Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar 31;132(12):4399-408.
doi: 10.1021/ja910717p.

Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes

Gretchen R Stanton  1 , Corinne N Johnson, Patrick J Walsh
Affiliations

Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes

Gretchen R Stanton et al. J Am Chem Soc. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Felkin-Ahn and Cram-chelation models
Scheme 1
Scheme 1
Overriding Substrate Control with Enantioenriched Stoichiometric Additives (A-C) and Catalysts (D).
Scheme 2
Scheme 2
One-pot Synthesis of (Z)-Disubstituted Allylic Alcohols in the Presence of BF3•OEt2 with unexpected anti-Felkin Stereoselectivity.
Scheme 3
Scheme 3
Evans’ Proposal for Chelation-Control with Aluminum Lewis Acids in the Asymmetric Mukayama Aldol Reaction (PG=protecting group).
Scheme 4
Scheme 4
One-pot Generation of (Z)-Trisubstituted Allylic Alcohols with High Diastereoselectivity.
Scheme 5
Scheme 5
Synthesis of RZnX via Conproportionation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Corey EJ, Cheng X-M. The Logic of Chemical Synthesis. Wiley; New York: 1989.
    1. Nicolaou KC, Snyder SA. Classics in Total Synthesis II : More Targets, Strategies, Methods. Wiley-VCH; Weinheim, Germany: 2003.
    1. Nicolaou KC, Sorensen EJ. Classics in Total Synthesis. VCH; Weinheim, Germany: 1996.
    1. Koskinen A. Asymmetric Synthesis of Natural Products. Wiley; Chichester, NY: 1993.
    1. Guillarme S, Ple K, Banchet A, Liard A, Haudrechy A. Chem. Rev. 2006;106:2355–2403. - PubMed

Publication types