RESUMO
We show that arylpalladium(II) reagents linked to biotin and indocyanine dye residues can be prepared by decarboxylative palladation of appropriately substituted electron-rich benzoic acid derivatives. When prepared under the conditions described, these organometallic intermediates are tolerant of air and water, can be stored for several months in solution in dimethyl sulfoxide, and permit biotin- and indocyanine dye-labeling of functionally complex olefinic substrates in water by Heck-type coupling reactions.
Assuntos
Alcenos/química , Corantes/química , Compostos Organometálicos/química , Paládio/química , Biotina/química , Água/químicaRESUMO
A highly enantioselective rhodium-catalyzed [4+2+2] cycloaddition of terminal alkynes and dienyl isocyanates has been developed. The cycloaddition provides a rapid entry to highly functionalized and enantioenriched bicyclic azocines. This reaction represents the first [4+2+2] cycloaddition strategy to construct nitrogen-containing eight-membered rings.
Assuntos
Azocinas/química , Azocinas/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Isocianatos/química , Ródio/química , Alcinos/química , Catálise , Estereoisomerismo , Especificidade por SubstratoRESUMO
This manuscript describes the development and scope of the asymmetric rhodium-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes and alkenyl isocyanates leading to the formation of indolizidine and quinolizidine scaffolds. The use of phosphoramidite ligands proved crucial for avoiding competitive terminal alkyne dimerization. Both aliphatic and aromatic terminal alkynes participate well, with product selectivity a function of both the steric and electronic character of the alkyne. Manipulation of the phosphoramidite ligand leads to tuning of enantio- and product selectivity, with a complete turnover in product selectivity seen with aliphatic alkynes when moving from Taddol-based to biphenol-based phosphoramidites. Terminal and 1,1-disubstituted olefins are tolerated with nearly equal efficacy. Examination of a series of competition experiments in combination with analysis of reaction outcome shed considerable light on the operative catalytic cycle. Through a detailed study of a series of X-ray structures of rhodium(cod)chloride/phosphoramidite complexes, we have formulated a mechanistic hypothesis that rationalizes the observed product selectivity.
Assuntos
Alcinos/química , Isocianatos/química , Ródio/química , Catálise , EstereoisomerismoRESUMO
CO! You had me at hello: The use of chiral biphenyl-based phosphoramidite ligands on rhodium provides an efficient [2+2+2] cycloaddition between terminal alkyl alkynes and alkenyl isocyanates (see scheme). The cycloaddition proceeds through a CO migration pathway, and facilitates a rapid four-step asymmetric synthesis of indolizidine (-)-209D.
Assuntos
Alcaloides/síntese química , Alcaloides Indólicos/síntese química , Indolizidinas/síntese química , Ródio/química , Alcaloides/química , Catálise , Ciclização , Alcaloides Indólicos/química , Indolizidinas/química , EstereoisomerismoRESUMO
Prins reaction of homoallenyl alcohols with aldehyde dimethylacetals in the presence of methoxyacetic acid directly affords tetrasubstituted pyrans relevant to halichondrins with complete control of the C27 stereogenic center. Regioselective Tsuji reduction of the resultant allylic acetates stereoselectively establishes the C25 stereogenic center and C26 exocyclic olefin. Building upon these findings, we achieved concise access to the halichondrin C14-C38 and eribulin C14-C35 fragments.
RESUMO
The use of mixed zinc reagents in Ni-catalyzed anhydride alkylation results in preferential transfer of substituents (Ph > Me > Et >> iPr approximately TMSCH2) for the ligands bipy, dppe, and iPrPHOX. Utilization of such mixed species allows the use of 0.55 equiv of the diorganozinc reagent, effectively transferring both desired substituents when used in conjunction with a suitable second zinc reagent.
Assuntos
Anidridos/química , Indicadores e Reagentes/química , Níquel/química , Zinco/química , AlquilaçãoRESUMO
Excess substrate has been identified as an unintended spectator ligand affecting enantioselectivity in the [2 + 2 + 2] cycloaddition of alkenyl isocyanates with tolanes. Replacement of excess substrate with an exogenous additive affords products with consistent and higher ee's. The increase in enantioselectivity is the result of a change in composition of a proposed rhodium(III) intermediate on the catalytic cycle. The net result is a rational probe of a short-lived rhodium(III) intermediate and gives insight that may have applications in many rhodium-catalyzed reactions.
Assuntos
Alcenos/química , Isocianatos/química , Ródio/química , Catálise , Ciclização , Ligantes , Estrutura Molecular , Ácidos Nicotínicos/químicaRESUMO
A rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition between alkenyl isocyanates and alkynes has been developed. Heating a mixture of an alkenyl isocyanate and a symmetrical internal alkyne in the presence of [Rh(ethylene)2Cl]2/P(4-OMe-C6H4)3 in toluene delivers substituted indolizinones and quinolizinones. Depending on the substrates, a rare fragmentation of the isocyanate unit can be involved within the cycloaddition process to furnish a vinylogous amide embedded in the indolizinone.
Assuntos
Alcenos/química , Alcinos/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Isocianatos/química , Catálise , Ciclização , Ródio/químicaRESUMO
The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides. Product selectivity seems to be governed by a combination of electronics and sterics, with smaller and/or more electron-deficient substituents favoring lactam formation. The use of homologous alkenyl isocyanates leads to an expedient asymmetric total synthesis of the alkaloid lasubine II.