Concerning the Structures of Alkali-Metal-MediatedorthoZincation of Benzamides and PhenylO-Carbamate

Abstract

As a further contribution to alkali-metal-mediated metalation, a method for converting C−H bonds directly to C−Zn bonds without the need for an additional salt metathesis step, reactions of the sodium TMP-zincate [(TMEDA)Na(μ-TMP)(μ- t Bu)Zn( t Bu)] (1) with three different electron-rich aromatic substrates, have been investigated. Under ambient-temperature conditions, N,N-diethylbenzamide, N,N-diethyl-3-methoxybenzamide, and N,N-diethyl phenyl O-carbamate were zincated ortho to the substituent group (in between both substituents in the second case) in the crystalline products [(TMEDA)Na(μ-TMP){μ-2-[1-C(O)NEt2]C6H4}Zn( t Bu)] (3), [(TMEDA)Na(μ-TMP){μ-2-(1-C(O)NEt2)(3-OMe)C6H3}Zn( t Bu)] (4), and [(TMEDA)Na(μ-TMP){μ-2-(1-OC(O)NEt2)C6H4}Zn( t Bu)] (6). X-ray crystallography established that, in each case, the deprotonated aromatic fragment is captured by the residue of the bimetallic base, giving rise to seven-membered (NaNZnCCCO) ring structures for 3 and 4 and an eight-membered (NaNZnCCOCO) ring structure for 6. The new zincated aromatics were also characterized by solution-state 1H and 13C NMR spectroscopy. Reactivity studies of 3, 4, and 6 were also performed with iodine. In each case, three molar equivalents of iodine in THF solution gave the ortho-iodo products N,N-diethyl-2-iodobenzamide (7), N,N-diethyl-2-iodo-3-methoxybenzamide (8), and N,N-diethyl-2-iodophenyl-O-carbamate (9) in quantitative, 71% and 75% yields as determined by NMR analysis, respectively.

After-effects of lithium-mediated alumination of 3-iodoanisole: isolation of molecular salt elimination and trapped-benzyne products

“…An interesting parallel can be drawn here with alkalimetal mediated zincations. Bisalkyl TMP zincates formulated as "R 2 Zn(TMP)Li" 34 (which are also adept at chemoselective deprotonations in both typical 34a, 35 and atypical 36 positions) display contrasting reactivity in the zincation of 3-halogenated substituted aromatic molecules; with the metallated product extruding benzyne when R = Me but not when R = t Bu, suggesting steric bulk is critical in preventing benzyne formation (Fig. 6a).…”

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

“…These studies – that have been structurally supported by X-ray crystallography in tandem with NMR spectroscopy – have uncovered the chemical synergy that these mixed-metal alternatives can exhibit, which enabled such reagents to perform special metallation reactions that cannot be reproduced by either of the single-metal components that constitute the mixed-metal reagent. While the alkali metal component is essential for the synergic metallation to follow its course, it is the less electropositive zinc that replaces the departing hydrogen atom, prompting metallations of this type to be best regarded as “Alkali-Metal-Mediated Zincations (AMM Zn )” [ 17 ].…”

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.…”