Transforming LiTMP Lithiation of Challenging Diazines through Gallium Alkyl Trans‐Metal‐Trapping

Abstract

This study establishes a new trans‐metal‐trapping (TMT) procedure based on a mixture of LiTMP (the base) and tris(trimethylsilylmethyl)gallium [Ga(CH2SiMe3)3, GaR3] (the trap) that, operating in a tandem manner, is effective for the regioselective deprotonation of sensitive diazines in hydrocarbon solution, as illustrated through reactions of pyrazine, pyridazine, and pyrimidine, as well as through the N‐S heterocycle benzothiazole. The metallo‐activated complexes of all of these compounds were isolated and structurally defined.

Trans-Metal-Trapping Meets Frustrated-Lewis-Pair Chemistry: Ga(CH2SiMe3)3-Induced C–H Functionalizations

“…TMT was then successfully used for regioselective metalation of challenging sensitive, unactivated diazines in hydrocarbon solutions as well as the N–S heterocycle benzothiazole. 31 Metalated intermediates of all of these reactions were isolated and structurally defined, showing remarkable stability. Remarkably, we can carry out these reactions under mild reaction conditions, using stoichiometric amounts of metalating reagents, and at room temperature, contrasting with previous reports that require large excesses of LiTMP (up to 4 equiv) as well as strict temperature control (−78 °C) to avoid decomposition of the lithio intermediates, and even under these restrictive conditions, yields tend to be moderate.…”

“…32 Scheme 3 summarizes some of our investigations of the metalation of pyrazine. 31 Reacting 1 equiv of a GaR 3 /LiTMP mixture using hexane as the solvent and the tridentate donor PMDETA (as a crystallization aid) afforded the 2-monogallated complex [1-(PMDETA)Li-3-(GaR 3 )C 4 H 3 N 2 ] ( 1 ; Scheme 3). Furthermore, to show stoichiometric control, two hydrogen atoms can be removed from the 2 and 5 positions of pyrazine when the base/trap/substrate ratio was doubled to 2:2:1 ( 2 in Scheme 3).…”

“…The Ga–sp 2 C(BIm) bond distance of 2.054(3) Å is in excellent agreement with the similar Ga–sp 2 C(btz) bond of 2.062(3) Å previously found in 6 . 31 While 2-picolyl anions can exhibit different coordination modes to metals depending on the degree of delocalization of the negative charge into the ring, 34 the geometrical parameters of 8 suggest that this fragment is best described as a carbanionic ligand, forming a Ga–CH 2 bond [Ga–C13 2.099(4) Å in Figure 5] that is comparable to the remaining Ga–C alkyl bonds in 8 (mean 2.027 Å). This particular bonding mode is further supported by the Li–N bond distance [Li1–N1 2.055(8) Å in Figure 5], which is noticeably longer than the corresponding bond found in the enamido complex [(2-CH 2 -pyridine)Li(PMDETA)] [Li–N 2.002(4) Å] 34e and is similar to that found in 7 [Li1–N2 2.063(6) Å].…”

Trans‐Metal‐Trapping: Concealed Crossover Complexes En Route to Transmetallation?

“…Establishing that TMT is not confined to Al‐based traps, tris(trimethylsilylmethyl)gallium [Ga(CH 2 SiMe 3 ) 3 , GaR 3 ] proved an effective trap combined with LiTMP in reactions with diazines . This important class of natural heterocycle finds application in commodities such as agrochemicals, foodstuffs, and pharmaceuticals.…”

“…Establishing that TMT is not confined to Al-based traps, tris(trimethylsilylmethyl)gallium [Ga(CH 2 SiMe 3 ) 3 ,G aR 3 ]p roveda ne ffectivet rap combined with LiTMPi nr eactions with diazines. [37] Scheme12. Synthesis of 2-bromo-4-iodo-6-chloroanisole using trans-metaltrapping showing the structures of the bimetallic Li/Al intermediates.…”