Highly Enantioselective Approach to Indolizidines:  Preparation of (+)-(1S,8aS)-1-Hydroxyindolizidine and (−)-Slaframine

Abstract

A highly stereoselective approach to (-)-slaframine and its probable biosynthetic precursor (+)-(1S,8aS)-1-hydroxyindolizidine has been developed based on a diastereofacially selective cycloaddition of dichloroketene with a chiral dienol ether.

3-(4-Chlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine and 3-(2,4-dichlorobenzoyl)-7-(N,N-dimethylamino)-1-phenylindolizine

“…The indolizines constitute the core structure of many naturally occurring alkaloids, viz. (À)-slaframine (Pourashraf et al, 2000;Cossy et al, 2002), (À)-dendroprimine (Diederich & Nubbemeyer, 1999), indalozin 167B (Chalard et al, 1999 and coniceine (Park et al, 2001). Heterocyclic compounds, such as indolizines, are important bioactive compounds that have a wide range of applications in biology, pharmacology and agrochemistry (Wu & Chen, 2003, and references therein).…”

Indolizidine and quinolizidine alkaloids

“…118 Kinetic resolution occurred during the cyclisation of racemic 3-(inden-1-yl)propylcarbamates with (Ϫ)-sparteine and sec-butyllithium to give benzo-fused bicyclic alcohol derivatives. 126 Somewhat better enantiomeric excesses were observed in the [2,3]-Wittig rearrangement of crotyl furfuryl ethers to give 1-(2-furyl)-2-methylbut-3-en-1-ol diastereomers (ee up to 43%), 127 and in similar rearrangements of crotyl benzyl ethers. Examples include the preparation of arylglycines by carboxylation of lithiated N-Boc benzylamine derivatives (ee up to 98%); 120 the enantiodivergent conversion of laterally lithiated 2-ethyl-5-methylbenzamide derivatives into the sesquiterpenes (Ϫ)-and (ϩ)-curcuphenol (ee up to 92%); 121 the synthesis of tetrahydroisoquinolin-1-ones by reaction of laterally lithiated 2-alkylbenzamides with imines (ee up to 81%); 122 and the generation of atropisomeric ortho-substituted N,Ndialkylbenzamides from 2-ethylbenzamide precursors (ee 69% for trimethylsilylation).…”

Silver-mediated C–H bond functionalization: one-pot to construct substituted indolizines from 2-alkylazaarenes with alkynes

“…NMR spectra were in CDCl 3 ( 1 H at 500 MHz and 13 C at 125 MHz). Column chromatography was performed on silica gel (300e400 mesh).…”