Divergent Synthesis of [3,4]-Fused 3-Alkenyl-Oxindoles via Propargyl Alcohol-Triggered C(sp³)–H Functionalization

Abstract

Fused oxindoles are the core structures of the naturally occurring oxindole alkaloids, and the fused tricyclic structures have distinguished themselves with unique biological activities. Herein, we developed a synthetic strategy for divergent synthesis of diverse types of [3,4]-seven-or six-membered ringfused 3-alkenyl-oxindoles incorporating benzazepine and significant building blocks from propargyl alcohols via the cascade nucleophilic substitution/site-selective hydride transfer/cyclization process unprecedentedly. In addition, a variety of nucleophiles, including H 2 O, were available for controllable construction of a wide range of conjugated alkenes, conjugated ketones, and allyl alcohols encompassing natural products and pharmaceutical motifs with the utilization of 4-amine substituted isatins and widespread terminal alkyne-derived propargyl alcohols. Furthermore, the synthetic utility of the methodology and mechanistic studies also were well presented.

Switchable construction of oxa-heterocycles with diverse ring sizes via chemoselective cyclization controlled by dibrominated compounds

“…13 Because of their wide range of biological and pharmacological activities, a tremendous amount of research has been devoted to achieving the efficient synthesis of spirooxindole and indole derivatives. 12,14,15 In particular, the mutual transformation between spirooxindoles and indoles provides a powerful tool for diversity-oriented synthesis. Hence, we designed the target ring-expansion reaction by treating spirooxindole-fused dibenzo[ b , f ]oxocine 3a with LiAlH 4 and silica gel (Table 3).…”

“…Recently, we have developed an oxindole-embedded four-atom synthon that could be effective for [4 + 1] and [4 + 2] cyclization reactions (Scheme 1, 1a and 1b), 11 and we wanted to further expand its application for the construction of many more types of skeletons with enhanced diversity (Scheme 1, 1c). As a continuation of our research interest in the rapid assembly of oxindole and indole derivatives, 12 herein we report the controllable synthesis of spirooxindole-fused dibenzo[ b , f ]oxocines and chromans from rationally designed four-atom synthons and dibrominated compounds through, respectively, [4 + 4] and [4 + 2] cyclization reactions (Scheme 1, 2d–f). In addition, besides the spirooxindole-fused eight-membered oxa-heterocycles, the indole-fused nine-membered oxa-heterocycles also could be accessed switchably through a ring expansion of dibenzo[ b , f ]oxocines by facile operation (Scheme 1, 2g).…”

Advances in chromone-based reactants in the ring opening and skeletal reconstruction reaction: access to skeletally diverse salicyloylbenzene/heterocycle derivatives

“…Benzo[ a ]azulenes are a subclass of azulenes by fusing a phenyl group with the five-membered ring of the azulene moiety. To expand the benzo[ a ]azulene library, Jørgensen and co-workers 68 described the diversity-oriented synthesis of (2-hydroxyphenyl)(benzo[ a ]azulenyl)methanones 103 from the easily accessible electron-deficient chromone-based α,β-unsaturated olefins 83 and 3-phenylindene-2-carbaldehyde 102 via an organocatalytic step-wise [10 + 4] cycloaddition reaction. First of all, the reaction of 102 with pyrrole led to the formation of 44A .…”

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

“…(2) The current application of the cascade [1,5]-hydride shift/cyclization strategy mainly focuses on the construction of five- and six-membered spiro-tetrahydroquinoline. However, exploration of building a spiro-architecture with a challenging ring size (like divergent synthesis of medium ring size) as well as conducting total synthesis of a structurally complex natural product remain elusive ( Li et al, 2018b ; Wang et al, 2018 ; Kataoka et al, 2019 ; Hu et al, 2020 ; Shen et al, 2020 ; Hu et al, 2021a ; Hu et al, 2021b ; Wang et al, 2021 ; Yang S. et al, 2021 ). (3) Notably, the application of [1,5]-hydride shift/cyclization strategy in stereoselective chemistry was barely reported ( Mori et al, 2018 ).…”