Synthesis of Isomerically Pure (Z)-Alkenes from Terminal Alkynes and Terminal Alkenes: Silver-Catalyzed Hydroalkylation of Alkynes

Abstract

Alkenes are an important class of compounds common among biologically active molecules and often used as intermediates in organic synthesis. Many alkenes exist in two stereoisomeric forms (E and Z), which have different structures and different properties. The selective formation of the two isomers is an important synthetic goal that has long inspired the development of new synthetic methods. However, the efficient synthesis of diastereopure, thermodynamically less stable, Zalkenes is still challenging. Here, we demonstrate an efficient synthesis of diastereopure Z-alkenes (Z:E > 300:1) through a silver-catalyzed hydroalkylation of terminal alkynes, using alkylboranes as coupling partners. We also describe the exploration of the substrate scope, which reveals the broad functional group compatibility of the new method. Preliminary mechanistic studies suggest that a 1,2-metallate rearrangement of the silver borate intermediate is the key step responsible for the stereochemical outcome of the reaction.

Recent Advances in the Functionalization of Terminal and Internal Alkynes

“…The same group has reported an interesting silver catalyzed hydroalkylation of terminal alkynes using alkylboranes as coupling partners (Scheme 3). [11] In this protocol, diastereopure Z ‐alkenes were formed with the combination of Tri AgCl (10 mol%) as the catalyst with triazole carbene ligand, LiO t ‐Bu (1.5 equiv.) as base and MeOH (1.1 equiv.)…”

Recent Advances in Silver‐Catalyzed Transformations of Electronically Unbiased Alkenes and Alkynes

“…[16] Most recently, Lalic et al have successfully reported a new hydroalkylation reaction between terminal alkynes and alkylboranes, providing a large number of functionalized alkenes with exclusively Z selectivity (Scheme 6). [17] For most alkynes and alkylboranes, the best results were obtained using silver chloride with a triazole carbene ligand (catalyst A) as catalyst, stoichiometric amounts of methanol and lithium tert-butoxide as additive in toluene. Nevertheless, to achieve higher efficiency, a catalytic amount of silver chloride with another kind of ligand (catalyst B) was also employed under some conditions, such as for the synthesis of alkenes with a pyridine or a thiophene group.…”

“…Most recently, Lalic et al . have successfully reported a new hydroalkylation reaction between terminal alkynes and alkylboranes, providing a large number of functionalized alkenes with exclusively Z selectivity (Scheme ) . For most alkynes and alkylboranes, the best results were obtained using silver chloride with a triazole carbene ligand (catalyst A) as catalyst, stoichiometric amounts of methanol and lithium tert ‐butoxide as additive in toluene.…”

Mechanism of Z-Selective Hydroalkylation of Terminal Alkynes

“…With control of the regioselectivity of the addition (Markovnikov vs anti-Markovnikov), different structural isomers of an alkene can be formed from the same alkyne precursor. For example, terminal alkynes can be used as a precursor to both 1,1-disubstituted alkenes and 1,2-disubtituted alkenes . Several methods have also been developed for the synthesis of trisubstituted alkenes through the hydroalkylation of internal alkynes, although controlling the regioselectivity in this case is still a challenge. , Another feature of hydroalkylation reactions is that they establish the double bond geometry of the resulting alkene, and either the E or Z isomer of a 1,2-disubstitute alkene can be accessed from the same terminal alkyne.…”