Stereospecific, Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling of Allylic Pivalates To Deliver Quaternary Stereocenters

Abstract

Recognizing the importance of all-carbon, quaternary stereocenters in complex molecule synthesis, a stereospecific, nickel-catalyzed cross-coupling of allylic pivalates with arylboroxines to deliver products equipped with quaternary stereocenters and internal alkenes was developed. The enantioenriched allylic pivalate starting materials are readily prepared, and a variety of functional groups can be incorporated on both the allylic pivalate and the arylboroxine. Additional advantages include the use of a commercially available and air-stable Ni(II) salt and BISBI ligand, mild reaction conditions, and high yields and ee’s. The observed stereoinversion of this reaction is consistent with an open transition state in the oxidative addition step.

Nickel-Catalyzed Hydroarylation of in Situ Generated 1,3-Dienes with Arylboronic Acids Using a Secondary Homoallyl Carbonate as a Surrogate for the 1,3-Diene and Hydride Source

“…Insertion of the terminal alkene moiety of the diene ligand to a Ni–H bond seems to take place due to the formation of the π-allylnickel intermediate III . Transmetalation between the intermediate III and borate species followed by the reductive elimination from intermediate IV would produce the desired coupling product 3aa along with the regeneration of nickel(0) species …”

Asymmetric synthesisviastereospecific C–N and C–O bond activation of alkyl amine and alcohol derivatives

“…As we considered an efficient and convenient approach to the synthesis of quaternary stereocenters substituted with internal alkenes, we were inspired to develop a stereospecific, nickel-catalyzed Suzuki–Miyaura cross-coupling of allylic pivalates and arylboronates (Scheme 20). 97 The secondary pivalates 111 were readily prepared in highly enantioenriched form using a CBS reduction. 98 Although electron-rich phosphine dppf gave high stereochemical fidelity, it afforded low yield, which we hypothesized was due to decomposition of starting material from redox activity with the ferrocene.…”

Indolylboronic Acids: Preparation and Applications

“…Selected examples show how chloro- [29], bromo- [30], bromoindolyl phosphate [31], and triflates [32] are all capable of coupling with boronic acids under mild reaction conditions. Yet, a wide variety of allylic alcohols [33], heterocyclic halides [34], bromoenol phosphates [35], sulfones [36], and sulfonates [37] have been used as electrophilic templates in reactions with indolylboronic acids under Suzuki-Miyaura reaction conditions involving, for example EvanPhos [38] and tri- tert -butylphosphine ligand [39], nickel [40], and rhodium [41] catalysts, as well as asymmetric transformations [42,43]. The abovementioned examples illustrate the practical application of the Suzuki-Miyaura reaction by means of both electrophilic and nucleophilic indolyl templates for the synthesis of substituted indoles.…”