title: Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes.
abstract: According to the Felkin-Anh and Cram-chelation models, nucleophilic additions to alpha-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 chelation-control in additions to alpha-silyloxy aldehydes. Dialkylzincs, functionalized dialkylzincs, and (E)-disubstituted, (E)-trisubstituted, and (Z)-disubstituted vinylzinc reagents add to silyl-protected alpha-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 alpha-carbon of the aldehyde. This method provides access to chelation-controlled addition products with high diastereoselectivity previously unavailable using achiral organometallic reagents.
authors.affiliation: P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
authors.forename: Gretchen R
authors.initials: GR
authors.lastname: Stanton
authors.forename: Corinne N
authors.initials: CN
authors.lastname: Johnson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Walsh
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000447:Aldehydes; D002614:Chelating Agents; D009942:Organometallic Compounds; D012821:Silanes; D014753:Vinyl Compounds; D015032:Zinc