Directed meta‐Metalation Using Alkali‐Metal‐Mediated Zincation

Abstract

Transforming a carbon-hydrogen bond of an organic compound into a more useful, more reactive carbon-metal bond (so-called deprotonative metalation), which, in turn, can be treated with an electrophile to create a new carbon-carbon or carbon-heteroatom bond, is one of the most fundamental synthetic approaches that chemists employ to construct compounds. [1,2] Many of these reactions involve a special type of deprotonative metalation, in which an activating functional group is positioned adjacent to the hydrogen atom (strictly a proton) that is to be replaced by the metal cation.

Structural Basis for Regioisomerization in the Alkali-Metal-Mediated Zincation (AMMZn) of Trifluoromethyl Benzene by Isolation of Kinetic and Thermodynamic Intermediates

“…Furthermore, it is only when the latter scenario occurs that unusual regioselectivities are observed for AMM Zn reactions, at positions not available for conventional monometallic reagents, where these favorable π-interactions between the metalated substrate and sodium are not feasible. 8,9,14 …”

Synthesis of Tetra‐, Hexa‐, and Octanuclear Organozinc Ring Systems

“…Alkali-metal-containing zinc complexes often exhibit synergic effects, whereby the reactivity of zinc is greatly enhanced. [7] Addition of Et 2 Zn (2.1 equiv) to a,a-diphenylglycine, Ph 2 C(NH 2 )CO 2 H, in refluxing toluene results in evolution of ethane and affords, following workup, large colorless prisms of 1 in approximately 60 % yield (Figure 1). …”

Heterobimetallic metallation studies of N,N-dimethylphenylethylamine (DMPEA): benzylic C–H bond cleavage/dimethylamino capture or intact DMPEA complex

“…Reagent 1 is a structurally well-defined crystalline compound [25] and efficient metallating (zincating) agent [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] [most recently with Nheterocyclic carbenes (NHCs) [42] ] though it has occasionally also been utilized as a nucleophilic t-butyl source. [43][44] Reagent 2 is a putative compound in that it has only been generated in situ by mixing LiTMP, Bu [45][46][47][48][49] which has been extensively studied.…”