Exploring chemical diversity via a modular reaction pairing strategy

Abstract

SummaryThe efficient synthesis of an 80-member library of unique benzoxathiazocine 1,1-dioxides by a microwave-assisted, intermolecular nucleophilic aromatic substitution (SNAr) diversification pathway is reported. Eight benzofused sultam cores were generated by means of a sulfonylation/SNAr/Mitsunobu reaction pairing protocol, and subsequently diversified by intermolecular SNAr with ten chiral, non-racemic amine/amino alcohol building blocks. Computational analyses were employed to explore and evaluate the chemical diversity of the library.

Chemistry of Bridged Lactams and Related Heterocycles

“…442 This protocol was recently employed for the synthesis of a 40-member library of bridged sultams bearing [4.2.1] scaffolds. 446 …”

“…As a part of the reaction pairing strategy to access structurally diverse sultams, − these researchers developed a sequential sulfonylation-S N Ar protocol starting from ortho -fluorobenzenesulfonyl chloride and cyclic amino alcohols to afford bridged sultams with [4.2.1] and [5.2.1] ring systems in good overall yields . This protocol was recently employed for the synthesis of a 40-member library of bridged sultams bearing [4.2.1] scaffolds …”

Synthesis of Stereochemically and Skeletally Diverse Fused Ring Systems from Functionalized C-Glycosides

“…The intramolecular S N Ar reaction has been widely used in the context of diversity-oriented synthesis (DOS) and small molecule synthesis in general . We envisioned employing a S N Ar cyclization to produce a [6,8,6] tricyclic scaffold containing an 8-membered lactam starting from allylic amine 2 .…”

Synthesis of Functionalized Bridged Bicyclic Sulfonamides with a Bridgehead Nitrogen Atom

“…The previously reported approaches to construction of bicyclic cores of type 3 relied on Bu 3 SnH‐mediated cyclization of unsaturated α‐bromosulfonamides 5 , intramolecular Heck reaction of 6 (a single example), intramolecular alkylation in α‐(2‐chloroethyl)sultam 7 and related bis‐alkylation of α‐carbomethoxy‐substituted sultams 8 (Scheme ) . A number of tri‐ and polycyclic sultams with the bridgehead nitrogen atom were also described; their syntheses relied on the retrosynthetic disconnections of the C–C or C–N bonds …”