Two Complementary Cyclization Reactions for the Chemoselective Synthesis of Spirooxindoles

Abstract

Two complementary cascade cyclization reactions, namely, the KHSO4‐promoted [1+2+3] cyclization and the TMSCl‐promoted four‐component cascade cyclization, are described for the concise synthesis of highly functionalized spirooxindoles in excellent yields. The improved TMSCl‐promoted cyclization reaction of isatins, N,N‐dimethylenaminones, and amines was carried out under milder conditions than those of the [1+2+3] cyclization to afford the desired products. The observed chemoselectivity of this TMSCl‐promoted cyclization is explained by the design and preparation of an intermediate bis(enaminone). A gram‐scale synthesis and synthetic applications of this transformation were also evaluated.

Synthesis of 2,3-Dihydro-4-pyridones and 4-Pyridones by the Cyclization Reaction of Ester-Tethered Enaminones

“…26,27 This unsymmetrical dialkenyl amine could rearrange to polysubstituted conjugated dienes 26 or afford spirooxindoles upon treatment with isatin. 27 Obviously, the synthetic potential of structure 1 has yet to be disclosed. Thus, we used the optimized reaction conditions shown in Table 1, entry 13, to synthesize a series of compounds 1, which were isolated in 32−85% yield (Table 2).…”

“…However, structure 1 is less common. A few examples involve N -trimethylsilyloxy derivatives (R = Me 3 SiO) obtained by silylation of β-substituted aliphatic nitro compounds, N-heteroaryl derivatives formed by the reaction of annelated 2-aminothiophene with methyl propiolate in refluxing toluene, bis­(chlorodifluoromethyl)­keto derivatives (ClF 2 CO instead of CO 2 Et in 1 ) formed by the self condenzation of the corresponding enamino ketone under basic conditions, and mixed keto–ester derivatives obtained by the reaction of enamino ketone with ethyl propiolate in the presence of a base. , This unsymmetrical dialkenyl amine could rearrange to polysubstituted conjugated dienes or afford spirooxindoles upon treatment with isatin . Obviously, the synthetic potential of structure 1 has yet to be disclosed.…”

Selectfluor-triggered fluorination/cyclization of o-hydroxyarylenaminones: A facile access to 3-fluoro-chromones

“…In addition, the groups of Kandula 71 and Zhao 72 also reported a Selectfluor-triggered tandem cyclization strategy for constructing 3-fluoro-chromones via direct elimination of 3,3-difluorinated 2-amino chromanones at room temperature in a short time ago. As our ongoing interest in enaminone chemistry, [73][74][75][76][77][78][79][80][81][82] herein, we report a fast and efficient Selectfluor-triggered fluorination/cyclization reaction of o-hydroxyarylenaminones for the construction of 3-fluoro-chromones promoted by potassium carbonate (Scheme 1(c)). Interestingly, this reaction is mechanistically different compared to the previously reported methods 71,72 where 2-(dimethylamino)-3,3difluorochroman-4-one.…”