RESUMO
A palladium-catalyzed cross-coupling of thioacetates and aryl halides is described herein. Using a catalyst screening kit, tBuBrettPhos Pd G3 was found to be a unique catalyst for this reaction, affording the desired thioarene products in high yields under mild reaction conditions. The thioacetate starting materials are readily available, allowing for quick access to these more lab friendly reagents. Reactions described herein range from the late-stage coupling of complex thioacetates to the first report of a mild set of conditions for thiomethylation of aryl halides.
RESUMO
The addition of terminal alkynes to racemic ß-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by a non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition.
Assuntos
Álcoois/síntese química , Alcinos/química , Ésteres/química , Cetonas/química , Zinco/química , Álcoois/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland-Claisen rearrangement to establish the necessary cis-relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.
Assuntos
Alcaloides de Veratrum/síntese química , Técnicas de Química Sintética/métodos , Ciclização , Estereoisomerismo , Alcaloides de Veratrum/químicaRESUMO
A sequential benzoylation and multihetero-Cope rearrangement of α-keto ester derived nitrones has been developed. The reaction furnishes a diverse array of complex α-imino ester derivatives. The products can be transformed into amino alcohols via LiAlH4 reduction.
RESUMO
A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to an array of ß-stereogenic α-keto esters. When the air-stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the α-keto acid substructure in biologically important molecules.
Assuntos
Ésteres/química , Cetoácidos/química , Compostos Organometálicos/química , Paládio/química , Catálise , Complexos de Coordenação/química , Ligantes , Estrutura Molecular , EstereoisomerismoRESUMO
An organocatalytic three-component reductive coupling reaction between dimethyl phosphite, benzylidene pyruvates, and aldehydes is reported. A chiral triaryliminophosphorane catalyst promotes Pudovik addition, which is followed by phospha-Brook rearrangement to transiently generate enolates that are trapped stereoselectively by aldehydes. This reductive coupling provides vicinal polyfunctionalized stereocenters from readily available prochiral starting materials with excellent diastereoselectivity, enantioselectivity, and yield.
Assuntos
Aldeídos/química , Compostos de Benzilideno/química , Organofosfonatos/química , Fosfitos/química , Piruvatos/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
A new method for the synthesis of 2-aminoimidazole products is described. The heterocyclic products are generated in good yields via Pd-catalyzed carboamination reactions of N-propargyl guanidines and aryl triflates. This methodology generates both a C-N and C-C bond during the annulation step and facilitates the rapid construction of 2-aminoimidazole products with different aryl groups. The utility of this methodology was demonstrated in the total synthesis of preclathridine A, preclathridine B, and dorimidazole B from a single intermediate.
Assuntos
Alcaloides/síntese química , Produtos Biológicos/síntese química , Imidazóis/síntese química , Paládio/química , Alcaloides/química , Produtos Biológicos/química , Técnicas de Química Combinatória , Guanidinas/química , Imidazóis/química , Estrutura MolecularRESUMO
A new approach to the synthesis of substituted 5-membered cyclic guanidines is described. Palladium-catalyzed alkene carboamination reactions between acyclic N-allyl guanidines and aryl or alkenyl halides provide these products in good yield. This method allows access to a number of different cyclic guanidine derivatives in only two steps from readily available allylic amines.