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Abstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

Chiral heterocyclic compounds are privileged structures in medicinal chemistry. Here, the authors report an in silico strategy for the enzymatic synthesis of pharmaceutically significant chiral N- and O-heterocycles via Baldwin cyclization of hydroxy- and amino-substituted epoxides and oxetanes using epoxide hydrolase mutants.

A diastereo- and enantioselective approach to access chiral CF2-functionalized aziridines from difluorodiazoethyl phenyl sulfone (PhSO2CF2CHN2) and in situ-formed aldimines is described. This multicomponent reaction is enabled by a combined strong Brønsted acid catalytic platform consisting of a chiral disulfonimide and 2-carboxyphenylboronic acid. The optical purity of the obtained CF2-substituted aziridines could be further improved by a practical dissolution–filtration procedure.

Here we report the design and synthesis of two new difluoro-diazoketone reagents (difluorophenylthiol diazoketone and difluoro-phenoxyl diazoketone) and their [3+2] cycloaddition reactions with aryldiazonium salts under silver catalysis conditions. This protocol enables regioselective access to a broad scope of difluorophenylthiol- and difluorophenoxyl-substituted tetrazole-carbinols in a one-pot operation. Further synthetic derivatizations including dephenylthiolation and unexpected phenylthiol group migration/fluorination allow the efficient preparation of α-difluoromethyl tetrazole-carbinols and α-trifluoromethyl tetrazole-thioethers. [ABSTRACT FROM AUTHOR]

Simple bifunctional thioureas, derived from the saccharides and chiral diamines, have promoted Michael-type addition of ketones to [alpha],[beta]-[gamma],[delta]-nitrodienes. The Michael adducts are obtained with high enantioselectivities and the products are transformed into more useful molecules.

The diastereoselective carbometalation reaction of cyclopropenyl esters followed by reaction with acylsilanes provides ?-silylated lactones that undergo a 'sila-Grob' fragmentation to give pyrone enolates as a new source of acyclic δ-diketones, δ-keto acid, and δ-keto ester derivatives possessing a quaternary stereocenter. [ABSTRACT FROM AUTHOR]

An efficient, catalytic, and enantioselective 1,2-addition of terminal 1,3-diynes to aromatic ketones was realized in the presence of 10 mol% of a Cu(OTf)2-hydroxycamphor-sulfonamide complex, affording chiral tertiary alcohols in up to 94% yield and 90% ee. [ABSTRACT FROM AUTHOR]