Intermolecular insertion of an N,N-heterocyclic carbene into a nonacidic C-H bond: Kinetics, mechanism and catalysis by (K-HMDS)(2) (HMDS = hexamethyldisilazide)

Guy C. Lloyd-Jones*, Roger W. Alder, Gareth J. J. Owen-Smith

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

ne reaction of 2-[C-13]-1-ethyl-3-isopropyl-3,4,5,6-tetrahydropyrimidin-1-ium hexafluorophosphate ([C-13(1)]-PF6) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide ("(K-HMDS)(2)") in toluene generates 2-[C-13]-3-ethyl-l-isopropyl-3,4,5,6-tetrahydropyrimid-2-yli- dene ([C-13(1)]-2). The hindered metastable N,N-heterocyclic carbene [C-13(1)]2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2-[C-13]-2-benzvl-3-ethyl-l-isopropyhexahydro- pyrimidine ([C-13(1)]-14) through formal C-H insertion of C(2) (the "carbene carbon") at the toluene methyl group. Despite a significant pK(a) mismatch (Delta pK(a) 1(+) and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (p=4.8(0.3)), and displayma substantial and rate-limiting primary (k(H)/k(D)=4.2(0.6)) and secondary (k(H)/k(D)=1.18(+/- 0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K-HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo-first-order decay in 2 arises from a first-order dependence on 2. a first-order dependence on toluene (in large excess) and, in the catalytic manifold. a complex noninteger dependence oil the K-HMDS dimer. The rate is not satisfactorily predicted by equations based on the Bronsted salt-effect catalysis law. However, the rate can be satisfactorily predicted by a mole-fraction-weighted net rate constant: -d[2]/dt = ({x(2)k(uncat)}1+{(1-x(2))k(cat)})[2](1)[toluene](1). in which x(2) is determined by a standard bimolecular complexation equilibrium term. The association constant (K,) for rapid equilibrium-complexation of 2 with (K-HMDS)(2) to form [2(KHMDS)(2)] is extracted by nonlinear regression of the C-13 NMR shift of C(2) in [C-13(1)]-2 versus [(K-HMDS)(2)] yielding: K-a =62(+/- 7)M-1: delta(C(2)) in 2 = 237.0ppm: delta(C(2)) in [2(K-HMDS)(2)]= 226.8ppm. It is thus concluded that there is discrete, albeit inefficient. molecular catalysis through the 1:1 carbene/(K-HMDS)(2) complex [2(KHMDS)(2)], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=k(cat)/k(uncat))(.) The greater reactivity of the complex [2(KHMDS)(2)] over the free carbene (2) may arise from local Bronsted salt-effect catalysis by the (K-HMDS)(2) liberated in the solvent cage upon reaction with toluene.

Original languageEnglish
Pages (from-to)5361-5375
Number of pages15
JournalChemistry - A European Journal
Volume12
Issue number20
DOIs
Publication statusPublished - 5 Jul 2006

Keywords

  • carbenes
  • homogeneous catalysis
  • isotope effects
  • kinetics
  • potassium
  • N-HETEROCYCLIC CARBENES
  • CHLORIDE COMPLEXES RHCL(L(R))(3)
  • ALIPHATIC DIAZO-COMPOUNDS
  • STABLE SINGLET CARBENES
  • ELECTRON-RICH ALKENES
  • RAY CRYSTAL-STRUCTURE
  • NUCLEOPHILIC CARBENES
  • COORDINATION CHEMISTRY
  • COUPLING REACTIONS
  • FORMING REACTIONS

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