Intermolecular Insertion of an N,N‐Heterocyclic Carbene into a Nonacidic CH Bond: Kinetics, Mechanism and Catalysis by (K‐HMDS)₂ (HMDS=Hexamethyldisilazide)

Abstract

The reaction of 2-[13C]-1-ethyl-3-isopropyl-3,4,5,6-tetrahydropyrimidin-1-ium hexafluorophosphate ([13C1]-1-PF6) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide ("(K-HMDS)2") in toluene generates 2-[13C]-3-ethyl-1-isopropyl-3,4,5,6-tetrahydropyrimid-2-ylidene ([13C1]-2). The hindered meta-stable N,N-heterocyclic carbene [13C1]-2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2-[13C]-2-benzyl-3-ethyl-1-isopropylhexahydropyrimidine ([13C1]-14) through formal C-H insertion of C2 (the "carbene carbon") at the toluene methyl group. Despite a significant pKa mismatch (Delta pKa 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 (rho = 4.8(+/-0.3)), and displaying 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 on the K-HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt-effect catalysis law. However, the rate can be satisfactorily predicted by a mole-fraction-weighted net rate constant: -d[2]/dt = ({x2 k(uncat)} + {(1-x2) k(cat)})[2]1[toluene]1, in which x2 is determined by a standard bimolecular complexation equilibrium term. The association constant (Ka) for rapid equilibrium-complexation of 2 with (K-HMDS)2 to form [2(K-HMDS)2] is extracted by nonlinear regression of the 13C NMR shift of C2 in [13C1]-2 versus [(K-HMDS)2] yielding: Ka = 62(+/-7) M(-1); delta(C(2)) in 2=237.0 ppm; delta(C(2)) in [2(K-HMDS)2] = 226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K-HMDS)2 complex [2(K-HMDS)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(K-HMDS)2] over the free carbene (2) may arise from local Brønsted salt-effect catalysis by the (K-HMDS)2 liberated in the solvent cage upon reaction with toluene.

Robust and Electron‐Rich cis‐Palladium(II) Complexes with Phosphine and Carbene Ligands as Catalytic Precursors in Suzuki Coupling Reactions

“…The use of the sterically hindered strong base KHMDS in the generation of NHCs has been documented. [43][44][45] The new complexes are air and moisture stable and poorly dissolve in common organic solvents. All the NMR spectra of 7-9 contain sharp signals.…”

Intramolecular C–H insertion in ring-expanded N-heterocyclic carbenes

“…Supplementary data (NMR numbering schemes for compounds [3][4][5][6] ), 2.29 (s, 3H, C 8 CH 3 ), 2.21 (s, 6H, C o CH 3 ), 2.18 (s, 3H, C 6 CH 3 ), 2.15 (s, 3H, C p CH 3 ), 1.73 (m, 1H, CH 2 2 0 ), 1.60 (m, 1H, CH 2 2 0 ), 1.53 (m, 1H, CH 2 3 0 ), 1.46 (m, 1H, CH 2 3 0 ). 13 C{ 1 H}: d 147.7 (s, C 9 ), 145.0 (s, C i ), 138.6 (s, C o ), 137.7 (s, C o ), 135.0 (s, C p ), 132.0 (s, C 7 ), 130.6 (s, C m ), 130.3 (s, C m ), 130.0 (s, C 4 ), 127.8 (s, C 6 ), 123.4 (s, C 5 ), 118.7 (s, C 8 ), 82.6 (s, C 2 ), 53.7 (s, C 4 0 ), 48.8 (s, C 1 0 ), 35.2 (s, C 3 ), 31.4 (s, C 3 0 ), 29.2 (s, C 2 0 ), 21.2 (s, C 6 CH 3 ), 21.1 (s, C p CH 3 ), 20.5 (s, C o CH 3 ), 20.4 (s, C o CH 3 ), 20.0 (s, C 8 CH 3 ).…”

“…Data for 6: 1 H NMR (see Supplementary data for assignments; 500 MHz, C 6 D 6 , 298 K): d 7.39 (s, 1H, CH 5 ), 6.80 (s, 1H, CH 7 ), 6.77 (s, 2H, CH m ), 6.70 (d, 1H, 3 J HH = 2.9 Hz, CH 2 ), 6.51 (d, 1H, 3 J HH = 2.9 Hz, CH 3 ), 3.88 (t, 2H, 3 J HH = 7.2 Hz, CH 2 1 0 ), 2.62 (t, 2H, 3 J HH = 7.2 Hz, CH 2 3 0 ), 2.48 (s, 3H, C 8 CH 3 ), 2.42 (s, 3H, C 6 CH 3 ), 2.17 (s, 3H, C p CH 3 ), 2.07 (s, 6H, C o CH 3 ), 1.58 (m, 2H, CH 2 2 0 ). 13 C{ 1 H}: d 144.2 (s, C o ), 134.1 (s, C 9 ), 131.8 (s, C i ), 131.5 (s, C 4 ), 130.4 (s, C p ), 130.2 (s, C m ), 129.6 (s, C 2 ), 129.1 (s, C 6 ), 127.2 (s, C 7 ), 120.6 (s, C 8 ), 119.9 (s, C 5 ), 102.0 (s, C 3 ), 47.4 (s, C 1 0 ), 46.4 (s, C 3 0 ), 34.3 (s, C 2 0 ), 21.7 (s, C 6 , 8.78; N, 8.63. C 22 H 28 N 2 requires: C, 82.45; H, 8.81; N, 8.74.…”

“…4 Indeed there is only one example of this class of carbenes reacting with non-acidic C-H bonds, 5 that being the low yielding insertion of a mixed N-Et/ N-i Pr six-membered carbene into a methyl C-H bond of toluene. 6 Substitution of the five-membered carbenes IMes and SIMes (Scheme 1: A and B, R = mesityl) into a range of ruthenium complexes, including Ru(PPh 3 ) 3 (CO)H 2 , Ru(PPh 3 ) 3 (CO)HX (X = F, Cl) and Ru(PPh 3 ) 3 HCl has been previously described. 7 Efforts to react these same precursors with 7-Mes 1 at elevated temperatures failed to generate any Ru-NHC containing products but instead, in all cases, gave the C-H insertion product 3 (Scheme 2).…”

Synthesis by self-assembly and structural characterization of a new co-crystal system {[Cu(NO3)2(H2O)2]L1(NO3)2} (L1 = 1,1′-dibenzyl-3,3′-butyl-diimidazolium-2,2′-diylidene) from copper nitrate and a carbene precursor

“…Recently carbene chemistry has become an active field of research towards applications in catalysis [1][2][3][4][5], NLO [6][7][8][9][10] and liquid crystals [11][12][13][14][15]. For liquid crystal applications, the imidazole rings in particular, provide an effective way to introduce large alkyl chains within the ligand and effectively tune the final properties of such compounds [16][17][18].…”