Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates.

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of α-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of α-alkyl- and α-aryl- acrylates, giving ß-borylated propionates. Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and C-C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of "Roche" ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in these reactions and rule out the possibility of a [L]Co-H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the ß-carbon of an η4-coordinated acrylate-cobalt complex is proposed as a plausible route.

Direct access to benzofuro[2,3-b]quinoline and 6H-chromeno[3,4-b]quinoline cores through gold-catalyzed annulation of anthranils with arenoxyethynes and aryl propargyl ethers.

This work reports a facile annulation of anthranils with aryloxyethynes or aryl propargyl ethers to construct useful benzofuro[2,3-b]quinoline and 6H-chromeno[3,4-b]quinoline frameworks, respectively; these heterocycles are not readily available from literature methods despite their biological significance. This high atom- and step-economy strategy is highlighted by a broad substrate scope. The reaction mechanism is proposed to proceed through sequential cyclizations among the oxyaryl group, gold carbene and benzaldehyde of the α-imino gold carbene intermediates.

Catalytic Transformations of Alkynes into either α-Alkoxy or α-Aryl Enolates: Mannich Reactions by Cooperative Catalysis and Evidence for Nucleophile-Directed Chemoselectivity.

The catalytic formation of gold enolates from alkynes, nitrones, and nucleophiles is described, and their Mannich reactions result in nucleophile-directed chemoselectivity through cooperative catalysis. For 1-alkyn-4-ols and 2-ethynylphenols, their gold-catalyzed nitrone oxidations afforded N-containing dihydrofuran-3(2H)-ones with syn selectivity. The mechanism involves the Mannich reactions of gold enolates with imines through an O-H-N hydrogen-bonding motif. For aryloxyethynes, their gold enolates react selectively with nitrones to deliver 3-alkylidenebenzofuran-2-ones, as controlled by a C-H-O hydrogen-bonding motif.

Hybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: SAR and docking studies.

A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 µg/mL, 12-35 µM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 µg/mL, 41 µM) as well as active (MIC 25.4 µg/mL, 45 µM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15. Cytotoxicity studies revealed that these molecules were non-toxic. The docking study of the compound 15 showed that there was binding with the active site of mycobacterial pantothenate synthetase. Further docking studies led to the synthesis of the compounds 16 and 17 and the antitubercular activity screening results showed that these compounds have significant antitubercular activity. The compounds 15-18 (MIC 11-29 µg/mL, 19-51 µM) can be used as starting points for further optimization. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures and the present results will be very useful in the development of a new class of antimycobacterial agents.