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

Damian M. Grainger, Alison Campbell Smith, Mark A. Vincent, Ian H. Hillier*, Andrew E H Wheatley, Jonathan Clayden

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Citations (Scopus)

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. IR and NMR spectroscopy and DFT have been used to investigate the mechanistic course of the rearrangement of aryl migration occurring within lithiated N'-aryl-N-benzyl ureas. An initial lithiated species was identified, which underwent rearrangement without a detectable dearomatised intermediate for a migrating phenyl ring, but with a detectable intermediate for a naphthalene ring.

Original languageEnglish
Pages (from-to)731-743
Number of pages13
JournalEuropean Journal of Organic Chemistry
Issue number4
Early online date6 Dec 2011
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Density functional calculations
  • IR spectroscopy
  • Lithiation
  • Lithium
  • Reaction mechanisms
  • Rearrangement

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