ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions: Stereoselective Allylation from 1,3-Diene Pronucleophiles

preprint
submitted on 22.07.2019 and posted on 23.07.2019 by Chengxi Li, Kwangmin Shin, Richard Liu, Stephen L. Buchwald
Recently, CuH-catalyzed reductive coupling processes involving carbonyl compounds and imines has become an attractive alternative to traditional methods for stereoselective addition to carbonyls due to the ability to use readily accessible and stable olefin-derived pronucleophiles as surrogates for organometallic reagents. However, the inability to use aldehydes, which traditionally reduce too rapidly in the presence of copper hydride complexes to be viable substrates, has been a major limitation. We show that by exploiting relative concentration effects through slow addition, we can invert this intrinsic reactivity and achieve the reductive coupling of 1,3-dienes with aldehydes. Using this method, both aromatic and aliphatic aldehydes can be transformed to valuable products with high levels of diastereo- and enantioselectivity and in the presence of many useful functional groups. Furthermore, using a combination of theoretical (DFT) and experimental methods, important mechanistic features of this reaction related to stereo- and chemoselectivity were uncovered.

Funding

GM122483

GM058160-17S1

History

Email Address of Submitting Author

kmshin@mit.edu

Institution

Massachusetts Institute of Technology (MIT)

Country

United States

ORCID For Submitting Author

0000-0002-1708-2351

Declaration of Conflict of Interest

No conflict of interest

Exports