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.

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.

Novel 7- and 8-endo 2-indolylacyl radical cyclizations: efficient construction of azepino- and azocinoindoles.

Regioselective 7- and 8-endo cyclizations of selenoester derived 2-indolylacyl radicals upon amino tethered alkenes have been used to synthesize azepino[3,2-b]- and azocino[4,3-b]indoles, which are tricyclic subunits present in the indole alkaloids mersicarpine and apparicine, respectively.

SmI(2)-promoted radical addition reactions with N-(2-Indolylacyl)oxazolidinones: synthesis of bisindole compounds.

The treatment of N-acyl oxazolidinones of N-benzyl 2-indolecarboxylic acids varying in the substitution pattern of the indole ring with samarium diiodide at -78 degrees C led to the formation of two indole dimer products. The major product isolated in yields from 55 to 59% represents an unsymmetrical dimer arising from 1,4-addition to the 2-indolecarboxylic acid derivative of a possible ketyl-type radical anion intermediate originating from the reduction of the exocyclic carbonyl group of the N-acyl oxazolidinone. The minor dimer, represented by a symmetrical diketone, was produced in yields ranging from 11 to 23%. Even in the presence of an alpha,beta-unsaturated amide, dimerization was the preferred pathway rather than the formation of a gamma-keto amide. Upon treatment with acid, the unsymmetrical indole dimer cyclized to form a diindolequinone. Finally, the N-acyl oxazolidinones of pyrrole-2-carboxylic acid and 3-indolecarboxylic acid preferred in both cases to undergo C-C bond formation with an acrylamide in the presence of SmI2 rather than dimerization.

Sequential N-acylamide methylenation-enamide ring-closing metathesis: construction of benzo-fused nitrogen heterocycles.

The dimethyltitanocene methylenation of N-acylamides derived from ortho-vinylanilines, ortho-allylaniline, and ortho-vinylbenzylamine provides the corresponding enamides, which upon exposure to the second generation Grubbs ruthenium catalyst give access to indoles, 1,4-dihydroquinolines, and 1,2-dihydroisoquinolines, respectively. This sequential protocol also allows the synthesis of dihydrobenzoazepines, although the ring-closing metathesis (RCM) step is complicated by the alkene isomerization processes. From certain substrates, the direct annulation is observed in the titanium-mediated step, which is likely to occur through an olefin metathesis-intramolecular olefination sequence.

A new radical-based route to calothrixin B.

[structure: see text] A high-yielding totally regioselective intramolecular homolytic acylation of a quinoline ring constitutes the key step in a new synthesis of the pentacyclic indolo[3,2-j]phenanthridine alkaloid calothrixin B.

Regioselective 6-endo cyclizations of 2-indolylacyl radicals: total synthesis of the pyrido[4,3-b]carbazole alkaloid guatambuine.

A regioselective 6-endo reductive cyclization of 2-indolylacyl radicals constitutes the key step of a straightforward synthetic entry to the olivacine skeleton, illustrated by a total synthesis of the tetrahydropyridine alkaloid guatambuine.

Regioselective intramolecular reactions of 2-indolylacyl radicals with pyridines: a direct synthetic entry to ellipticine quinones.

[reaction: see text] 2-Indolylacyl radicals generated from the corresponding selenoesters under hexabutylditin-hnu conditions undergo regioselective intramolecular reaction with unprotonated pyridines to give polycyclic indolylpyridyl ketones. For substrates bearing a (3-pyridyl)methyl moiety connected to the 3-position of the indole ring, the cyclization provides easy access to ellipticine quinones.

Intramolecular reactions of 2-indolylacyl radicals: access to 1,2-fused ring indole derivatives.

The generation of 2-indolylacyl radicals from the corresponding phenyl selenoesters under reductive conditions and their behavior in intramolecular addition reactions to carbon-carbon double bonds located at the indole nitrogen have been studied. [reaction: see text]

Total synthesis of the proposed structures of indole alkaloids lyaline and lyadine.

The harman-1,4-dihydropyridines 1 and 2, which constitute the originally proposed structures for the indole alkaloids lyaline and lyadine, have been synthesized, and their NMR data have been compared with those available for the natural products. Due to the discrepancies in the spectral data, the structures of lyadine and lyaline should be revised.

Chemoselective radical cleavage of Cbz-protected nitrogen compounds.

[reaction: see text] Tributylstannyl radicals promote the deprotection of N-Cbz derivatives of amides and nitrogen-containing heteroaromatic rings. These radical conditions do not affect N-Cbz derivatives of basic amines.

Generation and intermolecular reactions of 3-indolylacyl radicals.

The generation of 3-indolylacyl radicals from the corresponding phenyl selenoesters and the scope of their participation in intermolecular addition reactions to carbon-carbon double bonds under both reductive and nonreductive conditions have been studied.