| Autor: |
Kerrigan MH; P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA., Jeon SJ, Chen YK, Salvi L, Carroll PJ, Walsh PJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2009 Jun 24; Vol. 131 (24), pp. 8434-45. |
| DOI: |
10.1021/ja809821x |
| Abstrakt: |
(Z)-trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-alpha,alpha,beta-trisubstituted allylic alcohols. (Z)-trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metalate rearrangement that is followed by a boron-to-zinc transmetalation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z)-trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed, (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl-protected alpha- and beta-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl-protected alpha-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (-)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. Alpha-ethyl and alpha-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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