Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process

Abstract

A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an η(2)-arene:η(2)-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.

Two-step synthesis of chiral fused tricyclic scaffolds from phenols via desymmetrization on nickel

“…2). It is worth mentioning that despite much exploration of the use of chiral NHCs, there has been less reports with nickel-catalyzed reactions 31–40 . N -(2-Biphenyl)- ( L*1 ) and N -(2-isopropylphenyl)- ( L*2 ) substituted NHCs 41 were ineffective to give 3aa .…”

The Importance of Ligand‐Induced Backdonation in the Stabilization of Square Planar d10 Nickel π‐Complexes

“…For example, we are exploring the organometallicc hemistry of nickel, [10][11][12][13][14] which has undergone ar enaissance in recent years. [15][16][17][18][19][20][21] Our focus has been the structure and reactivityo fn ickel p-complexes, which have been reported in aw ide range of catalytic processes, including the coupling of CO 2 and ethylene, [5,[22][23][24][25][26][27][28][29][30][31][32] intermolecular Tischenkoc oupling, [33][34][35] benzoxasilole synthesis, [36,37] the aldol reaction, [38] allylic alkylation, [39] allylic amination, [40] allylic amidation, [41] epoxide functionalization, [42] and Suzuki-Miyaura coupling. [43] Nickel p-complexes of heteroarenes have also been identified as key intermediates in nickel-catalysed catalystt ransfer polycondensation to form polythiophenes.…”

Selective Si−C(sp3) Bond Cleavage in (Aminomethyl)silanes by Carbanionic Nucleophiles and Its Stereochemical Course

“…[14a] Next, it was of special interest to explore the ability of this new reaction to effect stereochemically controlled transformations of silicon-chiral tetraorganosilanes to obtain ad eeper mechanistic insight into this substitution reaction of triorgano(aminomethyl)silanes.S ubstantial progress in constructing asymmetrically substituted silicon centers and in developing new procedures for the transfer of stereochemical information has recently been achieved. [21,22] Thesiliconchiral benzylsilane (S)-1b (Scheme 1, top) is obtained in ah ighly enantiomerically enriched form (e.r. = 99:1) after resolution.…”