Synthesis of steroidal azides. Part 3. Addition of halogen azides to Δ6-steroids

Abstract

The reaction between halogen azides and Δ⁶-steroids has been investigated. The addition of bromine azide to 3,20-dioxopregna-4,6-dien-17α-yl acetate (5), for example, is shown to give 7α-azido-6β-bromo-3,20-dioxopregn-4-en-17α-yl acetate (10), whereas with 9α-fluoro-16α-methyl-20-oxo-2′-phenyl-2′H-pregna-2,4,6-trieno[3,2-c]pyrazole-11β,17α,21-triol 21-acetate (27), the products are 6ξ-azido-7ξ-bromo-9α-fluoro-16α-methyl-20-oxo-2′-phenyl-2′H-pregna-2,4-dieno[3,2-c]pyrazole-11β,17α,21-triol 21-acetates (32). The differing regiospecificity of addition to the Δ⁶-double bond, exhibited by these reactions, is rationalised in terms of conjugate addition of azide ion occurring in the former case and electrophilic addition of bromine in the latter. Addition of bromine azide to 17α-hydroxypregna-1,4,6-triene-3,20-dione (15) occurs primarily in the B ring under neutral conditions, whereas in the presence of hydrazoic acid, reaction takes place in ring A. Azide-ion-induced elimination from 7α-azido-6β-bromo-3,20-dioxopregn-4-en-17α-yl acetate (10) generates 4-azido-3,20-dioxopregna-4,6-dien-17α-yl acetate (8) and 6-bromo-3,20-dioxopregna-4,6-dien-17α-yl acetate (9) in the ratio of 5 : 1. However, elimination of hydrazoic acid from the same compound promoted by tetramethylammonium fluoride yields compound (9) as the major product.