Asymmetric Synthesis 1 Flashcards
What are the properties of a chiral molecule?
are devoid of a plane of symmetry
are non-superimposable upon their mirror image
are optically active
rotate plane polarised light
What are the four methods to achieve asymmetry in a reaction?
chiral reagent
chiral catalyst
chiral pool
chiral auxiliary
What is the problem with using an chiral substrate instead of an achiral substrate?
an achiral substrate produces a racemic mixture
- must be separated/resolved
a chiral substrate produces one enantiomer in excess
- no need for separation
How is the transition state of reactions which involve achiral substrates?
achiral substrates produce transition states which are enantiomeric
- are of equal activation energy
- product distribution produces equal amounts of R and S isomers
How is the transition states of reactions which involve chiral substrates?
chiral substrates produce transition states which are diastereoisomers
- are not of equal activation energy
- products are formed in unequal amounts
Which synthetic method requires the starting material to be a single enantiomer?
chiral pool
- start from natural products which are incorporated into the product
- starting material is a single enantiomer
What are the steps involved in the chiral pool method?
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
How does synthesis of an isoxazolidinone occur?
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
What are the steps involved in the chiral auxiliary method?
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
What is the purpose of the chiral auxiliary?
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
How does use of a chiral reagent cause asymmetric synthesis?
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
What are examples of asymmetric reactions that use a chiral catalyst?
sharpless epoxidation
noyori asymmetric hydrogenation
both use a metal catalyst with an asymmetrical ligand
What is enantiomer excess?
the proportion of the major isomer less than that of the minor isomer as a percentage
What are methods of determining enantiomer excess?
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