RESUMO
We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one-pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3-amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N-protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di- and tri-substituted piperidines, which ranks the topmost frequent N-heterocycle in commercial drugs.
Assuntos
Piperidinas , Pirrolidinas , Hidrogênio , Estereoisomerismo , Estrutura MolecularRESUMO
We present herein an unprecedented stereoselective synthesis of bridged biaryls with defined axial and central chirality from readily available starting materials. This N-heterocyclic carbene-catalyzed method proceeds through propargylic substitution of azolium enolates followed by two-directional cyclization, as supported by DFT calculation. A range of benzofuran/indole-derived bridged biaryls bearing an eight-membered lactone are accessed with uniformly high stereoselectivity (>98:2 dr, mostly >98% ee).
RESUMO
Described is an unprecedented NHC-catalyzed (NHC=N-heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters. A straightforward three-step procedure involving two catalytic enantioselective transformations has been developed and leads to a regio- and stereodivergent synthesis of either 1,2-amino alcohols/diamines or 1,4-fluoro alcohols with excellent diastereo- and enantiopurity.
RESUMO
Presented herein is an unprecedented transition-metal-free propargylic substitution reaction with either azolium enolates or acyl anions, which are generated from aldehydes under N-heterocyclic carbene catalysis. This new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathways to deliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.
RESUMO
We present herein an unprecedented, efficient and enantioselective synthesis of triarylmethanes and 1,1-diarylalkanes through N-heterocyclic carbene-catalyzed acylative desymmetrization of bisphenols. This method utilizes readily available substrates, reagents and a simple procedure to deliver the valuable products in excellent enantiopurity. DFT calculations reveal that the selectivity is governed by the C-C bond cleavage step of the tetrahedral intermediate leading to the ester product. A transition state model featuring a combination of intramolecular hydrogen bond and steric effect is developed to explain the enantioselectivity.
RESUMO
We present here a highly efficient NHC-catalyzed kinetic resolution of a wide range of 1,1'-biaryl-2,2'-diols and amino alcohols to provide them in uniformly ≥99% ee. This represents the first highly enantioselective catalytic acylation of axially chiral alcohols. The aldehyde backbone that is incorporated into the chiral acyl azolium intermediate was found to have a significant effect on the enantioselectivity of the process.
Assuntos
Amino Álcoois/química , Compostos Heterocíclicos/química , Metano/análogos & derivados , Acilação , Catálise , Cinética , Metano/química , Naftóis/química , Nitrogênio/química , EstereoisomerismoRESUMO
We report herein an efficient NHC-catalyzed kinetic resolution of acyclic tertiary propargylic alcohols that provides them in high to excellent enantioselectivity. This is the first example of kinetic resolution realized by enantioselective acylation. The recovered enantioenriched alcohols can be facilely converted into other valuable compounds such as densely functionalized tertiary alcohols and carbmates in high yields and excellent stereopurity. Density functional theory calculations were performed to determine the reaction mechanism and to understand the origin of enantiodiscrimination.
RESUMO
Herein we present a highly efficient N-heterocyclic-carbene (NHC)-catalyzed atroposelective acylation of amino bisphenols to provide access to a wide range of 1,1'-biaryl-2,2'-amino alcohols (NOBIN analogs) in high yield and with uniformly excellent enantioselectivity. This catalytic system is shown to proceed through a combination of desymmetrization and secondary kinetic resolution to produce the axially chiral products in excellent enantioselectivity.
RESUMO
The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.