Azido-ketones

Einige a-Azido-ketone konnen durch Natriumboranat zu 2-Amino-alkoholen7 reduziert werden z.B. auch in der Zuckerreihe8. 

The obtained spiro keto esters 2-181 could be converted into 2-183, employing among other transformations an intramolecular Schmidt rearrangement [101] of the azido ketones 2-182. 

In azido ketones both functions were reduced with lithium aluminium hydride in refluxing ether m-azidoacetophenone gave 49.5% yield of 2-amino-1-phenylethanol [600. ... 

One of the classical methods for the synthesis of pyrazines involves dimerization of an a-amino carbonyl compound and subsequent aromatization. Cyclic dimerization of the a-amino ketone, which is formed by reduction of a-azido ketone 149 with triphenylphosphine, leads to the formation of a pyrazine derivative 150 (Scheme 40) <1994JOC6828>. Reduced Te also dimerized a-keto azide 149 to give pyrazine 150 <2006JOG2797>. 

Photolysis of 3-phenyl-5(4//)-isoxazolone 152 gives 2,5-diphenylpyrazine 154 in 67% yield (Scheme 41) <1997JIC648>, probably through diradical intermediate 153. Radical chain reactions of a-azido ketones 155 with tributyltin hydride lead to symmetrical alkylpyrazines 156, albeit in low to moderate yields (Scheme 42) <2002T3485>. 

An important preparation of pyrazines (303) is from a-amino ketones RCOCH2NH2 or their monooximes which spontaneously condense to give 2,5-dihydropyrazines (302). The a-amino ketones are often prepared in situ by reduction of isonitroso ketones, and the dihydropyrazines are usually oxidized to pyrazines before isolation icf Section 3.2.2.3.3). Catalytic reduction of a-azido ketones also leads to 2,5-dihydropyrazines (80OPP265). Similarly, a-nitro ketones may be reduced to the a-amino ketones which dimerize spontaneously (69USP3453278). 

Conversion of a-azido ketones to pyrazines by treatment with triphenylphosphine in benzene (Scheme 42) proceeds in moderate to good yields (69LA(727)23l). 

Scheme 72 Preparation of bicyclic P-lactam 199 using azido-ketone cyclization...

Aza- Wittig reaction, cyclic imines. Treatment of the azido ketones 1 with triphenylphosphine at room temperature results in a cyclic imine (2) in good yield, formed by an intramolecular aza-Wittig reaction.2... 

One more example of high stereo- and regioselectivity of cycloaddition has been provided by the reaction of enantioenriched azido ketone 551 that bears a tethered nitrile group which undergoes cyclization to the bicyclic tetrazole 552 (Equation 107) <2005JA1313>. 

Recently Zbiral and Stroh reported that treatment of a-azido-ketones (obtained generally by reaction of the a-halogenoketone with sodium azide) with triphenylphosphine is a convenient route to 2,5-disubstituted pyrazines (Scheme 5). Thus, 2,5-diphenyl-, 2,5-bis(4-methoxyphenyl)-, and 2,5-diisopropylpyrazine have been obtained in 75, 45, and 44% yield, respectively. The intermediate P-iV-ylide undergoes intermolecular condensation to give a 2,5-dihydropyrazine which is subsequently aromatized.122... 

Reaction of otfi-unsaturated acetals with silyl nucleophiles. This trityl salt is an efficient catalyst for reaction of the dimethyl acetal (2) of cinnamaldehyde with successive silyl nucleophiles to form y,5-unsaturated p-azido ketones. The azide group can be reduced to an amino group by the Staudinger reaction.1... 

Thermal decomposition of 3-azido-2-formylfuran, -thiophene, and -selenoles has also been used to prepare furo[3,2-c]isoxazole (97), thieno[3,2-c]isoxazole (4), and selenolo[3,2-c]isoxazoles (98) (Equation (27)) <76CS165>. In contrast, some azido ketones eliminate nitrogen at ambient temperature and cyclize as exemplified in the reactions of 2-chloro-3-acetylindole (99) (Equation (28)) and 3-chloro-2-benzoylbenzothiophene dioxide (101) (Equation (29)) with sodium azide (78CB1521, 92JOC2127). 

