The mechanism of CF2-transfer from TMSCF3 (1), mediated by TBAT (2-12 mol%) or by NaI (5-20 mol%), has been investigated by in situ / stopped-flow 19 F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation, and competing TFE / c-C3F6 / homologous perfluoroanion generation, 13 C/ 2 H KIEs, LFERs, CF2-transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing auto-inhibition (TBAT) or stochastic auto-acceleration (NaI), and co-generating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3-anionoid to TMSCF3 (1) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 ( 1) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted.a Relative rates (krel) are for competitive first-order CF2 capture by the alkene/yne, not to overall rates of reaction. b Values in parenthesis by DFT. 26 See sections S3.7, S3.8 and S6.2 in the SI. Singlet CF2 as the ReactiveIntermediate. We began by studying the reaction of TMSCF3 (1) with alkenes 3i, and E/Z-4 and alkyne 5, Table 1. All underwent difluorocyclopropanation, to varying degrees of conversion, in the presence of TMSCF3 (1, 1.5 M) and 1-5 mol % TBAT, or NaI. Reactions of E/Z-4 proceeded stereospecifically, and with >98 % retention. The difluorocyclopropene 8, generated in low yield (12%) from alkyne 5, under the TBATmediated conditions, underwent partial decomposition to unidentified products. In contrast, 8 was quantitatively-generated, and stable, under NaI-mediated conditions, see section S3.3 in the SI. The same difluorocyclopropane products (6, 7) were obtained from 3i and E/Z-4 on thermalization with the zwitterionic CF2-source Ph3PCF2CO2. 22 The relative reactivities (krel) of alkenes 3i, E-4, and Z-4, and the LFER correlation for a-methylstyrenes (3i-vii, r + = -0.6), 23 were independent of the reagent (1 / Ph3PCF2CO2), and initiator (TBAT / NaI), Table 1, 24 within experimental error. Scheme 3. Experimental a and calculated b KIEs for rapid addition of transient singlet CF2 to 3i, at 300 K. 25 a Experimental (exp.) values in THF; and in PhCl, as solvent. 25 b Calculated (calc.) values by DFT, at the M06/6-31+G* level in Gauss-ian09 employing IEF-PCM single points to account for solvation, and goodvibes, kinisot and PyQuiver to compute free energy corrections and KIEs, see sections S1.6 and S6.2 in the SI. 26Kinetic isotope effects for the reaction of p-F-a-methylstyrene 3i with TMSCF3 (1) initiated by TBAT were obtained by a series of competitions of 13 C-and 2 H-labelled a-methylstyrenes 3i against aryl-D4-3i, monitored by 19 F NMR spectroscopy (aryl-DdF = 0.5 ppm). 25 The resulting primary and secondary kinetic isotope effects, Scheme 3, were consistent with thos...

The mechanism of CF3 transfer from R3SiCF3 (R = Me, Et, iPr) to ketones and aldehydes, initiated by M+X– (<0.004 to 10 mol %), has been investigated by analysis of kinetics (variable-ratio stopped-flow NMR and IR), 13C/2H KIEs, LFER, addition of ligands (18-c-6, crypt-222), and density functional theory calculations. The kinetics, reaction orders, and selectivity vary substantially with reagent (R3SiCF3) and initiator (M+X–). Traces of exogenous inhibitors present in the R3SiCF3 reagents, which vary substantially in proportion and identity between batches and suppliers, also affect the kinetics. Some reactions are complete in milliseconds, others take hours, and others stall before completion. Despite these differences, a general mechanism has been elucidated in which the product alkoxide and CF3– anion act as chain carriers in an anionic chain reaction. Silyl enol ether generation competes with 1,2-addition and involves protonation of CF3– by the α-C–H of the ketone and the OH of the enol. The overarching mechanism for trifluoromethylation by R3SiCF3, in which pentacoordinate siliconate intermediates are unable to directly transfer CF3– as a nucleophile or base, rationalizes why the turnover rate (per M+X– initiator) depends on the initial concentration (but not identity) of X–, the identity (but not concentration) of M+, the identity of the R3SiCF3 reagent, and the carbonyl/R3SiCF3 ratio. It also rationalizes which R3SiCF3 reagent effects the most rapid trifluoromethylation, for a specific M+X– initiator.

[2,3]-Sigmatropic rearrangement processes of allylic ylides or their equivalents can be applied to a variety of different substrates and generate products of wide interest/applicability to organic synthesis. This review describes the development and applications of stereoselective [2,3]-rearrangement reactions in which a substoichiometric amount of a catalyst is used in either the formation of the reactive intermediate or the [2,3]-rearrangement step itself.

Benzotetramisole promotes the catalytic asymmetric [2,3]-rearrangement of allylic quaternary ammonium salts (either isolated or prepared in situ from p-nitrophenyl bromoacetate and the corresponding allylic amine), generating syn-α-amino acid derivatives with excellent diastereo- and enantioselectivity (up to >95:5 dr; up to >99% ee).

A mechanistic study of the isothiourea-catalyzed enantioselective [2,3]-rearrangement of allylic ammonium ylides is described. Reaction kinetic analyses using 19F NMR and density functional theory computations have elucidated a reaction profile and allowed identification of the catalyst resting state and turnover-rate limiting step. A catalytically relevant catalyst–substrate adduct has been observed, and its constitution elucidated unambiguously by 13C and 15N isotopic labeling. Isotopic entrainment has shown the observed catalyst–substrate adduct to be a genuine intermediate on the productive cycle toward catalysis. The influence of HOBt as an additive upon the reaction, catalyst resting state, and turnover-rate limiting step has been examined. Crossover experiments have probed the reversibility of each of the proposed steps of the catalytic cycle. Computations were also used to elucidate the origins of stereocontrol, with a 1,5-S···O interaction and the catalyst stereodirecting group providing transition structure rigidification and enantioselectivity, while preference for cation−π interactions over C–H···π is responsible for diastereoselectivity.