Blechert indolizidine

The concise enantioselective total synthesis of (+)-monomorine I, a 3,5-dialkyl-substituted indolizidine alkaloid, was completed by S. Blechert et al. using a sequential cross-metathesis double reductive cyclization strategy. The enedione substrate was prepared in two steps. The Stetter reaction between the masked equivalent of acrolein and butyl vinyl ketone was followed by a retro Diels-Alder reaction under flash vacuum pyrolysis (FVP) conditions. 

Randl, S., Blechert, S. Concise Enantioselective Synthesis of 3,5-Dialkyl-Substituted Indolizidine Alkaloids via Sequential Cross-Metathesis-Double-Reductive Cyclization. J. Org. Chem. 2003, 68, 8879-8882. 

Scheme 212 Synthesis of (-l-)-monomorine I (1562) and (5f,9 )-indolizidine 195B (1564) by Randl and Blechert. Reagents and conditions (a) hept-1-en-3-one, 3-benzyl-5-(2-hydroxyethyl-4-methylthiazolium chloride (5 mol%), NEts, 65 °C, 18 h (b) flash vacuum pyrolysis, 500 °C, 15mbar (c) Hoveyda—Grubbs catalyst (7), CH2CI2, reflux, 4 h (d), H2 (1 atm), 10% Pd/C, MeOH, rt, 48 h, then chromatography.

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