A new method for alkaloid synthesis is described. The rhodium(I1)-acetate-catalyzed decomposition of 3-(4-acetoxypbenyl)-1-diazo-C(pyrro1-l-yl)-2-butanone (Sd) gave 6-(4-acetoxyphenyl)-5,6-dihydro-7(8H)-indolizinone (6d) in 82% yield via an intramolecular carbenoid reaction. The latter compound was converted in four steps in 13% overall yield to (+)-ipalbidine (Ib).Introduction. -Alkaloids containing the indolizidine ring system are found in several plant species and have attracted much attention as synthetic targets [ 11. Various methods have been devised for making the indolizidine skeleton. Most are 1,2-annelations of pyrrolidine or piperidine rings which exploit iminium ions [2], acyliminium ions [3], and enamines [4], or entail aldol [5], Claisen [6], and Dieckmann [7] condensations. Other methods involve the intramolecular N-alkylation of pyrrolidine [S], piperidine [8a] 191, pyridones and dihydropyridones [lo], and the cycloadditions of N-acylpiperidines [ 1 11 and a-aminoacyl radicals [12]. The simultaneous construction of both rings by the intramolecular bis-alkylation of an amine [13] and imino Diels-Alder reactions [14] has also been reported. Although pyrrole has been widely used as the starting point for building pyrrolizidine rings [15], its use for the synthesis of indolizidines has been restricted to the formation of the pyrrolidine part which was subsequently annelated by one of the above-mentioned methods [6] [Sa]. Similarly, carbenes have been used for making intermediates [6] [16], but rarely for the critical step [15a] [17]. We recently demonstrated that the decomposition of a (pyrrol-1 -yl) diazo ketone afforded dihydropyrrolizines and indolizines in high yields [18] (Scheme I). We now describe how this cyclization can be applied to the total synthesis of (&)-ipalbidine (lb), the aglycone of ipalbine (la) isolated from Ipamea alba L.Results and Discussion. ~ Our strategy is based on the retrosynthesis in which the bicyclic ketone 10 constitutes the key relay (Scheme 2). The 4-methoxy derivative 10 1191.
Racemic monomorine (12) is prepared in six steps in 26% overall yield from 2-butyl-IH-pyrrole and ethyl (E)-but-2-enoate by exploiting the rhodium(I1)-acetate-catalyzed decomposition of (4RS)-4-(2'-butyl-1 'H-pyrrol-1'-y1)-1 -diazopentan-2-one (7).Introduction. -Indolizidine alkaloids are found in several plant species and offer attractive targets for synthesis. Consequently, methods of great diversity have been devised for preparing them. We recently reported that the decomposition of l-diazo-4-(1H-pyrrol-l-yl)butan-2-one derivatives 1 using rhodium(I1) acetate as catalyst provides an economical means for constructing the dihydroindolizine ring 2 (Scheme 1). The synthesis of ipalbidine (3) has demonstrated the high propensity for intramolecular insertion at the C(2) position of the pyrrole nucleus [l]. We now show that this methodology permits the easy assembly of disubstituted octahydroindolizine alkaloids. As an illustration, we have selected racemic monomorine (12) which is a trail pheromone of the pharaoh ant (Monomorium pharaonis L.). Because of its unusual biological properties, many syntheses of racemic 12 [2] [3] and of its pure enantiomers [4] have been undertaken. However, several of them entail multi-step sequences lacking in regioselectivity. In contrast, the synthesis described here has the advantage of conciseness and simplicity.
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