26 三環性N-アシル-N,O-アセタールの不斉アリル化反応及びアルカロイド合成への展開(口頭発表の部)
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We have developed the general methodology for the asymmetric allylation of the tricyclic N-acyl-N,O-acetals incorporating (R)- or (S)-2-(1-aminoethyl)phenol [(R)- or (S)-10] as a chiral auxiliary, leading to the chiral (R)- or (S)-allylated piperidones and pyrrolidones. This methodology was successfully applied to alkaloid synthesis. The chiral tricyclic N-acyl-N,O-acetal 14a prepared from δ-ketodecanoic acid 6 and the chiral aminophenol (R)-10 was subjected to nucleophilic allylation with TiCl_4-allyltrimethylsilane to provide the (6R)-allylated piperidone 16 in high stereoselectivity (16: 1). The stereochemical outcome of this reaction can be rationalized on the basis of conformational control involving minimization of the allylic strain in the iminium intermediate. Subsequent four-step transformation of the chiral 6,6-dialkylpiperidone 16 thus obtained led to the first asymmetric synthesis of the coccinellid alkaloid (-)-(R)-adalinine (1), establishing the absolute configuration of natural (-)-adalinine to be R. The TiCl_4-induced allylation of the tricyclic N,O-acetal 21 installing the chiral auxiliary (S)-1O proceeded in high yield with retentive selectivity accounted for by a conformational model similar to that described above, yielding the (5S)-allylated pyrrolidone 22a. After conversion to the aldehyde 25, five-carbon chain elongation via the Horner-Emmons reaction with the phosphonate 26 led to the 5-(3-propanoyl-2-propenyl)pyrrolidone 28. Four-step conversion of 28 provided the Dendrobatid alkaloid (-)-indolizidine 167B (2). By applying a similar sequence, (-)-indolizidine 209D (3) was obtained from 25 via eight-carbon chain extension. Finally, the first total synthesis of marine alkaloid (-)-stellettamide B (4) has been achieved by a sequence based on amide coupling of the chiral 1-(aminomethyl)indolizidine fragment 33, prepared by TiCl_4-mediated asymmetric allylation of the tricyclic N-acyl-N,O-acetal 37 incorporating (R)-10, with the chiral trienoic acid fragment ent-34. This synthesis led to revision of the published relative stereochemistry of the natural product and established its absolute stereochemistry to be 1S,4S,8aR,6"R.
- 2001-09-01
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