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

Abstract

In situ NMR and IR spectroscopy studies were carried out on the rearrangement of lithiated N‐benzyl‐N′‐aryl ureas, which involves N‐to‐C aryl transfer with retention of configuration. The IR spectroscopy studies revealed that initial benzylic lithiation was followed by migration of the aryl ring to yield a lithiated urea product without a detectable dearomatised intermediate. Similar results were obtained by NMR spectroscopy, but when 1,3‐dimethyl‐3,4,5,6‐tetrahydro‐2(1H)‐pyrimidinone (DMPU) was added to the solvent mixture, a transient dearomatised intermediate was detectable during migration of a 1‐naphthyl ring. DFT calculations highlight the importance of coordinated lithium cations, and their migration from one site to another, in the rearrangement. Rearrangement is initiated by migration of a solvated lithium cation from the anionic centre of the starting organolithium to a site close the adjacent phenyl ring, allowing retentive attack of the anionic centre on the more remote ring with movement of the solvated lithium cation to the remote ring stabilising the developing negative charge. A short‐lived spirocyclic intermediate is predicted to undergo elimination by loss of the urea substituent, completing the migration. Coordination of the carbonyl group to a second solvated lithium cation appears to be essential for this step. Calculated shifts for this intermediate when a 1‐naphthyl ring is migrating are consistent with the transient signals observed by NMR spectroscopy. Alternative pathways involving (1) invertive migration and (2) attack on the urea C=O group were also calculated and were found to require significantly higher energy transition states.

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

“…When urea 1a was treated with t -BuLi or s -BuLi in THF at −78 °C for one hour, followed by protonation, carbolithiated products 2a and 2b were isolated in good yield (Scheme 1 and Table 1, entries 1 and 2). Similar reactivity was observed between urea 1a and less hindered organolithiums such as iPrLi or n -BuLi [3], but in THF even at −78 °C a rearrangement [14–18] of the intermediate benzyllithium reduces the yield of the simple carbolithiation product. However, by lowering the temperature to −85 °C rearrangement occured to only a limited extent, and the addition product 2c was obtained in 53% yield (Table 1, entry 3).…”

Lithium Choreography: Intramolecular Arylations of Carbamate‐Stabilised Carbanions and Their Mechanisms Probed by In Situ IR Spectroscopy and DFT Calculations

“…In the model used here, the carbonyl oxygen of the carbamate 2 a replaces one of the THF molecules of this dimer. As in our previous study of lithiated ureas, [38] we do not consider further implicit sol- Scheme 12. Intermediates proposed in the rearrangement of 2 c. Solvation of the lithium cation is assumed but not explicitly shown. Furthermore, we assume that deprotonation to form 2 aLi initially gives the reactant structure B in which the carbanion is bound to a solvated lithium ion.…”

The Truce–Smiles rearrangement and related reactions: a review

“…Another reaction that exhibits some parallels to the TruceSmiles rearrangement is the so-called 62 "Clayden rearrangement" (Scheme 19), a 1,4-aryl migration reaction 63,64 that could be viewed as proceeding through an intermediate that is highly related to a 5-membered spirocyclic Meisenheimer adduct, a hypothesis supported 65,66 by mechanistic studies.…”