Palladium-Catalyzed Amination of Aryl Halides with Aqueous Ammonia and Hydroxide Base Enabled by Ligand Development.

The conversion of aryl halides to primary arylamines with a convenient and inexpensive source of ammonia has been a long-standing synthetic challenge. Aqueous ammonia would be the most convenient and least expensive form of ammonia, but such a palladium-catalyzed amination reaction with a high concentration of water faces challenges concerning catalyst stability and competing hydroxylation, and palladium-catalyzed reactions with this practical reagent are rare. Further, most reactions with ammonia to form primary amines are conducted with -butoxide base, but reactions with ammonium hydroxide would contain hydroxide as base.

Cross-Coupling between Hydrazine and Aryl Halides with Hydroxide Base at Low Loadings of Palladium by Rate-Determining Deprotonation of Bound Hydrazine.

Reported here is the Pd-catalyzed C-N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product.

Synthesis and Antiribosomal Activities of 4'-O-, 6'-O-, 4″-O-, 4',6'-O- and 4″,6″-O-Derivatives in the Kanamycin Series Indicate Differing Target Selectivity Patterns between the 4,5- and 4,6-Series of Disubstituted 2-Deoxystreptamine Aminoglycoside Antibiotics.

Chemistry for the efficient modification of the kanamycin class of 4,6-aminoglycosides at the 4'-position is presented. In all kanamycins but kanamycin B, 4'-O-alkylation is strongly detrimental to antiribosomal and antibacterial activity. Ethylation of kanamycin B at the 4″-position entails little loss of antiribosomal and antibacterial activity, but no increase of ribosomal selectivity.

Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxyl and amino groups.

The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin, and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2' and 6' substituents of ring I.

An approach to seco-prezizaane sesquiterpenoids: enantioselective total synthesis of (+)-1S-minwanenone.

A strategy of general applicability toward seco-prezizaane sesquiterpenes, from a chiral, tricyclic synthon, readily available via an enzymatic resolution step from the Diels-Alder adduct of cyclopentadiene and p-benzoquinone, has been devised. Our approach enables harnessing of the stereochemical proclivities of the norbornyl system to install the desired stereochemistry at the key stereogenic centers. Recourse to an interesting stratagem to realign a stereochemical divergence into stereoreconvergence forms the cornerstone of our successful approach.

Enantioselective total synthesis of bioactive natural product (+)-Sch 642305: a structurally novel inhibitor of bacterial DNA primase and HIV-1 Tat transactivation.

The total synthesis of the bioactive natural product (+)-Sch 642305 has been achieved from a readily available chiral building block using an RCM protocol to construct the key decalactone moiety; our approach is notable for its built-in flexibility and is diversity oriented.