Steven J. Coote

Asymmetric palladium catalysed allylic substitution using phosphorus containing oxazoline ligands

Abstract A series of new phosphorus-containing oxazoline ligands has been developed. The use of these ligands for asymmetric palladium catalysed allylic substitution of 1,3-diphenylprop-2-enyl-1-acetate 12 with the sodium salt of dimethylmalonate has been achieved with 90 – 94% ee and 88 – 99% yield.

Preparation of novel sulfur and phosphorus containing oxazolines as ligands for asymmetric catalysis

Abstract The preparation of enantiomerically pure liginds which contain both an oxazoline group and an additional sulfur or phosphorus donor atom are described. Methyithiomethyl, o -thioanisyl and thienyl oxazolines have been prepared in one step, and o -diphenylphosphinophenyl oxazolines have been prepared in two steps in good yields from commercially available starting materials.

Sulfides tethered to oxazolines: Ligands for enantioselective catalysis

Sulfides tethered to oxazolines function as effective ligands for palladium catalysed allylic substitution, affording good to excellent levels of enantioselectivity (56 to >96% ee). Both the tether length between the nitrogen and sulfur atoms and also the nature of the sulfide have been shown to affect the performance of these ligands.

Bromobenzofurans : a new class of potent, non-peptide antagonists of angiotensin II

This paper describes the synthesis and pharmacology of a novel series of benzofurans which are antagonists of angiotensin II. One of these, the bromobenzofuran 11b, is a potent (apparent pKB=9.8) and specific antagonist of angiotensin II which, after oral administration (10mg/Kg), causes marked and long-lasting ( > 24h) falls in blood pressure in renal hypertensive rats.

Enantiospecific synthesis of (+)-(R)-1-phenyl-3-methyl-1,2,4,5-tetrahydrobenz[d]azepine from (+)-(S)-N-methyl-1-phenyl ethanolamine (halostachine) via arene chromium tricarbonyl methodology

Abstract Acid promoted cyclisation of homochiral (R)-N-(3,4-dimethoxyphenethyl) halostachine chromium tricarbonyl is stereospecific, proceeding with retention of configuration, to afford, after decomplexation, homochiral (+)-(R)-1-phenyl-3-methyl-1,2,4,5-tetrahydrobenz[d]azepine.

3-Substituted-1,2,4-Oxadiazolin-5-one; A Useful Amidine Precursor and Protecting Group

Abstract 5-Benzyloxy-1,2,4-oxadiazoles and 1,2,4-oxadiazolin-5-ones are useful precursors to, and protecting groups for the amidine moiety. The latter compounds are readily prepared from amidoximes or alternatively via cycloaddition of nitrile oxides to trichloroacetonitrile and subsequent hydrolysis. Both protecting groups may be readily removed upon hydrogenation, liberating the parent amidine. In addition, 1,2,4-oxadiazolin-5-ones may be utilised for the facile synthesis of N-alkyl amidines.

Tricarbonylchromium(0) promoted stereoselective cyclisations of the N-3,4-dimethoxyphenethyl derivatives of the 1-phenyl ethanolamines halostachine, ephedrine and pseudoephedrine to 1-phenyl-N-methyl-7,8-dimethoxy-1,2,4,5-tetrahydrobenzazepines

Acid promoted cyclisation of homochiral (R)-N-(3,4-dimethoxyphenethyl)-halostachine proceeds with almost total racemisation to yield 1-phenyl-N-methyl-1,2,4,5-tetrahydrobenz[d]azepine (e.e. 6%). Coordination of the cyclisation precursor to the tricarbonylchromium(0) moiety renders the cyclisation completely stereospecific to afford, after decomplexation, homochiral (+)-(R)-1 -phenyl-N-methyl-1,2,4,5-tetrahydrobenz[d]azepine. (−)-(1R,2S)-N-(3,4-Dimethoxyphenethyl)ephedrine undergoes acid mediated cyclisation to furnish trans-(−)-(1R,2S)-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine as a single diastereoisomer. In contrast, the epimeric cyclisation precursor (−)-(1R,2R)-N-(3,4-dimethoxyphenethyl)pseudoephedrine cyclises to give a mixture (ratio 91:9) of trans- and cis-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine. However, cyclisation of the tricarbonylchromium(0) complex of(−)-(1R,2R)-N-(3,4-dimethoxyphenethyl)pseudo-ephedrine is completely stercoselective to yield trans-(+)-(1S,2R)-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine after decomplexation.

Thrombin inhibitors based on [5,5] trans-fused indane lactams

A series of trans-fused lactams containing the indane nucleus has been prepared. Compound 19 has much enhanced plasma stability compared with its lactone counterpart and shows appreciable in vitro anticoagulant activity.

Stereoselective synthesis of cis-1,3-disubstituted 1,3-dihydroisobenzofurans via arenechromium tricarbonyl methodology

Abstract Phthalanchromium tricarbonyl is converted by t-butyllithium and alkyl halides completely stereoselectively into the corresponding exo -1-methyl, ethyl and benzyl derivatives. Double methylation of phthalanchromium tricarbonyl generates completely stereoselectively exco - cis -1,3-dimethylphthalanchromium tricarbonyl, from which cis -1,3-dimethylphthalan is liberated on oxidation. In contrast, double methylation of phthalan itself produces a 40/60 mixture of cis - and trans -1,3-dimethylphthalan.

The tandem insertion of trimethylsilylcyanide and alkenes, alkynes, isocyanates or ketones into zirconacyclo-pentanes and -pentenes

Abstract The tandem insertion of trimethylsilyl cyanide and alkenes, alkynes, ketones, or isocyanates into zirconacyclo-pentanes or -pentenes gives cyclopentylamines with an alkyl, alkenyl, 1-hydroxyalkyl, or carboxamide substituent alpha to the amine group.