Ag/Brønsted Acid Co-Catalyzed Spiroketalization of β-Alkynyl Ketones toward Spiro[chromane-2,1′-isochromene] Derivatives

Abstract

A new Ag/Brønsted acid co-catalyzed spiroketalization of β-alkynyl ketones with para-quinone methides (p-QMs) has been established, enabling multiple C-C and C-O bond-forming events to access densely functionalized spiro[chromane-2,1'-isochromene] derivatives with generally excellent diastereoselectivity and good yields. A reasonable mechanism for forming these 6,6-dibenzannulated spiroketals involving 6-endo-dig oxo-cyclization and 1,6-addition-cyclization cascades is proposed.

Bimetallic Catalytic Asymmetric Tandem Reaction of β‐Alkynyl Ketones to Synthesize 6,6‐Spiroketals

“…However, the vicinal C(sp 3 )−H bond functionalization of Int A was still challenging for the low reactivity. Recently, Jiang, Tu and co‐workers disclosed that β‐alkynyl ketones could also undergo an intramolecular oxo‐cyclization/H‐transfer sequence in the presence of silver salts, and generated the novel electron‐donating alkene Int ‐ B , which spiroketalized with quinone precursors at the site of the exocyclic double bond (Scheme a) ,. It could also be trapped by diarylphosphine oxide radicals, nitro radicals or N ‐fluorobenzenesulfonimide ,,.…”

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.…”

Oxidative Catalytic Spiroketalization Leading to Diastereoselective Synthesis of Spiro[benzofuran‐2,1′‐isochromene]s

“…Since the group of Yamamoto pioneered AuCl 3 ‐catalyzed benzannulation of β ‐alkynyl ketones with alkynes, catalytic cyclization cascades of β ‐alkynyl ketones have been investigated extensively . Recently, we have developed a Ag/Brønsted acid co‐catalyzed bicyclization reaction of β ‐alkynyl ketones with para ‐quinone methides ( p ‐QMs), which provided a series of functionalized benzannulated 6,6‐spiroketals . During this project, we reasoned that catalytic conversion of β ‐alkynyl ketones into electron‐rich methyleneisochromenes enables 1.4‐addition and nucleophilic cyclization with quinone imine ketals (QIKs), generated in situ from N ‐(4‐hydroxyphenyl) sulfonamides, to access new functionalized benzannulated 5,6‐spiroketals.…”