Difluorocarbene Generation from TMSCF: Kinetics and Mechanism of NaI-Mediated and Si-Induced Anionic Chain Reactions.

The mechanism of CF transfer from TMSCF (), mediated by TBAT (2-12 mol %) or by NaI (5-20 mol %), has been investigated by in situ/stopped-flow F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation and competing TFE/CF/homologous perfluoroanion generation, C/H KIEs, LFERs, CF transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF anionoid to TMSCF () has been elucidated.

Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones a concerted asynchronous [2 + 2] cycloaddition: a synthetic and computational study.

The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (R = CF, CF, CF) is reported. Following optimisation, high diastereo- and enantioselectivity was observed for β-lactone formation using CF- and CF-substituted ketones at room temperature (26 examples, up to >95 : 5 dr and >99 : 1 er), whilst -78 °C was necessary for optimal dr and er with CF-substituted ketones (11 examples, up to >95 : 5 dr and >99 : 1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity.

Anion-Initiated Trifluoromethylation by TMSCF: Deconvolution of the Siliconate-Carbanion Dichotomy by Stopped-Flow NMR/IR.

The mechanism of CF transfer from RSiCF (R = Me, Et, iPr) to ketones and aldehydes, initiated by MX (<0.004 to 10 mol %), has been investigated by analysis of kinetics (variable-ratio stopped-flow NMR and IR), C/H 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 (RSiCF) and initiator (MX).

Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of α-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement.

A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity.

Catalytic Enantioselective [2,3]-Rearrangements of Allylic Ammonium Ylides: A Mechanistic and Computational Study.

A mechanistic study of the isothiourea-catalyzed enantioselective [2,3]-rearrangement of allylic ammonium ylides is described. Reaction kinetic analyses using F 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 C and N isotopic labeling.

An isothiourea-catalyzed asymmetric [2,3]-rearrangement of allylic ammonium ylides.

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).

Diastereoselective synthesis of CF3-substituted, epoxide-fused heterocycles with β-(trifluoromethyl)vinylsulfonium salts.

CF(3)-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF(3) substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1).