Copper-Catalyzed Annulation–Cyanotrifluoromethylation of 1,6-Enynes Toward 1-Indanones via a Radical Process

Abstract

A new Cu(II)-catalyzed annulation-cyanotrifluoromethylation of 1,6-enynes with Togni's reagent and trimethylsilyl cyanide (TMSCN) has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields. This reaction was performed by using low-cost Cu(OTf) 2 as the catalyst and Togni's reagent as both the radical initiator and a CF 3 source, providing an efficient protocol for building up an 1-indanone framework with wide functional group compatibility. The reaction mechanism was proposed through a radical triggered addition/5-exo-dig cyclization/oxidation/nucleophilic cascade.

Exploiting the reactivities ofortho-alkynyl aryl ketones: opportunities in designing catalytic annulation reactions

“…In another work of Cu( ii )-catalyzed annulative cyanotrifluoromethylation, 1,6-enynes were reacted with Togni's reagent and trimethylsilyl cyanide (TMSCN), as reported by the same research group, and used to produce a wide range of 1-indanones 29 with a quaternary carbon center in generally good yields (Scheme 12). 37 Notably, complete stereoselectivity was detected in most cases. The reaction mechanism is similar to the above copper-catalyzed halofluoroalkylation, which may include a radical-triggered addition, 5- exo-dig carboyclization, and reductive elimination cascade.…”

“…The reaction mechanism is similar to the above annulative bifunctionalizations of 1,6enynes. 37 When the methyl group linked to the terminal alkene unit was replaced by an aryl group, the reaction of 1,7-enynes could allow a different radical-induced 6-exo-dig/5-endo-trig bicarbocyclization process. By making use of this strategy, Jiang's group synthesized a wide range of substituent-diverse tetracyclic 1-naphthalenones in good yields with the aid of photocatalysts or metal catalysts starting from different radical donors, such as sulfinic acids, 54 DMSO/H 2 O, 55 PhSiH 3 56 and ICF 2 CO 2 Et 57 (Scheme 20).…”

Difunctionalization of Dienes, Enynes and Related Compounds via Sequential Radical Addition and Cyclization Reactions

“…Using benzene-tethered and carbonyl-containing 1,6-enynes as a substrate for Cu-catalyzed radical reaction for the construction of cyanotrifluoromethylated 1-indanones was introduced by the Jiang group in 2020. The reaction of benzene-tethered 1,6-enynes, Togni’s reagent and trimethylsilyl cyanide (TMSCN) under the catalysis of Cu(OTf) 2 gave product 60 in good yields ( Scheme 60 ) [ 72 ]. A reaction mechanism suggests that the trifluoromethyl radical generated from Togni’s reagent under the catalysis of Cu II adds to the C=C double bond of 1,6-enyne followed by 5- exo cyclization, formation of Cu III -complex containing CN, and reductive elimination of the Cu-catalyst to give product 60a .…”

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes

“…Due to the advantage of introducing two groups at the same time (namely, cyano and trifluoromethyl), as well as the good functional group tolerance, and mild reaction conditions, the cyanotrifluoromethylation difunctionalization strategy also gained wide recognition in other chemical platforms, such as remote cyanotrifluoromethyl difunctionalization [ 112 , 113 , 114 ] and construction of functionalized cyclic compounds [ 115 , 116 , 117 ].…”