Asymmetric Synthesis 1

Question 1

What are the properties of a chiral molecule?

Answer 1

are devoid of a plane of symmetry
are non-superimposable upon their mirror image
are optically active
rotate plane polarised light

Question 2

What are the four methods to achieve asymmetry in a reaction?

Answer 2

chiral reagent
chiral catalyst
chiral pool
chiral auxiliary

Question 3

What is the problem with using an chiral substrate instead of an achiral substrate?

Answer 3

an achiral substrate produces a racemic mixture
- must be separated/resolved

a chiral substrate produces one enantiomer in excess
- no need for separation

Question 4

How is the transition state of reactions which involve achiral substrates?

Answer 4

achiral substrates produce transition states which are enantiomeric

• are of equal activation energy
• product distribution produces equal amounts of R and S isomers

Question 5

How is the transition states of reactions which involve chiral substrates?

Answer 5

chiral substrates produce transition states which are diastereoisomers

• are not of equal activation energy
• products are formed in unequal amounts

Question 6

Which synthetic method requires the starting material to be a single enantiomer?

Answer 6

chiral pool

• start from natural products which are incorporated into the product
• starting material is a single enantiomer

Question 7

What are the steps involved in the chiral pool method?

Answer 7

must start with a single enantiomer
- which is incorporated into the final product

addition of a methyl group at the carboxylic acid
- forms an ester
addition of a side chain
- amino group attacks the side chain

Question 8

How does synthesis of an isoxazolidinone occur?

Answer 8

uses the amino acid phenylalanine
- can use either the R or S enantiomer

the bulky benzyl group blocks the lower or upper face of the molecule
- forces the reactant to come in from the opposite side
= directs the stereochemistry of the reaction

Question 9

What are the steps involved in the chiral auxiliary method?

Answer 9

diastereoselective reaction takes place

addition of the auxiliary to the starting material 
- is covalently bonded 
forms an enolate 
alkylation via a new reagent 
removal of the auxiliary

Question 10

What is the purpose of the chiral auxiliary?

Answer 10

provides steric control
- reaction can only occur from the upper face as the phenyl group blocks the lower face
= ensures you only form one enantiomer

Question 11

How does use of a chiral reagent cause asymmetric synthesis?

Answer 11

do not covalently bond to the substrate but instead interact with it

• achiral reducing agents produce one enantiomer in excess over the other
  = NaBH4, LiAlH4
• enantioselecive agents produce only one enantiomer

Question 12

What are examples of asymmetric reactions that use a chiral catalyst?

Answer 12

sharpless epoxidation
noyori asymmetric hydrogenation

both use a metal catalyst with an asymmetrical ligand

Question 13

What is enantiomer excess?

Answer 13

the proportion of the major isomer less than that of the minor isomer as a percentage

Question 14

What are methods of determining enantiomer excess?

Answer 14

must involve a chiral environment

• chiral HPLC = need a chiral column
• chiral GC = need a chiral column

NMR of a mixture of optical isomer will not give enantiomeric excess
- enantiomers would have the same NMR
= must add a chiral reagent