Three‐Component Alkene Difunctionalization by Direct and Selective Activation of Aliphatic C−H Bonds

Abstract

Catalytic alkene difunctionalization is ap owerful strategy for the rapid assembly of complex molecules and has wide range of applications in synthetic chemistry.D espite significant progress,acompelling challenge that still needs to be solved is the installation of highly functionalizedC (sp 3)hybridized centers without requiring pre-activated substrates. We herein report that inexpensive and easy-to-synthesize decatungstate photo-HAT, in combination with nickel catalysis,p rovides av ersatile platform for three-component alkene difunctionalization through direct and selective activation of aliphatic CÀHb onds.C ompared with previous studies,t he significant advantages of this strategy are that the most abundant hydrocarbons are used as feedstocks,a nd various highly functionalizedtertiary,secondary,and primary C(sp 3)hybrid centers can be easily installed. The practicability of this strategy is demonstrated in the selective late-stage functionalization of natural products and the concise synthesis of pharmaceutically relevant molecules including Piragliatin. Scheme 1. Catalytic three-component difunctionalization of alkenes.

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…It is also applied as a powerful catalyst in polymerization [249,250], C-C coupling [251], oxygen [252] or hydrogen evolution [253], or even cycloaddition reactions [254]. Its accessibility and high catalytic activity have been well-explored also in C-H activation processes [255][256][257][258][259]. Some of the discoveries led to the formation of important biologically active substances that play a crucial role in pharmaceutical studies, as exemplified by a work published by Ackermann and co-workers in 2019 [260].…”

Photoredox catalysis in nickel-catalyzed C–H functionalization

“…Nickel-catalyzed alkene 1,2-difunctionalization is considered as useful method for preparing complex molecules in a single-step reaction [137][138][139]. In this aspect, the groups by Kong [140] and Molander [141] independently demonstrated photoredox/nickelcatalyzed approaches to olefin difunctionalizations involving C(sp 3 )-H activation. Thus, Kong devised a synthetic method combining nickel catalysis with tetrabutylammonium decatungstate (TBADT) as photocatalyst for the three component reaction of alkanes 16, alkenes 92, and aryl bromides 3 (Scheme 48) [140].…”

“…Similarly, the scope of aryl bromides 3 and alkenes 92 were found to be broad. A possible catalytic cycle was proposed to account for the mechanism of the reaction (Figure 22) [140]. In a recent report, Gutierrez and Molander realized the threecomponent dicarbofunctionalization of alkenes by means of the combination of phororedox HAT catalysis and nickel catalysis [141].…”

“…In this aspect, the groups by Kong [ 140 ] and Molander [ 141 ] independently demonstrated photoredox/nickel-catalyzed approaches to olefin difunctionalizations involving C(sp 3 )–H activation. Thus, Kong devised a synthetic method combining nickel catalysis with tetrabutylammonium decatungstate (TBADT) as photocatalyst for the three component reaction of alkanes 16 , alkenes 92 , and aryl bromides 3 ( Scheme 48 ) [ 140 ]. Here, TBADT enables the generation of alkyl radicals from various alkane substrates via a HAT process under near-ultraviolet light irradiation.…”

“…Similarly, the scope of aryl bromides 3 and alkenes 92 were found to be broad. A possible catalytic cycle was proposed to account for the mechanism of the reaction ( Figure 22 ) [ 140 ]. Photoexcited decatungstate 22-II undergoes a HAT process with the C(sp 3 )–H substrate to form a carbon-centered radical species 22-III and reduced decatungstate 22-IV .…”