Atrolactic acid asymmetric synthesis

One of the first examples of this type of reaction, using a chiral alcohol as an auxiliary, was the asymmetric synthesis of 2-hydroxy-2-phenylpropanoic acid (atrolactic acid, 3, R1 =C6H5 R3 = CH3) by diastereoselective addition of methyl magnesium iodide to the men-thyl ester of phcnylglyoxylie acid4,5 (Table 22). 

Recently, the improved chiral ethyl ketone (5)-141, derived in three steps from (5)-mandelic acid, has been evaluated in the aldol process (115). Representative condensations of the derived (Z)-boron enolates (5)-142 with aldehydes are summarized in Table 34b, It is evident from the data that the nature of the boron ligand L plays a significant role in enolate diastereoface selection in this system. It is also noteworthy that the sense of asymmetric induction noted for the boron enolate (5)-142 is opposite to that observed for the lithium enolate (5)-139a and (5>139b derived from (S)-atrolactic acid (3) and the related lithium enolate 139. A detailed interpretation of these observations in terms of transition state steric effects (cf. Scheme 20) and chelation phenomena appears to be premature at this time. Further applications of (S )- 41 and (/ )-141 as chiral propionate enolate synthons for the aldol process have appeared in a 6-deoxyerythronolide B synthesis recently disclosed by Masamune (115b). 

An efficient asymmetric synthesis of 3-phenylalkanals has been developed, based on a chiral homoenolate equivalent, using a recoverable chiral auxiliary derived from atrolactic acid (Scheme 10). ... 

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