Modular Synthesis of Multifunctionalized CF₃-Allenes through Selective Activation of Saturated Hydrocarbons

Abstract

Catalytic 1,4-dicarbofunctionalization of 1,3-enynes is a powerful strategy for the synthesis of polysubstituted allenes. Despite impressive progress, such a strategy is still restricted to the use of alkylmetallic reagents or pre-activated radical precursors, thus limiting its functional group compatibility and atom economy. Herein, we report that through the combination of decatungstate photo-hydrogen atom transfer and nickel catalysis, a three-component 1,4-dicarbofunctionalization of 2-trifluoromethyl-1,3-enynes is achieved. This strategy allows the modular synthesis of tetrasubstituted CF 3 -allenes under exceptionally mild conditions. A variety of electrophiles such as aryl bromides, alkenyl bromides, acyl chlorides, and alkynyl bromides were successfully employed as traps to lead to the desired products. Another significant advantage is that the most abundant hydrocarbons are used as feedstocks, and a wide range of synthetically versatile functional groups and complex drug-like structures can be easily incorporated. Based on experimental and density functional theories, a possible catalytic cycle involving 1,3-nickel rearrangement is proposed.

Direct acylation and alkynylation of hydrocarbons via synergistic decatungstate photo-HAT/nickel catalysis

“…Based on the above experimental results and previous reports, 7–10 a plausible mechanism for this dual photo-HAT/nickel-catalyzed C(sp 3 )–H acylation and alkynylation is depicted in Scheme 4B. The decatungstate anion A is initially excited by near-ultraviolet light to generate the excited-state decatungstate catalyst B , which can selectively abstract a hydrogen atom from the aliphatic substrate, delivering the corresponding alkyl radical R˙ and the reduced decatungstate C .…”

“…8 However, the synthesis of other carbonylated derivatives such as esters and amides by Ni/TBADT co-catalysis has not been reported. 9 Due to our ongoing interest in the development of dual Ni/TBADT catalyzed C(sp 3 )–H functionalization, 10 we herein describe the direct functionalization of abundant hydrocarbon feedstocks via dual decatungstate-HAT and nickel catalysis, providing a straightforward and complementary approach to rapidly assemble high-value ketones, amides, esters, and diverse alkynes with excellent site-selectivity (Scheme 1B).…”

Remote Radical 1,3-, 1,4-, 1,5-, 1,6- and 1,7-Difunctionalization Reactions

“…In 2022, the Kong and Wang groups introduced a photoredox reaction for dicarbonation of trifluoromethylated 1,3-enynes ( Scheme 31 ) [ 65 ]. In the presence of TBADT and Ni(dibbpy)Br 2 catalysts and under near-ultraviolet light irradiation, the reaction of 1,3-enynes with alkanes and alkyl halides afforded tetrasubstituted CF 3 -allenes 32 .…”

Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis

“…Chiral allenes represent a very important group of functional molecules. − One of the most important groups of allenes are allenols incorporating an allene and an adjacent carbinol functionality. , The chiral allenol motif occurs in furanomycin, leiodolide, , allopregnanolone, adenallene, and related drugs and drug intermediates (Figure a). CF 3 -allenes with potential axial chirality − are also attractive targets due to the beneficial pharmacological effects of CF 3 groups. , …”

“…37,57,58 Based on previous studies the enantioselectivity is determined in the 12 → 14 process, while 47,50,53 the diastereoselectivity is controlled by the chirality transfer in the allenylboration step 14 → 15. Finally, ethanolysis of 15 leads to formation of the boric ester of product 5 (16) and regeneration of the catalyst.…”