Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Cyclization–[4+3] Annulation Cascades between 2‐(1‐Alkynyl)‐2‐alken‐1‐ones and Anthranils

Abstract

This work reports gold‐catalyzed [4+3]‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybenzoazepine products with excellent exo‐diastereoselectivity (dr>25:1). The utility of this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these [4+3]‐cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9 %. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo‐stereoselection.

Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings

“…Very recently, Liu and co‐workers disclosed the highly diastereo‐and enantioselective gold‐catalyzed cyclization/[4+3] annulation cascade between 2‐(1‐alkynyl)‐2‐alken‐1‐ones 48 and anthranils 190 to yield epoxybenzoazepine products 191 (Scheme 49). [57] Treatment of species 191 a with Zn powder in DCM at room temperature led to an N−O bond cleavage to deliver benzoazepine derivative 192 in excellent yield without erosion of enantioselectivity.…”

TBAI‐Catalysed Formal [4+4]‐Cycloaddition: Easy Access to Oxa‐Bridged Eight‐Membered Heterocycles

“…For example, Luo and co‐workers reported a Sc(OTf) 3 ‐catalysed [4+3]‐annulation reaction with cyclopropane 1,1‐diesters, [8a] which provided a practical and straightforward access to biologically important tetrahydro‐1‐benzazepines. In addition, various [3+4]‐cyclization reactions of anthranils with different substrates, such as γ ‐butyrolactone‐fused cyclopropanes, [8b] vinylcyclopropanes (VCPs), [8c] α ‐halo hydroxamates, [8d] and 2‐(1‐alkynyl)‐2‐alken‐1‐ones, [8e] have been established to access oxa‐bridged heterocycles. However, these approaches are restricted to build oxa‐bridged seven‐membered heterocycles.…”

Chemo- and Diastereoselective Cycloisomerization/[2 + 3] Cycloaddition of Enynamides: Synthesis of Spiropyrazolines as Potential Anticancer Reagents

“…6,7 This strategy has been applied in various cascade cycloisomerization/[4 + n] cycloaddition reactions using different types of reaction partners. 8 For example, in 2019, Chi and co-workers disclosed the Au(I)/Nheterocyclic carbene (NHC) relay catalytic cycloisomerization/[4 + 2] cyclization reactions of enynamides with enals for the synthesis of furo [2,3-b]pyridine derivatives (Scheme 1A). 9 In 2020, Zhao et al elegantly demonstrated a highly stereoselective access to polyfunctionalized furan-fused ninemembered heterocycles by sequential Au(I) and Pd catalytic cycloisomerization/[4 + 5] annulation with vinyl ethylene carbonates (VECs).…”