Palladium-catalyzed intramolecular carbene insertion into C(sp3)-H bonds

A palladium‐catalyzed carbene insertion into C(sp3)−H bonds leading to pyrrolidines was developed. The coupling reaction can be catalyzed by both Pd0 and PdII, is regioselective, and shows a broad functional group tolerance. This reaction is the first example of palladium‐catalyzed C(sp3)−C(sp3) bond assembly starting from diazocarbonyl compounds. DFT calculations revealed that this direct C(sp3)−H bond functionalization reaction involves an unprecedented concerted metalation-deprotonation step

Facile synthesis of azocino[4,3-b]indoles by ring-closing metathesis

The azocino[4,3-b]indole system, tricyclic substructure of the indole alkaloids apparicine and ervaticine, is efficiently assembled by ring-closing metathesis of 2-allyl-3-(allylaminomethyl)indoles. The metathesis sites are introduced into the indole nucleus by reductive amination of a 3-formyl derivative with allylamine, followed by a-lithiation with subsequent electrophilic trapping with acrolein

Sequential ring-closing metathesis-vinyl halide Heck cyclization reactions: access to the tetracyclic ring system of ervitsine

A chemoselective indole-templated ring-closing metathesis is used to assemble the cyclohepta[b]indole substructure of the indole alkaloid ervitsine. A subsequent intramolecular Heck coupling of the resulting alkene functionality with an amino-tethered vinyl halide accomplishes the closure of the unique 2- azabicyclo[4.3.1]decane framework of the alkaloid with concomitant incorporation of the exocyclic Eethylidene substituent

Exploration of Ring‐Closing Enyne Metathesis for the Synthesis of Azonino[5,4‐b]indoles

The use of the ring‐closing enyne metathesis (RCEYM) as a methodology for the synthesis of the azonino[5,4‐b]indole system, featuring the tricyclic substructure of the alkaloids cleavamine and quebrachamine, has been explored. Three series of enyne substrates were studied for their compatibility with the RCEYM reaction. In addition to the usual substrates bearing either a terminal or an internal alkyne, for the first time enynes with an alkynyl halide moiety were also considered. Although the metathesis cyclization allowed for assembly of the azoninoindole nucleus in all three series, an effective catalytic cycle was only noted for internal alkyne substrates. On the basis of the experimental results, the "yne‐then‐ene" pathway seems to be the mechanism at play in these reactions

Palladium catalysis in intramolecular carbene C-H insertion of α-diazo-α-(methoxycarbonyl)acetamides to form β-lactams

The intramolecular carbene C-H insertion of α‐diazo‐α‐(methoxycarbonyl)acetamides leading to β‐lactams is effectively catalyzed by palladium complexes. It is found that although Pd0 catalysts typically produce mixtures of β‐lactams together with Buchner‐type reaction products, the use of PdII catalysts results in highly chemoselective transformations. According to DFT calculations, this insertion reaction occurs stepwise and involves an unprecedented PdII‐promoted Mannich‐type reaction through a metallacarbene‐induced zwitterionic intermediate

Rapid Synthesis of the Ervitsine Alkaloid Skeleton by a Sequential RCM-Heck Cyclization Approach

An efficient approach to the bridged framework of the indole alkaloid ervitsine, featuring a ring-closing metathesis reaction from a 2,3-disubstituted indole followed by a vinyl halide Heck cyclization upon the resulting cycloheptene ring, is described

Transition Metal-catalysed intramolecular carbenoid C-H insertion for pyrrolidine formation by decomposition of α-diazoesters

The use of Pd‐, Rh(II)‐ and Ru(II)‐based catalysts has been explored in the transition metal‐catalysed intramolecular carbenoid C−H insertion of α‐diazoesters leading to pyrrolidines. Although the outcome of the reaction was highly substrate‐dependent, in general, it was possible to control the chemoselectivity of the process towards pyrrolidines by adequate catalyst selection. The Pd(0)‐catalysts were as efficient as [Rh(Ph3CCO2)2]2 in promoting the C(sp3)−H insertion of ortho‐substituted anilines. In contrast, for anilines bearing meta‐ and para‐substituents, the Rh(II)‐catalyst provided the best chemoselectivities and reaction yields. On the other hand, [Ru(p‐cymene)Cl2]2 was the most efficient catalyst for the insertion reaction of the N‐benzyl‐N‐phenyl and N,N‐dibenzyl α‐diazoesters, while the C(sp3)−H insertion of the N‐benzylsulfonamide substrate was only promoted by [Rh(Ph3CCO2)2]2. According to density functional theory (DFT) calculations, the mechanism involved in the Pd(0)‐ and Ru(II)‐catalysed C(sp3)−H insertions differs considerably from that typically proposed for the Rh(II)‐catalysed transformation. Whereas the Pd(0)‐catalysed reaction involves a Pd‐mediated 1,5‐H migration from the C(sp3)−H bond to the carbenoid carbon atom leading to the formal oxidation of the transition metal, a Ru(II)‐promoted Mannich type reaction involving a zwitterionic intermediate seems to be operative in the Ru(II)‐catalysed transformation. Keywords: carbenoid insertion; diazo compounds; pyrrolidines; palladium-catalysis; density functional theory calculation

Total Synthesis of the Brdged 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

Moléculas indicativas de adrenoceptores

Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Granados Jarque, Ricardo; Álvarez Domingo, Mercedes. 1980.El diseño de fármacos, en su concepción' más reciente, se apoya en el posible conocimiento del mecanismo físico-químico de la función que interesa estimular o Tolo quear por el fármaco potencial que se proyecta. En el caso de fármacos específicos estructuralmente, tal conocimiento va ligado al del lugar concreto en el que ña de producirse la interacción química entre la Mofase y el fármaco para proporcionar una respuesta bioló gica adecuada en el material de experimentació

Primera síntesis total y reasignación estereoquímica del alcaloide indolico vinoxina

[spa] La vinoxina es un alcaloide indólico minoritario aislado en 1967 de la apocinácea Vinca minor L., cuya constitución y estereoquímica se determinaron algunos años más tarde. Su estructura es poco común ya que carece de la unidad de triptamina, característica de una gran mayoría de alcaloides indólicos y, al mismo tiempo, posee un núcleo de 2,7-diazabiciclo (3.3.1)nonano. Este núcleo también se halla presente en la pleiocarpamina, análogo pentacíclico de la vinoxina aislado de diversas especies de apocináceas como Pleiocarpa mutica, Hunteria eburnea, y Amsonia elliptica, y en algunos alcaloides aislados del curare de la calabaza como la C-mavacurina, la C-fluorocurina y el C-alcaloide Y(alcaloides pertenecientes al grupo de la C-mavacurina). Se han descrito diversas utas sintéticas conducentes a estructuras pentacíclicas relacionadas con la pleiocarpamina y con los alcaloides pertenecientes al grupo de la C-mavacurina. Por el contrario, no existe hasta el presente ningún precedente de síntesis para el alcaloide indólico vinoxina. En este contexto, el objetivo de la presente Tesis ha consistido en el estudio y desarrollo de vías de síntesis conducentes a análogos estructurales del alcaloide vinoxina con el fin de alcanzar en una última etapa la primera síntesis total del mismo