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Diastereoselective Intramolecular Ritter Reaction: Generation of a cis-Fused Hexahydro-4aH-indeno [1,2-b]pyridine Ring System with 4a,9b-Diangular Substituents.-Optimized reaction conditions for the intramolecular Ritter reaction of cyanoethylindanol derivatives (I) are presented, which allow for highly diastereoselective formation of the title cis-fused hexahydroindenopyridine system (II), a key intermediate in the synthesis of constrained analogues of non-peptide NK 1 -antagonists. -(VAN EMELEN, KRISTOF; DE WIT, TOM; HOORNAERT, GEORGES J.; COMPERNOLLE, FRANS; Org. Lett. 2 (2000) 20, 3083-3086; Dep. Chem., Kathol. Univ. Leuven, B-3001 Leuven, Belg.; EN)

Synthesis of cis-Fused Hexahydro-4aH-indeno[1,2-b]pyridines via Intramolecular Ritter Reaction and Their Conversion into TricyclicAnalogues of NK-1 and Dopamine Receptor Ligands.-Reaction of cyanoethylindanone (III) with Grignard reagent affords the corresponding indanol (V) in moderate diastereoselectivity, which undergoes an intramolecular Ritter reaction to furnish the fused piperidinone (VI) as single diastereomer. Further functionalization of the ester group proceeds via the free acid. In the presence of Et 3 N and diphenylphosphoryl azide, an amination reaction takes place [cf. (IX)], while under more drastic conditions, a Curtius rearrangement is observed to afford an isocyanate intermediate. This intermediate can be quenched with methanol or amines. Reduction of the lactone carbonyl group is achieved with BH 3 ·Me 2 S in all cases. A variety of fused piperidines (X), (XII) and (XV) is obtained on these and similar ways. Biological screening reveals that they do not bind to NK1 or dopamine receptors. -(VAN EMELEN, KRISTOF; DE WIT, TOM; HOORNAERT, GEORGES J.; COMPERNOLLE, FRANS; Tetrahedron 58 (2002) 21, 4225-4236; Dep. Chem., Kathol. Univ. Leuven, B-3001 Leuven, Belg.; EN)