Indolizidines, synthesis including reductive

Abstract This review is devoted to the stereoselectivity of intermolecular (intramolecular cycloadditions are not included) 1,3-dipolar cycloadditions of sugar-derived nitrones. Stereoselective cycloaddition (transformation of isoxazolidine followed by reduction of the N O bond to produce both an amino and a hydroxy function) allows the synthesis of tailor-made products of possible biological interest such as pol>4iydroxylated pyrrolidines, pyrrolizidines, indolizidines, fi-aminocarbonyl compounds, and disaccharides. Attention is focused on the preparation of isoxazolidinyl nucleosides and to the catalysis of the cycloaddition by Lewis acids. This review has concentrated on the new developments achieved from 1999 to February 2007. 

Alkaloids with polycyclic skdetal frameworks are, when it comes to their synthesis, excellent candidates for RCM. Illustrative are the indolizidines rhynchophylline (43) and its C(7)-epimer ixo-rhynchophylhne (44), both isolated from the plant Uncaria rhynchophytta (Rubiaceae) [26]. Deiters total synthesis of 43 and 44 started with the efficient construction of diallylamine 39 via amide formation between indole-3-acetic acid (38) and diallylamine (Scheme 2.10). One-pot RCM-carbomagnesation of 39 was smoothly achieved with only 1 mol% of [Ruj-I catalyst and 4 equiv. of EtMgCl to afford the 2-ethyl-3-butene-amine derivative in 71% yield. It appeared that the electron-withdrawing carbonyl moiety was critical to the success of the RCM-carbomagnesation steps. Amide reduction and subsequent treatment with acryloyl chloride dehvered the second metathesis precursor 40. Cyclization with [Ruj-I (5 mol%) then furnished the a,j8-unsaturated lactam 41 in a high yield of 91%. Continuation of the total synthesis of alkaloids 43 and 44 included a Bischler-Napieralski cychzation (42) and subsequent rearrangement into the oxindole framework. 

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