Radical Cyclizations of Cyclic Ene Sulfonamides Occur with β-Elimination of Sulfonyl Radicals to Form Polycyclic Imines

Abstract

Radical cyclizations of cyclic ene sulfonamides provide stable bicyclic and tricyclic aldimines and ketimines in good yields. Depending on the structure of the precursor, the cyclizations occur to provide fused and spirocyclic imines with five-, six-, and seven-membered rings. The initial radical cyclization produces an α-sulfonamidoyl radical that undergoes elimination to form the imine and a phenylsulfonyl radical. In a related method, 3,4-dihydroquinolines can also be produced by radical translocation reactions of N-(2-iodophenylsulfonyl)tetrahydroisoquinolines. In either case, very stable sulfonamides are cleaved to form imines (rather than amines) under mild reductive conditions.

Single‐Electron/Pericyclic Cascade for the Synthesis of Dienes

“…Generation of either an anion or radical using the vinyl halide would lead to a 6-endo cyclization to form the cyclic hydrazide 2, [12,13] followed by elimination of the sulfonamide to form the key cyclic diazene 3. [14] The diazene 3 will then readily undergo a cycloreversion to form the desired diene 4. [15] Each of these reactions will have low activation energies, thus the entire process should proceed during a single reaction step.…”

Synthesis of the Bicyclic Lactone Core of Leonuketal, Enabled by a Telescoped Diels–Alder Reaction Sequence

“…Reduction of the α,β‐unsaturated ketone with sodium cyanoborohydride in acetic acid afforded an inseparable mixture of the desired product [2.2.2]‐ 5 with a second product, [3.2.1]‐ 24 . This reaction favored the formation of compound 5 in an approximately 2:1 ratio in most cases; however, this selectivity was somewhat variable and was occasionally reversed, for reasons that remain to be identified . The reduction step was found to proceed with complete exo ‐selectivity to give a single C5‐alcohol epimer ( 6 ), but a competing cyclization reaction on either carbonyl group of the cyclic anhydride led to the concomitant formation of either a six‐membered lactone (solid arrow; Scheme ) to give the favored, desired product [2.2.2]‐ 5 , or a five‐membered lactone (dashed arrow; Scheme ) to afford [3.2.1]‐ 24 .…”

“…Reduction of the a,b-unsaturated ketone with sodium cyanoborohydride in acetic acid afforded an inseparable mixture of the desired product [2.2.2]-5 with as econd product, [3.2.1]-24.T his reaction favored the formation of compound 5 in an approximately 2:1r atio in most cases;h owever, this selectivity was somewhat variable and was occasionallyr eversed, for reasonst hat remain to be identified. [15] The reduction step was found to proceed with complete exo-selectivity to give as ingle C5-alcoholepimer (6) [5] We recognized that Scheme4.Optimizedtelescoped four-stepD iels-Alder sequence to afford the bicyclic lactone core of leonuketal (1). TFA = trifluoroacetic acid.…”

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

“…Simple imines are not easily reduced by Bu 3 SnH alone, but ionic reductions can be effected by adding Lewis bases (such as HMPA) or by using Lewis acidic tin hydrides (such as Bu 2 SnClH) [ 16 – 17 ]. Potential catalysts of hydride reduction such as benzenesulfinic acid (PhSO 2 H) and tributyltin benzenesulfinate (PhSO 2 SnBu 3 ) could form under these conditions [ 11 ].…”

“…Recent work from our group considerably strengthened the case for α-sulfonamidoyl radical elimination reactions. We were able to isolate stable imines from treatment of an assortment of ene-sulfonamides bearing radical precursors [ 11 ]. Typical examples are the cyclizations of bromide precursors 1 mediated by Bu 3 SnH ( Fig.…”