RESUMO
An efficient asymmetric synthesis of 11-ß-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.
Assuntos
11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Naftóis/síntese química , Propano/análogos & derivados , 11-beta-Hidroxiesteroide Desidrogenases/química , Catálise , Cetonas/química , Naftóis/química , Propano/síntese química , Propano/química , EstereoisomerismoRESUMO
A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper-catalyzed acylation along with the implementation of the BI-DIME ligands for a ligand-controlled Suzuki cross-coupling and an unprecedented bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer.
Assuntos
Inibidores de Integrase de HIV/síntese química , Integrase de HIV/química , HIV/enzimologia , Acilação , Catálise , Cobre/química , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/química , Humanos , Ligantes , Estereoisomerismo , Sulfonamidas/químicaRESUMO
Carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl aldimines and ketimines to provide α-amino amides. The methodology enables the direct introduction of a carbonyl group without the requirement of unmasking steps as with other nucleophiles. The products may be converted to α-amino esters or 1,2-diamines. Iterative application of the reaction enabled the stereoselective synthesis of a dipeptide. Spectroscopic and computational studies support an anion structure with η(2) coordination of lithium by the carbonyl group.
Assuntos
Amidas/química , Amidas/síntese química , Iminas/química , Técnicas de Química Sintética , Dipeptídeos/síntese química , Dipeptídeos/química , Modelos Moleculares , Conformação Molecular , Estereoisomerismo , Especificidade por SubstratoRESUMO
A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.
Assuntos
Óxidos P-Cíclicos/síntese química , Fosfinas/síntese química , Óxidos P-Cíclicos/química , Ligantes , Estrutura Molecular , Fosfinas/química , EstereoisomerismoRESUMO
A solvent- and metal-free process has been developed for the direct methallylboration of ketones employing the stable B-methallylborinane 1, which was accelerated by tertiary alcohols. In the presence of 2.0 equiv of readily available tertiary alcohols such as tert-amyl alcohol, the methallylation products were prepared at room temperature in excellent yields. The salient features of the described process include simple operation, high efficiency, and mild reaction conditions.
Assuntos
Álcoois/química , Álcoois/síntese química , Boranos/química , Cetonas/química , Estrutura MolecularRESUMO
A practical one-pot and regiospecific three-component process for the synthesis of 2,3-disubstituted indoles from 2-bromoanilides was developed via consecutive palladium-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.
Assuntos
Amidas/química , Anilidas/química , Hidrocarbonetos Bromados/química , Indóis/síntese química , Paládio/química , Catálise , Ciclização , Indóis/química , Estrutura Molecular , Compostos Organometálicos/química , OxirreduçãoRESUMO
A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.
Assuntos
Quinina/química , Sulfonamidas/síntese química , Compostos de Sulfônio/síntese química , Indicadores e Reagentes/química , Estrutura Molecular , Estereoisomerismo , Sulfonamidas/química , Compostos de Sulfônio/químicaRESUMO
A one-pot process has been developed for the synthesis of 8-arylquinolines via Pd-catalyzed borylation of quinoline-8-yl halides and subsequent Suzuki-Miyaura coupling with aryl halides using n-BuPAd(2) as ligand. Yields of up to 98% were obtained.
Assuntos
Hidrocarbonetos Halogenados/química , Paládio/química , Quinolinas/síntese química , Catálise , Ligantes , Estrutura Molecular , Quinolinas/químicaRESUMO
A new chiral sulfinyl transfer auxiliary derived from readily available phenylglycine was developed. This auxiliary is utilized to synthesize a diverse array of alkyl- and arylsulfinamides and sulfinylferrocenes in high yields and excellent ee's. The desired products are produced in a one-pot sequence from the oxathiazolidine 2-oxide by two sequential nucleophilic additions that proceed in a stereospecific manner.
Assuntos
Amidas/síntese química , Compostos Ferrosos/síntese química , Glicina/química , Compostos de Sulfidrila/síntese química , Amidas/química , Compostos Ferrosos/química , Glicina/análogos & derivados , Metalocenos , Estrutura Molecular , Estereoisomerismo , Compostos de Sulfidrila/químicaRESUMO
A superior, mild, high-yielding one-pot process for rapid access to oxo anilides has been developed that involves three cascade reactions: iodine-magnesium exchange, regiospecific ortho N-Fries rearrangement, and in situ trapping of the formed aniline anion. Coupled with McMurry cyclization, the two-step process allows ready synthesis of strained 1,2,3-trisubstituted indoles regioselectively.
Assuntos
Anilidas/química , Indóis/síntese química , Iodo/química , Magnésio/química , Ânions , Indóis/químicaRESUMO
[Structure: see text] A practical one-pot, regiospecific three-component process for the synthesis of 2,3-disubstituted indoles was developed via consecutive Pd-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.
Assuntos
Técnicas de Química Combinatória , Indóis/síntese química , Catálise , Estrutura Molecular , Paládio/químicaRESUMO
[reaction: see text] A one-step method was developed for elaboration of a variety of polycyclic indole skeletons via a novel palladium-catalyzed intramolecular indolization of 2-chloroanilines bearing tethered acetylenes. This novel intramolecular indolization method unveils an unusual syn amidopalladation pathway of a tethered alkyne.
Assuntos
Alcaloides Indólicos/síntese química , Paládio/química , Alcinos/química , Catálise , Técnicas de Química Combinatória , Alcaloides Indólicos/química , Estrutura MolecularRESUMO
[reaction: see text] A general process for the efficient synthesis of sulfinyl transfer agents has been developed using cinchona alkaloids quinine and quinidine as chiral auxiliaries. The importance of these new and unique sulfinyl transfer agents is exemplified by the expedient synthesis of several sulfoxides in excellent enantiopurities and high yields.
Assuntos
Alcaloides de Cinchona/química , Ácidos Sulfínicos/síntese química , Sulfóxidos/síntese química , Química Orgânica/métodos , Estrutura Molecular , Quinidina/química , Quinina/química , Estereoisomerismo , Ácidos Sulfínicos/análise , Sulfóxidos/análiseRESUMO
[reaction: see text] An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.
Assuntos
Ciclobutanos/síntese química , Ácidos Sulfínicos/química , Ciclobutanos/química , Radical Hidroxila/química , Indicadores e Reagentes , Estrutura Molecular , Solventes , EstereoisomerismoRESUMO
A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.
Assuntos
Compostos Aza/química , Aziridinas/síntese química , Aziridinas/química , Catálise , Ésteres , Estrutura Molecular , EstereoisomerismoRESUMO
[reaction: see text] The first practical and economical process for synthesis of 2,3-disubstituted indole compounds has been developed with high regioselectivity by palladium-catalyzed indolization of 2-bromo- or chloroanilines and their derivatives with internal alkynes.
RESUMO
A highly concise and convergent synthesis of HCV polymerase inhibitor Deleobuvir (BI 207127, 1) was achieved, featuring efficient Pd-catalyzed one-pot borylation-Suzuki coupling where TFP was identified as the unique ligand effective for these transformations.
Assuntos
Acrilatos/síntese química , Acrilatos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Acrilatos/química , Antivirais/química , Benzimidazóis/química , Catálise , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Ligantes , Estrutura Molecular , Paládio/químicaRESUMO
(S)-3,3'-F2-BINOL has been synthesized for the first time and demonstrated as a highly active organocatalyst for asymmetric methallylation of ketones. Up to 98:2 enantioselectivity and 99% yield were obtained with 5 mol % catalyst loading. The catalyst (S)-3,3'-F2-BINOL could be easily recovered and reused.