Fundamentals 2 Flashcards
What was the first system for specifying absolute configuration
- D/L devised by Disher and Rosanoff
- Based on Fischer projections
- The +enantiomer of glyceraldehyde was selected by Rosanoff as an arbitrary reference compound
- The + enantiomer was designated D as the OH group attached to C2 is on the right side
How do you draw Fischer Projections
- Longest carbon chain is vertical and the ligand with the highest oxidation level is placed at the top
- All the vertical bonds point down into the page and all the horizontal bonds point upwards
- The interchange of any two ligands at a stereogenic centre changes the configuration of that centre
How were other compounds described using the D/L descriptors
- With D-(+)-glyceraldehyde as a reference compound other enantiopure compounds could be related to it by a series of reactions or degradations
- Compounds that could be correlated either directly or indirectly to the reference compound using chemical reactions that don’t lead to racemisation at the chiral centre were labelled D
- All amino acids- L
- Almost all carbs- D
Is there a link between D/L and direction in which a compound rotates plane-polarised light
- No link
What are the failings of using the D/L notation
- It only allows the specification of the absolute configuration of a single stereocenter in a molecule - not always clear which stereocenter should be described
- It is restricted to molecules that can be unambiguously drawn as Fischer projections and which obey all relevant rules
- All organic compounds increase in complexity, it becomes more and more impractical to chemically correlate them to glyceraldehyde
- Some organic compounds are well correlated to either glyceraldehyde - leads to different names
What is the classical way of reporting the enantiomeric composition of a chiral compound
- Enantiomeric excess (ee)
- Tells you what percentage of the mixture is not a racemate
What ee does a racemic mixture and a mixture containing only one enantiomer have
- Racemic = 0%
- 1 enantiomer = 100%
What is the formula for ee
- eeR=R-S/R+S *100
- eeS=S-R/S+R *100
Why is ee not used so much now
- The optical purity of a compound as measured by polarimetry can be equated with %ee, provided that these two quantities are linearly related
- Historical use of polarimetry is why %ee is defined how it is
- The phrase optically pure for enantiopure compounds is strongly discouraged because polarimetry is no longer used to measure %ee and not all enantiopure compounds exhibit measurable optical activity
What is the more modern way of reporting enantiomeric composition
- Enantiomeric ratio (er)
- Ratio of one to the other
What is the formula for er
- er=R/S or er= S/R
- Typically written as ratio xx:yy normalised to 100 e.g. 97:3
- 3 in 100 have S config- 6% racemic
- 94% = ee%
What is diastereomeric ratio (dr)
- Used instead to report relative amounts of diastereomers
- It is again usually normalised to 100
What non-carbon atoms show stereogenicity
- Tetrahedral stereocentres at silicon, phosphorus, sulfur and nitrogen
- Heteroelements from Group IV-VI with tetrahedral are also stereogenic if the 4 ligands are all different
- Chiral@Si compounds are known and have even been prepared in enantiopure form
- But this is more commonly encountered for oxides of organic phosphorus or sulfur compounds in their P(V) or S(VI) oxidation states, and is also known for N-oxides or ammonium salts of amines
Which non-carbon atoms have trigonal pyramidal stereocentres
- If 3 ligands are different
- Nitrogen, sulfur and phosphorus
Describe amines that are stereogenic only at nitrogen
- They are usually subject to rapid pyramidal inversion (invertomers) and are macroscopically achiral on a time average
- If there is another stereocenter within the molecule such that the nitrogen invertomers are diastereomeric, the amine will generally adopt the most thermodynamically stable configuration - least strained
- In suitably constrained amines, the lone pair inversion can become impossible on account of structural rigidity
How can inversion of nitrogen lone pairs be slowed and in what molecules is this seen
- Increasing the s-character of the N lone pair by:
- Increasing the electronegativity of the ligand(s)
- Or ring strain
- Chiral oxaziridines
Do phosphorus and sulfur undergo rapid inversion
- Inversion is extremely slow for heavier atoms like P and S
- Therefore simple phosphines and sulfoxides are configurationally-stable and their enantiomers can be resolved
What is another structural unit apart from stereogenic centres that are capable of generating stereoisomers
- A molecule that is permanently twisted bears an axis that can become stereogenic with appropriate substitution- stereogenic axis
- If this leads to chirality it is termed axial chirality as opposed to central chirality for stereogenic centres
What are two examples of molecules with stereogenic axes
- Allenes
- Rotationally restricted biaryls
How do allenes have stereogenic axes
- Three double bonded carbons connected
- Central carbon is SP-hybridised
- The remaining two p orbitals on the central carbon overlap with the p orbitals on the terminal carbons to produce two pi bonds.
