期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 12, 页码 5062-5070出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b01784
关键词
-
资金
- National Institutes of Health [GM122483, GM46059, GM058160-17S1, GM128779]
- Bristol Myers Squibb
- NSF
Chiral tertiary alcohols are important building blocks for the synthesis of pharmaceutical agents and biologically active natural products. The addition of carbon nucleophiles to ketones is the most common approach to tertiary alcohol synthesis but traditionally relies on stoichiometric organometallic reagents that are difficult to prepare, sensitive, and uneconomical. We describe a mild and efficient method for the copper-catalyzed allylation of ketones using widely available 1,3-dienes as allylmetal surrogates. Homoallylic alcohols bearing a wide range of functional groups are obtained in high yield and with good regio-, diastereo-, and enantioselectivity. Mechanistic investigations using density functional theory (DFT) implicate the in situ formation of a rapidly equilibrating mixture of isomeric copper(I) allyl complexes, from which the Curtin-Hammett kinetics determine major isomer of the product. A stereochemical model is provided to explain the high diastereo-enantioselectivity of this process. Finally, this method was applied to the preparation of an important drug, (R)-procyclidine, and a key intermediate in the synthesis of several pharmaceuticals.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据