TMP-cadmiate: A Base for Efficient and Chemoselective Deprotonative Metallation Reactions of Aromatic Compounds

Abstract

Efficient deprotonative cadmiation reactions of functionalized aromatics including heterocycles have been realized using TMP-cadmiate, (TMP) 3 CdLi (TMP = 2,2,6,6-tetramethylpiperidino). The reagent is compatible with reactive functional groups (amide, ester, nitrile and even ketone functions), heavy halogens (Br, I), five-membered aromatic heterocycles (furan, thiophene, oxazole, thiazole, and pyrrole derivatives) and even aromatic aza-heterocycles (pyridine, diazine compounds). Some heterocycles benefiting from doubly activated positions can be dimetallated at room temperature. The deprotonative cadmiation pathways/mechanisms have been studied using computational/theoretical techniques. The lithium arylcadmiates such generated have been evidenced using iodine. Alternative trappings of the species are palladium-catalyzed cross-coupling reactions or simple quench with acid chlorides.

Metal exchange in lithiocuprates: implications for our understanding of structure and reactivity

“…Interest in methods for refining the regioselective functionalization of aromatics by using more selective bases has grown significantly since the inception 1 of what have become known as ‘synergic bases’. 2 These heterobimetallic systems – in their simplest form R m M(NR′ 2 ) n AM (R = organyl; m = 0, 2, 3; M = less polarizing metal; NR′ 2 = amide; n = 1, 2, 3; AM = more polarizing (alkali) metal) – have afforded new levels of reactivity, 3 regioselectivity 4 and functional group tolerance 5 not hitherto available through traditional main group organometallic bases. Recently, a fruitful area of synergic base chemistry that has developed has involved directed cupration using lithium cuprate reagents.…”

Deprotometalation of substituted pyridines and regioselectivity-computed CH acidity relationships

“…Cd 9 ), have been reported for their ability to deprotometalate sensitive aromatics including pyridines.…”

Enantioselective deprotometalation of alkyl ferrocenecarboxylates using bimetallic bases

“…45 While the use of 1 equivalent of (endo-S)3CdLi [59][60][61] led to the diiodide 1-diI with a 75% yield, reducing the amount to 0.5 equivalent provided 1-I with 79% yield (8% of 1-H also recovered) and 44% ee (in favor of the RP). As already documented, 41,[62][63][64] the replacement of zinc by cadmium in mixed lithium-metal amides (or mixture of amides) generally led to an increased reactivity (Scheme 2, bottom left).…”