Enantiospecific, Regioselective Cross‐Coupling Reactions of Secondary Allylic Boronic Esters

Abstract

An original­ syn: The first enantioselective Suzuki–Miyaura cross‐coupling of chiral, enantioenriched secondary allylic boronic esters is described (see scheme; DME=dimethoxyethane, Bpin = pinacolboryl, dba = dibenzylideneacetone). Mechanistic studies show that the reactions proceed via γ‐selective transmetalation followed by reductive elimination. The reaction provides the first independent confirmation that the transmetalation of boronic esters proceeds via a syn pathway.

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

“…The ensuing transmetallation may occur through either an S E or S E 0 mechanism. The S E 0 mode of transmetallation is thought to be prevalent with phosphine-ligated Pd(II) species 25,29 . Thus, in these conditions, both XPhos and (4-CF 3 -C 6 H 4 ) 3 P are expected to first provide s-bonded allylic Pd(II) complex B via a syn-S E 0 pathway made favourable through coordination of the electron-deficient Pd(II) to the electron-rich alkene.…”

“…With allylic boronates, the challenge of controlling selectivity is aggravated by the need to address a third type of selectivity arising from the possibility of forming two different regioisomers (Fig. 1c) [22][23][24][25][26][27][28][29] . Regioisoselectivity (or 'site selectivity') tends to be governed by the intrinsic steric and electronic effects dictated by the allylic substrate.…”

“…Organ 27 , then Yang and Buchwald 28 recently achieved this feat with a simple allylboronate devoid of stereochemistry. Crudden and co-workers 29 reported highly stereoretentive coupling with optically enriched acyclic allylboronates, however without controlling the formation of both regioisomers.…”

Development of New Synthetic Strategies, Tactics and their Applications

“…Along similar lines, in 2013, Chausset‐Boissarie et al . described the regioselective SM cross‐coupling reaction starting with secondary allylic boronate ester ( E )‐ 116 (Scheme ).…”

At the Forefront of the Suzuki–Miyaura Reaction: Advances in Stereoselective Cross-Couplings

“…Furthermore, upon subjection of a branched boronate 40 and a linear boronate 41 to the reaction conditions in a competitive situation, it was observed that there was a complete selectivity for the branched boronate, an indication that there is an important role imparted upon the benzylic nature of the boronate functionality (Scheme 9b). Recently, it was found that these reaction conditions can also be applied towards the stereospecific cross-coupling of optically enriched allylic and propargylic boronates [70]. In a later report [71], it was found that the amount of triphenylphosphine had a direct impact on both the yield and stereochemical outcome of the reaction.…”