Stereoselective Fluoroalkylacylation of Alkynes via Cooperative N-Heterocyclic Carbene/Palladium Catalysis.

Herein, a cooperative N-heterocyclic carbene- and palladium-catalyzed three-component reaction of alkynes with aldehydes and fluoroalkyl iodides is developed. A series of biologically valuable CF2R-incorporated α-substituted enones was obtained in moderate to good yields. This mild catalytic method exhibits exclusive regio- and stereoselectivity, excellent functional group tolerance, and a broad substrate scope including terminal and internal alkynes. Mechanistic investigations disclose that this alkyne fluoroalkylacylation proceeds via a radical relay process in which vinyl iodides serve as putative reaction intermediates.

Ketones from aldehydes via alkyl C(sp3)-H functionalization under photoredox cooperative NHC/palladium catalysis.

Direct synthesis of ketones from aldehydes features high atom- and step-economy. Yet, the coupling of aldehydes with unactivated alkyl C(sp3)-H remains challenging. Herein, we develop the synthesis of ketones from aldehydes via alkyl C(sp3)-H functionalization under photoredox cooperative NHC/Pd catalysis. The two-component reaction of iodomethylsilyl alkyl ether with aldehydes gave a variety of ß-, γ- and δ-silyloxylketones via 1,n-HAT (n = 5, 6, 7) of silylmethyl radicals to generate secondary or tertiary alkyl radicals and following coupling with ketyl radicals from aldehydes under photoredox NHC catalysis. The three-component reaction with the addition of styrenes gave the corresponding ε-hydroxylketones via the generation of benzylic radicals by the addition of alkyl radicals to styrenes and following coupling with ketyl radicals. This work demonstrates the generation of ketyl radical and alkyl radical under the photoredox cooperative NHC/Pd catalysis, and provides two and three component reactions for the synthesis of ketones from aldehydes with alkyl C(sp3)-H functionalization. The synthetic potential of this protocol was also further illustrated by the late-stage functionalization of natural products.

N-Heterocyclic Carbene Catalyzed Three-Component Reaction for the Synthesis of Multi-substituted Benzenes.

An N-heterocyclic carbene-catalyzed three-component reaction of ketone, acetylenedicarboxylate, and enal for the synthesis of multisubstituted benzenes has been developed. The key features of this reaction are mild reaction conditions and high efficiency and chemoselectivity. The corresponding pentasubstituted benzenes are obtained in good to high yields.