Peter Somfai

Enantioselective total synthesis of (−)-indolizidines 209B and 209D via a highly efficient aza-[2,3]-wittig rearrangement of vinylaziridines

Abstract A novel protocol for the enantioselective synthesis of (−)-indolizidines 209B (2) and 209D (1) is described, in which the key step is the highly efficient aza-[2,3]-Wittig rearrangement of vinylaziridines 11a,b into tetrahydropyridines 12a,b. Functional group manipulation and chain elongation then gave esters 16a,b which were converted to the target alkaloids via lactams 17a,b.

C2-symmetric bis(aziridines) : a new class of chiral ligands for transition metal-mediated asymmetric synthesis

Abstract The readily available C2-symmetric bis(aziridines) 1 can act as ligands in a variety of asymmetric transformations mediated by transition metals. In the best cases, >95% ee can be obtained.

Aza-[2,3]-Wittig rearrangements of vinylaziridines as a novel entry to indolizidine alkaloids. Enantioselective total synthesis of indolizidine 209D

An enantioselective total synthesis of indolizidine 209D (1) from epoxy alcohol 4 is described. The key step in the sequence involves an aza-[2,3]-Wittig rearrangement of vinylaziridine 7 to yield the cis-2,6-disubstituted tetrahydropyridine 8 in 98% yield and as a single detectable diastereomer.

Palladium-catalyzed transformation of a chiral vinylaziridine to a β-lactam. An enantioselective route to the carbapenem (+)-PS-5

Abstract The regio- and stereoselective carbonylation of optically pure trans vinylaziridine 5 to trans 3-vinylazetidinone 6 is catalyzed by Pd(0). Compound 6 is then transformed to a known key intermediate for the total synthesis of the carbapenem antibiotic (+)-PS-5.

Improved procedure for cyclization of vinyl azides into 3-substituted-2H-azirines

A significantly improved procedure for the preparation of 3-substituted 2H-azirines has been developed. By cyclization of the corresponding vinyl azides in low boiling solvents in closed vessels at elevated temperature, high purity, short reaction time and simple isolation of the product were achieved.

Regioselective nucleophilic ring opening of 2,3-aziridino alcohols

Abstract Nucleophilic ring-opening of trans and cis aziridino alcohols 1 ( 1′ ) and 2 ( 2′ ) by hydride- and by methyl-transfer reagents has been studied. In general, good to excellent C-2 selectivity was observed (the regioselectivity being better for the trans isomers) and the results can be interpreted in terms of directive effects exerted by the C-1 hydroxyl group. However, complete C-3 selectivity was observed in the reactions of 1 and 2 with AlMe 3 , indicating a complexation effect of the C-4 benzyloxy group in those cases.

Enantioselective synthesis of anti-β-hydroxy-α-amido esters via transfer hydrogenation.

The asymmetric transfer hydrogenation of α-amido-β-keto esters to provide the corresponding anti-β-hydroxy-α-amido esters in good to excellent yields, diastereoselectivity, and enantioselectivity is reported. The procedure is operationally simple, and delicate handling of the catalyst is not necessary.

Carboncarbon bond formation via N-tosyliminium ions

Abstract Addition of carbon nucleophiles to cyclic N-tosyliminium ions, derived from α-hydroxy and α-methoxy tosylamides (5a,b and 6a,b, respectively) is described. In general, good to excellent yields were obtained when allytrimethylsilane, 1-tbutyldimethylsilyloxy-1-ethoxyethane, and trimethylsilyl cyanide were used as nucleophiles.

Asymmetric synthesis of (+)-1-deoxynojirimycin and (+)-castanospermine

Asymmetric total syntheses of (+)-1-deoxynojirimycin (1) and (+)-castanospermine (2) are described. Starting from diene 3, the required absolute stereochemistry is introduced by an asymmetric hydroxylation followed by epoxidation. An intramolecular cyclization of amine 17 gives access to the corresponding tetrasubstituted piperidine 18, which is a precursor to compounds 1 and 2. (+)-Deoxynojirimicyn (1) was obtained in 36% yield over 11 steps from diene 3, while (+)-castanospermine (2) was achieved in 13% after 19 steps from the same starting material.

A short and enantioselective synthesis of (+)-Anatoxin-a

Abstract A short and enantioselective total synthesis of the neurotoxic alkaloid (+)-Anatoxin-a ( 1 ) from the L-pyroglutamic acid derivative 2 is described. The key step involves an intramolecular cyclisation of an N-tosyl iminium ion derived from the corresponding α-methoxy sulfonamide.