Nitrimines reduction

The reaction of 9(1 l)-dehydro steroids with nitrosyl fluoride was studied by Grantz and Rosenthal in pursuit of an alternate source for the important 9a-fluoro-11-oxygenated steroids. As expected, reaction at the more hindered 9(1 l)-double bond proceeds more slowly than at either the 4- or 5-double bonds. After 10 days at 3°, 3 -acetoxy-5a-pregn-9(l l)-en-20-one (50) affords a 45% yield of the 9a-fluoro-ll-nitrimine (51). Other 9a-fluoro-ll-nitrimines were prepared and it was found that the presence of additional keto groups, particularly the 3-keto group gives rise to side products with a concomitant reduction in yield of the desired 9a-fluoro-ll-nitrimines. In the case of the A" -3-ketones the yield is reduced to 10 %. The steric hindrance... 

A few other A-substituted imines have occasionally been reduced to amine derivatives. Thus, A(-nitro imines (nitrimines) are reduced by NaBH4/dioxane %tOH/AcOH to A -nitroamines (Table 16, entry 14), and nitronate salts are reduced by BH3/THF to hydroxylamines (entry 15) via oximes. Isocyanates are reduced by LiBHEts, LiAlH(OBu )3 (at low temperature), or PhsSnH to formamides, which may be hydrolyzed in acidic workup to amines,while reduction with LAH affords A/-methylamines. ... 

Nitrosyl fluoride reacts slowly (10 days at 3 °C) with 9(ll)-unsaturated steroids to produce 9a-fluoro-ll-nitrimines in 10—70% yield. The nitrimines may be reduced catalytically or with Raney nickel (without affecting 4-en-3-one functions) to 11-imines or by sodium borohydride to nitramines. Both the 11-imines and the 11-nitrimines can be hydrolysed to the corresponding 11-ketones (61— 100% yields), thereby providing another method for the preparation of 9a-fluoro-11-ketones. Further reduction of the 9-fluoro-l 1-imines either catalytic-ally or with sodium borohydride gives 9a-fluoro-11-amino-derivatives, although reduction with sodium and propan-l-ol affords, after acetylation, 1 l( -acetamido-pregnanes with loss of fluorine. 

Oximes and Related Derivatives.—Beckmann fragmentation of a-hydroxy-ketoximes occurred with dichlorocarbene. For example, a chloroform-ethyl acetate solution of the 5a-hydroxy-6-oximinocholestane (134) gave the keto-nitrile (135) with acqueous NaOH in the presence of benzyltriethylammonium chloride. Improved reduction of nitrimines to nitramines with NaBH4 and acetic acid has been reported and is exemplified by the conversion of the nitrimino-cholestane (136) into the 6 8-nitramino-compound (137). ... 

Hydroxylamines and Nitramines.—Oximes are readily reduced to hydroxylamines under various conditions, but when the reduction is carried out using sodium borohydride in the presence of a carboxylic acid alkylation also takes place, affording a useful new synthesis of NiV-dialkylhydroxylamines (Scheme 12). The yields of nitramines obtained from the reduction of nitrimines by sodium borohydride may be improved by carrying out the reactions in the presence of acetic acid. ... 

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