Ni(II)-catalyzed asymmetric alkenylations of ketimines

Mao Quan,Xiaoxiao Wang,Wanbin Zhang,Guoqiang Yang,Ilya D Gridnev,Liang Wu

doi:10.1038/s41467-018-04645-3

Mao Quan, Xiaoxiao Wang + Show 4 more

Open Access

https://doi.org/10.1038/s41467-018-04645-3

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Abstract

Chiral allylic amines are not only present in many bioactive compounds, but can also be readily transformed to other chiral amines. Therefore, the asymmetric synthesis of chiral allylic amines is highly desired. Herein, we report two types of Ni(II)-catalyzed asymmetric alkenylation of cyclic ketimines for the preparation of chiral allylic amines. When ketimines bear alkyl or alkoxycarbonyl groups, the alkenylation gives five- and six-membered cyclic α-tertiary allylic amine products with excellent yields and enantioselectivities under mild reaction conditions. A variety of ketimines can be used and the method tolerates some variation in alkenylboronic acid scope. Furthermore, with alkenyl five-membered ketimine substrates, an alkenylation/rearrangement reaction occurs, providing seven-membered chiral sulfamide products bearing a conjugated diene skeleton with excellent yields and enantioselectivities. Mechanistic studies reveal that the ring expansion step is a stereospecific site-selective process, which can be catalyzed by acid (Lewis acid or Brønsted acid).

Highlights

Chiral allylic amines are present in many bioactive compounds, but can be readily transformed to other chiral amines
Our study began with the reaction of cyclic ketimine (1a) with phenyl alkenylboronic acid (2a) (Table 1)
After screening various reaction conditions including solvent and reaction temperature, we found that the desired product could be obtained with excellent yield and moderate enantioselectivity by a NO H DPC 082

Summary

Introduction

Chiral allylic amines are present in many bioactive compounds, but can be readily transformed to other chiral amines. We report two types of Ni(II)-catalyzed asymmetric alkenylation of cyclic ketimines for the preparation of chiral allylic amines. We report two types of Ni(II)-catalyzed asymmetric alkenylations of cyclic ketimines for the preparation of a series of chiral α-tertiary and α-secondary allylic amines under mild reaction conditions. The addition of alkenylboron reagents to ketimines, especially for the first-row late transition-metal-catalysis (including nonasymmetric process), remains highly desirable. The preparation of seven-membered chiral sulfamides via the asymmetric addition of organoboron reagents to imines has not been previously reported, possibly due to the lack of a method for the synthesis of related substrates. We report a Ni(II)-catalyzed asymmetric cascade alkenylation/ring-expansion of unstrained five-membered cyclic ketimines via an α,α-dialkenyl substituted five-membered sulfamide intermediate (Fig. 1d, reaction ii), providing a series of sevenmembered cyclic α-substituted chiral sulfamides[59, 60]. We found that in our reaction, the ring expansion step is a site-selective and stereospecific process

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