Cooperative Photoredox- and Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

Abstract

Cooperative photoredox- and nickel-catalyzed alkylative cyclization reactions of iodoalkynes with 4-alkyl-1,4-dihydropyridines as alkylation reagents under visible light irradiation have been achieved to afford the corresponding alkylated cyclopentylidenes in good to high yields. Introduction of substituents at the propargylic position of iodoalkynes has led to the stereoselective formation of E-isomers. The present reaction system provides a novel synthetic method for alkylative cyclization reactions of both terminal and internal alkynes with cooperative photoredox and nickel catalysis.

Photoredox‐ and Nickel‐Catalyzed Hydroalkylation of Alkynes with 4‐Alkyl‐1,4‐dihydropyridines: Ligand‐Controlled Regioselectivity

“…On the other hand, 1‐(benzyloxy)‐2,2,6,6‐tetramethylpiperidine ( 9 a ), [50] the TEMPO‐trapped benzyl adduct, was obtained in 41 % or 47 % yield in the Markovnikov or anti ‐Markovnikov‐type optimized reaction conditions, respectively (Figure 1a). The experimental results demonstrate that the formation of a benzyl radical as a reactive intermediate is involved in the main catalytic reaction pathway [7,10,11,13,15,31,33,35,37–39,51] . Subsequently, Stern–Volmer analyses for emission quenching of fac ‐[Ir(Fppy) 3 ] by 1 a or 2 a was performed in THF, where the quenching rate constants were determined to be k 1a =(7.8±0.4) ×10 7 M −1 s −1 and k 2a =(1.81±0.04) ×10 8 M −1 s −1 , respectively, based on the slope obtained by the Stern–Volmer plot [52] and the excited‐state lifetime of fac ‐[Ir(Fppy) 3 ] at τ =1.6 μs, [47] thus indicating that the quenching of photoexcited fac ‐[Ir(Fppy) 3 ] by 2 a can occur twice as fast as that by 1 a .…”

“…The experimental results demonstrate that the formation of a benzyl radical as a reactive intermediate is involved in the main catalytic reaction pathway. [7,10,11,13,15,31,33,35,[37][38][39]51] Subsequently, Stern-Volmer analyses for emission quenching of fac-[Ir(Fppy) 3 ] by 1 a or 2 a was performed in THF, where the quenching rate constants were determined to be k 1a = (7.8 � 0.4) × 10 7 M À 1 s À 1 and k 2a = (1.81 � 0.04) × 10 8 M À 1 s À 1 , respectively, based on the slope obtained by Scheme 4. Hydroalkylation of internal alkyne.…”

“…Both the light on/off experiment as well as the quantum yield measurement have clarified that the rate-determining step of the catalytic formation of 3 aa or 4 aa proceeds not according to a radical chain process but rather by sequential redox pathways, [58] in which alkyl radicals are mainly generated by the SET process between 4-alkyl-1,4-dihydropyridines and an excited-state photoredox catalyst. [31,[35][36][37]59,60] In order to get more information on the reaction pathway for the E to Z isomerization which occurs for aryl-substituted alkenes [36,45] in the anti-Markovnikov-type reaction conditions, a time course study was further investigated. As shown in Figure 1d, formation of both (E)-4 aa and (Z)-4 aa follow pseudo zeroth order kinetics for the first 24 h with E/Z ratio kept at 55 : 45 < E/Z < 59 : 41.…”

“…On the other hand, 4‐alkyl‐1,4‐dihydropyridines have recently been shown to work as powerful alkylation reagents to mediate a variety of alkylative reactions in photoredox‐catalyzed molecular transformations, declaring that 4‐alkyl‐1,4‐dihydropyridines can act as mild alkylation reagents alternative to classical but highly reactive, organometallic alkylation reagents [29–39] . In this reaction system, SET processes from the visible light‐excited photoredox catalysts to 4‐alkyl‐1,4‐dihydropyirines give rise to the formation of alkyl radicals, [18,29,30] which enables simple alkylation [31–34] as well as alkylative reactions [35–42] along with other transformations such as cross‐coupling reactions in the presence of supplementary catalysts.…”

Selective Fluoromethyl Couplings of Alkynes via Nickel Catalysis

“…The recent expansion of Ni‐catalyzed cross‐electrophile coupling [11] in domino reactions has engaged Csp 3 ‐hybridized electrophiles such as alkyl halides as efficient coupling agents, further expanding the molecular diversity of the resulting substituted alkenes [12] . Despite impressive progress, the development of a general and selective Ni‐catalyzed cross‐electrophile dialkylation of alkynes with two dissimilar alkyl halides, which can install two sp 3 ‐hybridized frameworks in one single operation, remains underexploited, [12c,i,j] due to the inherent challenges in the control of chemo‐ and regioselectivity between two alkyl electrophiles, particularly in a multicomponent reaction system. Furthermore, there has been no report of utilizing readily available fluoromethyl halides in the Ni‐catalyzed domino couplings of alkynes for the expedient construction of fluoromethyl‐incorporated alkenes [13] .…”