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.

A General Strategy for the Asymmetric Preparation of α‐Stereogenic Allyl Silanes, Germanes, and Boronate Esters via Dual Copper Hydride‐ and Palladium‐Catalysis

“…The use of dppbz‐ligated Pd‐precatalyst was key to the success of the transformation, as the use of catalysts derived from ligands that are known to undergo oxidative addition more readily, such as BrettPhos, primarily resulted in net reduction of the enol triflate to the corresponding olefin (entry 6). These observations are consistent with our previous work on olefin and alkyne hydroalkenylation [16b–c] . The use of other copper(I) salts (entries 2–4), or chiral Cu ancillary ligands (entry 5) resulted in diminished yields of 3 a .…”

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-metal-catalyzed cross-coupling reactions, including Heck couplings 10 , ene-yne couplings 11 , hydrovinylation of alkynes 12 , alkenyl-alkenyl couplings 13 – 15 , and boroalkenylation of alkynes 16 – 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.…”

Stereoselective Synthesis of Highly Substituted 1,3-Dienes through Dual 1,3-Sulfur Rearrangement of Dithianes with Alkynylsilanes

“…5 In 2022, Zhu realized an iron-catalyzed vinylzincation of terminal alkynes with available vinylzinc reagents for excellent chemoselective preparation of 1,3-dienes. 5 Meanwhile, Chu reported a dual photoredox-and nickel-catalyzed carbobromination reaction of alkynes with alkenyl bromides for the construction of brominated 1,3-dienes. 7 Very recently, Xie realized the manganese-catalyzed branched-selective hydroalkenylation of alkynes with alkenyl boronic acids for the construction diverse Dithiane compounds are a class of powerful acyl equivalents in organic synthesis.…”

“…Due to their importance, efforts have been devoted to developing methods to access these compounds in a regio- and stereoselective manner . The olefination of alkyne compounds and functionalized alkenyl reagents has provided an attractive route for the stereoselective synthesis of 1,3-dienes (Scheme a). − In particular, Buchwald developed a dual CuH- and Pd-catalyzed stereoselective process for the preparation of substituted 1,3-dienes employing widely available alkynes and enol triflates . In 2022, Zhu realized an iron-catalyzed vinylzincation of terminal alkynes with available vinylzinc reagents for excellent chemoselective preparation of 1,3-dienes .…”