Diastereoselective Synthesis of 1,3-Diyne-Tethered Trifluoromethylcyclopropanes through a Sulfur Ylide Mediated Cyclopropanation/DBU-Mediated Epimerization Sequence

Abstract

A one-pot synthesis of 1,3-diyne-tethered trifluoromethylcyclopropanes starting from 2-CF 3 -3,5-diyne-1-enes and sulfur ylides via a sulfur ylide mediated cyclopropanation and a DBU-mediated epimerization sequence is described in this work. This process is highly diastereoselective with broad substrate scope. Moreover, a series of synthetic transformations based on the diyne moieties were conducted smoothly, affording cyclopropanes featuring trifluoromethyl-substituted all-carbon quaternary centers.

Recent advance: Sulfur ylides in organic synthesis

“…When treated with NaOH and heating with toluene gave terminal diynes as products. A CuI-catalyzed azide-alkyne Huisgen cycloaddition of compound 98 was done with benzyl azide which gave the product 1,2,3-triazole [45]. by the synthesis of benzothiophene fused pyran derivatives 101, 102, and 103 (Scheme 21) [46].…”

“…In 2020, Liu et al worked on a diastereoselective synthesis of 1,3 diyne in their tethered trifluorimethyl n ‐cyclopropane through sulfur reality meditated cyclopropanation/DBU‐mediated epimerization sequences via scheme showing the synthetic transformation of 96 (Scheme 20) [45]. Here cyclopropane was treated with NaOH, heating I toluene led to the results with terminal dynes 97 or 98 in 78% and 65% yield, respectively.…”

“…Meng et al researched on substrate-controlled domino reactions of crotonate-derived sulfur ylides 100S C H E M E 1 9 Reaction showing formation of 2-aryl terephthalates (Satham and Namnoothiri [44]). F I G U R E 1 5 Plausible reaction mechanism.S C H E M E 2 0 Synthetic transformation reactions (Liu et al[45]). …”

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

“…The same group [38] extended the reaction to 2‐trifluoromethyl‐3,5‐diyne‐1‐enes 91 (Scheme 31). In that case, the diastereoselectivities were outstanding and the reaction could be applied to a wide range of substituents both on the electrophile (R 1 ) and on the stabilized sulfur ylide (R) 92 .…”

Divergent Synthesis of Fluorinated Alkenes, Allenes, and Enynes via Reaction of 2-Trifluoromethyl-1,3-enynes with Carbon Nucleophiles

“…To further expand the 2-trifluoromethyl-1,3-enynes substrate space and obtain more complex CF 3 -substituted functionalized allenes, we become interested in the regioselective nucleophilic addition of 2-trifluoromethyl-1,3-enynes with various carbon nucleophiles. Up to now, the nucleophilic addition of 1,3-dicarbonyl compounds, TMSCN, N -acetylated 2-aminomalonates, sulfur ylides, and 2,2,2-trifluorodiazoethane to 2-trifluoromethyl-1,3-enynes have been explored (Scheme B). , To retain three C–F bonds, organic base or strong electron-deficient enynes were highly depended on during this research. To overcome the above limitation, we would like to choose various carbon nucleophiles with different nucleophilicity to tune the stability of the in situ formed intermediates to access target CF 3 -allenes.…”