Nickel-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents in the presence of 1,3-butadiene: mechanistic studies of four-component coupling and competing cross-coupling reactions.

Takanori Iwasaki,Asuka Fukuoka,Nobuaki Kambe,Masahiro Ehara,Tao Yang,Ichiro Hisaki,Wataru Yokoyama,Xin Min,Hitoshi Kuniyasu

doi:10.1039/c7sc04675h

Abstract

We describe the mechanism, substituent effects, and origins of the selectivity of the nickel-catalyzed four-component coupling reactions of alkyl fluorides, aryl Grignard reagents, and two molecules of 1,3-butadiene that affords a 1,6-octadiene carbon framework bearing alkyl and aryl groups at the 3- and 8-positions, respectively, and the competing cross-coupling reaction. Both the four-component coupling reaction and the cross-coupling reaction are triggered by the formation of anionic nickel complexes, which are generated by the oxidative dimerization of two molecules of 1,3-butadiene on Ni(0) and the subsequent complexation with the aryl Grignard reagents. The C-C bond formation of the alkyl fluorides with the γ-carbon of the anionic nickel complexes leads to the four-component coupling product, whereas the cross-coupling product is yielded via nucleophilic attack of the Ni center toward the alkyl fluorides. These steps are found to be the rate-determining and selectivity-determining steps of the whole catalytic cycle, in which the C-F bond of the alkyl fluorides is activated by the Mg cation rather than a Li or Zn cation. ortho-Substituents of the aryl Grignard reagents suppressed the cross-coupling reaction leading to the selective formation of the four-component products. Such steric effects of the ortho-substituents were clearly demonstrated by crystal structure characterizations of ate complexes and DFT calculations. The electronic effects of the para-substituent of the aryl Grignard reagents on both the selectivity and reaction rates are thoroughly discussed. The present mechanistic study offers new insight into anionic complexes, which are proposed as the key intermediates in catalytic transformations even though detailed mechanisms are not established in many cases, and demonstrates their synthetic utility as promising intermediates for C-C bond forming reactions, providing useful information for developing efficient and straightforward multicomponent reactions.

Highlights

Metal-catalyzed multicomponent coupling reactions are useful and straightforward synthetic methods, because they canEdge Article organoaluminium reagents.[7,8] This reaction could introduce two different carbon moieties into the 2,6-octadiene framework
Aiming at the construction of carbon skeletons, we recently developed the multicomponent coupling reaction of two molecules of 1,3-butadiene, aryl Grignard reagents, and alkyl uorides to give a 1,6-octadiene bearing an alkyl group arising from the alkyl uorides at the 3-position, and an aryl group arising from the aryl Grignard reagents at the 8-position (Scheme 1).[12]
When unsubstituted aryl Grignard reagents were employed instead, the competing reaction of direct crosscoupling of alkyl uorides with aryl Grignard reagents occurred, resulting in a mixture of cross-coupling and four-component coupling products (Scheme 1).[14]. In these reactions as well as our previously reported cross-coupling reactions,[15] an anionic nickel complex B generated by the reaction of the bis(p-allyl) nickel complex A with the Grignard reagent is likely the key intermediate, which reacts with electrophiles at the Ni center to promote the cross-coupling reaction or at the gcarbon of the s-allyl giving rise to four-component coupling products

Summary

Introduction

Edge Article organoaluminium reagents.[7,8] This reaction could introduce two different carbon moieties into the 2,6-octadiene framework. The structures and chemical characteristics of anionic complexes of transition metals (the so-called ate complexes16) have rarely been studied, except for the case of cuprates,[17] even though ate complexes have been proposed as key intermediates in catalytic C–C bond formations.[18,19,20,21] In addition, theoretical calculations of ate complexes have not been well-established because of a lack of structural information of ate complexes (especially the counter cation). Another challenge in this study is to develop a means for theoretical calculations of ate complex-mediated transformations

Reaction using aryl Grignard reagents

Mechanistic studies

Computational studies

Conclusions