Regioselective Reductive Coupling of Alkynes and Aldehydes Leading to Allylic Alcohols
Kazuhiko Takai,* Shuji Sakamoto and Takahiko Isshiki
*Department of Applied Chemistry, Faculty of Engineering, Okayama
University, Tsushima, Okayama 700-8530, Japan, Email: ktakai
cc.okayama-u.ac.jp
K. Takai, S. Sakamoto, T. Isshiki, Org. Lett., 2003, 5, 653-655.
DOI: 10.1021/ol0272996
Abstract
Slow addition of a terminal alkyne and water to a mixture of an aldehyde, CrCl2, NiCl2 and a catalytic amount of triphenylphosphine in DMF at 25°C generates a 1,2-disubstituted allylic alcohol regioselectively.
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Details
The document describes a regioselective method for synthesizing 1,2-disubstituted allylic alcohols from terminal alkynes and aldehydes using CrCl2, NiCl2, and triphenylphosphine in DMF at 25 °C. The process involves the addition of a metal-hydride species to a terminal alkyne, generating alkenylmetal compounds that react with aldehydes to form allylic alcohols. Traditional methods like hydroboration, alumination, and zirconation produce 3-alkyl-substituted allylic alcohols, but the direct synthesis of 2-alkyl-substituted allylic alcohols is challenging. The new method employs a mixture of alkyne, CrCl2, NiCl2, and water, leading to the formation of alkenylchromium species via transmetalation from alkenylnickel intermediates. The reaction is enhanced by triphenylphosphine, preventing nickel(0) deposition and improving yields. The method is effective for various alkynes and aldehydes, producing 2-substituted allylic alcohols selectively, except for phenyl acetylene. The reaction tolerates hydroxyl groups and selectively adds to aldehydes over ketones. The study was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Nagase Science and Technology Foundation. Detailed experimental procedures and compound characterizations are available online.
Key Words
Alkynes, Coupling, Allylic Alcohols, Chromium Compounds
ID: J54-Y2003-370
