Synthesis of an Azasteroid Using an Acyl Iminium Ion-Initiated Tandem Cyclization

Abstract

An acyl iminium ion-initiated tandem cyclization gave an unexpected dienone product, a seco-azasteroid (2). The factors governing the formation of 2 were investigated in an attempt to optimize its formation. The reaction was applied to a more elaborate system, resulting in the synthesis of the full steroid skeleton of 13-azaandrosta-1,4-diene-3,17-dione (3), which contains the unusual substitution of a chlorine atom for the axial 19-methyl.

Reactions of Pyridine Analogues of Aza-o-xylylenes Generated from 1,3-Dihydroisothiazolo[4,3-b]pyridine 2,2-Dioxides (Pyridosultams) − Formation of 2:1 Adducts withN-Phenylmaleimide

“…[37] In recent years various methodologies for the total synthesis of azasteroid skeletons have been developed. For example, 13-azaandrosta-1,4-diene-3,17-dione was obtained by an acyliminium ion initiated tandem cyclization, [38] 8,13-diazagonane derivatives were obtained by condensation of 1-(1,2,3,4-tetrahydroisoquinolyl)acetates with butyrolactims, [39] 13-azasteroids and their 4,13-diaza analogues were obtained from thermal intramolecular cycloaddition of nitrones to acetylenes, [40] 9-azaestra-1,3,5(10)-trien-17-one was obtained through the intramolecular DielsϪAlder reaction of aza-o-xylylene generated from a (2-aminobenzyl)ammonium salt, [35] and 3,4-cyclopentano-1,2,3,4-tetrahydronaphthyridine, a 7-azasteroid skeleton, was formed in an intramolecular DielsϪAlder reaction undergone by the aza-o-xylylene generated by thermal extrusion of SO 2 from 3- [41] Scheme 2. tr ϭ traces Scheme 3 Scheme 4 In diazasteroids, 136 positional isomers with nitrogen atoms replacing the carbon atoms in the steroid framework are possible. To the best of our knowledge the diazasteroid skeleton bearing nitrogen atoms in positions 10 and 14 has not yet been synthesized.…”

“…Oil. 1 H NMR (500 MHz): δ ϭ 0.69 (t, J ϭ 7.4, 6 H), 1.45 (tq, J ϭ 7.4, 4 H), 3.12 (t, J ϭ 7.4, m/z (%) ϭ 252 (34) [M ϩ ], 187 (15), 183 (48), 170 (51), 159(17), 145(18), 131(12), 119 (100), 106(27), 92(38), 83(17), 82 (23), 65(16), 55(13). HRMS for C12 H 16 N 2 O 2 S calcd.…”

A Dearomatization/Debromination Strategy for the [4+1] Spiroannulation of Bromophenols with α,β‐Unsaturated Imines

“…Next, we studied the behavior of other halophenols (X=Cl, I) for this new reaction, and unprecedented reactivities for both the chloro‐ and iodo‐substrates ( 1 a I , 1 a II , 4 c I , 4 c II ) were observed (Scheme ). Generally, chloro‐substrates ( 1 a I , 4 c I ) showed good reactivities, while iodo‐substrates ( 1 a II , 4 c II ) led to the lower yields of their corresponding products 3 a and 5 c , respectively.…”

Enantioselective Reactions of N‐Acyliminium Ions Using Chiral Organocatalysts

“…[63] Many of these azasteroids have been synthesized through N-acyliminium ion-initiated cationic polycyclization reactions, which were first presented by Speckamp.…”