ABSTRACT
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.
Subject(s)
HIV Integrase Inhibitors/chemical synthesis , HIV Integrase/chemistry , HIV/enzymology , Acylation , Catalysis , Copper/chemistry , HIV Integrase/metabolism , HIV Integrase Inhibitors/chemistry , Humans , Ligands , Stereoisomerism , Sulfonamides/chemistryABSTRACT
(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.
Subject(s)
Ketones/chemistry , Naphthols/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
The palladium catalyzed alkoxycarbonylation and aminocarbonylation of vinyl tosylates are described. A variety of ketone and aldehyde derived vinyl tosylates may be carbonylated in the presence of primary, secondary, and tertiary alcohols, or primary and secondary amines, to provide the corresponding esters and amides in good yields. The alkoxycarbonylation was applied to a short synthesis of isoguvacine.
Subject(s)
Alcohols/chemistry , Palladium/chemistry , Vinyl Compounds/chemistry , Amination , Anions/chemistry , Catalysis , Free Radicals/chemistry , Ligands , Molecular StructureABSTRACT
Reaction of 4-bromo-NH-1,2,3-triazoles 2 with alkyl halides in the presence of K(2)CO(3) in DMF produced the corresponding 2-substituted 4-bromo-1,2,3-triazoles 5 in a regioselective process. Subsequent Suzuki cross-coupling reaction of these bromides provided an efficient synthesis of 2,4,5-trisubstituted triazoles 3. In addition, reduction of the bromotriazoles by hydrogenation furnished an efficient synthesis of 2,4-disubstituted triazoles 8.
