S,O‐Ligand‐Promoted Pd‐Catalyzed C–H Olefination of Thiophenes

Abstract

An efficient PdII catalyzed C–H olefination of thiophenes has been developed using an easily accessible bidentate S,O‐ligand. The catalytic system promotes the C‐2 olefination of a wide range of thiophenes bearing both, electron donating and withdrawing groups under mild conditions. This methodology provides a direct path towards the synthesis of 2,3‐disubstituted thiophenes, which are difficult to obtain via other C–H functionalization routes. The S,O‐ligand is responsible for the broad substrate scope and high levels of C‐2 selectivity in 3‐substituted thiophenes.

Pd-Catalyzed Intermolecular Dehydrogenative Heck Reactions of Five-Membered Heteroarenes

“…Surprisingly, the addition of metallic co-oxidants may have a negative effect on the aerobic DHR [22]. The Pd(OAc)2/MOF-808-L1/PhCO3t-Bu procedure (Equation (16)) mainly led to C3 alkenylation of 1methyl-1H-indole (Equation (43)) [ (43) Other aerobic procedures have been proposed. The PdX2/acid/DMSO method is very sensitive to the nature of X and the acid, Pd(OAc)2/CF3CO2H being the optimum (Equation (44)) [81].…”

“…), led to aldehydes or ketones (Equation (6)) through hydrogen migration [41] as that occurs from the Heck reaction of such substrates [42]. (6) Procedures using palladium associated to various ligands have been reported for olefination with acrylates, enones, acrylamides, styrenes, vinyl phosphonates, or sulfones (Equations (7) and (8) [24], Equations (9) and (10) [43], Equations (11) and (12) [44], Equation (13) [45], and Equation 14, respectively [46]). The aerobic DHR with allylic alcohols disclosed by Jiang's team (In contrast to the captions of the publication tables [41], oxygen was the sole oxidant.…”

Regioselective Olefination of 3‐Substituted Five‐Membered Heteroarenes

“…In order to broaden the practicality of this type of transformation, Fernández‐lbáñez and co‐workers developed a bidentate S,O–ligand, which enabled the C2‐olefination of thiophene‐derivatives with the heteroarene as the limiting reagent. [ 12 ] Moderate to good selectivities were observed with 3‐alkyl and 3‐aryl thiophenes as starting materials (Scheme 2, 3a‐b , 3d‐b , and 3e‐b ). After proving the generality of their catalyst with diverse 3‐substituted thiophenes, they further tested different activated olefins.…”

“…First reports towards the C5‐selective olefination of 3‐substituted thiophenes by Carrow, Chao, and Fernández Ibáñez. [ 11,12,20 ] …”

“…Another example of a heteroarene‐limited C–H olefination, which functionalizes the sterically more accessible C5‐position through a ligand‐promoted Pd‐catalyzed process, was reported by Fernández‐Ibáñez and co‐workers, who applied their bidentate S,O‐ligands to functionalize a thiophene bearing an electron‐withdrawing group (Conditions C, 1g , 1 equiv). [ 12 ] The product 3g‐b was formed in good yield and with a moderate ratio of product isomers (C5/C2 = 3:1).…”