Domino Heck–Aza‐Michael Reactions: A One‐Pot, Sequential Three‐Component Approach to 1,1‐Dioxido‐1,2‐benzisothiazoline‐3‐acetic Acid

Abstract

The development of a new method for the synthesis of 1,1-dioxido-1,2-benzisothiazoline-3-acetic acid by a domino process is reported whereby a classical Heck reaction is coupled to an intramolecular aza-Michael reaction. Ultimately, this method has been expanded to a one-pot, sequential three-component protocol to generate diverse benzofused γ-sultams from a range of commercially available α-bromobenzenesulfonyl chlorides, amines and Michael acceptors.

Synthesis of Amino-Benzothiaoxazepine-1,1-dioxides Utilizing a Microwave-Assisted, SNAr Protocol

“…8 In this regard, efforts have focused on the development of a variety of methodologies and protocols for the generation of diverse sultam collections. 9 These methodologies include the development of a variety of protocols namely, “Click-Click-Cyclize”, 10 complementary ambiphile pairing (CAP), 11 and reagent-based diversity-oriented synthesis (DOS). 12 Building on these methods, we herein report the design and synthesis of a 126-member library of amino-benzothiaoxazepine-1,1-dioxides via a microwave-assisted, intermolecular S N Ar diversification of core benzothiaoxazepine-1,1-dioxides scaffolds (Scheme 1).…”

Synthesis of a Unique Isoindoline/Tetrahydroisoquinoline-based Tricyclic Sultam Library Utilizing a Heck-aza-Michael Strategy

“…17 In addition, domino HaM protocols have been developed in our laboratory for the synthesis of a library of functionalized 1,1-dioxido-1,2-benzisothiazolines. 18 Along these lines, we envisioned the construction of a tricyclic sultam library via integration of a HaM protocol with vinylsulfonamides, as outlined in Scheme 1. In this approach, the secondary sulfonamide linchpin 3 can easily be synthesized via a Heck reaction of substituted bromobenzene 1 and vinylsulfonamide 2 .…”

α-Haloarylsulfonamides: multiple cyclization pathways to skeletally diverse benzofused sultams

“…In this regard, we have has previously reported a one-pot domino Heckaza-Michael protocol for the synthesis of 1,2-benzisothiazoline-3-acetic acid 1,1-dioxides 24 xxvi. Such domino protocols are attractive strategies for the incorporation of multiple points of diversity in a one-pot multi-component transformation.…”