Lithium azide reduction with

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

Butyl alcohol in synthesis of phenyl 1-butyl ether, 46, 89 1-Butyl azidoacetate, 46, 47 hydrogenation of, 46, 47 1-Butyl chloroacetate, reaction with sodium azide, 46, 47 lre l-4-i-BUTYLCYCLOHEXANOL, 47,16 4-(-Butylcyclohexanonc, reduction with lithium aluminum hydride and aluminum chloride, 47, 17 1-Butyl hypochlorite, reaction with cy-clohexylamine, 46,17 l-Butylthiourea, 46, 72... 

Cyclic sulfites (68) also are opened by nucleophiles, although they are less reactive than cyclic sulfates and require higher reaction temperatures for the opening reaction. Cyclic sulfite 77, in which the hydroxamic ester is too labile to withstand ruthenium tetroxide oxidation of the sulfite, is opened to 78 in 76% yield by reaction with lithium azide in hot DMF [82], Cyclic sulfite 79 is opened with nucleophiles such as azide ion [83] or bromide ion [84], by using elevated temperatures in polar aprotic solvents. Structures such as 80 generally are not isolated but as in the case of 80 are carried on (when X = N3) to amino alcohols [83] or (when X = Br) to maleates [84] by reduction. Yields are good and for compounds unaffected by the harsher conditions needed to achieve the displacement reaction, use of the cyclic sulfite eliminates the added step of oxidation to the sulfate. 

LVI) was proved 54) by Esohweiler-Clarke methylation to methyl-holaphylline and was further confirmed by a synthesis from pregnenolone (LIX) via 3 8-tosyloxy-20-oximinopregn-5-ene (LX) which on treatment with sodium azide in methanol yielded a mixture of 3 3-azido-20-oximino-pregn-5-ene (LXI) and the 3a,6a-cyclo-6 -azido isomer. Selective reduction with lithium aluminum hydride followed by acid hydrolysis yielded holaphyllamine along w ith its 3,5-cyclo isomer which could be separated by chromatography (55). 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Cleavage of 5a,6a- and 6a,7a- epoxides with azide ion and subsequent reduction with hydrazine has led to the preparation of 6 -amino-steroids, although similar treatment of 16a,17a-epoxypregnenolone acetate was accompanied by D-homoannulation to give, after reduction, the 16j3-amino-Ha-ketone. Azide displacement (lithium azide in DMF) of 3a,20j8-diacetoxy-... 

Synthesis from aldonolactone Syntheses of casuarines 249, 253, 261 and 262 from lactone 245 have been reported (Schemes 24 and 25). The triflate in 245 was displaced with azide ion to give the inverted azide, which on reduction with lithium borohydride... 

Tri-O-benzyl-L-galactitol was converted into the isopropylidene mesylate 24. Treatment of 24 with lithium azide in DMF gave the azide 25 with inversion of the configuration. Reduction of the azide 25 with lithium aluminum hydride gave the amine 26 To protect the amino group, N-ethoxycarbonylphthalimide was used with triethylamine as solvent to give the phthaloyl derivative 27... 

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