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

Abstract

A new strategy for the coupling of a broad scope of electronically diverse aromatics to boronic esters is reported. The coupling sequence, which relies on the directed ortho-lithiation of chromium arene complexes followed by boronate formation and oxidation, occurs with complete ortho-selectivity and enantiospecificity to give the coupling products in excellent yields and with high functional group tolerance. An intermediate chromium arene boronate complex was characterized by X-ray, NMR, and IR experiments to elucidate the reaction mechanism.

Photoinduced Transition-Metal-Free Alkynylation of Alkyl Pinacol Boronates

“…1,2 In the past decades, various organoboron compounds have been developed and applied in chemical synthesis. However, as one of the widely accessible organoboron compounds, alkyl pinacol boronates (alkyl-Bpin) have been less explored in C-C bond formation, although 1,2-boronate rearrangements (including Zweifel olefination [3][4][5] and Aggarwal coupling [6][7][8][9][10][11][12][13][14][15][16] ) have solved some problems. Arylboronates have been proven to be the great C-C bond-forming coupling partners in the powerful and versatile Suzuki-Miyaura couplings.…”

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

“…We recently initiated a research program focused on developing alternative, transition-metal-free coupling strategies that proceed through 1,2-metalate rearrangements of in situ generated arylboronate complexes ( Figure 2 A). 7 The rearrangements are triggered by electrophilic attack (S E Ar) of a nucleophilic π-system by a halogenating agent, with subsequent elimination of the boron and halide moieties from the dearomatized intermediate providing the coupled product. A limitation of this method is the requirement for meta -electron-donating groups, which promote the S E Ar pathway, whereas those bearing ortho - or para -substituents react through an undesired S E 2 pathway.…”

“…Such a protocol would provide a convenient method for the synthesis of chiral ortho - and para -substituted anilines, products that are currently inaccessible using our previously developed coupling reactions. 7 Herein, we describe the successful development of such a method in which unactivated secondary and tertiary alkylboronic esters undergo stereospecific, transition-metal-free coupling with ortho - and para -lithiated aryl hydrazines. The resulting aniline products are generated in high yield and with complete enantiospecificity for a range of structurally diverse boronic esters.…”

“…We recognized that this C–N bond cleavage-triggered coupling reaction could be extended to a related N–N bond cleavage if hydrazine derivatives were implemented in the place of benzylic amines (Figure C). Such a protocol would provide a convenient method for the synthesis of chiral ortho - and para -substituted anilines, products that are currently inaccessible using our previously developed coupling reactions . Herein, we describe the successful development of such a method in which unactivated secondary and tertiary alkylboronic esters undergo stereospecific, transition-metal-free coupling with ortho - and para -lithiated aryl hydrazines.…”

“…In addition to cyclohexylboronic ester 5 , other cyclic secondary boronic esters, including cyclododecanyl ( 12 ) and N -Boc-piperidinyl ( 13 ), underwent efficient coupling to generate the aniline products in high yield. Given the well-documented stereospecificity of 1,2-metalate rearrangements of boronate complexes formed from enantioenriched alkylboronic esters, ,− we next investigated the application of this reaction to the coupling of enantioenriched chiral boronic esters. Gratifyingly, para -bromophenyl hydrazine 4a reacted with an enantioenriched secondary boronic ester to give the aniline product 14 in excellent yield and enantiospecificity (es) .…”