Enantiospecific sp²–sp³ Coupling of ortho‐ and para‐Phenols with Secondary and Tertiary Boronic Esters

Abstract

The coupling of ortho‐ and para‐phenols with secondary and tertiary boronic esters has been explored. In the case of para‐substituted phenols, after reaction of a dilithio phenolate species with a boronic ester, treatment with Ph3BiF2 or Martin's sulfurane gave the coupled product with complete enantiospecificity. The methodology was applied to the synthesis of the broad spectrum antibacterial natural product (−)‐4‐(1,5‐dimethylhex‐4‐enyl)‐2‐methyl phenol. For ortho‐substituted phenols, initial incorporation of a benzotriazole on the phenol oxygen atom was required. Subsequent ortho‐lithiation and borylation gave the coupled product, again with complete stereospecificity.

ortho‐Directing Chromium Arene Complexes as Efficient Mediators for Enantiospecific C(sp2)–C(sp3) Cross‐Coupling Reactions

“…These processes rely on four basic steps: 1) boronate formation, 2) activation of the aromatic group, 3) stereospecific 1,2‐migration of the alkyl group, and 4) elimination and rearomatization. Suitable activators were found for aromatics with electron‐donating groups in the meta ‐positions and electron‐rich heterocycles (Scheme a),, phenols (Scheme b), and pyridines (Scheme c) …”

Chiral Aniline Synthesis via Stereospecific C(sp3)–C(sp2) Coupling of Boronic Esters with Aryl Hydrazines

“…In related work, we showed that activation of heteroatoms of nitrogen- or oxygen-containing arylboronate complexes could also induce a 1,2-metalate rearrangement to provide coupled products. 9 − 11 For example, we demonstrated that boronate complexes formed from ortho -lithiated benzylamines undergo acylation and 1,2-metalate rearrangement ( Figure 2 B). Subsequent 1,3-borotropic shift of the dearomatized intermediate provides enantioenriched benzylic boronic esters.…”

Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

“…Ortho ‐ and para ‐substituted phenols provide a different opportunity for triggering 1,2‐migration of aryl boronate complexes (Scheme ) . In the coupling of para ‐lithiated phenolates 99 with boronic esters, following formation of boronate complex 100 , 1,2‐migration occurred upon the activation of the phenolate with Martin's sulfurane (Ph 2 S[OC(CF 3 ) 2 Ph]) or triphenylbismuth difluoride (Ph 3 BiF 2 ), forming boronate complexes 102 and 103 , respectively (Scheme a).…”