they&amp;#39;re going to have the same physical properties so they&amp;#39;re going to have the same boiling point the same melting point and and when you get into the lab they&amp;#39;ll have similar uh or they&amp;#39;ll have the same physical properties when you want to separate them if I call them chromatography diastereomers on the other hand have different physical properties so they will have when you compare these two molecules they&amp;#39;re going to have different boiling points different melting points Isn&amp;#39;t that cool so that&amp;#39;s a key thing to remember when it comes to physical properties enantiomers have the same physical properties diastereomers have different physical properties now let&amp;#39;s delve in and look at diastereomers a little bit more because they are very very important all right let&amp;#39;s take a look at this molecule when you look at it how many stereocenters do you see that one and that one so we have two stereocenters now look at what that can actually do to us to us here we could have it come out as a wedge for both of them like this and when we figure out the r and s we can see that we have an R here and an S there but these stereocenters could have very well have been drawn like this both as dashes all right and if they were drawn that way then they would have been the opposite like that what&amp;#39;s the relationship between these two molecules if I call that molecule a and molecule B what&amp;#39;s the relationship between those two if you look really really hard you will see that if you take this molecule here and flip it 180 degrees you will see that they are mirror images of one another so if I take molecule B and rotate it 180 degrees so I&amp;#39;ll call it B Prime because I&amp;#39;m just taking molecule B and rotating it it looks like it looks like this that&amp;#39;s a wedge do you see how B Prime here and a there are mirror images of one another but if I try to take b or B Prime and put it on top and superimpose you&amp;#39;ll see that they&amp;#39;re non-superimposable so by definition that makes these two compounds enantiomers of one another okay so those are enantiomers right there now but now we can have different combinations of these stereocenters I could make it this one a wedge and this one a dash so what&amp;#39;s the stereo Center here here that would be a r and that&amp;#39;s an R like that but then I could have had a different another combination and I&amp;#39;ll drop below here I could have had that one as a dash and this one as a wedge so what&amp;#39;s that going to do for us that&amp;#39;s going to make that an s and that an s look at that so what&amp;#39;s the relationship between these two green ones hopefully you can see that they are mirror images of one another so that makes them enantiomers and let&amp;#39;s give them letter designations we&amp;#39;ll say that&amp;#39;s uh molecule C and molecule d and you can&amp;#39;t see that I&amp;#39;ll put it right there so molecule d huh so now I could say okay those are enantiomers those are enantiomers but what&amp;#39;s the relationship between molecule a and moleculed C what&amp;#39;s the relationship between those two well what you have to do is draw the molecules out so all draw a molecule a here as shown like this so that&amp;#39;s molecule a then I&amp;#39;ll draw molecule C so let&amp;#39;s molecule C now what&amp;#39;s the relationship between a and C what I try to do is I try to take one of them typically for summary it&amp;#39;s it doesn&amp;#39;t matter but I always go to the right one I take this right molecule and I flip it and rotate it to find a mirror image so what I&amp;#39;m going to do is take C and I&amp;#39;m just going to flip it 180 degrees and so when I flip it 180 degrees it&amp;#39;s going to look like this h and my methyl so I just took that molecule and flipped it 180. so you saw how it went from a wedge to a dash and a wedge or a dash to a wedge okay now I look and why did I flip it 180 degrees because I wanted these substituents like a a mirror image and I see that the methyls are wedges and wedges so those are mirroring but that&amp;#39;s a wedge that&amp;#39;s a Dash It&amp;#39;s Not Mirror so the whole molecule is not a mirror image so when I look at a and C I&amp;#39;m like okay they&amp;#39;re not mirror images so I have a little check box here and I have the question are they mirror images and are they superimposable okay and I see that they are not mirror images so x no are they superimposable no so that is a diastereomer by definition a diastereomers are two molecules that are not mirror images and not superimposable but when I do that same analysis for A and B and I have my little check boxes here mirror and superimposable I look at a and b and I&amp;#39;m like okay they are mirror images