Fundamentals 2

Question 1

What was the first system for specifying absolute configuration

Answer 1

1. D/L devised by Disher and Rosanoff
2. Based on Fischer projections
3. The +enantiomer of glyceraldehyde was selected by Rosanoff as an arbitrary reference compound
4. The + enantiomer was designated D as the OH group attached to C2 is on the right side

Question 2

How do you draw Fischer Projections

Answer 2

1. Longest carbon chain is vertical and the ligand with the highest oxidation level is placed at the top
2. All the vertical bonds point down into the page and all the horizontal bonds point upwards
3. The interchange of any two ligands at a stereogenic centre changes the configuration of that centre

Question 3

How were other compounds described using the D/L descriptors

Answer 3

1. With D-(+)-glyceraldehyde as a reference compound other enantiopure compounds could be related to it by a series of reactions or degradations
2. 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
3. All amino acids- L
4. Almost all carbs- D

Question 4

Is there a link between D/L and direction in which a compound rotates plane-polarised light

Answer 4

1. No link

Question 5

What are the failings of using the D/L notation

Answer 5

1. It only allows the specification of the absolute configuration of a single stereocenter in a molecule - not always clear which stereocenter should be described
2. It is restricted to molecules that can be unambiguously drawn as Fischer projections and which obey all relevant rules
3. All organic compounds increase in complexity, it becomes more and more impractical to chemically correlate them to glyceraldehyde
4. Some organic compounds are well correlated to either glyceraldehyde - leads to different names

Question 6

What is the classical way of reporting the enantiomeric composition of a chiral compound

Answer 6

1. Enantiomeric excess (ee)
2. Tells you what percentage of the mixture is not a racemate

Question 7

What ee does a racemic mixture and a mixture containing only one enantiomer have

Answer 7

1. Racemic = 0%
2. 1 enantiomer = 100%

Question 8

What is the formula for ee

Answer 8

1. eeR=R-S/R+S *100
2. eeS=S-R/S+R *100

Question 9

Why is ee not used so much now

Answer 9

1. The optical purity of a compound as measured by polarimetry can be equated with %ee, provided that these two quantities are linearly related
2. Historical use of polarimetry is why %ee is defined how it is
3. 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

Question 10

What is the more modern way of reporting enantiomeric composition

Answer 10

1. Enantiomeric ratio (er)
2. Ratio of one to the other

Question 11

What is the formula for er

Answer 11

1. er=R/S or er= S/R
2. Typically written as ratio xx:yy normalised to 100 e.g. 97:3
3. 3 in 100 have S config- 6% racemic
4. 94% = ee%

Question 12

What is diastereomeric ratio (dr)

Answer 12

1. Used instead to report relative amounts of diastereomers
2. It is again usually normalised to 100

Question 13

What non-carbon atoms show stereogenicity

Answer 13

1. Tetrahedral stereocentres at silicon, phosphorus, sulfur and nitrogen
2. Heteroelements from Group IV-VI with tetrahedral are also stereogenic if the 4 ligands are all different
3. Chiral@Si compounds are known and have even been prepared in enantiopure form
4. 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

Question 14

Which non-carbon atoms have trigonal pyramidal stereocentres

Answer 14

1. If 3 ligands are different
2. Nitrogen, sulfur and phosphorus

Question 15

Describe amines that are stereogenic only at nitrogen

Answer 15

1. They are usually subject to rapid pyramidal inversion (invertomers) and are macroscopically achiral on a time average
2. 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
3. In suitably constrained amines, the lone pair inversion can become impossible on account of structural rigidity

Question 16

How can inversion of nitrogen lone pairs be slowed and in what molecules is this seen

Answer 16

1. Increasing the s-character of the N lone pair by:
2. Increasing the electronegativity of the ligand(s)
3. Or ring strain
4. Chiral oxaziridines

Question 17

Do phosphorus and sulfur undergo rapid inversion

Answer 17

1. Inversion is extremely slow for heavier atoms like P and S
2. Therefore simple phosphines and sulfoxides are configurationally-stable and their enantiomers can be resolved

Question 18

What is another structural unit apart from stereogenic centres that are capable of generating stereoisomers

Answer 18

1. A molecule that is permanently twisted bears an axis that can become stereogenic with appropriate substitution- stereogenic axis
2. If this leads to chirality it is termed axial chirality as opposed to central chirality for stereogenic centres

Question 19

What are two examples of molecules with stereogenic axes

Answer 19

1. Allenes
2. Rotationally restricted biaryls

Question 20

How do allenes have stereogenic axes

Answer 20

1. Three double bonded carbons connected
2. Central carbon is SP-hybridised
3. The remaining two p orbitals on the central carbon overlap with the p orbitals on the terminal carbons to produce two pi bonds.
4. These pi bonds are perpendicular so the molecule is twisted.
5. Requires unsymmetrical substitution at both ends

Question 21

How do rotationally restricted biaryls exhibit axial chirality

Answer 21

1. The restricted rotation
2. E.g BINOL, where steric crowding prevents co-planarity of the two napthyl rings and they are unable to slip past each other

