Recent Advances in Asymmetric Organocatalytic Construction of 3,3′‐Spirocyclic Oxindoles

Abstract

The asymmetric organocatalysis is definitely one of the most powerful and versatile tools for the rapid construction of various spirocyclic oxindoles. In the past few years, a number of successful strategies based on organocatalysis have been developed for the construction of 3,3′‐spirocyclic oxindoles in high yields and excellent enantioselectivities under mild conditions. In this review, recent advances in this area are summarized and classified according to the spiro ring fused at the 3‐position of the oxindole core.

One‐pot Two‐Step Cycloaddition Reaction for Convenient Synthesis of Polycyclic Spirooxindole‐fused [1,3]Oxazines

“…[28][29][30][31][32][33][34][35][36][37][38][39][40] Recently, we successfully found that spiro[indoline-3,1'-quinolizin]-2-ones, which were generated from the three-component reaction of substituted pyridine, acetylenedicarboxylate and 3-phenacylideneoxindoles, could undergo Diels-Alder reaction with the typical dienophiles such as maleic anhydride and N-phenylmaleimides. [41][42][43] Alternatively, spiro[3H-indole-3,2'-[2H,9aH-pyrido [2,1-b] [1,3]oxazine], which were formed from three-component reaction of the substituted pyridines, electron-deficient alkynes and isatins, also underwent Diels-Alder reaction with 3-phenacylideneoxindoles (eq. 1 in Scheme 1).…”

“…[1][2][3] Thus, spirooxindole has attracted much interests in synthetic and medical chemistry. [4][5][6][7][8][9] In many elegant synthetic methods for various spirooxindole systems, the multicomponent reactions or domino reactions have emerged as one of the efficient strategies, [10][11][12] which can provide diverse spirooxindoles in an operationally simple one-pot procedure from readily available chemical reagents.…”

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The novel spirooxindoline fused [1,3]oxazines were efficiently synthesized from Diels-Alder reaction of, which were generated in situ from three-component reactions of substituted pyridines and isatins with methyl propiolate, or dimethyl acetylenedicarboxylate. The stereochemistry of the products was clearly clarified by the analysis of 1 H NMR data and single crystal structures of the obtained polycyclic compounds.

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Multi-component synthesis of spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-triones using zinc terephthalate metal-organic frameworks

“…It has been suggested that the sharing of the 3-carbon indole atom during the production of spiroindoline derivatives can greatly increase biological activity (6). Many efficient and applied methods have been reported for the synthesis of versatile spirooxindole-fused heterocycles (7)(8)(9).…”

The Synthesis of New Spirolactones from Substituted Isatins

“…Such developments are of interest not only for the possible total synthesis of therapeutically useful spirooxindoles [6][7][8][9][10][11][12][13][14][15], but also for the preparation of synthetic analogs [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] in order to improve our knowledge in structure-activity relationships [12-14, 31, 32]. So-called butenolide functionalized spirooxindoles 1 provide the most interesting subject for synthetic investigations in view of the large and ever increasing number of the members of this family which have furan-2(5H)-one 2 as a building block (Scheme 1).…”