check are they superimposable no so that makes them enantiomers because that&amp;#39;s the definition enantiomers are mirror images but are not superimposable so what do you think is the relationship between B and C B and C what is the relationship what do you think the relationship is between a and d that is those are questions I want you to figure out and you can we can talk about them during class if or you could show me what you&amp;#39;ve got and we can discuss it okay but based off of the exercise that I just did you should be able to figure that out but look at the craziness of this you have one molecule that I could have drawn that we started off drawing like this we started off with it looking like this right but we got four different stereoisomers and this is the cool thing slash crazy thing difficult thing about organic chemistry and Pharmacy and medical school is let&amp;#39;s just say this is all hypothetical but the hypothetical principles that I&amp;#39;m sharing apply is what if you wanted to design this molecule as a drug to cure an illness but when you synthesize it you make four isomers and what if only isomer a cured the disease and isomers b c and d kill you or have a negative effect like birth defects so you have to synthesize only this one but if you ever have a trace amount of b c and d then you&amp;#39;re going to have negative effects so this stereoisomers are very very important in Pharmacy and in the medical field is because some enantiomers some diastereomers can kill you cause side effects or have no effect and that&amp;#39;s one of the challenges that we face when we&amp;#39;re designing and synthesizing drugs the different stereoisomers yeah and the reason why it&amp;#39;s that&amp;#39;s the case why not all four of these could um help with the disease is because in biology you have what&amp;#39;s called what you have molecules that are called enzymes and enzymes they recognize molecules based off of their shape they&amp;#39;re three-dimensional shape and the shape of a is going to be different than b c and d and so the molecule the enzyme may only recognize that shape and not those so biology and chemistry coming together is a really fun fun concept and you&amp;#39;ll get more of that when you take biochemistry all right so there&amp;#39;s a formula that we can look can use by looking at a molecule and using this formula 2 to the n that equal sign will tell us how many isomers we would expect so when we would look at this molecule and we&amp;#39;re like how many isomers stereoisomers can we have remember the answer it was four so when you look at a molecule you identify how many stereocenters there are and there&amp;#39;s two so two to the n equals 4. now this equation says it is the maximum amount okay the maximum amount of stereoisomers running out of board space there now let&amp;#39;s just tack on another stereocenter how many stereocenter or stereoisomers would we expect 2 to the 3 is what eight I&amp;#39;m not going to draw all eight of these out but that would be a good exercise to look at that if you like but the idea here is that this equation is going to tell you the maximum amount of stereoisomers it can be less depending on the molecule and the reason why it can be less than this number that you calculate is because you will find that some compounds are going to be miso all right you have miso compounds and we will talk about those later but what that means okay but miso compounds is going to um reduce this number okay so we&amp;#39;ll talk about meso compounds in a bit but I just need you to understand that this formula gives you the maximum it can be less another interesting thing about this is look how complex the chemistry can be if you just have three stereocenters in your molecule you can have eight different steroisomers and what if that molecule you&amp;#39;re trying to make is only an active drug in one of those eight isomers so it&amp;#39;s going to be really really difficult to synthesize just one of those isomers so that is one problem what if the other seven isomers hurt you so you got to figure out so all these problems so this is one reason why Pharmaceuticals are so expensive is because they have stereocenters and it just complicates um synthesizing these drugs now organic chemists are getting better and better every day on figuring out how to make the isomer of interest and make that one only instead of a mixture of these so and we&amp;#39;ll talk more about that and if you want to learn more about um synthesizing molecules with just one serial isomer then that&amp;#39;s a graduate level concept but it&amp;#39;s a lot of fun all right so let&amp;#39;s see what do we want to do next here so let&amp;#39;s take a molecule okay and make a statement here that is cyclohexane which I did not draw