We have studied copper-catalyzed cross-coupling of chiral α-CF₃-substituted allylboronic acids with α-diazoketones. The reaction proceeds with excellent regioselectivity and stereoselectivity via allylic rearrangement. The method is useful for formation a new allylic C(sp³)–C(sp³) bond with high selectivity. The poor yield is a limitation of this reaction.

18F-labelling of nitrogen-containing arenes via copper-mediated radiofluorination (CMRF) was investigated. The studies targeted the analogues of the anti-cancer drug melflufen with an alkylating bis(2-chloroethyl)amino pharmacophore. Studies of the melflufen analogues and various model compounds indicated that the copper mediated boron-fluorine-18 exchange reaction is affected differently by the three nitrogen-containing groups in the target compound. The largest inhibitory effects on the fluorine labelling process were exerted by the tertiary amine based bis(2-chloroethyl)amino pharmacophore. The best results were achieved by applying bipyridyl ligands for the copper mediator.

Density functional theory calculations have been performed to investigate the mechanism for the BINOL-catalyzed asymmetric homologation of alkenylboronic acids with CF₃-diazomethane. The reaction proceeds via a chiral BINOL ester of the alkenylboronic acid substrate. The calculations reveal a complex scenario for the formation of the chiral BINOL-alkenylboronate species, which is the key intermediate in the catalytic process. The aliphatic alcohol additive plays an important role in the reaction. This study provides a rationalization of the stereoinduction step of the reaction, and the enantioselectivity is mainly attributed to the steric repulsion between the CF₃ group of the diazomethane reagent and the γ-substituent of the BINOL catalyst. The complex potential energy surface obtained by the calculations is analyzed by means of microkinetic simulations.

Homologation of trisubstituted fluoroalkenes followed by allylboration of aldehyde, ketone and imine substrates is suitable for synthesis of β-fluorohydrin and amine products. In the presence of (R)-iodo-BINOL catalyst enantioselectivities up to 99 % can be achieved by formation of a single stereoisomer with adjacent stereocenters, of which one is a tertiary C−F center.

We have developed a new three-component catalytic coupling reaction of alkynyl boronates, diazomethanes, and aliphatic/aromatic ketones in the presence of BINOL derivatives. The reaction proceeds with a remarkably high enantio- and diastereoselectivity (up to three contiguous stereocenters) affording tertiary CF₃-allenols in a single operational step. The reaction proceeds under mild, neutral, metal-free conditions, which leads to a high level of functional group tolerance.

A broad range of aliphatic, aromatic, and heterocyclic boronic acids were successfully homologated using trifluorodiazoethane in the presence of BINOL derivatives to provide the corresponding chiral trifluoromethyl containing boronic acid derivatives in high yields and excellent enantioselectivity. The in situ conversion of the chiral transient boronic acids to the corresponding alcohols or β-CF3 carboxylates are also demonstrated. 

We report herein a new method for the synthesis of densely functionalized chiral allyl SCF3, SCF2R, SCN and SAr species with a separate CF3 functionality. The synthetic approach is based on selenium-catalyzed sulfenofunctionalization of chiral α-CF3 allylboronic acids. The reactions proceeded with remarkably high stereo-, diastereo- and site-selectivity, based on the formation of a stable thiiranium ion followed by rapid deborylative ring opening. © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a-COCF3 functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of this new method was demonstrated by the synthesis of fluorine-18 labelled neutrophil elastase inhibitors, which are potentially useful for detection of inflammatory disorders.

The electrophilic fluorination of geminal alkyl substituted vinyl-Bmida derivatives proceeds via bora-Wagner-Meerwein rearrangement. According to DFT modelling studies this rearrangement occurs with a low activation barrier via a bora-cyclopropane shaped TS. The Bmida group has a larger migration aptitude than the alkyl moiety in the Wagner-Meerwein rearrangement of the presented electrophilic fluorination reactions.

1,1-Disubstituted styrenes with internal oxygen and nitrogen nucleophiles undergo oxidative fluorocyclization reactions with in situ generated chiral iodine(III)-catalysts. The resulting fluorinated tetrahydrofurans and pyrrolidines contain a tertiary carbon–fluorine stereocenter. Application of a new 1-naphthyllactic acid-based iodine(III)-catalyst allows the control of tertiary carbon–fluorine stereocenters with up to 96% ee. Density functional theory calculations are performed to investigate the details of the mechanism and the factors governing the stereoselectivity of the reaction.