Synthesis of Sulfonyloxindoles via Functional Group Exchange Between 3‐Sulfonylphthalide and Isatylidenemalononitrile

Abstract

An unusual reactivity of 3-sulfonylphthalides with isatylidenemalononitriles has been exploited to provide an efficient entry into 3-sulfonyloxindoles. Although a Hauser-Kraus mechanism can be visualized for the observed transformation, a more probable mechanism, based on control experiments and spectroscopic studies, involves Michael addition of sulfonylphthalide to isatylidenemalononitrile followed by elimination and re-addition of sulfonyl and malononitrile functionalities in an overall functional group exchange between phthalide and oxindolyl moieties. We have also demonstrated the synthetic applications of the sulfonyloxindoles in selected reactions such as conjugate addition and aromatization.

Synthesis of Natural Products, Carbocycles, and Heterocycles by Hauser–Kraus Annulation

“…For the first time, our group demonstrated the reactivity of sulfonylphthalides 9 as sulfonylation reagents in their reaction with isatilydenemalononitriles 138 (Scheme 27 ). 40 This transformation is mainly dependent on the nucleofuge at the C3 position of the phthalide and the nitrile on the 3-olefinic oxindole 138 . Replacing the phthalide with 3-(phenylsulfonyl)isobenzofuran-1(3 H )-thione did not result in a product.…”

Reactions of Sulfonylphthalide with Diverse Activated Imines for the Synthesis of Enaminophthalides, Spiro-isoquinolinones, and Homalicine Natural Products

“…In recent years, our group has explored the reactivity of 3-sulfonylphthalide with various Michael acceptors bearing a nucleophilic site at the ortho position leading to various spiro and fused heterocycles via [4 + 4] annulation followed by a series of rearrangements. − Later, the [4 + 2] H–K annulation of 3-sulfonylphthalide was also carried out with several activated olefins that led to various spiro - and fused quinones and aminophenanthrenes. − We further investigated other reactivities of 3-sulfonylphthalide such as [4 + 1] annulation, addition–elimination, sulfonyl migration, etc. with different activated olefins under suitable conditions. , Although several Michael acceptors were employed in the H–K annulation (Scheme a) and an ester phthalide was added to imines in a 1,2-fashion (Scheme b), there are no reports, to our knowledge, on the reactivity of sulfonylphthalide with activated imines. Therefore, we report herein a base mediated reaction of 3-sulfonylphthalide with different activated imines that led to the formation of diverse products, namely unsaturated phthalides and heterocycles (Scheme c).…”

“…with different activated olefins under suitable conditions. 19,20 Although several Michael acceptors were employed in the H−K annulation (Scheme 1a) and an ester phthalide was added to imines in a 1,2-fashion (Scheme 1b), 21 there are no reports, to our knowledge, on the reactivity of sulfonylphthalide with activated imines. Therefore, we report herein a base mediated reaction of 3-sulfonylphthalide with different activated imines that led to the formation of diverse products, namely unsaturated phthalides and heterocycles (Scheme 1c).…”

Michael Addition‐Elimination and [4+1] Annulation of Sulfonylphthalide with Hydroxychalcones for the Synthesis of Alkylidenephthalides and Indanediones

“…But since these groups are leaving groups and will not be part of the product, we have chosen benzenesulfonylphthalide 1 a as a representative substrate to investigate the reactivity of hydroxychalcones 2 and 5. In our recent studies on the addition of various phthalides to oxindolylidenemalononitrile, [35] we observed that thiophthalide (C=S instead of C=O) is not a good phthalide donor and addition of sulfinylphthalide (SPh instead of SO 2 Ph) stops at the Michael addition stage presumably because sulfinyl group is not a good leaving group compared to sulfonyl group. Some of the above possibilities and studies on the reactivity of thiol and amino analogs of chalcones 2/5 will be taken up soon and the results will be reported in due course.…”