Question 22

What is atropisomerism

Answer 22

1. When restricted rotation is the cause of stereoisomerism

Question 23

What is a stereogenic plane

Answer 23

1. Another way of generating chirality
2. A planar unit in a molecule which is constrained in such a way as to place atoms/groups permanently out of plane
3. Just as for centres of axes, non-symmetrical substitution is required on the plane to render it stereogenic
4. Chirality arising this way is sometimes called planar chirality

Question 24

Where is planar chirality most commonly encountered

Answer 24

1. Organometallic sandwich complexes
2. Form basis of many chiral enantiopure organocrystals and ligands

Question 25

Where else is planar chirality encountered

Answer 25

1. (E)-cyclooctene
2. Cyclophanes- consist of benzene ring with a bridging chain between two non-adjacent ring positions
3. When a second benzene ring is present in the bridging chain, they are forced to sit flat on top of one another

Question 26

What are diastereomers

Answer 26

1. Stereoisomers that are related as non-mirror images
2. Includes E/Z isomers
3. Molecule must contain at least 2 stereogenic units to exhibit diastereoisomerism

Question 27

What is difference between diastereomers and enantiomers

Answer 27

1. Diastereomers differ in relative configuration whereas enantiomers differ in absolute configuration

Question 28

What is the max number of stereoisomers present in a molecule containing n stereocentres

Answer 28

1. 2^n stereoisomers - including enantiomers
2. But number can be lower if achiral (meso) diastereomers are possible

Question 29

Define meso compound

Answer 29

1. An achiral diastereomer that also has one or more chiral diastereomers

Question 30

Describe scalar properties of diastereomers

Answer 30

1. Diastereomers show different scalar physical properties in either an achiral or chiral environment
2. Any similarities are purely coincidental

Question 31

How do you draw racemic compounds

Answer 31

1. Can just draw straight line
2. Or wiggly line
3. Not dashed or block

Question 32

How do you draw enantiopure compounds

Answer 32

1. Block or dashed- what is drawn is what is meant

Question 33

How do you draw racemic compounds with 2 stereocentres

Answer 33

1. Either both blocked or both dashed
2. Don’t mix if doing chemical reaction

Question 34

How can you distinguish between an enantiopure diastereomer and a racemic diastereomer if both drawn the same

Answer 34

1. Use stereodescriptors to denote the enantiomeric composition
2. e.g. (1RS,3RS)- For racemic diastereomer
3. e.g. (1S, 3S)- For enantiopure diastereomer

Question 35

When would you use single line in a diastereomer

Answer 35

1. At one centre- mixture of diastereomers or single diastereomer but conformation unknown
2. At both centres- mixture of racemic diastereomers or configuration at both centres is unknown

Question 36

How can you specify relative configurations with a variety of different descriptors

Answer 36

1. (RS,RS), (RS,SR)
2. or (R,R), (R,S)

Question 37

What are soft stereodescriptors

Answer 37

1. When stereodescriptors are ambiguous without a structural drawing
2. 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
3. For a cyclic molecule it must be used in conjunction iwth a diagram to avoid ambiguity

Question 38

What are Cis/trans used for

Answer 38

1. Describes the relative spatial disposition of two ligands attached to separate atoms- either connected with double bond or contained within a ring
2. Cis= same side
3. E/Z takes precedent for double bonds

Question 39

What is E/Z used for

Answer 39

1. Approved stereochemical descriptors for double bonds
2. Group with highest CIP priority is compared to other side
3. Z= same side
4. Placed in brackets after R/S descriptors if necessary

Question 40

Define a stereoselective reaction

Answer 40

1. When there is preferential formation of one product stereoisomer over another

Question 41

Define a stereospecific reaction

Answer 41

1. When two different stereoisomeric starting materials (dia/enantiomers) react to give two different stereoisomeric (major) products

Question 42

Is a stereospecific reaction always 100% stereoselective

Answer 42

1. No
2. Does not necessarily proceed with 100% stereoselectivity

Question 43

Define stereoconvergent

Answer 43

1. 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).
2. E.g some reactions proceeding via a carbocation intermediate are stereoconvergent

Question 44

Define enantioselective

Answer 44

1. A reaction where there is preferential formation of one product enantiomer over the other

Question 45

What does an enenationselective reaction require

Answer 45

1. Requires an enantiopure reagent/ catalyst to discriminate between enantiotopic faces/groups within a prochiral substrate

Question 46

Define diastereoselective

Answer 46

1. When there is preferential formation of one product diastereoisomer over another
2. Simple and induced diastereoselection

Question 47

Define simple diastereoselection

Answer 47

1. Pertains to the relative configuration between two newly-formed stereocentres

Question 48

Define induced diastereoselection

Answer 48

1. Pertains to the relative configuration between a newly-formed stereocentre and a pre-existing stereocentre on the substrate/reactant

Question 49

Can a reaction be both enantioselective and diastereoselective at the same time

Answer 49

1. A reaction can be both
2. Then we quote values for both dr and er