RESUMEN
Rhodium-catalyzed hydroacylation using alkynes substituted with pendant nucleophiles, delivers linear α,ß-unsaturated enone intermediates with excellent regioselectivity. These adducts are used to construct a broad range of diversely substituted, saturated O-, N- and S-heterocycles in a one-pot process. Judicious choice of cyclisation conditions enabled isolation of O-heterocycles with high levels of diastereoselectivity. A variety of derivatisation reactions are also performed, generating functionalised hydroacylation products. This sequence serves as a general approach for the synthesis of fully saturated heterocycles.
RESUMEN
The desymmetrization of meso-compounds is a useful synthetic method, as illustrated by numerous applications of this strategy in natural product synthesis. Cu-catalyzed allylic desymmetrizations enable the enantioselective formation of carbon-carbon bonds, but these transformations are limited in substrate scope and by the use of highly reactive premade organometallic reagents at cryogenic temperatures. Here we show that diverse meso-bisphosphates in combination with alkylzirconium nucleophiles undergo highly regio-, diastereo- and enantio-selective Cu-catalyzed desymmetrization reactions. In addition, C2-symmetric chiral bisphosphates undergo stereospecific reactions and a racemic substrate undergoes a Cu-catalyzed kinetic resolution. The reaction tolerates functional groups incompatible with many common organometallic reagents and provides access to a broad range of functionalized carbo- and hetero-cyclic structures. The products bear up to three contiguous stereogenic centers, including quaternary centers and spirocyclic ring systems. We anticipate that the method will be a useful complement to existing catalytic enantioselective reactions.
RESUMEN
The total synthesis of dehydromicroscleroderminâ B and microscleroderminâ J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp-2-CO2 H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.
Asunto(s)
Péptidos Cíclicos/química , Conformación Molecular , Péptidos Cíclicos/síntesis químicaRESUMEN
The utility of the tethered aminohydroxylation (TA) has been demonstrated by synthesis of the complex ß-amino acid residue of microsclerodermins A and B. The TA provided a regio- and stereoselective functionalization of a complex homoallylic alcohol. The route includes late-stage introduction of the aliphatic side chain via a cuprate addition and cross metathesis, a tactic designed to render the synthesis applicable to other microsclerodermins.
Asunto(s)
Aminoácidos/química , Péptidos Cíclicos/síntesis química , Alcoholes/química , Hidroxilación , Estructura Molecular , Péptidos Cíclicos/química , EstereoisomerismoRESUMEN
This article describes the examination of several synthetic methodologies that have been developed in our laboratories, by application to the construction of a variety of natural product targets.
Asunto(s)
Productos Biológicos/síntesis química , Productos Biológicos/química , Modelos Moleculares , Estructura MolecularRESUMEN
Difluoroalkenylzinc reagents prepared from 1-(2'-methoxy-ethoxymethoxy)-2,2,2-trifluoroethane and 1-(N,N-diethylcarbamoyloxy)-2,2,2-trifluoroethane at ice bath temperatures underwent Negishi coupling with a range of aryl halides in a convenient one pot procedure. While significant differences between the enol acetal and carbamate reagents were revealed, the Negishi protocol compared very favourably with alternative coupling procedures in terms of overall yields from trifluoroethanol.
Asunto(s)
Hidrocarburos Fluorados/química , Compuestos Organometálicos/síntesis química , Temperatura , Trifluoroetanol/química , Estructura Molecular , Compuestos Organometálicos/química , EstereoisomerismoRESUMEN
N-Unsubstituted vinyl aziridines were synthesized via an amine-promoted regioselective nucleophilic aziridination of alpha,beta,gamma,delta-unsaturated carbonyl compounds. The reaction is completely regioselective (>95: 5) for the alpha,beta-alkene and completely diastereoselective, affording the trans-vinyl aziridine in moderate-to-good yields.
Asunto(s)
Aminas/química , Aziridinas/síntesis química , Aziridinas/química , Estructura Molecular , EstereoisomerismoRESUMEN
A concise, seven step synthesis of the aryl tetralin lignan lactone epi-picropodophyllin from piperonal is described. The key steps are a silene diene Diels-Alder reaction and the Hosomi-Sakurai reaction of the resultant silacyclohexene.
Asunto(s)
Podofilotoxina/análogos & derivados , Silene/química , Podofilotoxina/síntesis química , EstereoisomerismoRESUMEN
Silacyclic allyl silanes, derived from silene-diene Diels-Alder reactions, combine with acetals in the presence of Lewis acids to afford, following oxidation of the intermediate fluorosilane, either butane-1,4-diols or tetrahydronaphthalenes containing four contiguous chiral centres with moderate to good diastereoselectivity.