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. 2017 Mar 1;8(3):1981-1985.
doi: 10.1039/c6sc04466b. Epub 2016 Nov 24.

Enantioselective Narasaka-Heck cyclizations: synthesis of tetrasubstituted nitrogen-bearing stereocenters

Nicholas J Race  1 , Adele Faulkner  1 , Gabriele Fumagalli  1 , Takayuki Yamauchi  1 , James S Scott  2 , Marie Rydén-Landergren  3 , Hazel A Sparkes  1 , John F Bower  1
Affiliations

Enantioselective Narasaka-Heck cyclizations: synthesis of tetrasubstituted nitrogen-bearing stereocenters

Nicholas J Race et al. Chem Sci. .

Abstract

The first examples of highly enantioselective Narasaka-Heck cyclizations are described. A SPINOL-derived P,N-ligand system enables Pd-catalyzed 5-exo cyclization of a range of oxime esters with sterically diverse trisubstituted alkenes to generate dihydropyrroles containing tetrasubstituted nitrogen-bearing stereocenters in 56 to 86% yield and 90 : 10 to 95 : 5 e.r. These processes are rare examples of reactions that proceed via enantioselective migratory insertion of alkenes into Pd-N bonds, and the first where trisubstituted alkenes are used to generate tetrasubstituted stereocenters with high enantioselectivity.

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Figures

Scheme 1
Scheme 1
Scheme 2
Scheme 2. Development of an enantioselective protocol.
Scheme 3
Scheme 3
Scheme 4
Scheme 4. Reductive manipulations of the cyclization products.
See this image and copyright information in PMC

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