Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

Abstract

An efficient palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides has been developed. The reaction proceeds under mild reaction conditions with high efficiency and excellent functional group tolerance, even towards formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction.

Keywords: Heck-type reaction; alkenes; cross-coupling; palladium; secondary trifluoromethylated alkyl bromides.

Scheme 1

Palladium-catalyzed Heck-type reaction of 2-bromo-1,1,1-trifluorohexane (2a) with alkenes 1. Reaction conditions (unless otherwise specified): 1 (0.4 mmol, 1.0 equiv), 2a (2.0 equiv), DCE (3 mL), 80 °C, 16 h. All reported yields are those of isolated products. ^aThe reaction was conducted at 100 °C.

Scheme 2

Palladium-catalyzed Heck-type reaction of fluorinated secondary bromides (iodides) 2 with alkenes 1. Reaction conditions (unless otherwise specified): 1 (0.4 mmol, 1.0 equiv), 2 (2.0 equiv), DCE (3 mL), 80 °C, 16 h. All reported yields are those of isolated products. ^aThe reaction was carried out in 0.2 mmol scale. ^bEthyl 2,2-difluoro-2-iodoacetate was used.

Scheme 3

Radical clock experiment for mechanistic studies.

Scheme 4

Proposed mechanism.