M.-Lluïsa Bennasar

Studies on the synthesis of akuammiline-type alkaloids. Construction of the hexahydro-1,5-methanoazocino[3,4-b)indole fragment

Abstract A three step route to the title tetracyclic substructure of akuammiline-type alkaloids consisting in the nucleophilic addition of an ester α-anion to an N -alkylpyridinium salt, acid-induced cyclization of the resultant 1,4-dihydropyridine, and stereoselective elaboration of the ethylidene substituent is reported.

Synthesis of 3,5-diacyl-4-phenyl-1,4-dihydropyridines

Abstract 3,5-Diacyl-4-phenyl-1,4-dihydropyridines have been synthesized via a regio- and chemoselective addition of Ph 2 Cu(CN)Li 2 to β-substituted N -alkylpyridinium salts, followed by acylation of the intermediate 1,4-dihydropyridines with trichloroacetic anhydride and subsequent haloform-type reaction. A similar sequence using an N -silylpyridinium salt and PhMgBr allows the preparation of the corresponding N -unsubstituted dihydropyridines.

Palladium-Catalyzed Intramolecular Carbene Insertion into C(sp3)−H Bonds

A palladium-catalyzed carbene insertion into C(sp(3) )-H bonds leading to pyrrolidines was developed. The coupling reaction can be catalyzed by both Pd(0) and Pd(II) , is regioselective, and shows a broad functional group tolerance. This reaction is the first example of palladium-catalyzed C(sp(3) )-C(sp(3) ) bond assembly starting from diazocarbonyl compounds. DFT calculations revealed that this direct C(sp(3) )-H bond functionalization reaction involves an unprecedented concerted metalation-deprotonation step.

Studies on the synthesis of akuammiline alkaloids. Access to 3,4-secoakuammilan derivatives

Abstract Cleavage of the C-3/N-4 bond of tetracycles 1 and 6 with chloroformates or acyl chlorides, followed by reduction, led to tetrahydrocarbazoles 4a,b and 8b-d, from which dithioacetal 12 and sulfoxides 5a,b, 11, and 17 were prepared. Whereas attempts to construct the quaternary C-7 centre of akuammiline alkaloids either by DMTSF-promoted cyclization of 12 or by Pummerer cyclization of sulfoxides 5a,b and 11 resulted in failure, sulfoxide 17 underwent cyclization on the indole 3-position to give the tetracyclic 3,4-secoakuammilan-type derivative 18.

A short route for the construction of the tetracyclic ring system of silicine-methuenine alkaloids

Abstract A general synthetic entry to the tetracyclic ring system of silicine-methuenine alkaloids, involving the partial hydrogenation of dihydropyridines 2 followed by PPSE-induced cyclization of the resulting tetrahydropyridine esters 3, is reported.

Synthetic applications of 2-cyanopiperidines. Model studies in the synthesis of bridged indole alkaloids

Abstract Acid cyclization of 4-(indol-1- and -3-ylmethyl)-2-cyanopiperidines 5 led to the bridged tetracyclic indole- systems 1 and 2. The required 2-cyanopiperidines 5 were prepared by catalytic hydrogenation of 2-cyano-1,2,3,6-tetrahydropyridines 4 and by DIBAL reduction of lactams 7 followed by cyanide ion addition to the intermediate enamine.

Construction of the pentacyclic ring system of apogeissoschizine

Abstract The synthesis of pentacyclic apogeissoschizine-type compounds is reported. It involves the construction of the seven-membered E ring by addition of the enolate derived from methyl 1-indolepropionate to the γ-position of a pyridinium salt, with subsequent acid-promoted cyclization of the resulting 1,4-dihydropyridine, and the closure of the C ring by cyclization on the indole 3-position in the last synthetic step.

Total synthesis of the indole alkaloids ngouniensine and epingouniensine

Abstract The first total synthesis of ngouniensine and epingouniensine, by cyclization of a suitable 1-(3-indolylethyl)piperidine-2-carboxylic acid followed by the elaboration of the exocyclic methylene group, is reported.

Total synthesis and stereochemical reassignment of the indole alkaloid vinoxine

Abstract The first total synthesis of the indole alkaloid vinoxine and the reassignment of the relative configuration at carbon-16 in this alkaloid is reported.

A Synthetic Entry to Ervatamine Alkaloids − Synthesis of (±)-6-Oxo-16-episilicine and (±)-6-Oxosilicine

Catalytic hydrogenation of several 3-acyl-4-[2-(indolyl)carbonylmethyl]-5-(methoxycarbonyl)-1,4-dihydropyridines 4 gives chemoselectively the corresponding 1,2,3,4-tetrahydropyridyl esters 5, which have been elaborated into the tetracyclic 2,3-diacylindole system 6 of oxosilicine alkaloids. Barton decarboxylation of the N-benzyl derivative 6e, followed by debenzylation and subsequent stereoselective reduction of the 5,16-double bond gives (±)-6-oxo-16-episilicine. This compound is converted into (±)-6-oxosilicine by base-catalyzed epimerization.