A one-pot formal [4 + 2] cycloaddition approach to substituted piperidines, indolizidines, and quinolizidines. total synthesis of indolizidine (-)-209I.
[reaction: see text] Heating a mixture of substituted N-benzyl gamma-chloropropylamines, conjugated alkynoates or alkynones, sodium carbonate, and a catalytic amount of sodium iodide in i-PrOH at 70-83 degrees C delivers substituted piperidines in good yields. This transformation goes through a cascade Michael addition/alkylation process and represents a facile one-pot formal [4 + 2] cycloaddition approach to piperidine ring. Using secondary cyclic gamma-chloropropylamines as substrates, this process produces substituted indolizidines or quinolizidines. On the basis of this approach, indolizidine (-)-209I is elaborated in 11 steps from methyl 2-hexenoate.
Yu
Shanghai
S
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China.
Zhu
Wei
W
Ma
Dawei
D
D007212:Indolizines / Q000138:chemical synthesis*
D007212:Indolizines