N to C Aryl Migration in Lithiated Carbamates: α-Arylation of Benzylic Alcohols

Abstract

We report a new mode of reactivity displayed by lithiated O-benzyl carbamates carrying an N-aryl substituent: upon lithiation, the N-aryl group is transferred cleanly from N to C. An arylation of the carbamate results, providing a route to alpha,alpha-arylated secondary or tertiary alcohols. We also report density functional theory calculations supporting the proposal that arylation proceeds through a dearomatizing attack on the aromatic ring, a significantly lower energy pathway than the 1,2-acyl transfer observed with related N-alkyl carbamates.

The Mechanism of the Stereospecific Intramolecular Arylation of Lithiated Ureas: The Role of Li+ Probed by Electronic Structure Calculations, and by NMR and IR Spectroscopy

“…We previously reported preliminary calculations of the corresponding reaction of a carbamate 6 (Scheme 2) by employing a small model similar to M1. [17] We found that in this case inversion is favoured; a feature we attribute to the preferred binding of Li + to the carbamate's benzylic oxygen atom rather than to the phenyl ring, as found herein for the urea.…”

“…Finally, we note that, although we have located two alternative pathways leading to a 1,4-aryl shift in the ureas studied herein, we believe that we cannot infer from these results the reasons for the stereochemical outcomes observed in the carbamates [17,18] or thiocarbamates; [22] each system requires individual investigation.…”

“…LDA has been used experimentally as an alternative to alkyllithiums in rearrangements of more sensitive ureas, [16,19] and is essential for stereospecific rearrangements of the corresponding 1,4-aryl shift in carbamates. [17,18] We note that a crystal structure of an LDA-THF complex [35] shows a dimer with each Li + ion coordinated to a single THF molecule and sharing two amide ligands with the second lithium ion. In the system studied herein, the carbonyl oxygen replaces one of the THF molecules of this dimer.…”

“…In complementary experimental work, we have shown that, when carbamates carry an NЈ-aryl substituent, the lithio derivatives (formed with either alkyllithiums or N-lithioamines) of benzylic ureas [15,16] 5 and carbamates [17,18] 6 undergo a remarkable NǞC aryl migration (Scheme 2). Furthermore, related reactions occur with allylic ureas, [19] cyclic ureas, [20] lithiated ureas generated by carbolithiation, [21] and benzylic thiocarbamates.…”

Umpolung reactions at the α-carbon position of carbonyl compounds

“…On the other hand, upon treatment with less hindered organolithium (n-BuLi), the rearranged product 41a was obtained by N → C migration of the Nphenyl ring of 40a. 16,17 The product 41a was easily converted to the tertiary alkylamine 42a by heating in n-butanol, indicating that this "alkylarylation" of enamine 38a could constitute a useful new method for the construction of multiply branched alkylamines. Table 4 shows the results of treating N-vinylureas 38a-f with RLi.…”