Lewis acid complexed heteroatom carbanions; a new concept for α-metallation of tertiary amines

Abstract

BF3 complexes of typical benzylic, allylic and saturated N-methyl tertiary amines were a-lithiated, with lithium tetramethylpiperidide (LTMP) or sec-butyllithium, and were treated with electrophiles.This Communication describes the concept of facilitating a-deprotonation of heteroatom compounds by complexation with a Lewis acid, and shows its utility for regioselective formation of C-C bonds in some tertiary amines (Scheme 1). $ Tertiary amines offer a real test of this idea since nitrogen, unlike phosphorus and sulphur, does not provide sufficient t Part of this work was presented at the 17th IUPAC International

Thermochemical Data of Organic Ions Obtained from Investigations in the More or Less “Diluted” Gas Phase

“…Whereas deprotonation of N-methyl-1,2,3,4-tetrahydroisoquinoline (1) and its Cr(CO) 3 complex 1 a with n-butyllithium occurs at C4 in the absence of Lewis acids, [9,10] the formation of 1 b by complexation of 1 with boron trifluoride gives rise to deprotonation at C1. [11,12] Instead of Scheme 2. Regioselective deprotonation of free and complexed 1.…”

Thermochemische Daten organischer Ionen aus Untersuchungen in der mehr oder weniger „verdünnten” Gasphase

“…Während NMethyl-1,2,3,4-tetrahydroisochinolin 1 ohne Lewis-Säure oder nach {Cr(CO) 3 }-Komplexierung zu 1 a mit n-Butyllithium an C4 deproniert wird, [9,10] führt die Komplexierung mit Bortrifluorid (31 b) zur Deprotonierung an C1. [11,12] Anstelle der Komplexe 2 a und der freien Basen 2 entstehen hierbei mit hoher Regioselektivität die leicht isolierbaren Komplexe 3 a, und man gelangt zu den 1-Alkylisochinolinen 3. Mit dieser Methode wurde kürzlich die Alkylierung von Tröger-Basen an den Benzylpositionen erheblich verbessert.…”

The aporhoeadane alkaloids

“…In one example, Kessar et al described a chilenine synthesis that used the known base induced carbinol-carbonyl transposition, 6,61 but constructed the substrate, prechilenine, from simple building blocks (Scheme 80). 63 Their synthesis began with the known condensation 64 of dihydroisoquinoline 217 and 6,7-dimethoxyphthalide (258), which was prepared from ovanillin. 65 The lactam that resulted (259) could be oxidized to ketone 260, however, since the ketone was unstable, the lactam was oxidized directly to hydroxyketone 7 using excess PCC and longer reaction times.…”

“…The benzazepine was accompanied by a 29% yield of an undesired benzylisoquinoline side product. Reduction of both olefins of the benzazepine with sodium cyanoborohydride was accompanied by intramolecular cyclization that formed the N7-C8 bond giving the tetrahydroisoindolobenzazepine core (53). The removal of the undesired ester at C6 was accomplished by DIBAL reduction to the aldehyde (54) and decarbonylation with bis(triphenylphosphine)rhodium(I) carbonyl chloride, ultimately yielding lennoxamine (11).…”