Preparation of Solid Polyfunctional Alkynylzinc Pivalates with Enhanced Air and Moisture Stability for Organic Synthesis

Abstract

We report the preparation of solid and air-stable polyfunctionalized alkynylzinc pivalates from the corresponding alkynes using TMPZnOPiv (TMP=2,2,6,6-tetramethylpiperidyl) as base. These organozinc pivalates are obtained as powders under mild conditions in excellent yields and can be manipulated in air for several hours without significant decomposition. These zinc reagents show an excellent reactivity in various carbon-carbon bond- forming reactions and 1,3-dipolar cycloadditions. An alkynylzinc pivalate has been used to prepare a carboxyamidotriazole with potential antineoplastic activity in eight steps and 38 % overall yield.

Versatile OPiv-Supported Organozinc Reagents for Transition-Metal-Catalyzed Cross-Couplings

“…The preparation of solid organozinc reagents was not only limited to the (hetero)aryl-and benzylzinc pivalates, but also successfully on the development of solid allylic zinc reagents (21), [22] salt-stabilized zinc amide enolates ( 22) [23] and solid alkynyl zinc reagents (23) [24,25] through OPiv-coordination. [26] As expected, all of these OPiv-supported organozinc pivalates showed enhanced bench-stability and high reactivity in palladium-catalyzed C-C bond-forming reactions.…”

Organozinc Pivalates for Cobalt-Catalyzed Difluoroalkylarylation of Alkenes and Mechanistic Insights

“…Remarkably, Knochel and coworkers recently developed a solid organozinc pivalates (RZnX Mg(OPiv) 2 LiCl, which is abbreviated henceforth as RZnOPiv for the sake of clarity), [16] which show greatly enhanced air and moisture stability after solvent evaporation. [17] These novel organozinc reagents, including (hetero)aryl, [17][18][19][20][21][22] alkynyl, [23][24] and alkyl zinc pivalates, [25] exhibited good reactivity in Pd-catalyzed cross-coupling reactions with unsaturated halides, which further proved to be broadly applicable for the late-stage functionalizations of biologically active molecules. [26] Although palladium catalysts are very useful, the 3d transition-metals, [27][28][29][30][31][32][33][34] especially cobalt [35][36][37][38][39] have recently found numerous applications due to its low toxicity, low-cost and natural abundance.…”

Mechanochemical Activation of Zinc and Application to Negishi Cross‐Coupling

“…[6] Indeed, such an approach often leads to al oss of the broad functional group tolerance afforded by organozinc reagents because they have been prepared via more reactive organometallic species.K nochel and co-workers realized as olution to this through direct zincation of CÀH bonds using zinc-amide bases. [7] An alternative tactic involves the metalation of C À X bonds (B,S cheme 1), as trategy where metal-halogen exchange is particularly popular, but again such an approach leads to al oss of the broad functional group tolerance afforded by organozinc reagents. [8] More attractively,for CÀX bonds,i st he direct oxidative insertion of Zn 0 from an activated zinc metal.…”