Catalytic Synthesis of Trifluoromethyl Cyclopropenes and Oligo‐Cyclopropenes

Abstract

The synthesis of trifluoromethylated cyclopropenes is often associated with important applications in drug discovery and functional materials. In this report, we describe the use of readily available chiral rhodium(II) catalysts for a highly efficient asymmetric cyclopropenation reaction of fluorinated donor–acceptor diazoalkanes with a broad variety of aliphatic and aromatic alkynes. Further studies highlight the unique reactivity of fluorinated donor–acceptor diazoalkanes in the synthesis of oligo‐cyclopropenes. Subsequent C−H functionalization of trifluoromethyl cyclopropenes furnishes densely substituted cyclopropene frameworks and also allows the alternative synthesis of bis‐cyclopropenes.

Photochemical Cyclopropenation of Alkynes with Diazirines as Carbene Precursors in Continuous Flow

“…When employing bis-alkynes 1,3-diethynylbenzene and 1,4-diethynylbenzene, monocyclopropenes 2al and 2am were obtained in 53% and 14% yield, respectively, along with products resulting from C–H insertion which was isolated in the case of 2al′ . In these cases, no bis-cyclopropenes were obtained contrary to a previous report with trifluoro-methyl metal carbenes …”

“…In these cases, no bis-cyclopropenes were obtained contrary to a previous report with trifluoromethyl metal carbenes. 33 The scope of trifluoromethyl diazirine substrates was investigated with diphenyl acetylene (Scheme 3). The reaction of 3-(naphthalen-2-yl)-3-(trifluoromethyl)-3H-diazirine 1b and 3-(4-(benzyloxy)phenyl)-3-(trifluoromethyl)-3H-diazirine 1c under irradiation at 420 nm resulted in cyclopropenes 2b and 2c in 78% and 79% yield, respectively.…”

“…Cyclopropenes are essential building blocks in organic synthesis and are also valuable to the pharmaceutical sector in drug discovery . However, studies covering the synthesis of trifluoromethyl cyclopropenes have only been recently reported via the cyclopropenation reaction of alkynes using diazo compounds catalyzed by transition metals. − …”

Comparison of 1,2-Diarylcyclopropanecarboxylates with 1,2,2-Triarylcyclopropanecarboxylates as Chiral Ligands for Dirhodium-Catalyzed Cyclopropanation and C–H Functionalization

“… They are sterically demanding catalysts capable of overcoming the natural electronic tendency of the carbenes to insert into tertiary C–H bonds, and by appropriate modifications, they can be tuned to select specific primary or secondary , C–H bond. Some of the most significant Rh-TPCP catalysts developed to date are 2a–2e , and they have been shown to be effective chiral catalysts in a range of carbene transformations. − …”

Nucleophilic Migratory Cyclopropenation of Activated Alkynes: A Nonmetal Approach to Unbiased Cyclopropenes

“…To show the synthetic complementarity of this reaction to the transition-metal carbenoid method, cyclopropenes 36 and 37 were selectively prepared from α-keto esters 1u and 1v bearing an alkenyl or an alkynyl group with suitable alkynones in good yields, respectively, which otherwise would be quite cumbersome to prepare by transition-metal-catalyzed carbene transfer to alkynes (Figure ). For the synthesis of 36 , the metal carbenoid intermediate bearing the allyl group prefers intramolecular cyclopropanation. , On the other hand, the discrimination of the metal carbenoid toward the two alkynyl units with small electronic and steric differences in the diyne 38 is apparently challenging …”