- These pi bonds are perpendicular so the molecule is twisted.
- Requires unsymmetrical substitution at both ends
How do rotationally restricted biaryls exhibit axial chirality
- The restricted rotation
- E.g BINOL, where steric crowding prevents co-planarity of the two napthyl rings and they are unable to slip past each other
What is atropisomerism
- When restricted rotation is the cause of stereoisomerism
What is a stereogenic plane
- Another way of generating chirality
- A planar unit in a molecule which is constrained in such a way as to place atoms/groups permanently out of plane
- Just as for centres of axes, non-symmetrical substitution is required on the plane to render it stereogenic
- Chirality arising this way is sometimes called planar chirality
Where is planar chirality most commonly encountered
- Organometallic sandwich complexes
- Form basis of many chiral enantiopure organocrystals and ligands
Where else is planar chirality encountered
- (E)-cyclooctene
- Cyclophanes- consist of benzene ring with a bridging chain between two non-adjacent ring positions
- When a second benzene ring is present in the bridging chain, they are forced to sit flat on top of one another
What are diastereomers
- Stereoisomers that are related as non-mirror images
- Includes E/Z isomers
- Molecule must contain at least 2 stereogenic units to exhibit diastereoisomerism
What is difference between diastereomers and enantiomers
- Diastereomers differ in relative configuration whereas enantiomers differ in absolute configuration
What is the max number of stereoisomers present in a molecule containing n stereocentres
- 2^n stereoisomers - including enantiomers
- But number can be lower if achiral (meso) diastereomers are possible
Define meso compound
- An achiral diastereomer that also has one or more chiral diastereomers
Describe scalar properties of diastereomers
- Diastereomers show different scalar physical properties in either an achiral or chiral environment
- Any similarities are purely coincidental
How do you draw racemic compounds
- Can just draw straight line
- Or wiggly line
- Not dashed or block
How do you draw enantiopure compounds
- Block or dashed- what is drawn is what is meant
How do you draw racemic compounds with 2 stereocentres
- Either both blocked or both dashed
- Don’t mix if doing chemical reaction
How can you distinguish between an enantiopure diastereomer and a racemic diastereomer if both drawn the same
- Use stereodescriptors to denote the enantiomeric composition
- e.g. (1RS,3RS)- For racemic diastereomer
- e.g. (1S, 3S)- For enantiopure diastereomer
When would you use single line in a diastereomer
- At one centre- mixture of diastereomers or single diastereomer but conformation unknown
- At both centres- mixture of racemic diastereomers or configuration at both centres is unknown
How can you specify relative configurations with a variety of different descriptors
- (RS,RS), (RS,SR)
- or (R,R), (R,S)
What are soft stereodescriptors
- When stereodescriptors are ambiguous without a structural drawing
- Syn and anti notation is used to specific the relative orientation of substituents attached to carbon chain with ‘syn’ meaning same side and ‘anti’ meaning opposite
- For a cyclic molecule it must be used in conjunction iwth a diagram to avoid ambiguity
What are Cis/trans used for
- Describes the relative spatial disposition of two ligands attached to separate atoms- either connected with double bond or contained within a ring
- Cis= same side
- E/Z takes precedent for double bonds
What is E/Z used for
- Approved stereochemical descriptors for double bonds
- Group with highest CIP priority is compared to other side
- Z= same side
- Placed in brackets after R/S descriptors if necessary
Define a stereoselective reaction
- When there is preferential formation of one product stereoisomer over another
Define a stereospecific reaction
- When two different stereoisomeric starting materials (dia/enantiomers) react to give two different stereoisomeric (major) products
Is a stereospecific reaction always 100% stereoselective
- No
- Does not necessarily proceed with 100% stereoselectivity
Define stereoconvergent
- When two different stereoisomeric starting materials react to give the same stereoisomer of the product (or the same stereoisomeric mixture if the stereochemistry is imperfect).
- E.g some reactions proceeding via a carbocation intermediate are stereoconvergent
Define enantioselective
- A reaction where there is preferential formation of one product enantiomer over the other
What does an enenationselective reaction require
- Requires an enantiopure reagent/ catalyst to discriminate between enantiotopic faces/groups within a prochiral substrate
Define diastereoselective
- When there is preferential formation of one product diastereoisomer over another
- Simple and induced diastereoselection
Define simple diastereoselection
- Pertains to the relative configuration between two newly-formed stereocentres
Define induced diastereoselection
- Pertains to the relative configuration between a newly-formed stereocentre and a pre-existing stereocentre on the substrate/reactant
Can a reaction be both enantioselective and diastereoselective at the same time
- A reaction can be both
- Then we quote values for both dr and er
