Visible light-induced one-pot synthesis of CF₃/CF₂-substituted cyclobutene derivatives

Abstract

An efficient one-pot approach for the controllable synthesis of trifluoromethyl/gem-difluoromethylene substituted cyclobutene derivatives has been developed. The mechanism may involve visible light-induced [2+2]-cycloaddition of quinolinones with 1-bromo-1-trifluoromethylethene, followed by base-promoted...

2‐Bromo‐3,3,3‐Trifluoropropene: A Versatile Reagent for the Synthesis of Fluorinated Compounds

“…Recently, Xu and co‐workers developed an efficient one‐pot approach for the controllable synthesis of trifluoromethyl/ gem ‐difluoromethylene substituted cyclobutene derivatives 49 / 50 through the visible light‐induced [2+2]‐cycloaddition of 1‐benzylquinolin‐2(1H)‐one 48 with BTP (Scheme 25 and 26). [36] A broad range of substrates were compatible with this transformation and the reaction gave the desired products in moderate to good yields. Various functional groups could be tolerated in the reaction, such as cyano, ester, carbonyl, aldehyde and halogen groups.…”

“…[24][25][26][27][28][29][30][31][32] Interestingly, the application of BTP as a coupling partner to the CÀ H bond functionalization would be of significant value for the synthesis of trifluoromethylated compounds. [33,34] Furthermore, due to its unique structure, BTP has recently been utilized as a C 2 synthon in cycloaddition reactions for the construction of trifluoromethyl-containing (hetero)cyclic compounds, such as cyclopropane, [35] cyclobutene, [36] pyrazoles, [37][38][39][40][41] isoxazole, [42,43] benzoxazoles, [44] benzofuran and indole derivatives. [45] Other reactions have also been reported sporadically, such as S N 2'-type reactions [46,47] and intermolecular Stetter reactions.…”

Visible Light-Induced Diastereoselective Construction of Trifluoromethylated Cyclobutane Scaffolds through [2+2]-Photocycloaddition and Water-Assisted Hydrodebromination

“…Anhydrous THF was distilled with Na using benzophenone as monitor. 1aa – l , 1b – d , 1g – k , 1m , and 1q were synthesized according to literature procedures. , 1r – u and 2 were commercially available and used as received.…”

“…An alternative method was given by Jørgensen’s and Paixao’s group, in which visible light was employed as a sole initiator for the radical-mediated reduction of alkyl and aryl bromides with TTMSS, avoiding the use of any metal or organic additives (Scheme b). Based on our previous work for the fluorinated cyclobutenes and inspired by the great synthetic potential revealed in the one-pot reaction, we examined the possibility of merging [2+2]-photocycloaddition with reductive debromination to construct fluorinated cyclobutane scaffolds. To the best of our knowledge, many elegant protocols to introduce fluorine atoms or fluoroalkyl groups into a cyclobutane ring have been developed, while most of them were generally subjected to ultraviolet light, high temperature, and especially lack of stereoselectivity .…”

“…Therefore, the exploitation of complementary strategies and reagents to develop milder and greener methodologies for the rapid assembly of stereodefined fluorinated cyclobutanes is highly desirable. As part of our systematic work, , we herein disclosed a photo-induced strategy for the diastereoselective synthesis of trifluoromethylated cyclobutane frameworks through [2+2]-photocycloaddition followed by hydrodebromination (Scheme c). Thioxanthone (TX) acted as both a photosensitizer and a hydrogen atom transfer (HAT) agent.…”