very well okay what we can say is if a molecule let&amp;#39;s look at this one down here if a molecule has one stereocenter okay it will always be chiral we can make that bold statement one stereocenter it&amp;#39;s chiral but if you take a compound like here our dice substituted cyclohexane ring this molecule has two stereocenters let&amp;#39;s make those look like stars when it has two stereocenters it is not a guarantee that the molecule is chiral it may be chiral and it may not and what I&amp;#39;m going to discuss now is how can I tell how can I tell when I look at a compound if it has two stereocenters if it&amp;#39;s chiral or not and the way that we do that is does it have a plane asymmetry or does it have a axis of rotation okay so what we&amp;#39;re going to look at is rotational symmetry and we&amp;#39;re going to look at playing a symmetry arguments here so let&amp;#39;s take a look at this molecule right here and we&amp;#39;ll draw our methyl group like this we see that there are two stereocenters so what is it is it a chiral or not well if you can find a plane of symmetry anywhere in the molecule okay or any plane if you find any plane of symmetry in the molecule the molecule will be a chiral so look at this if I took this molecule and draw drew a plane right through the middle all right so I&amp;#39;m taking a plane and going right through the molecule what do we see this half right there is the exact same half over there do you see how they match perfectly if I took this plane of symmetry I could sandwich the two halves together so whenever you have a plane of symmetry found in your molecule it&amp;#39;s always going to be a chiral even though there are two stereocenters plane of symmetry is always going to give you a a chiral molecule now what if we take a look at the isomer of that what if we looked at a molecule that looks like this all right now when I&amp;#39;m looking here is there a plane of symmetry right here all right is this half matched this half exactly no it does not this half has a dash and this half has a wedge so there&amp;#39;s no plane of symmetry here would there be a plane of symmetry right here so let&amp;#39;s get rid of this line here all right is there a plane of symmetry well that has all hydrogens and then this side has the methyl group so no there&amp;#39;s no plane of symmetry there so there&amp;#39;s no plane of symmetry we do know those are stereocenters but what does this guy have here this molecule has a rotational symmetry all right now a rotational symmetry is if you can take a molecule and rotate it and it looks exactly the same way as before you rotated it all right so what I&amp;#39;m trying to say is if you look at this molecule here okay and what we&amp;#39;re going to do is take this molecule and rotate it 180 degrees all right all right what you have to do is you play this little trick in your mind if I take this molecule close my eyes and rotate it 180 degrees and then I open up my eyes and if it looks exactly the same then I know we have a rotational symmetry so if I numbered if I could number these okay I&amp;#39;ll put a one there and a 2 there and I&amp;#39;m just putting these one and two here just to keep track of it but when we open our eyes and look at the molecule we do not see these ones in these twos okay if they&amp;#39;re not there so if I take this molecule close my eyes flip it 180 degrees what am I going to see I&amp;#39;m going to see that we&amp;#39;ll see that&amp;#39;s number one that&amp;#39;s number two but remember these ones and twos are just there to um help us guide us to not see where the carbons are going but the principle is if you took this molecule close your eyes and flipped it over and then you saw this do you see how there&amp;#39;s no difference between the two so that is a rotational symmetry there now this rotational symmetry here is very different than a plane of symmetry this molecule here yes it has a rotational symmetry but this molecule is still chiral all right it is still chiral okay let&amp;#39;s summarize this and so the reason why I showed you these two uh different types of symmetries because they&amp;#39;re different so what we&amp;#39;ve learned is that if a molecule has a plane of symmetry if you find any plane with symmetry then the molecule is always going to be a chiral if you find a molecule has rotational symmetry that is irrelevant if it&amp;#39;s chiral or not I just showed you that there&amp;#39;s just a different form of symmetry going on here okay so rotational symmetry does not tell you if it&amp;#39;s chiral or not it&amp;#39;s irrelevant okay just know that there is a thing called rotational symmetry you&amp;#39;ll be able you&amp;#39;ll be using that more in orgo too it&amp;#39;s just to introduce the concept okay now there&amp;#39;s