9 アルケニルクロム(III)化合物の分子内環化反応を利用する : 中南米産矢毒蛙アルカロイドの高立体選択的合成(口頭発表の部)

抄録

Remarkably high regio- and stereoselective approach for the syntheses of dendrobatid alkaloids (+)-homopumiliotoxin 223G (1), (+)-allopumiliotoxin 267A (2) and (+)-allopumiliotoxin 339A (3) have been developed. As a model study for the syntheses of these alkaloids, we initially undertook intramolecular chromium(II)-mediated cyclization of the racemic N-iodoalkenyl piperidine 9, which smoothly proceeded by treatment with CrCl_2 (5 equiv) and catalytic NiCl_2 (2.5mol%) in DMF to form a 1.3:1 epimeric mixture of 2-hydroxy-3(E)-alkylidene-trans-quinolizidines 20a and 20b. When the alternative chiral N-iodoalkenyl piperidine 18 was subjected to the identical cyclization conditions, the 3(E)-alkylidene-trans-quinolizidine 22a with the axially oriented 2-hydroxy group was formed as a single isomer. The first total synthesis of (+)-homopumiliotoxin 223G (1) has been achieved from 22a via deprotection of a benzyl group and removal of the acetoxy group in a single operation. Based on these model studies, we then undertook the enantioselective total synthesis of (+)-allopumiliotoxin 267A (1). For the synthesis of (+)-allopumiliotoxin 267A (1) coupling of the two segments, (E)-vinyl iodide 33, obtained via stereospecific palladium-catalyzed hydrostannation, and the pyrrolidine derivative 38, gave the N-iodoalkenyl pyrrolidine 39, which underwent intramolecular chromium(II)-mediated cyclization after cleavage of the dimethyl acetal, exclusively providing 41 with complete retension of the required E alkenyl geometry. Subsequent cleavage of the benzyl group furnished 2. Synthesis of allopumiliotoxin 339A (3) was next investigated by employing the strategy developed for 2. The side chain segment, (E)-vinyl iodide 50, was prepared via high degree of stereo- and regioselective reactions involving Evans alkylation and palladium-catalyzed hydrostannation. Intramolecular nickel(II)/chromium(II)-mediated cyclization of the N-iodoalkenyl pyrrolidine 54, available via coupling 50 with pyrrolidine derivative 52, led to exclusive formation of 55, which was deprotected to afford 3.