Nucleophilic transformations of azido-containing carbonyl compounds via protection of azido group

A series of 3-indolylalkylaminoalcohols have been obtained from the lithium aluminum hydride reduction of the amides prepared by the reaction of 3-indoleglyoxylyl chloride and 2-methyl-3-indoleglyoxylyl chloride with primary aminoalcohols. When acetone was used as solvent in the reaction of 3-indoleglyoxylyis chloride and either 2-aminoethanol or 3-aminopropanol, the solvent participated in the reaction resulting in the formation of 2,2-dimethyl-3-(3-indoleglyoxyl)oxazolidine and 2,2-dimethyl-3-(3-indoleglyoxyl)tetrahydro-1,3-oxazine respectively. When the latter two compounds were reduced by lithium aluminum hydride, both carbonyl groups were completely reduced and reductive cleavage of the oxazolidine and tetrahydro-1,3-oxazine rings occurred to form the corresponding open-chain alcohols.

Reduction of dimethyl 3-hydroxy-4,4,8-trimethyl-6-oxo-cis-bicyclo[3.3.0]octa-2,7-diene-1,2-dicarboxylate (8) with lithium and ammonia gives dimethyl 3-hydroxy-4,4,exo-8-trimethyl-6-oxo-cis-bicyclo[3.3.0]oct-2-ene-1,2-dicarboxylate (9), which on acetylation, reduction with sodium borohydride, and methanolysis gives dimethyl 3,exo-6-dihydroxy-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]oct-2-ene-1,2-dicarboxylate (12). This on 2-decarbomethoxylation followed by treatment with lithium acetylide in the presence of cerium trichloride gives methyl 3-ethynyl-3,exo-6-dihydroxy-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]octane-1-carboxylate (21), which on hydration, diacetylation, and treatment with tri-n-butyltin hydride and azoisobutyronitrile is converted to methyl exo-6-acetoxy-3-acetyl-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]octane-1-carboxylate (31). Methanolysis of 31. tert-butyldimethylsilylation, and reaction with potassium tert-butoxide in tert-butyl alcohol gives exo-4-tert-butyldimethylsilyloxy-exo-2,6,6-trimethyl[5.3.11,5]undecane-8,10-dione (35). This on treatment with lithium aluminum hydride followed by oxidation and hydrogenation provides the corresponding 10-deoxo compound, 39. Reaction of this with methyllithium, dehydration, and desilylation with hydrogen fluoride in acetonitrile gives a mixture of (±)-α-biotol (1) and (±)-β-biotol (2); desilylation with hydrogen chloride in methanol gives solely (±)-1.