194656-60-5

Upstream product

• 194656-44-5 (R)-4-Ethyl-4-((S)-2-methoxymethyl-pyrrolidine-1-carbonyl)-3-trimethylsilanyl-cyclohexa-2,5-dienone 

Downstream Products

• 194656-54-7 (S)-4-Ethyl-4-((S)-2-methoxymethyl-pyrrolidine-1-carbonyl)-cyclohex-2-enone 
• 4880-88-0 vinburnine 

Relevant academic research and scientific papers

Desymmetrization of benzoic acid in the context of the asymmetric Birch reduction-alkylation protocol. Asymmetric total syntheses of (-)-eburnamonine and (-)-aspidospermidine

The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)- aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7 → 8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 °C gave an 18:1 mixture of 17 and its C(3) β- epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

Asymmetric synthesis of 4,4-disubstituted-2-cyclohexen-1-ones from a chiral 2-(trimethylsilyl)benzamide

Birch reduction-alkylation of the chiral 2-(trimethylsilyl)benzamide 4 provides 1,4-cyclohexadienes 5b-5e with diastereomer ratios of >100:1. The conversions of 5b-5e to the 4,4-disubstituted-2-cyclohexen-1-ones 8b-8e are described.