Catalyst-Enabled Scaffold Diversity: Highly Chemo- and Stereoselective Synthesis of Tricyclic Ketals and Triarylmethanes

Abstract

The first catalytic cascade reaction of activated isocyanides with para-quinone methide-aryl esters is presented. Catalyst-enabled divergent pathways have also been achieved to deliver skeletally diverse products. While Ag catalysis leads to an unprecedented highly diastereoselective synthesis of tricyclic ketals, a simple procedure employing Cu catalysis produces oxazole-containing triarylmethanes in high efficiency through an unexpected C-C bond cleavage.

Recent Advances in the Chemistry of Isocyanides with Activated Methylene Group

“…The first strategy of catalytic cascade reaction with activated isocyanides 1 and para ‐quinone methide‐aryl esters 157 was performed by Zhao, Liao and Ni. [ 81 ] Depending on the nature of the catalyst, various routes have been developed for the synthesis of skeletally diverse products. Using Ag 2 O catalysts leads to an unprecedented cascade cyclization with formation of highly diastereoselective tricyclic ketals 158 .…”

Advances in The Catalytic Synthesis of Triarylmethanes (TRAMs)

“…Since in both the process i.e., the 1,6‐conjugate addition and intramolecular cyclization, require catalytic activation, selecting the most suitable catalytic system was a challenging task for this reaction (Scheme ) . A common intermediate 98a was observed when either silver oxide or copper acetate were used as a catalyst.…”

Brønsted Acid Catalyzed Domino 1,6-Addition/Intramolecular Cyclization­ Reactions: Diastereoselective Synthesis of Dihydro­coumarin Frameworks

“…p-QMs 1 and azlactones 2 were synthesized according to the literature methods. 12,18,19 Dihydrocoumarins 3; General Procedure Diphenyl hydrogen phosphate (4f, 0.01 mmol), a p-QM 1 (0.1 mmol) and an azlactone 2 (0.15 mmol) were mixed in acetonitrile (1 mL) in a dried tube, and the mixture was stirred at room temperature for 5 h (except for 3ba-3da: 8 h). When the reaction was complete (determined by TLC), the mixture was concentrated in vacuo.…”

“…16 The Enders group has reported an elegant synthesis of chromans through a domino oxa-Michael/1,6-addition reaction. 17 In addition, the Zhao group 18 and the Tu/Jiang group 19 have achieved metal-catalyzed domino reactions of As part of our continuous interest in synthesizing bioactive heterocyclic compounds 20 and developing reactions involving quinone methides, 9c,11c we envisioned that a Brønsted acid catalyzed domino 1,6-addition/intramolecular cyclization reaction of p-QMs 1 with azlactones 2 could be achieved, providing a series of functionalized dihydrocoumarins (Scheme 1, b). In this transformation, the catalyst, the Brønsted acid, may play a crucial role not only in activating the two substrates, but also in controlling the diastereoselectivity of the reaction via a hydrogen-bonding interaction.…”