42206-19-9Relevant articles and documents
Overriding felkin control: A general method for highly diastereoselective chelation-controlled additions to α-silyloxy aldehydes
Stanton, Gretchen R.,Johnson, Corinne N.,Walsh, Patrick J.
experimental part, p. 4399 - 4408 (2010/06/14)
According to the Felkin-Anh and Cram-chelation models, nucleophilic additions to α-silyloxy aldehydes proceed through a nonchelation pathway due to the steric and electronic properties of the silyl group, giving rise to Felkin addition products. Herein we describe a general method to promote chelationcontrol in additions to α-silyloxy aldehydes. Dialkylzincs, functionalized dialkylzincs, and (E)-disubstituted, (E)-trisubstituted, and (Z)-disubstituted vinylzinc reagents add to silyl-protected α-hydroxy aldehydes with high selectivity for chelation-controlled products (dr of 10:1 to 20:1) in the presence of alkylzinc halides or triflates, RZnX. With the high functional group tolerance of organozinc reagents, the mild Lewis acidity of RZnX, and the excellent diastereoselectivities favoring the chelation-controlled products, this method will be useful in the synthesis of natural products. A mechanism involving chelation is supported by (1) NMR studies of a model substrate, (2) a dramatic increase in reaction rate in the presence of an alkylzinc halide, and (3) higher diastereoselectivity with larger alkyl substituents on the α-carbon of the aldehyde. This method provides access to chelation-controlled addition products with high diastereoselectivity previously unavailable using achiral organometallic reagents.