a third point that you need to understand and I&amp;#39;m going to read it to you it says a compound that lacks a plane of symmetry will most likely be chiral although there are rare exceptions which can mostly be ignored for our purposes okay so a compound that lacks the plane of symmetry more often than not is going to be uh chiral so if we take a look at this molecule right here yes it has rotational symmetry but there is absolutely no plane asymmetry and since there&amp;#39;s no plane of symmetry with a really high chance we can say it&amp;#39;s going to be chiral there are exceptions and we&amp;#39;re just going to ignore those exceptions okay no but so that&amp;#39;s what you can basically it&amp;#39;s just all around this if there&amp;#39;s a plane of symmetry a chiral no plane asymmetry chiral more often than not okay sorry okay we&amp;#39;re not going to look at any exceptions there so let&amp;#39;s take this molecule here and figure out how many stereoisomers we would expect for this compound so how do we proceed well we have to find the stereocenters and we see two right there so 2 to the 2 equals 4 and that is the maximum amount of stereoisomers we would detect so let&amp;#39;s start drawing them out okay we could see one where we have a da a wedge and a Dash like that we could have a second molecule where the o h here is a dash and now it&amp;#39;s a wedge here what&amp;#39;s the relationship between these two they&amp;#39;re not superimposable but they are mirror images so so those two would be enantiomers of one another we could draw another one where both our wedges right and then we could then draw them both as dashes so 2 to the 2 or 2 to the n 2 to the N is the formula we see that we have four one two three four so when we analyze these things we can see these are enantiomers of one another A and B are enantiomers but then when we look at these two right here look at what happens what if I took this molecule right here and flipped it 180 degrees can you see that if I took this molecule and flipped it 180 degrees what would it look like it would match this guy so in reality this isomer and this isomer are not isomers of one another they are identical molecules so how many are we actually going to get how many stereoisomers we&amp;#39;re only going to get three well that is the max but what is the actual number that&amp;#39;s going to be three stereoisomers and the reason why do we only have three is because these two are identical they&amp;#39;re the same molecule so we can just erase that okay now when we take a look at this compound here we can call that c compound C has a special name called a meso compound and meso compounds are molecules that have to at least two stereocenters and they have what a plane of symmetry so that makes the meso compound a chiral so meso compounds let&amp;#39;s just say it one more time what makes a meso compound meso well it&amp;#39;s a molecule with at least two stereocenters and it has a plane of symmetry which makes it a chiral so that&amp;#39;s what you have to look out for when I give you a molecule and I say how many serial isomers are present you could say in a free response question there is a maximum of four but if I ask the question and I&amp;#39;m saying how many draw them all you&amp;#39;re going to find out that there&amp;#39;s only three in this particular example so you&amp;#39;ve got to watch out for those meso compounds what we have now is to take and look at molecules in a different way we&amp;#39;ve looked at zigzag structures we&amp;#39;ve looked at Newman and now we have what&amp;#39;s called a fissure projection and Fisher projections will take a molecule right here the zigzag and convert it into this right here this is a fissure projection and the way I keep Fischer projections and Newman projections separate and distinct is official projection does look like fish bones that&amp;#39;s what I&amp;#39;m visualizing and Fischer projections are typically used when you&amp;#39;re looking at sugars so this molecule right here is a sugar and Dr Fisher here just wanted a quicker and easier way to look at sugars this way okay so what we want to learn how to do is go from a zigzag to a fissure and then a fissure to a zigzag now in order to do that we need to take back up a little bit and understand what A Fischer projection is so if I have a molecule that looks like this ethyl group a hydrogen and a ch3 group we can see that it&amp;#39;s also that&amp;#39;s Central carbon right there it is a carbon okay so that&amp;#39;s the Fischer projection what the Fischer projection is telling us okay is that we have that Central carbon and the horizontal lines okay are representing wedges h o h and the vertical lines are representing dashes that bit of information is super super important you have to