Bicyclic Sultams with a Nitrogen at the Bridgehead and a Sulfur Atom in the Apex Position: Facile Preparation and Conformational Properties

Abstract

A practical synthesis of bicyclic sultams with a pyramidal bridgehead nitrogen atom and a sulfur atom in the apex position has been elaborated. Compounds with 1-azathiabicyclo[2.2.1]heptane (12a), -bicyclo[3.2.1]octane (12b, 12d), and -bicyclo[3.3.1]nonane (13b) skeletons were obtained by direct twofold inter/intramolecular alkylation of corresponding monocyclic sultams 9 and 10 with α,ω-dihalides 11 in

Chemistry of Bridged Lactams and Related Heterocycles

“…440,441 In 2006, Paquette reported the synthesis of a bridged sultam containing a [4.2.1] ring system via an intramolecular alkylation reaction (Scheme 106a). 440 Attempts to close the bicyclic system via RCM proved unsuccessful (Scheme 106b).…”

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

“…Previously used conditions viz. carrying out the reaction in MeCN in the presence of pyridine at rt gave poor results [ 17 – 20 ]. Thus, in case of aniline 7a the desired sulfonamide 8a was obtained in only 7% yield.…”

“…Earlier on, our group has developed versatile syntheses of sultams based on the transformation of methanesulfonamides bearing an additional α-acceptor (EWG) group [ 17 – 20 ]. Thus, intermolecular cyclodialkylation of α-substituted methanesulfonamides, upon treatment with α,ω-dibromoalkanes and bases, provides a rather simple and efficient route to five-, six- and seven-membered sultams.…”

“…Thus, intermolecular cyclodialkylation of α-substituted methanesulfonamides, upon treatment with α,ω-dibromoalkanes and bases, provides a rather simple and efficient route to five-, six- and seven-membered sultams. Moreover, bridged sultams with a pyramidal nitrogen atom and a sulfur atom in the apex positions were prepared from the same kind of starting materials in good to excellent yields [ 20 ]. Quite recently, Xu et al employed 1-diazo-1-ethoxycarbonylmethanesulfonamides for the synthesis of benzo-γ-sultams.…”

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 …”