M.-Lluı̈sa Bennasar

Total Synthesis of the Bridged Indole Alkaloid Apparicine

An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents.

A New Acyl Radical-based Route to the 1,5-Methanoazocino[4,3-b]indole Framework of Uleine and Strychnos Alkaloids

C-4 or C-12 ethyl substituted 1,5-methanoazocino[4,3-b]indoles, which constitute the tetracyclic framework of uleine alkaloids as well as the ABDE substructure of the Strychnos alkaloid family, have been synthesized by novel 6-exo and 6-endo cyclizations of selenoester-derived 2-indolylacyl radicals upon 5-ethyl-1,2,3,6- and 3-ethyl-1,2,5,6-tetrahydropyridines, respectively.

Addition of organocopper reagents to N-alkylpyridinium salts. A flexible access to polysubstituted dihydropyridines

Abstract The addition of a series of organocopper (alkyl, vinyl, allyl, and ethynyl) reagents to 3-acyl- N -alkylpyridinium salts, followed by acylation of the intermediate 1,4- or 1,2-dihydropyridines with trichloroacetic anhydride has been studied.

Synthesis of 4-functionalized aryl-3,5-diacyl-1,4-dihydropyridines

Abstract The valuable N-unsubstituted 4-aryl-3,5-diacyl-1,4-dihydropyridines 12b–f , bearing an electron-withdrawing substituent at the benzene ring, have been synthesized by the copper-mediated addition of functionalized arylmagnesium reagents 2b–f to N-benzhydrylpyridinium salt 9 , followed by acylation with trichloroacetic anhydride and the subsequent haloform reaction and N-deprotection.

A synthetic entry to 3,5-disubstituted pyridines

Abstract A straightforward entry to 3,5-disubstituted pyridines from 3-substituted pyridines, based on the acylation of N -alkyl-1,4-dihydropyridine derivatives followed by a tandem N -dealkylation–oxidation sequence is reported.

Nucleophilic addition to chiral pyridinium salts: stereoselective synthesis of (−)-Na-methylervitsine

Abstract Chiral non-racemic 4-substituted 3,5-diacyl-1,4-dihydropyridines 8 are prepared by the regio- and diastereoselective addition of organocopper reagents to chiral pyridinium salt 2 , followed by acylation with trichloroacetic anhydride and subsequent haloform reaction. Additionally, (−)- N a -methylervitsine is synthesized by reaction of the enolate derived from 2-acetylindole 9 with pyridinium salt 2 , followed by electrophile (Me 2 N + CH 2 I − )-induced cyclization and subsequent elaboration of the 16-methylene and (20 E )-ethylidene substituents.

Addition of chiral enolates to N-alkyl-3-acylpyridinium salts. Total synthesis of (+)-16-epivinoxine and (−)-vinoxine

Abstract Chiral enolates of indolylacetyl derivatives 6a–f undergo addition to pyridinium salt 7 with complete trans-selectivity and varied diastereofacial selectivities to give, after acid-induced cyclization of the intermediate 1,4-dihydropyridines, the vinoxine-related tetracycles 8a–f. Starting from (S)-prolinol indolylacetamide 6e, subsequent elaboration of the ethylidene substituent from tetracycle 8e and removal of the chiral auxiliary has resulted in a straightforward synthesis of (+)-16-epivinoxine and (−)-vinoxine.

3-Indolylacyl Radical Cyclizations upon Pyridines and Tetrahydropyridines: Access to Ergoline-Related Indole [cd]-fused Isoquinolines

Cyclizations of selenoester-derived 3-indolylacyl radicals, involving the homolytic acylation of pyridines or the addition to double bonds included in tetrahydropyridine rings, have been used to synthesize indole [cd]-fused isoquinolines related to the natural ergoline system.

Generation and reactions of 1-(2-indolyl)vinylcopper derivatives with pyridinium salts

Abstract 1-(2-Indolyl)vinylstannane 1b has been transmetallated into both the corresponding HO mixed cyanocuprate and the Cu-catalysed organomagnesium reagent, and the reactivity of these species towards N -alkyl-3-acylpyridinium salts 8 and 17 has been tested.