remember these horizontal lines are wedges okay now why is that so important to understand is because look at this molecule here what is the stereochemistry sorry what is the um configuration is it an r or an s well when we look at it we can prioritize things that&amp;#39;s going to be Priority One two and three and then priority four right so what would the what is the configuration well we go one two so we&amp;#39;re going clockwise one two three so that would be an R because they&amp;#39;re going clock guys right whoa whoa four is the lowest priority and it is what a wedge what have we always said the lowest priority has to be facing in the back it has to be a dash and so what&amp;#39;s the trick when we see the lowest priority as a wedge we just take the opposite of what we&amp;#39;ve calculated so one two three clockwise so that should be an R but our lowest priority is a wedge so we have to take the opposite so that is a s but you can do that in the Fischer projection one two three four you can still do it but you have to realize what the Fischer projection is those are wedges so one two three so R but that&amp;#39;s a way so we have to take the opposite so that would be a s that is the important thing one of the important things to remember about Fischer projections is that&amp;#39;s what it&amp;#39;s showing us so what I recommend you to do is you could take this molecule here and draw it or I want you to go and make a model of it just like this all right and when you make that model you&amp;#39;ll be able to see that Fischer projections can look like this okay you can actually take a molecule like this okay and you can grab it and spin it in such a way that you can make it look like this so you can take that molecule and Orient it in such a way to make it look like this that you have two groups pointing out at you and then two groups pointing away from you so you can make take a very simple molecule like methane and you can position up just like that highly encourage you to get a model system and do that so now what we&amp;#39;re going to do is now take these simple principles and apply it to a sugar which is a little bit more complicated because it has what it has six carbons there and it&amp;#39;s going to have how many stereocenters when we take a look at this molecule here we see one two three four so we have four stereocenters so if we number this zigzag one two three four five six whenever we have a zigzag you&amp;#39;re going to find the aldehyde or the carboxylic acid or a ketone and those are typically found on either end it doesn&amp;#39;t matter which end it&amp;#39;s just you need to find the end where that aldehyde or carboxylic acid or just let&amp;#39;s say carbonyl compound carbonyl functional group you&amp;#39;re going to find that and you&amp;#39;re going to just number hey there&amp;#39;s six carbons and you&amp;#39;re going to place that carbonyl at the very top of your fissure projection so that&amp;#39;s going to be one two three four five and six now this is very very important because carbons two three four and five they are what stereocenters and if you take this o h and this hydrogen swap it you have now made a different sugar you cannot swap these they&amp;#39;re not interchangeable that sugar is defined by the stereochemistry and so when you come over to the Fischer projection the stereochemistry here has to match has to be perfectly matched so how do you go from the zigzag and looking at Carbon too how do I know the oh is on my left and not the right and then vice versa when you look at Carbon 4 how do you know okay look so now that&amp;#39;s what we&amp;#39;re going to do next is I&amp;#39;m going to show you the tricks that I use to figure out the stereochemistry on the Fisher projection the first thing that you&amp;#39;re going to do is I&amp;#39;m going to take this molecule and just redraw it by rotating it 90 degrees okay so just to save time I&amp;#39;m going to pause the video but rotate this 90 degrees and redraw it so I&amp;#39;ve taken this molecule and I&amp;#39;ve just rotated it 90 degrees and you see that if we number the carbons again the stereochemistry has not changed you can see in carbon two it&amp;#39;s a wedged hydroxyl wedged hydroxyl okay everything has to match if I made a mistake then you call me out on it but double checking carbon 3 is dashed o h okay carbon four is dashed oh carbon 5 is dastilates okay so everything matches now how you do this how do you figure out the answer here well here&amp;#39;s how you do it remember that these horizontal lines means that they&amp;#39;re wedges they&amp;#39;re sticking out at us and in order to see that we have to look at this vertical molecule here and approach it from the carbon that is pointed right so you see how Carbon 2 is pointing this way okay so