Lithium Diisopropylamide-Mediated Reactions of Imines, Unsaturated Esters, Epoxides, and Aryl Carbamates:  Influence of Hexamethylphosphoramide and Ethereal Cosolvents on Reaction Mechanisms

Abstract

Several reactions mediated by lithium diisopropylamide (LDA) with added hexamethylphosphoramide (HMPA) are described. The N-isopropylimine of cyclohex-anone lithiates via an ensemble of monomer-based pathways. Conjugate addition of LDA/HMPA to an unsaturated ester proceeds via di-and tetra-HMPA-solvated dimers. Deprotonation of norbornene epoxide by LDA/HMPA proceeds via an intermediate metalated epoxide as a mixed dimer with LDA. Ortholithiation of an aryl carbamate proceeds via a mono-HMPA-solvated monomer-based pathway. Dependencies on THF and other ethereal cosolvents suggest that secondary-shell solvation effects are important in some instances. The origins of the inordinate mechanistic complexity are discussed.

Mechanism of Lithium Diisopropylamide-Mediated Ortholithiation of 1,4-Bis(trifluoromethyl)benzene under Nonequilibrium Conditions: Condition-Dependent Rate Limitation and Lithium Chloride-Catalyzed Inhibition

“…20 The tetrasolvated dimers have occasionally been implicated 1,2,23 and attributed to triple ions. 24 Although triple ion computations are of no quantitative value because of their ionic bonds, 25 the cationic and anionic fragments of transition structure 7 are both computationally viable.…”

“…The dimer-based mechanism shifts from a rate-limiting aggregation event at high ArH to rate-limiting metalation—[A 2 S 4 (ArH)] ‡ —at low ArH. Confronted by evidence of highly solvated dimers, 1,2,23 we have routinely invoked triple ions similar to 7 . Although triple ions are difficult to examine computationally because of electron correlation problems associated with ionic bonds, 25 they are amply documented in the structural lithium amide and organolithium literature.…”

Synthesis of a 7-Azaindole by Chichibabin Cyclization: Reversible Base-Mediated Dimerization of 3-Picolines

“…The third-order dependence on the THF concentration (measured 2.9 ± 0.2) was surprising. Precedent suggests that the THF order could include secondary-shell solvation effects 20. Nonetheless, using 2,2,5,5-Me 4 THF as a polar, but chemically inert cosolvent afforded no reduction in the THF order 20.…”

“…Precedent suggests that the THF order could include secondary-shell solvation effects 20. Nonetheless, using 2,2,5,5-Me 4 THF as a polar, but chemically inert cosolvent afforded no reduction in the THF order 20. Evidence of high coordinate lithium support such a highly solvated transition structure as possible 21.…”

Selenolatos metálicos em reações multicomponentes do tipo Michael-aldol: adutos de Morita-Baylis-Hillman e derivados

“…Neste sentido, buscando novas transformações destes substratos, decidimos investigar a possibilidade de enolização de ésteres derivados de MBH afim de verificar possíveis transformações induzidas por esta nova espécie. De particular interesse seria a formação de lactonas de seis membros (194), oriundas da ciclização intramolecular de ésteres de MBH (192) A nitrila foi substituída por um éster, que levaria à formação de um enolato como intermediário e, a porção aromática provenienter do aldeído foi substituída por uma cadeia alquílica, eliminando efeitos de conjugação (198)…”