Diastereo‐ and Enantioselective Propargylation of 5H‐Thiazol‐4‐ones and 5H‐Oxazol‐4‐ones as Enabled by Cu/Zn and Cu/Ti Catalysis

Abstract

Reported is the asymmetric propargylic substitution (APS) reaction of 5H-thiazol-4-ones using a Cu/Zn dual metal catalytic system and the APS reaction of 5H-oxazol-4-ones using a Cu/Ti catalytic system. These reactions furnish functional-group-rich, terminal-alkyne-containing products with two vicinal stereocenters in high yields and with good to excellent diastereo- and enantioselectivities. This study demonstrates the use of dual metal catalytic systems as a viable approach to improve the selectivity profiles of the copper-catalyzed APS reactions.

Copper‐Catalyzed Enantioselective Construction of Tertiary Propargylic Sulfones

“…According to previous mechanistic studies on related propargylic substitution reactions– and our experimental observations, a plausible mechanism is proposed as shown in Scheme . An in situ formed catalyst [Cu]* first activates the alkyne fragment in A through a π complex (not shown).…”

“…Whereas significant advances have been achieved in Cu‐catalyzed APS reactions with various reagents including N‐, O‐, and C‐based nucleophiles (Scheme B), the employment of sulfur‐centered nucleophiles in these transformations has not yet been achieved . Additionally, extension of Cu‐catalyzed APS reactions to substrates that allow the construction of quaternary centers still remains limited –. The apparent challenge in this domain is to achieve a high degree of enantiofacial control upon substituting a sterically hindered center– with a potentially coordinating nucleophile that easily leads to transition‐metal (TM) catalyst deactivation…”

Enantioselective Construction of Vicinal Sulfur‐functionalized Quaternary and Tertiary Stereocenters via Organocatalytic Michael Addition of 5H‐Thiazol‐4‐ones to 1‐Azadienes

“…In particular, the catalytic enantioselective carbon‐hydrogen bond functionalization of thiazol‐4‐one derivatives to construct a quaternary stereogenic center at the C5 position attracted much attention. Impressive results on the catalytic asymmetric reaction of 5 H ‐thiazol‐4‐ones have been achieved by the research groups of Palomo, Hartwig, Lan and Lu, Jiang, Zhou, Luo and Gong, and Zhang and Niu . Among these researches, 5 H ‐thiazol‐4‐ones were successfully involved in the organocatalytic enantioselective 1,4‐additions of different Michael acceptors including nitroalkenes (Scheme A), enones (Scheme B), azodicarboxylates (Scheme C), [8c], and N ‐maleimides (Scheme D) .…”

Recent Advances in Catalytic Asymmetric Reactions of Thiazolones, Rhodanines and Their Derivatives

“…The enantioselective propargylic substitution of 5Hthiazol-4-ones 79 with propargyl carbonates 80 was disclosed by Niu and Zhang et al using a Cu/Zn dual metal catalytic system (Scheme 23). [30] With the aid of ligand C27, the terminal-alkyne-containing products 81 was obtained in 59-99% yields with 85-95% ee and 5:1-> 19:1 dr. Notably, dual metal catalytic systems were demonstrated as a practical tool to improve the stereoselectivity profiles of the coppercatalyzed asymmetric propargylation.…”