what we have to do is approach that point so I&amp;#39;ve got to move my box here so we need to approach it from this side so I&amp;#39;m going to see my pointer finger I&amp;#39;m basically going to take my eyeball and look at that carbon carbon two my eyeball is right here I&amp;#39;m looking at that point now when I&amp;#39;m looking at that point I&amp;#39;m now going to use my handlebar analogy and I see that the o h is a wedge so that&amp;#39;s sticking out of the board so that&amp;#39;s going to be my left hand and then the hydrogen is a dash so that&amp;#39;s in the board so that&amp;#39;s in my right hand I&amp;#39;m going to grab them like handlebars and then I&amp;#39;m going to ride my bike over and then turn and paste it right onto the board you see how the hydrogen was in my right hand and the oh was in my left they match now if we do that same approach now with carbon 3 now it would be a mistake to take my eyeball and look at Carbon 3 this way why because we&amp;#39;re trying to find the point on that Apex on that carbon so that is not the approach that we have to take we have to approach our eyeball from this direction now looking at Carbon three I see that the o h is in the board so in my left hand and then the hydrogen is out of the board in my right hand and then I take it go to carbon three boom hydrogen to my right oh to my left and then it&amp;#39;s just do it all over again let&amp;#39;s take a look at Carbon four so we have a wedged hydrogen so that&amp;#39;s over here in my left hand the dashed oh is in the board so that&amp;#39;s in my right hand take it drive it over boom Oh hydrogen and you just keep doing that all right so what so that&amp;#39;s how you go from zigzag to Fisher now you I also want you to be able to go from the fissure to the zigzag and so what you&amp;#39;re going to do is just the exact opposite okay the exact opposite of what I&amp;#39;ve just showed you and so we&amp;#39;ll get practice we&amp;#39;ll get some practice problems to look at that what&amp;#39;s another thing that we can do with Fischer projections here we can look at these look at those stereocenters and figure out if they&amp;#39;re RS figure out the configuration now we can use this as a reference here let&amp;#39;s figure out the stereocenter here at Carbon two so we had to prioritize things so that&amp;#39;s going to be let&amp;#39;s do a different color here what&amp;#39;s this what&amp;#39;s the configuration at Carbon 2. so that&amp;#39;s one I&amp;#39;m prioritizing in pink so that would be three and four okay so we&amp;#39;re prioritizing things so we&amp;#39;re going one two three so we&amp;#39;re going in the counterclockwise Direction the lowest priority is a dash so that&amp;#39;s perfect so one two three counterclockwise so that makes that a s so that means this carbon has to be an S it has to be if we prioritize we can prioritize right on the Fischer projection that&amp;#39;s one because we&amp;#39;re looking at this carbon that&amp;#39;s two and then all of this down here is three and that would be priority four okay now we look at it we count it one two three we&amp;#39;re going clockwise one two three so that&amp;#39;s an R no hold on what did we say about Fischer projections those are wedges so we have to say that okay yes this is the numbering scheme one two three clockwise but we have to remember that the H and o h are wedges so that makes the lowest priority a wedge so we just have to take the opposite so that would be an s okay so we keep doing that and you so you could do that for every single stereocenter and you should be able to do that okay let&amp;#39;s see what time do we have here Let&amp;#39;s see we have a few moments well class I think that&amp;#39;s going to be a good stopping point so let me just give you some words of advice here everything that we&amp;#39;re learning in these this chapter here is very visual and it can be difficult for some people to see it in their head and so what you can do is get your model kit draw build these molecules and make those connections to what the molecule looks like on a on a board or a piece of paper to what it actually looks like in three dimensions and building those models takes time but I promise you the time that you invest in building these models will pay out handsome rewards like good good stuff can come from it um and then as always if you ever need help don&amp;#39;t wait till the last minute these concepts are very difficult to cram in right before an exam you have to get help with well in advance okay so I&amp;#39;ll leave you with that if you need any help reach out to the Tas reach out to me we&amp;#39;re more than happy to

Transcript for:Lecture on Stereochemistry: Configurational Isomers

Transcript for:
Lecture on Stereochemistry: Configurational Isomers