A Dual CuH- and Pd-Catalyzed Stereoselective Synthesis of Highly Substituted 1,3-Dienes

Abstract

Conjugated dienes are versatile building blocks and prevalent substructures in synthetic chemistry. Herein, we report a method for the stereoselective hydroalkenylation of alkynes, utilizing readily available enol triflates. We leveraged an in situ generated and geometrically pure vinyl-Cu(I) species to form the Z,Z- or Z,E-1,3-dienes in excellent stereoselectivity and yield. This approach allowed for the synthesis of highly substituted Z-dienes, including pentasubstituted 1,3-dienes, which are difficult to prepare by existing approaches.

Ligand-controlled stereodivergent alkenylation of alkynes to access functionalized trans- and cis-1,3-dienes

“…Olefinations of carbonyls are widely embraced methods to access 1,3-dienes, while typically leading to E/Z isomers 8,9 . Alternatively, transition-metalcatalyzed cross-coupling reactions, including Heck couplings 10 , ene-yne couplings 11 , hydrovinylation of alkynes 12 , alkenyl-alkenyl couplings [13][14][15] , and boroalkenylation of alkynes [16][17][18][19] , have emerged as a powerful strategy for the stereoselective synthesis of 1,3-dienes. Despite enabling, these methods generally lead to thermodynamically more stable E-isomers, or rely on the use of stereochemically well-defined organometallic agents or electrophiles.…”