Michael Shipman

Regiospecific intramolecular [2π+2σ] cycloadditions of methylene cyclopropanes

Abstract Intramolecular cyclisation of methylene cyclopropanes with acetylenic acceptors affords highly functionalised bicyclononane derivatives. The regiospecificity of these cyclisations is dependent on the nature of the transition metal employed.

Palladium-catalyzed multicomponent synthesis of 2-aryl-2-imidazolines from aryl halides and diamines

An efficient palladium-catalyzed three-component reaction that combines aryl halides, isocyanides, and diamines provides access to 2-aryl-2-imidazolines in yields up to 96%. Through variation of the diamine component, the reaction can be extended to the synthesis of 2-aryl-1H-benzimidazoles and 2-aryl-1,4,5,6-tetrahydropyrimidines.

INTRAMOLECULAR PALLADIUM CATALYSED 3+2 CYCLOADDITIONS OF METHYLENECYCLOPROPANES WITH ACETYLENIC ACCEPTORS

Abstract The synthesis and intramolecular palladium catalysed cycloaddition reactions of eight methylenecyclopropanes containing alkyne acceptors are described. Bicyclo[3.3.0]octane and bicyclo[4.3.0]nonane rings systems can be successfully accessed using this chemistry. The nature of the substituents attached to the alkyne acceptor play a key role in the efficiency of the cycloaddition.

Synthesis of optically active arylaziridines by regio- and stereospecific lithiation of N-Bus-phenylaziridine

Alpha,alpha-disubstituted aziridines can be produced in good yields by selective lithiation of N-tert-butylsulfonyl-2-phenylaziridine (n-BuLi/TMEDA, Et(2)O) at the benzylic position and subsequent trapping with a range of electrophiles. Repetition of the lithiation/electrophilic trapping sequence provides a stereocontrolled route to trisubstituted aziridines. Using (R)-N-tert-butylsulfonyl-2-phenylaziridine, the alpha,alpha-disubstituted aziridines can be produced as single enantiomers (er >98:2), indicating that the intermediate organolithium is configurationally stable. Efficient aziridine ring-opening reactions leading to 1,2-diamines and 1,4-diamines are also reported.

INTRAMOLECULAR CYCLOADDITIONS OF METHYLENECYCLOPROPANES - A NOVEL CHELATION EFFECT

In contrast to the palladium catalysed reactions of methylenecyclopropane (1), cyclisation of methylenecyclopropane (7) yields trans fused bicyclo[3.3.0]octanes (8) and (9). Intramolecular chelation by an appended ether unit is proposed to account for the observed selectivities.

An improved preparation of diphenylmethylenecyclopropanes and their use in intramolecular palladium catalysed [3+2] cycloadditions

Abstract The synthesis and intramolecular palladium catalysed cycloaddition reactions of diphenylmethylenecyclopropanes 1 and 2 containing olefinic and acetylenic acceptors are described. This strategy provides a useful entry into some highly functionalised bicyclo[3.3.0]octane systems.

Preparation and reactivity of imino glycals: stereocontrolled, divergent approach to imino sugars

The synthesis of 3,4,6-tri-O-acetyl imino D-glucal 2 from D-glucal is reported. This imino glycal participates in a variety of Lewis acid mediated carbon-carbon bond forming reactions by allylic displacement of the C-3 acetate group by added nucleophiles. Allyl silanes, trimethylsilyl enol ethers, alkenes and dialkyl zinc reagents serve as suitable reaction partners. In all the cases studied, the beta-anomer is predominant. Using imino glycal 8, epimeric at C-5, it is established that the configuration at C-5 of the piperidine ring plays a major role in controlling the stereochemical outcome. These results are rationalised by invoking the intermediacy of a conjugated N-acyliminium ion. A short stereocontrolled synthesis of (+)-deoxoprosophylline is achieved using this chemistry. Additionally, imino glucal 2 is transformed into bromo piperidine 16, whose X-ray crystal structure is determined. Bromide 16 participates in palladium catalysed Stille and Suzuki cross-couplings allowing access to C-2 substituted imino sugars 17 and 18. In other studies, imino sugar C-glycosides 21 and 22 are made by combining the Lewis acid mediated carbon-carbon bond forming reactions with stereospecific dihydroxylations.

OBSERVATIONS ON THE SYNTHESIS OF FUNCTIONALISED METHYLENEAZIRIDINES

Abstract N-Triphenylmethyl-2-methyleneaziridine 8 was synthesised from N-(2-bromo-2-propenyl)-amine7 by treatment with sodium amide in liquid ammonia and its structure established using x-ray crystallography. Using modified conditions, (S)-N-(1-phenylethyl)-2-methyleneaziridine 9 was prepared in enantiomerically enriched form. Studies directed towards the synthesis of N-tosyl and N-Boc methyleneaziridines 14 and 15 respectively reveal limitations with this methodology.

Stereochemical aspects of intramolecular palladium catalysed [3+2] cycloadditions of methylenecyclopropanes

The preparation and intramolecular palladium catalysed [3+2] cycloaddition reactions of a range of substrates containing either stereochemically defined 2,3-disubstituted methylenecyclopropanes 3 or acrylate accepters 12-15 are described. Evidence is presented which supports the hypothesis that these cycloaddition reactions proceed via palladium-trimethylenemethane type intermediates and that the two carbon-carbon bonds are formed in a highly asynchronous manner.

Synthesis of substituted piperidines, decahydroquinolines and octahydroindolizines by radical rearrangement reactions of 2-alkylideneaziridines

Abstract Rearrangement of a variety of 3-(2-methyleneaziridin-1-yl)propyl radicals, generated using Bu 3 SnH/AIBN by homolytic cleavage of phenylselenide substituted 2-methyleneaziridines, produces 3-methylenepiperidines in yields ranging from 58 to 68%. By combining this radical rearrangement with an additional 5- exo -trig cyclisation, this method provides an octahydroindolizine with moderate levels of diastereocontrol (d.r.=4:1). This rearrangement works with related 2-isopropylideneaziridines, but cannot be successfully extended to 4-(2-methyleneaziridin-1-yl)butyl radicals.