康 · 学术 | Reaction of the Day No. 1757

Bench-Stable Solid Organozinc Reagents: Synthesis and Application

Sanjai R Yogaraj, Keerthika Selvam, Mohanavelu M Vijayan, Ramesh Rasappan*

School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Vithura, Thiruvananthapuram, Kerala 695551, India

—Chemrxiv, 2026. Doi: org/10.26434/chemrxiv.15003620/v1

Recommended by Shi Li _ MOC

KEYWORDS:Ni catalysis,Negishi coupling (反应类型), alkyl halides, aryl halides  (原料), aryl and alkyl-zinc reagents (产物), C(sp2)-ZnX, C(sp3)-ZnX, Csp2-Csp3 (成键类型)

ABSTRACT: Organozinc reagents transformed organic synthesis due to their compatibility with functional groups. Nonetheless, organozinc reagents are susceptible to air and moisture and are often produced in solution form, which restricts their industrial application. Solid organozinc pivalates (RZnX·Mg(OPiv)2·nLiCl) were developed by the reaction of RMgX with Zn(OPiv)2·2LiCl. (CF3)2Zn·TMEDA was synthesized from air-stable (DMPU)2Zn(perfluoroalkyl)2, which was derived from ZnEt2 and perfluoroalkyl iodide. A method that generates stable monomeric organozinc species in a single step, eliminates solvents such as DMA, uses commercial Zn, and eliminates stoichiometric additives like LiCl is very desirable. The authors demonstrate the direct synthesis of stable solid organozinc reagents (15 examples), including sterically demanding tBuZnBr, from commercial zinc. They exhibit high stability at room temperature and offer excellent yields in open-air palladium catalysis. These reagents are monomeric, devoid of complex mixtures. Single-crystal XRD, and especially the NMR spectrum, were obtained for these reagents.

Background and This Work

Optimization

Substrate Scope

Application

Proposed mechanism

Summary and Comments

Ramesh Rasappan et al. synthesized 17 organozinc reagents, of which 15 were obtained as solids. Aryl and alkyl-zinc reagents, containing diverse functional groups, were produced. The stability of these novel organozinc reagents was thoroughly assessed; when maintained at 4 oC, they exhibit stability for years to come. They demonstrate significant stability at ambient temperature when stored in a conventional vial sealed with a septum. These reagents were highly efficient in cross-coupling reactions with alkyl and aryl halides. The practical applicability is evidenced by the synthesis of 10 g of PhZnBr and its subsequent utilization in the synthesis of bioactive derivatives. The sterically demanding tBuZnBr was employed in 1,4-addition. Remarkably, their reactivity remained unchanged after one hour of exposure to air. Additionally, an excellent yield was achieved when the palladium-catalyzed coupling of PhZnBr and aryl bromide was performed in air. Single-crystal XRD and HRMS investigations verified that the organozinc complex is monomeric and devoid of complex mixtures, potentially streamlining the transition state model in assessing the reaction process. The NMR spectra were obtained for these organozinc reagents. The ring expansion of cyclopropyl methyl bromide to c-BuZnBr suggests the reaction proceeds via the SET. The current research is focused toward the synthetic applications and the synthesis of CD?ZnX and CF3ZnX.