Asymmetric syntheses of (-)-hastanecine, (-)-turneforcidine and (-)-platynecine

TETRAHEDRON

卷:72

Article

Brambilla, Marta¹  Davies, Stephen G.¹  Fletcher, Ai M.¹  Roberts, Paul M.¹  Thomson, James E.¹ 

[1] Univ Oxford, Chem Res Lab, Dept Chem, Mansfield Rd, Oxford OX1 3TA, England

关键词: (-)-Hastanecine;    (-)-Turneforcidine;    (-)-Platynecine;    Lithium amide;    Conjugate addition;    Asymmetric synthesis;    Pyrrolizidines;   

DOI  :  10.1016/j.tet.2016.06.011

来源: Elsevier

【 摘 要 】

Concise total asymmetric syntheses of three diastereoisomeric 1-hydroxymethyl-7-hydroxy substituted pyrrolizidines, (-)-hastanecine, (-)-turneforcidine and (-)-platynecine, are reported. The doubly diastereoselective conjugate additions of lithium (R)- or (S)-N-benzyl-N-(alpha-methylbenzyl)amide to tertbutyl (R,E)-4-(triethylsilyloxy)hepta-2,6-dienoate [which was prepared (in 96:4 e.r.) via Lewis acid mediated catalytic asymmetric allylation of tert-butyl (E)-4-oxobut-2-enoate] proceeded in both cases under the dominant control of the lithium amide reagent. Subsequent diastereoselective enolate allylations installed the required stereogenic centres, and the pyrrolizidine ring system was rapidly accessed by a two-step protocol (viz. ozonolysis and one-pot hydrogenolysis/double reductive cyclisation), to complete the asymmetric syntheses of (-)-hastanecine, (-)-turneforcidine and (-)-platynecine in 17, 8 and 24% overall yield, respectively, in eleven steps from commercially available 2,2-dimethoxyacetaldehyde in each case. (C) 2016 Elsevier Ltd. All rights reserved.

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