Synthesis of 2,4-disubstituted piperidines via radical cyclization: unexpected enhancement in diastereoselectivity with tris(trimethylsilyl)silane
| Autor: | Alexander G. Russell, Angela E. Brodwolf, Benson M. Kariuki, Neil Spencer, John S. Snaith, Tatyana Gueveli, Lucile A. Gandon |
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| Rok vydání: | 2006 |
| Předmět: |
Tris
chemistry.chemical_classification Trimethylsilyl Free Radicals Molecular Structure Organic Chemistry Diastereomer Tributyltin hydride Stereoisomerism General Medicine Silanes Silane Medicinal chemistry Chemical synthesis Radical cyclization Sulfonamide chemistry.chemical_compound chemistry Piperidines Cyclization Organic chemistry Smiles rearrangement Piperidine |
| Zdroj: | The Journal of organic chemistry. 71(14) |
| ISSN: | 0022-3263 |
| Popis: | A novel approach to 2,4-disubstituted piperidines is reported, involving the radical cyclization of 7-substituted-6-aza-8-bromooct-2-enoates. Cyclization with tributyltin hydride affords the trans piperidines with trans/cis diastereomeric ratios ranging typically from 3:1 to 6:1. Cyclization with tris(trimethylsilyl)silane affords the same products with diastereomeric ratios of up to 99:1 in certain cases. The enhancement in diastereoselectivity results from the selective rearrangement of the minor stereoisomer through a cascade process involving radical cyclization to the piperidine radical, 1,5-radical translocation, and attack of the translocated radical onto the sulfonamide with extrusion of SO2 in a Smiles-type rearrangement. Slower trapping of the piperidine radical by tris(trimethylsilyl)silane compared to tributyltin hydride accounts for the occurrence of the rearrangement cascade in the former case. |
| Databáze: | OpenAIRE |
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