Andrew J. A. Watson

Ruthenium-Catalyzed N-Alkylation of Amines and Sulfonamides Using Borrowing Hydrogen Methodology

The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. N-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols require more forcing conditions than primary alcohols but are still effective alkylating agents in the presence of this catalyst.

Ruthenium-Catalyzed Oxidation of Alcohols into Amides

The synthesis of secondary amides from primary alcohols and amines has been developed using commercially available [Ru(p-cymene)Cl(2)](2) with bis(diphenylphosphino)butane (dppb) as the catalyst.

Borrowing Hydrogen Methodology for Amine Synthesis under Solvent-Free Microwave Conditions

Application of microwave heating to the Borrowing Hydrogen strategy to form C-N bonds from alcohols and amines is presented, removing the need for solvent and reducing the reaction times while still yielding results comparable with those using thermal heating.

Chiral heterocyclic ligands. Part IV. Synthesis and metal complexes of 2,6-Bis(pyrazol-1-ylmethyl)pyridine and chiral derivatives

Synthesis of the new tridentate ligand, 2,6-bis(pyrazol-1-ylmethyl)pyridine ( 6 ) and its chiral derivatives ( 11–15 ) are described. The preparations of complexes of these ligands with several divalent transition metal ions (Fe 2+ , Ni 2+ , Cu 2+ , Ru 2+ , Pd 2+ ) are reported. X-ray crystal structures have been determined for the [Ni( 6 ) 2 ](ClO 4 ) 2  16 and [Cu( 13 )(NCS) 2 ] 17 complexes. The salt 16 crystallises in the orthorhombic space group P 2 1 2 1 2 with a = 10.125(1), b = 17.657(4), c = 8.579(2) A and Z = 2. The structure was refined to a conventional R factor of 3.9% and shows the nickel atom to lie on a crystallographic two-fold rotation axis in a ‘symmetrical’ octahedral environment. The complex 17 crystallises in the orthorhombic space group P 2 1 2 1 2 1 with a = 15.795(3), b = 20.433(3), c = 9.618(1) A and Z = 4. The structure was refined to R = 4.7% and shows the bonding geometry at the five-coordinate copper atom to be intermediate between square pyramidal and trigonal bipyramidal. In both structures the six-membered chelate rings exist in boat conformations.

Chiral heterocyclic ligands: III. A structural study of the cyclopalladation of (4S, 7R)-7,8,8-trimethyl-1-phenyl-4,5,6,7-tetrahydro-4,7-methano-1H-indazole

Abstract Reaction of the ligand (4 S , 7 R )-7,8,8-trimethyl-1-phenyl-4,5,6,7-tetrahydro-4,7-methano-1 H -indazole, LHV, with lithium tetrachloropalladate gives a trans -Pd(LH) 2 Cl 2 complex, which on further reaction undergoes cyclopalladation to [PdLCl] 2 . These compounds were characterised spectroscopically and their structures confirmed by single crystal X-ray analyses, with refinement to R values of 0.028 and 0.036 respectively.

Protecting-Group-Free One-Pot Synthesis of Glycoconjugates Directly from Reducing Sugars†

The conversion of sugars into glycomimetics typically involves multiple protecting-group manipulations. The development of methodology allowing the direct aqueous conversion of free sugars into glycosides, and mimics of oligosaccharides and glycoconjugates in a high-yielding and stereoselective process is highly desirable. The combined use of 2-azido-1,3-dimethylimidazolinium hexafluorophosphate and the Cu-catalyzed Huisgen cycloaddition allowed the synthesis of a range of glycoconjugates in a one-step reaction directly from reducing sugars under aqueous conditions. The reaction, which is completely stereoselective, may be applied to the convergent synthesis of triazole-linked glycosides, oligosaccharides, and glycopeptides. The procedure provides a method for the one-pot aqueous ligation of oligosaccharides and peptides bearing alkyne side chains.

Chiral heterocyclic ligandsVI. (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-1H(2H)-indazole and X-ray structure of a copper(II) complex

Abstract Dichlorobis[(4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-in-dazole]copper(II), C22H32Cl2N4Cu, crystallizes in the monoclinic space group C2 with a = 23.110(5), b = 7.533(1), c = 7.041(1) A, β = 105.25(2)° and Z = 2. The structure was refined to R = 2.9%. The copper atom lies on a crystallographic two-fold rotation axis and has coordination geometry intermediate between tetrahedral and square-planar. A system of bifurcated (intra- and intermolecular) NH ⋯Cl hydrogen bonds connects the molecules in chains. The crystal structure and NMR studies of a palladium(II) complex show that the title ligand complexes through the more sterically hindered N(1) nitrogen. It is proposed that for unsymmetrical pyrazoles, the relative stabilities of the tautomers of the ligand is an important factor in determining the choice of the siteof coordination to metal ions.

Achiral 2-Hydroxy Protecting Group for the Stereocontrolled Synthesis of 1,2-cis-α-Glycosides by Six-Ring Neighboring Group Participation

Glycosylation of a fully armed donor bearing a 2-O-(trimethoxybenzenethiol) ethyl ether protecting group is completely α-selective with a range of carbohydrate alcohol acceptors. Low-temperature NMR studies confirm the intermediacy of cyclic sulfonium ion intermediates arising from six-membered β-sulfonium ring neighboring group participation. Selective protecting group removal is achieved in high yield in a single operation by S-methylation and base-induced β-elimination.

Anionopentaaminecobalt(III) complexes with polyamine ligands. 25. The resolution and base hydrolysis kinetics of mer-[CoCl(en)(NH2CH2CH NCH2CH2NH2)]ZnCl4, a complex with an unsymmetrical triamine ligand

Abstract Racemic mer -[CoCl(en)(NH 2 CH 2 CHNCH 2 CH 2 NH 2 )]ZnCl 4 , which contains no dissymetric chelate rings, no asymmetric carbon centers and no asymmetric nitrogen centers, has been resolved using sodium arsenic(III)—(+)-tartrate. The chirality arises by virtue of the coordinated unsymmetric tridentate ligand and the less soluble diastereoisomeride is associated with the (+)-cation. The rate of base hydrolysis was measured spectrophotometrically using tris buffers. Kinetic parameters (25 °C, \3m; ∼ 0.04 M) are k OH = 1.28 X 10 3 M −3 s −1 , E a = 87.0 ± 0.7 kJ mol −1 and Δ S #; = +98 ± 1.4 J K −1 mol −1 . Complete racemisation accompanies the base hydrolysis reaction and the rate of loss of optical activity is 0.5 times that of base hydrolysis. These data are interpreted in terms of the formation of a symmetrical trigonal bipyramid intermediate generated from the conjugate base.

Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis

A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain.