One-Pot, Tandem Wittig Hydrogenation: Formal C(sp3)-C(sp3) Bond Formation with Extensive Scope
Rory Devlin, David J. Jones and Gerard P. McGlacken*
*School of Chemistry and Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork, Cork T12 YN60, Ireland,
Email: g.mcglacken
ucc.ie
R. Devlin, D. J. Jones, G. P. McGlacken, Org. Lett., 2020, 22, 5223-5228.
DOI: 10.1021/acs.orglett.0c01874
Abstract
A one-pot, tandem Wittig hydrogenation of aldehydes with stabilized ylides enables a formal C(sp3)-C(sp3) under mild conditions. The reaction is high yielding and broad in scope. Early insights suggest that the chemoselectivity observed in the reduction step is due to partial poisoning of the catalyst.
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Details
The document discusses a one-pot, tandem Wittig hydrogenation of aldehydes with stabilized ylides, enabling formal C(sp3)−C(sp3) bond formation. This method operates under mild conditions, is high yielding, and has broad scope. The process is chemoselective for olefin reduction, attributed to partial catalyst poisoning after the first step. This methodology is demonstrated in synthesizing lapatinib analogues and (±)-cuspareine. The Wittig reaction followed by olefin hydrogenation is performed in aqueous conditions using 1 atm of hydrogen gas, forming C(sp3)−C(sp3) bonds in various substrates with excellent yields. The study highlights the reaction's efficiency with different aldehydes, including aryl, heteroaromatic, and aliphatic types, and its tolerance to various functional groups. The chemoselectivity observed is due to in situ catalyst modulation by phosphorus species, allowing access to substrates difficult to obtain via a two-step protocol. The method's application is showcased in the preparation of novel lapatinib derivatives and a formal synthesis of (±)-cuspareine. The document concludes that this one-pot procedure is an attractive alternative to standard C(sp3)−C(sp3) bond-forming reactions, offering significant advantages in terms of simplicity, yield, and scope.
Key Words
Wittig reaction, esters, hydrogen
ID: J54-Y2020
