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

Abstract

A protocol for the stereoselective synthesis of alkylidenephthalides and indanediones has been developed through the reaction of o-hydroxychalcones and their styrenyl analogues, respectively, with 3-sulfonylphthalide. The mechanism for the former synthesis involves Michael addition-E 2 elimination sequence, while the latter involves a [4 + 1] Hauser-Kraus annulation. The mechanistic studies reveal that the strategically positioned phenolic group plays a pivotal role in the observed reactivities. The alkylidenephthalides, which are latent 1,4dicarbonyl compounds, were further converted to triarylfurans under Paal-Knorr conditions in good to excellent yields. This protocol unravels several key features such as substrate specific product formation, namely, alkylidenephthalides from chalcones, and indanediones from vinylogous chalcones in their reaction with 3-sulfonylphthalide as well as the role of alkylidenephthalides as 1,4-dicarbonyl surrogates in Paal-Knorr furan synthesis.

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

“…For the first time, we have demonstrated the reactivity of sulfonylphthalides 9b as one-carbon sources in reactions with o -hydroxychalcones 125 and 127 for the stereoselective syntheses of alkylidenephthalides 126 and indanediones 128 , respectively (Scheme 24 ). 39 Unlike the classical H–K annulation, the formation of alkylidenephthalides 126 involves Michael addition of the phthalide 9b to o -hydroxychalcones 125 , followed by direct E 2 elimination of a sulfone. The product core resembles the molecular structure of naturally occurring microcarpine.…”

Preparation of 3‐Alkylidenephthalides: Recent Advances

“…As a part of the ongoing work on the reactivity of 3‐sulfonylphthalide with various acceptors, the group of Namboothri investigate, in 2021, the behavior of o ‐hydroxybenzoyl derived chalcones (Scheme 4). [9] In basic conditions, they established an olefination protocol based on sequence including a Michael addition followed by an elimination reaction to afford the corresponding alkylidenephthalides in good yields and as a single isomer. From the mechanistic point of view, the first step would be a base mediated Michael addition of phthalide to chalcone resulting in the formation of the corresponding enolate.…”

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).…”