John F. Malone

X=y-zh systems as potential 1,3-dipoles—5 : Intramolecular cycloadditions of imines of α-amino acid esters

Abstract Azomethine ylides are readily generated from imines of α-amino acid esters by a formal 1,2-H shift. A suitably positioned unactivated double or triple bond in either of the two precursors of the imines (aldehyde or α-amino ester) leads to an intramolecular cycloaddition generating fused ring systems in good yield. Cis stereochemistry is assigned to the newly created ring junction of the cycloadducts based on NOE difference spectroscopy and, in the case of 8a, by a single crystal X-ray structure. Equilibration of the kinetically formed dipole leads to mixtures of epimeric cycloadducts for imines of phenylglycine methyl ester but equilibration is not observed for other imines. Reasons for this are discussed. The intramolecular cycloaddition is sensitive to ring size with 6/5 and 5/5 cis-fused systems being most easily formed depending in which moiety (aldehyde or amino acid) the dipolarophile is located. Intramolecular trapping of the azomethine ylide by an alkyne is accompanied by variable amounts of aromatized pyrrolic products.

Palladium-catalysed polycyclisation-anion capture processes

Abstract Aryl iodides containing appropriately located 1, n-diene, -diyne, and -enyne moieties undergo palladium catalysed bis-cyclisation with anion capture (H − , Ph − ) apart from the 1, n-enyne which undergoes a tri-cyclisation without anion capture. The reactions lead to the regio- and stereo-specific creation of ring junction-, spiro- and remote ring-tetrasubstituted carbon centres.

Chiral induction in cycloaddition reactions of azomethine ylides derived from secondary α-amino acids by the decarboxylative route

Abstract Cyclic secondary α-amino acids react with isatin and menthyl acrylate via decarboxylative azomethine ylide formation and subsequent cycloaddition involving an endo-transition state to give cycloadducts in 67-82% d.e. The stereochemistry of the major cycloadduct is assigned from a single crystal X-ray structure and a transition state model is proposed for the process.

X=Y-ZH systems as potential 1,3-dipoles. Part 21 activation of the ZH proton in imines.

Abstract A range of substituents is capable of inducing thermal 1,3-dipole formation in imines by activation of the CH proton as shown by trapping experiments with dipolarophiles.

X=Y-ZH compounds as potential 1,3-Dipoles. Part 281,2 the iminium ion route to azomethine ylides. background and reaction of amines with bifunctional ketones.

Abstract The reaction of isatin, ninhydrin and acenaphthenequinone with primary and secondary amines gives rise to stereospecific formation of intermediate azomethine ylides which can be trapped by cycloaddition to methyl acrylate or N-methylmaleimide. The regiochemistry of the cycloadditions to methyl acrylate is controlled by both frontier orbital and steric interactions with the latter dominating in the examples studied.

Asymmetric induction in the creation of tri- and tetra-substituted carbon stereocentres by the intramolecular heck reaction

Abstract A preliminary survey of the use of aminoethers as chiral auxiliaries, in combination with both chiral and achiral phosphines, for palladium catalysed cyclisations is reported. A 55% d.e. was observed for a process creating a tetrasubstituted carbon centre and > 95% d.e. for a process creating a trisubstituted carbon centre.

X=Y-ZH systems as potential 1,3-dipoles. Part 34. generation of nitrones from oximes. Tandem michael addition-1,3-dipolar cycloaddition reactions. class 2 processes utilising bifunctional michael acceptor-dipolarophile components. ☆ ☆☆

Aldoximes and ketoximes react with a range of bifunctional Michael acceptor-dipolarophile substrates comprising functionalised 1,3-, 1,4- and 1,5-dienes via a tandem process involving an N-alkenyl nitrone intermediate. The 1,3-dienes react regio- and stereo-specifically to give 1-aza-7-oxabicyclo[2.2.1]heptanes whilst sterically unencumbered aryl aldoximes and 1,4-dienes give 1-aza-2-oxabicyclo[3.2.1]octane derivatives. Ketoximes and 1.4-dienesgive mixtures of 1-aza-2-oxa- and 1-aza-8-oxa-bicyclo[3.2.1]octanes. 1,5-Dienes and ketoximes react regio-and stereo-specifically to give 1-aza-8-oxabicyclo[3.2.1]octane derivatives whilst benzaldoxime gives a 1:1 mixture of epimeric 1-aza-8-oxabicyclo[3.2.1]octanes together with traces of two epimeric 1-aza-2-oxabicyclo[3.2.1]octanes. The regio- and stereo-chemical outcome of the tandem process is controlled by the length and nature of the linking chain in the bifunctional substrate and the steric interactions between substituents on the oxime and dipolarophile in the transition state. A crystal structure of one of the 1-aza-7-oxabicyclo[2.2.1]heptanes is reported.

X=Y−ZH compounds as potential 1,3-dipoles. Part 43. Metal ion catalysed asymmetric 1,3-dipolar cycloaddition reactions of imines and menthyl acrylate☆

Abstract Metallo-azomethine ylides, generated from imines by the action of amine bases in combination with LiBr or AgOAc, undergo cycloaddition with both 1R, 2S, 5R- and 1S, 2R, 5S-menthyl acrylate at room temperature to give homochiral pyrrolidines in excellent yield. The stronger the base the faster the cycloaddition and the greater the yield with: 2- 2-t-butyl-1,1,3,3-tetramethylguanidine > DBU > NEt 3 . X-Ray crystal structures of representative cycloadducts establish that the absolute configuration of the newly established pyrrolidine stereocentres is independent of the metal salt and the size of the pyrrolidineC(2)-substituent for a series of aryl and aliphatic imines.

Metal ion catalysed asymmetric 1,3-dipolar cycloaddition reactions of imines of α-amino esters

Abstract Cycloaddition of a range of imines of α-amino esters to homochiral menthyl acrylate proceeds with complete asymmetric induction at room temperature in the presence of silver(I), lithium(I) and thallium(I) salts. The imine of 2-aminomethylpyridine reacts similarly. Reversal of cycloaddition regiochemistry, together with complete asymmetric induction, occurs when titanium (IV) complexes are used as catalysts. The absolute configuration of one of the cycloadducts has been established by X-ray crystallography.

Chemoenzymatic synthesis of carbasugars (+)-pericosines A-C from diverse aromatic cis-dihydrodiol precursors.

cis-Dihydrocatechols, derived from biological cis-dihydroxylation of methyl benzoate, iodobenzene and benzonitrile, using the microorganism Pseudomonas putida UV4, were converted into pericosines A, C, and B, respectively. This approach constitutes the shortest syntheses, to date, of these important natural products with densely packed functionalities.