A frontier molecular orbital treatment of fulvene cycloadditions : Molecular orbital calculations and photoelectron spectra of substituted fulvenes

MO calculations have been carried out on substituted fulvenes by several semiempirical methods. The results of these calculations are compared with those by other methods, and with photoelectron spectroscopic data obtained here for several substituted fulvenes. Predictions about the periselectivity ([6+4] or [4+2]) of fulvene cycloadditions with dienes, 1,3-dipoles, and ketenes are made and compared with experimental data, where available.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrones.

Efficient routes to the synthesis of norbornadiene-tethered nitrones have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in moderate to good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Synthesis of novel spiropyrrolidine/pyrrolizine-oxindole scaffolds through 1,3-dipolar cycloadditions

The one-pot, three-component condensation of sarcosine or proline Schiff bases with several aromatic aldehydes and the Knöevenagel adduct of isatin-malononitrile successfully affords spiropyrrolidine-oxindoles and spiropyrrolizine-oxindoles.     

Intramolecular 1,3-dipolar cycloadditions of aliphatic nitrile oxides

Treatment of functionalized 1-chloro-oximes ( 3c and 4a,b ) with triethylamine originates nitrile oxides ( 1c and 2a,b ) which undergo an intramolecular cycloaddition providing fused-ring isoxazole derivatives ( 7c and 8a,b ). The latter reaction was not observed for one substrate ( 2c ).     

Directed 1,3-dipolar cycloadditions of ylidene piperazine-2,5-diones

The reactivities and selectivities of 1,3-dipolar cycloaddition reactions of ylidene piperazine-2,5-diones with mesitonitrile oxide are reported. The stereoselectivities of reactions with chiral ylidene piperazine-2,5-diones can be directed by judicious choice of substituents on the N- and/or C-substituents of the piperazinedione ring.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrile oxides.

Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Theoretical interpretation of experimental data on 1,3-dipolar cycloadditions

Using the MINDO/3 method it has been shown that the two-steps mechanism, proposed in a previous paper¹ for the 1,3-dipolar cycladditions, is compatible with several existing experimental results. Firstly, the effects of the introduction of different substituents on the mechanism of the cycloadditions were studied. Secondly, the slight influence of the polarity of the solvent on the reaction rate has been interpreted by solvation calculations. Finally, the stereospecificity observed has been explained.     

Double 1,3-dipolar cycloadditions of meso-ionic heterocycles with N-phenylmaleimide

3-Phenylsydnone and 2,4-diphenyl-3-methyloxazolium 5-oxide undergo double 1,3-dipolar cycloadditions with two molecules of N-phenylmaleimide to produce 4,8-iminobenzo[1,2-c:4,5-c′]dipyrrole-1,3,5,7-tetrone derivatives in a stereoselective manner.     

Intramolecular low-temperature 1,3-dipolar cycloadditions of nitrones: synthesis of chromano-heterocycles

In contrast to the reported facile intramolecular 1,3-dipolar cycloadditions of in-situ generated nitrone on heterocyclic systems, reactions of 2-(N-allyl/crotyl/cinnamyl-anilino)-3-formylchromones with N-phenyl-/methylhydroxylamine under comparable conditions, afford fused isoxazolidines only in low to moderate yields; the corresponding amides derived from rearrangement of in situ generated nitrones are formed as major products. However, when reactions were carried by stirring the reactants at an ice-cold temperature in dichloromethane, highly stereoselective intramolecular 1,3-dipolar cycloadditions lead to novel fused isoxazolidines in high yields (80-90%).     

Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron-deficient olefins

[reaction: see text] A general strategy for highly enantioselective 1,3-dipolar cycloaddition of diazoesters to beta-substituted, alpha-substituted, and alpha,beta-disubstituted alpha,beta-unsaturated pyrazolidinone imides is described. Cycloadditions utilizing less reactive alpha,beta-disubstituted dipolarophiles require elevated reaction temperatures, but still provide the corresponding pyrazolines with excellent enantioselectivities. Finally, an efficient synthesis of (-)-manzacidin A employing this cycloaddition methodology as a key step is illustrated.     

A kinetic study of 1,3-dipolar cycloadditions in micellar media

The kinetics of the 1,3-dipolar cycloadditions (DC) of benzonitrile oxide with a series of N-substituted maleimides in micellar media have been investigated. Surfactants studied include anionic sodium dodecyl sulfate, cationic cetyltrimethylammonium bromide, and a series of nonionic alkyl poly(ethylene oxide) surfactants (CxEy). The kinetic data have been analyzed by using the pseudo-phase model for bimolecular reactions. Much larger micellar accelerations (up to a factor of 17) were observed for these reactions than was previously found for Diels-Alder (DA) reactions (J. Org. Chem. 2002, 67, 7369-7377). This is explained by the smaller solvent sensitivity of DC reactions, which causes the micellar rate constants to be much closer to the value of water (km/kw approximately 0.25-0.45 for DC reactions vs 0.02-0.05 for DA reactions). Further evidence is presented, that a water/1-propanol mixture ([H2O] ca. 15 M) is a fairly good mimic of the micellar reaction environment for these reactions. Isobaric activation parameters have been determined for the reaction in the micellar phase of C16E20, using micellar rate constants. They correspond well to values obtained for the aforementioned micelle mimic.     

Theoretical study of the mechanism of the 1,3-dipolar cycloadditions

By means of the MINDO/3 method the potential energy hypersurfaces for the 1,3-dipolar cycloadditions of carbonyl and azomethine ylides to ethylene have been studied. In the first place, the synchronous formation of the two new sigma bonds has been considered. In the second place, the asynchronous region of the surface has been explored. The asynchronous mechanism appears to be more favourable, there being two transition states and an intermediate. Finally, the physical meaning of the results obtained is discussed.     

Monofunctionalization of dendrimers with use of microwave-assisted 1,3-dipolar cycloadditions

Monofunctionalized polyamide-based dendrimers containing either a terminal azide or alkyne moiety have been designed and synthesized via a convergent synthetic approach. The monofunctionalization allows for the single attachment of a functional moiety in quantitative yields by using 1,3-dipolar cycloadditions, thereby opening the possibility for targeted dendrimer functionalization.     

1,3-dipolar cycloadditions of aromatic azoxy compounds to strained cyclo-alkenes

The 1,2,3-oxadiazolidines resulting from the addition of 4,4′-dicyano-azoxybenzene to trans-cyclooctene or cis, trans-cycloocta-1,5-diene are not stable, bu suffer 1,3-dipolar cycloreversion to give an azomethine imine; this intermediate is either captured by a second molecule of the strained cycloalkene to give 1:2 adducts in high yields or it tautomerizes to an enehydrazine. 4,4′-Dinitroazoxybenzene and benzo[c]cinnoline N-oxide react analogously.     

Double 1,3-dipolar cycloadditions of meso-ionic heterocycles to N-substituted maleimides

Double 1,3-dipolar cycloadditions of 2,4-diphenyl-3-methyloxazotium 5-oxide and 3-phenylsydnone to two molecules of N-substituted maleimide afforded one or two isomeric 4,8-iminobenzo[1,2-c:4,5-c′]dipyrrole-1,3,5,7-tetrone derivatives owing to the types of heterocycles as well as N-substituents of maleimides.