Carbon atom 2 of the oxazole ring is also supplied by aldehydes in their reaction with a- (hydroxylamino) ketones, which proceeds in the presence of sulfuric acid and acetic anhydride (equation 109). Three further oxazole syntheses involving incorporation of a C(2) fragment are the condensation of triethyl orthoformate with the hydrochlorides of a-aminoacetophenones (equation 110), the reaction of acyl chlorides with a-azido ketones or a-azido esters in the presence of triphenylphosphine (equation 111), and the preparation of 2-aminobenzoxazole and benzoxazoleimines from o-aminophenols and cyanogen bromide (equation 112). 

Miscellaneous Reactions.—Irradiation of acetoxy-steroids in HMPA-H20 at 254 nm gives the corresponding hydrocarbons in high yields.255 Photolysis of either a 12a-azido- (326) or a 9a-azido-ll-ketone (328) gave the corresponding aza-c-homo-compound (N-acylimine) (327) or (329), respectively. Azido-ketones in rings A or D gave complex mixtures of products.256... 

Steroidal alkenes, with lead(IV) azide/acetate, can yield cleaved derivatives such as (87),or its des-azido analog, or the uncleaved azido ketone,or the allylic azide, according to conditions, as well as the 1,2-diazi s mentioned earlier (Section 3.S.3.2). 

In the absence of iron(III) chloride the reaction leads to 1,2-diazides (Section 7.2.2.4.). Furthermore, a-azido ketones are obtained in the presence of oxygen10. 

The reaction of alkenes with iodosobenzene in acetic acid in the presence of sodium azide offers a simple and high yield route to 1,2-diazides (Table 3)76. a-Azido ketones are side products or the exclusive product from the reaction with conjugated alkenes. Allylic azides or oxonitriles, resulting from oxidative cleavage of the C-C double bond, are alternatively obtained from trisubstituted steroid alkenes77. 

Only the predominant diastereomer is shown. b The corresponding a-azido ketone is formed in 14% yield. 

Treatment of triisopropylsilyl enol ethers of cyclic ketones with ammonium cerium nitrate (3 equiv) and sodium azide (4.5 equiv) in acetonitrile at — 20 °C gave a-azido ketones in good yields124. By varying the ratio of the reagents the yields were lower or the formation of byproducts, difficult to separate, increased. Mixture of diastereomers (ratio not reported) were generally obtained from substituted substrates, except from the bicyclic ketones 16. 

Trimethylsilyl enol ethers proved to be unsuitable substrates due to the ease of hydrolysis to the ketone. Presumably, for the same reason, the yield of the a-azido ketone prepared from 17 dropped to less than 50% on reaction scales larger than 100 mg125. 

J-Hydroxy Azides, 1,2-Diazides and a-Azido Ketones From Steroid Alkenes... 

Lead acetate azides, Pb(OAc)4 (N3)n, prepared in situ from lead tetraacetate and azidotrimethylsilane, react with alkenes to yield a variety of products, depending on the structure of the alkene 1,2-diazides. 1,2-acetoxy azides, a-azido ketones, allylic azides, and <5-oxo nitriles (by the oxidative cleavage of cyclohexene rings)97. The diazides and acetoxy azides are formed by preferential syn addition, but the diastereoselectivity (up to 3 1) is far from satisfactory with both acyclic and cyclic alkenes98,99. 

If the reaction of unsubstituted cycloalkenes, including steroids, is performed in dichloro-methane at — 20 CC, a-azido ketones, e.g., 1-3, were obtained in a one-step regio- and diastereoselective reaction. The azido group was introduced in the axial position, however, the more stable /1-isomers were readily obtained on treatment with silica gel100. 

Synthesis of Stereoidal a-Azido Ketones General Procedure10 ... 

Disubstituted steroid olefins are converted by the reagent into a-azido ketones. Thus A -cholestene (9) reacts with the reagent in dichloromethane at —20° to give 3a-azidocholestanone-2 (10) in 50-60% yield. A possible mechanism is formulated. The... 

In contrast to ammonia, primary, secondary, and tertiary amines can add to aldehydes and ketones to give different kinds of products. Primary amines give imi-nes and secondary amines gives enamines (10-69). This section will focus on imines. Reduction of co-azido ketones leads to the amino-ketones, which cyclizes to form a 2-substituted pyrroline. Reduction of nitro-ketones in the presence... 

---