RESUMO
α-Lithiated terminal epoxides and N-(tert-butylsulfonyl)aziridines undergo eliminative cross-coupling with α-lithio ethers, to give convergent access to allylic alcohols and allylic amines, respectively. The process can be considered as proceeding by selective strain-relieving attack (ring-opening) of the lithiated three-membered heterocycle by the lithio ether and then selective ß-elimination of lithium alkoxide.
RESUMO
An efficient and versatile synthesis of cis-hexahydrobenzophenanthridines starting from readily available tetralins has been developed using an intramolecular Friedel-Crafts alkylation as a key step. The substrates were prepared via a highly stereocontrolled rhodium-catalyzed ring-opening reaction of meso-oxabicyclic alkenes and a hydrogenation sequence. Thus, a wide variety of complex tetracyclic compounds have been isolated with a high level of regio-, diastereo-, and enantioselectivity.
RESUMO
Catalyst-controlled asymmetric ring opening of a racemic oxabicyclic alkene leads to two readily separable regioisomeric products both in excellent ee. A cationic Rh catalyst, with added NH(4)BF(4) to modulate reactivity, was required to obtain synthetically useful yields. The utility of each substituted aminotetralin product has been demonstrated by their conversion to different biologically relevant molecules in a highly efficient and practical manner.
Assuntos
Tetra-Hidronaftalenos/síntese química , Estrutura Molecular , Estereoisomerismo , TemperaturaRESUMO
New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)-norchelidonine.
Assuntos
Benzofenantridinas/síntese química , Alcaloides de Berberina/síntese química , Compostos Organometálicos/química , Paládio/química , Benzofenantridinas/química , Alcaloides de Berberina/química , Ácidos Borônicos/química , Catálise , Conformação Molecular , EstereoisomerismoRESUMO
The scope and limitations of lithium 2,2,6,6-tetramethylpiperidide (LTMP)-modified reductive alkylation of epoxides is detailed. A variety of organolithiums are added to terminal and 2,2-disubstituted epoxides in the presence of LTMP to generate alkenes in a completely regio- and highly stereoselective manner. Arylated alkenes, dienes, allylsilanes, and enynes are accessed using this procedure. The methodology is applied in the synthesis of the roller leaf moth pheromone, (3E,5Z)-dodecadienyl acetate. The corresponding reaction without LTMP has also been examined, and a study using deuterated epoxides provides insight into the mechanism. In the presence of LTMP, Grignard reagents are also shown to produce E-alkenes directly from epoxides.
Assuntos
Compostos de Epóxi/química , Compostos de Lítio/química , Piridinas/química , Acetatos/química , Alcenos/química , Amidas/química , Deutério/química , Dodecanol/análogos & derivados , Estrutura Molecular , Compostos Organometálicos , Atrativos Sexuais , Silanos/química , EstereoisomerismoAssuntos
Alcenos/química , Benzofenantridinas/síntese química , Alcaloides de Berberina/síntese química , Ácidos Borônicos/química , Paládio/química , Alcaloides/química , Benzofenantridinas/química , Alcaloides de Berberina/química , Catálise , Hidroxilação , Ligantes , Estrutura Molecular , Naftalenos/química , EstereoisomerismoRESUMO
N-Tosyl-protected 3-hydroxypyrrolidines are prepared by reaction of dimethylsulfoxonium methylide with readily available epoxysulfonamides.
Assuntos
Amidas/química , Aziridinas/química , Compostos de Epóxi/química , Metanol/química , Pirrolidinas/química , Sulfóxidos/química , Enxofre/química , Cristalografia por Raios X , Hidroxilação , Modelos Moleculares , Estrutura Molecular , Pirrolidinas/síntese químicaRESUMO
[reaction: see text]. Regio- and stereodefined allylic N-sulfonylamines are synthesized in high yields and under experimentally straightforward conditions by reaction of N-sulfonylaziridines with excess dimethylsulfonium methylide.
RESUMO
E-Alkenes (including arylated alkenes, dienes, and allylsilanes) are efficiently prepared by alpha-deprotonation of terminal epoxides using lithium 2,2,6,6-tetramethylpiperidide, followed by in situ trapping with organolithiums or Grignard reagents.