Enantioselective and stereodivergent hydromonofluoroalkylation of conjugated and remote diene

Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chem-icals,enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underdeveloped.Transition-metal-catalyzed asymmetric hydrofluoroalkylation of readily available di-enes represents a novel route to achieve this goal,yet receives scarce study.Here we report an intrigu-ing palladium-catalyzed enantioselective hydromonofluoroalkylation reaction of conjugated dienes.Both monosubstituted and internal dienes proceed well with the transformation and furnish alkyl fluorides in generally>80%yield and>90%ee.A stereodivergent hydromonofluoroalkylation protocol via Pd/Cu co-catalysis is also established for the access to all four stereoisomers of corresponding moieties bear-ing a fully-substituted F-stereogenic center and vicinal tertiary carbon center.In addition,asymmetric migratory hydromonofluoroalkylation of skipped dienes is developed to realize the direct allylic C-H flu-oroalkylation.A compound library of enantioenriched cyclic fluorides is thus built to highlight the trans-formation potential of present methodology.

Catalytic asymmetric synthesis of 1,4-enynes

1,4-Enyne units are ubiquitous skeletons in biologically active molecules and natural products.Especially,they represent versatile building blocks for abundant downstream derivatizations via controllable modifications of both alkene and alkyne units independently.Recently,great efforts have been made to establish efficient protocols to achieve optically active 1,4-enynes.Considering the enormous application potential of enantioenriched 1,4-enyne units but no related review on this topic has been described,here we aim to provide a comprehensive summary on the catalytic methods established for enantioselective constructions of these intriguing skeletons.According to the reaction types,this review is divided into five parts,including asymmetric allylic substitution,asymmetric propargylic substitution,asymmetric alkynylallylic substitution,asymmetric hydroalkynylation and asymmetric 1,2-addition of alkynes to conjugated imines or ketones.

An Unconventional trans-exo-Selective Cyclization of Alkyne-Tethered Cyclohexadienones Initiated by Rhodium(III)-Catalyzed C-H Activation via Insertion Relay

Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process,herein,the authors present a novel strategy to allow trans-exo-selective arylative cyclization of 1,6-enynes.Through initiation of rhodium(III)-catalyzed C-H activation,a diverse range of N-heterocyclic directing groups,including pyridine,pyrazole,imidazo[1,2-a]pyridine,benzoxazole,benzothiazole,and purine,was feasible for the cascade transformation,exhibiting high efficiency(up to 92%yield),broad substrate scope,and excellent functional group compatibility.Moreover,the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility.Based on density functional theory(DFT)calculations,a key three-membered ring intermediate through the insertion relay,rather than the direct E/Z isomerization of alkenyl rhodium species,controlled the stereochemical outcome for this trans-exo-selective cyclization.The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity.