Ian P. Andrews

Practical methylation of aryl halides by Suzuki–Miyaura coupling

Abstract A number of aryl halides (X=Cl, Br, I) can be converted to the corresponding toluenes in an operationally simple manner using trimethylboroxine (TMB) as a partner for palladium-catalysed Suzuki–Miyaura coupling.

Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation.

In this study we performed the total synthesis of the terpene indole alkaloid (+)-ibophyllidine through a pathway involving asymmetric phosphine catalysis, with our novel l-4-hydroxyproline-derived chiral phosphine mediating the key [3 + 2] annulation. Hydrogenation of the [3 + 2] adduct allowed the rapid formation of the stereochemically dense pyrrolidine ring of (+)-ibophyllidine in excellent yield with exceptionally high levels of both diastereo- and enantioselectivity. We constructed the remainder of the pentacyclic skeleton through an intramolecular alkylation and an intramolecular aza-Morita-Baylis-Hillman reaction.

Phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters: facile synthesis of 3-carbethoxy-2-alkyl-3-pyrrolines

An array of N-tosylated α-aminoalkylallenic esters was prepared and their cyclization under the influence of nucleophilic phosphine catalysts was explored. The α-aminoalkylallenic esters were prepared through aza-Baylis-Hillman reactions or novel DABCO-mediated decarboxylative rearrangements of allenylic carbamates. Conversion of these substrates to 3-carbethoxy-2-alkyl-3-pyrrolines was facilitated through Ph(3)P-catalyzed intramolecular γ-umpolung addition.

Phosphorus mediated cyclisation of a β-arylaminoacrylamide to a quinoline: A simple synthesis of SK&F 96067

Abstract The reversible (H+/K+)ATPase inhibitor SK&F 96067 1 was prepared in two steps from Meldrum’s Acid by cyclisation of the acrylamide 4 with Ph3P/C2Cl6/Et3N. Evidence for the formation of imidoylketene imine 3 was obtained by trapping with phenyl isocyanate. Thermal degradation of an amidine such as 12 also gave SK&F 96067 1.

USE OF METHYLLITHIUM IN METAL/HALOGEN EXCHANGE; A MILD AND EFFICIENT METHOD FOR THE SYNTHESIS OF ORTHO SUBSTITUTED TOLUENES

Methyllithium, in the presence of excess methyl iodide, can be used to convert suitably substituted aromatic bromides to the corresponding toluenes under mild conditions and in high yield.

A practical synthesis of the milbemycin SB-201561

Abstract A 6-step synthesis of the potent anthelmintic SB-201561 is described. The key stage of the synthesis is a novel Beckmann type oxime fragmentation to give a lactone, followed by a 2-step reassembly of the spirolcetal moiety.

Phosphine-Catalyzed [3 + 2] Annulation: Synthesis of Ethyl 5-(tert-Butyl)-2-Phenyl-1-Tosyl-3-Pyrroline-3-Carboxylate

Ethyl 5,5-dimethylhexa-2,3-dienoate Ethyl (triphenylphosphoranylidene)acetate 3,3-Dimethylbutyryl chloride Triethylamine Ethyl 5-(tert-butyl)-2-phenyl-1-tosyl-3-pyrroline-3-carboxylate (E)-N-Benzylidene-4-methylbenzenesulfonamide Tributylphosphine Keywords: phosphine-catalyzed [3 + 2] annulation; ethyl 5-(tert-butyl)-2-phenyl-1-tosyl-3-pyrroline-3- carboxylate; nucleophilic tertiary phosphines; geranylgeranyltransferase type-I (GGTase-1) inhibitors (GGTIs)