SYNTHESIS OF 20-DEETHYLSILICINE FROM A 2ND-GENERATION 2-CYANO-DELTA-3-PIPERIDINE SYNTHON

The Zn2+ ion mediated reaction of the 2-cyano-DELTA3-piperidine 9a (X = SO2C6H5) with the silyl enol ether of Na-methyl-2-acetylindole (24) led to formation of compounds 29a,b (70%) resulting from introduction of the acetylindole moiety at the exocyclic (C-7) carbon center and migration of the phenylsulfonyl group from C-7 to C-4. In contrast, reaction of 2-Cyano-DELTA3-piperidine 9b (X = CN) with 24 gave the desired C-4 acetylindole-substituted products 36a,b (1:1.3 mixture; 72% overall yield). Attempts to cyclize intermediates 36 to the tetracyclic enamine 27 were unsuccessful. Alternatively, the Zn2+-catalyzed reaction of synthons 9a and 9b with indole gave the C-7 indole-substituted aminonitriles 37a,b and 38, respectively. These intermediates were converted to DELTA2-piperidine 40 on reaction with sodium dimethyl malonate and AgBF4. Stereoselective hydrogenation of the enamine double bond in 40 furnished the required cis 3,4-disubstituted piperidine 41, which was cyclized under acidic conditions to the target molecule, 20-deethylsilicine (20).