Acyclic Stereoselection. 12. Double Stereodifferentiation with Mutual Kinetic Resolution. A Superior Class of Reagents for Control of Cram's Rule Stereoselection in Synthesis of erythro-α-Alkyl-β-hydroxy Carboxylic Acids from Chiral Aldehydes

Article abstract of DOI:10.1021/jo00324a017

Chiral α-<(trimethylsilyl)oxy> ketones 7-9 have been prepared and their aldol condesations studied.Compound 8 shows from good to excellent inherent diastereoface selectivity in reactions with achiral aldehydes.Stereoselectivity is related to the size of the alkyl group attached to the aldehyde carbonyl; highest selectivity is observed with diphenylacetaldehyde (>10:1) and pivaldehyde (>19:1).Ketone 8 also shows high diastereoface selectivity in its reactions with chiral, racemic aldehydes 21, 25, 29, and 17, only one stereoisomeric aldol being obtained in each case.Furthermore, the four aforementioned aldehydes show much higher diastereoface selectivity with ketone 8 than they do with the related ketone 1.As a result, the reactions of racemic 8 with these chiral, racemic aldehydes show a high degree of "mutual kinetic resolution".In fact, the rate of the (R)-enolate plus (R)-aldehyde condensation is at least 35 times the rate of the (R)-enolate plus (S)-aldehyde condensation.It is shown by simple logical argument that such mutual kinetic resolution is expected in reactions between two chiral racemic compounds and that the magnitude of the effect should be proportional to the inherent diastereoselectivity shown by each compound in its reaction with achiral reaction partners.Thus, reagents such as 8 can be used to obtain the benefits of double stereodifferentiation even in the racemic form.As an application of the chemistry developed, (+/-)-blastmycinone (47) has been prepared in four steps from ketone 9 (20percent overall yield).