ABSTRACT
A new method to access ß-keto-gem-diborylalkanes, by direct deoxygenative radical addition of aromatic carboxylic acids to gem-dibortlalkenes, is described. The reaction proceeds under mild photoredox catalysis and involves the photochemical C-O bond activation of aromatic carboxylic acids in the presence of PPh3 . It generates an acyl radical, which further undergoes an additional reaction with gem-diborylalkenes to form an α-gem-diboryl alkyl radical intermediate, which then reduces to the corresponding anion, which after protonation, affords the ß-keto-gem-diborylalkane product. Moreover, the same scenario has been extended to the vinyl boronic esters, for example, gem-(Ar, Bpin)-alkenes, and gem-(Alkyl, Bpin)-alkenes. Importantly, this protocol provides a general platform for the late-stage functionalization of bio-active and drug molecules containing a carboxylic acid group.
Subject(s)
Boron , Esters , Esters/chemistry , Oxidation-Reduction , Carboxylic Acids/chemistry , Alkenes/chemistryABSTRACT
A palladium-catalyzed decarboxylative asymmetric allylic alkylation (Pd-DAAA) of benzo-fused and non-benzo-fused δ-valerolactams is disclosed. This methodology gives access to chiral lactams bearing C3-quaternary stereocenters, which are central to many natural products and biologically active compounds. The reaction proceeds via palladium-catalyzed ionization of an allyl ester, followed by carbon dioxide extrusion and recombination of the electrophilic Pd-π-allyl complex with the in situ generated lactam enolate. This final step converts racemic allylic ester starting materials into enantiomerically enriched substituted lactams with high yield and enantiomeric excess.
ABSTRACT
In(OTf)3-catalyzed robust and sustainable one-pot access to previously unknown and synthetically demanding polysubstituted pyrroles via [3 + 2] annulation of α-oxoketene-N,S-acetals with ß-nitrostyrenes has been achieved under solvent-free conditions. The merit of this domino Michael addition/cyclization sequence is highlighted by its operational simplicity, short reaction time (5-10 min), good to excellent yields, tolerance of a large variety of functional groups, and efficiency of producing two new (C-C and C-N) bonds and one highly functionalized pyrrole ring in a single operation, which make it an ideal alternative to existing methods.
Subject(s)
Acetals/chemistry , Alkenes/chemistry , Chemistry, Organic/methods , Ethylenes/chemistry , Ketones/chemistry , Mesylates/chemistry , Pyrroles/chemical synthesis , Acetals/chemical synthesis , Alkenes/chemical synthesis , Catalysis , Molecular Conformation , Pyrroles/chemistryABSTRACT
A highly convergent and regioselective heteroannulation protocol for the synthesis of hitherto unreported highly substituted 2-amino-4-(aryl/alkyl)-5-(aroyl/heteroaroyl)-3-(cyano/carboalkoxy)-6-methylthio-4H-thiopyran derivatives has been developed. This one-pot three-component domino coupling of ß-oxodithioesters, aldehydes, and malononitrile/ethyl or methyl cyanoacetate is promoted by 4-dimethylamino pyridine (DMAP) in solvent (dichloromethane (DCM)) as well as under solvent-free conditions. Systematic optimization of reaction parameters identified that the three-component coupling (3CC) protocol is tolerant to a wide array of functionality providing densely functionalized 4H-thiopyrans in excellent yields. The merit of this cascade Knoevenagel condensation/Michael addition/cyclization sequence is highlighted by its high atom-economy, excellent yields, and efficiency of producing three new bonds (two C-C and one C-S) and one stereocenter in a single operation.