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Catalytic diastereo- and enantioselective additions of versatile allyl groups to N-H ketimines.

Catalytic diastereo- and enantioselective additions of versatile allyl groups to N-H ketimines.

Authors :
Jang H
Romiti F
Torker S
Hoveyda AH
Source :
Nature chemistry [Nat Chem] 2017 Dec; Vol. 9 (12), pp. 1269-1275. Date of Electronic Publication: 2017 Jul 17.
Publication Year :
2017

Abstract

There are many biologically active organic molecules that contain one or more nitrogen-containing moieties, and broadly applicable and efficient catalytic transformations that deliver them diastereoselectively and/or enantioselectively are much sought after. Various methods for enantioselective synthesis of α-secondary amines are available (for example, from additions to protected/activated aldimines), but those involving ketimines are much less common. There are no reported additions of carbon-based nucleophiles to unprotected/unactivated (or N-H) ketimines. Here, we report a catalytic, diastereo- and enantioselective three-component strategy for merging an N-H ketimine, a monosubstituted allene and B <subscript>2</subscript> (pin) <subscript>2</subscript> , affording products in up to 95% yield, >98% diastereoselectivity and >99:1 enantiomeric ratio. The utility of the approach is highlighted by synthesis of the tricyclic core of a class of compounds that have been shown to possess anti-Alzheimer activity. Stereochemical models developed with the aid of density functional theory calculations, which account for the observed trends and levels of enantioselectivity, are presented.

Details

Language :
English
ISSN :
1755-4349
Volume :
9
Issue :
12
Database :
MEDLINE
Journal :
Nature chemistry
Publication Type :
Academic Journal
Accession number :
29168479
Full Text :
https://doi.org/10.1038/nchem.2816