The direct enantioselective hydroxymethylation of aldehydes employing the a,a-diarylprolinol trimethylsilyl ether system as an organocatalyst has been developed. This methodology serves as an advancement of auxiliary based methods in that it enables a direct installation of the C1 synthon, formaldehyde, without the pre-installment of a chiral auxiliary to induce stereoselectivity. This strategy has proven efficient in accessing �-hydroxycarboxylic acids and siloxymethyl-protected �-hydroxyaldehydes in moderate to high yields and excellent enantioselectivities alongside of a broad range of functional group tolerance. Details regarding reaction optimization, mechanistic insights, and intermediate versatility will be discussed. Finally, the utility of the hydroxymethylation in a formal synthesis of the apoptosis inducer (-)-rasfonin will be described.

Development of a direct enantioselective organocatalytic hydroxymethylation of aldehydes catalyzed by the a,a-diarylprolinol trimethylsilyl ether system: Application to a formal synthesis of (-)-rasfonin

248th National Meeting (2014)

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