NHC-Ni catalyzed enantioselective synthesis of 1,4-dienes by cross-hydroalkenylation of cyclic 1,3-dienes and heterosubstituted terminal olefins

Yang Chen,Liang Dang,Chun-Yu Ho

doi:10.1038/s41467-020-16139-2

Yang Chen, Liang Dang + Show 1 more

Open Access

https://doi.org/10.1038/s41467-020-16139-2

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Abstract

Enantioenriched 1,4-dienes are versatile building blocks in asymmetric synthesis, therefore their efficient synthesis directly from chemical feedstock is highly sought after. Here, we show an enantioselective cross-hydroalkenylation of cyclic 1,3-diene and hetero-substituted terminal olefin by using a chiral [NHC-Ni(allyl)]BArF catalyst. Using a structurally flexible chiral C2 NHC-Ni design is key to access a broad scope of chiral 1,4-diene 3 or 3′ with high enantioselectivity. This study also offers insights on how to regulate chiral C2 NHC-Ni(II) 1,3-allylic shift on cyclic diene 1 and to build sterically more hindered endocyclic chiral allylic structures on demand.

Highlights

Enantioenriched 1,4-dienes are versatile building blocks in asymmetric synthesis, their efficient synthesis directly from chemical feedstock is highly sought after
Complications related to undesired steric competitions and terminal olefin consumptions by both facile isomerization and oligomerization are hard to solve[26]
We have discovered a cross-hydroalkenylation of cyclic 1,3-diene 1 with heterosubstituted terminal olefin 2 by using achiral IPr-Ni(II) as a catalyst[26,27,28,29,30] (IPr = 1,3-bis(2,6diisopropylphenyl)−1,3-dihydro-2H-imidazol-2-ylidene)

Summary

Introduction

Enantioenriched 1,4-dienes are versatile building blocks in asymmetric synthesis, their efficient synthesis directly from chemical feedstock is highly sought after. 1234567890():,; Other than asymmetric allylic substitutions and Diels-Alder reactions[1,2,3], cyclic 1,3-diene chiral insertion into a transition metal catalyst represents one of the most important ways to build endocyclic chiral allylic structures for drugs synthesis[4]. Significant advances along this line have been made by using M-boryl species, in which notable chiral ligand designs fit at lowsubstitution degree have been established[5,6,7,8,9,10] (Fig. 1a). We develop a [chiral C2 NHC–Ni(allyl)]BArF catalyst a Boration by Chiral L-M-Bpin

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