Dipole LUMO control

PM3 calculations of the 2 + 3-cycloaddition of t-butylphosphaacetylene with 2,4,6-triazidopyridine are consistent with the dipole-LUMO-controlled reaction type. An FTIR spectroscopic study of the 1,3-dipolar cycloaddition of aryl azides with acetylenes shows that the rate of reaction increases logarithmically with pressure (below 1 GPa). The 3 -I- 2-cycloaddition between an azide (69) and a maleimide (70) has been greatly accelerated by utilizing molecular recognition between an amidopyridine and a carboxylic acid [see (71)] (Scheme 24). ... 

Perfluorinated and partially fluorinated substituents directly bonded to hetero multiple bond systems lower the energies of FMOs Consequently, they are highly reactive in H0MO (l,3-dipole)-LUMO (dipolarophile)-controlled [3+2] cycload-... 

The 1,3-dipolar cycloaddition of organic azides with nitriles could give rise to two regioisomers. Since organic azides are Type II 1,3-dipoles on the Sustmann classification (approximately equal HOMO-LUMO gaps between the interacting frontier orbital pairs) the reactions could be dipole HOMO or LUMO controled and the regioselectivity should be determined by the orbital coefficients for the dominant HOMO-LUMO interaction. Such systems show U-shaped kinetic curves in their... 

Diazo compounds also undergo cycloaddition with fullerenes [for reviews, see (104),(105)]. These reactions are HOMO(dipole)-LUMO(fullerene) controlled. The initial A -pyrazoline 42 can only be isolated from the reaction of diazomethane with [60]fullerene (106) (Scheme 8.12) or higher substituted derivatives of Ceo (107). Loss of N2 from the thermally labile 42 resulted in the formation of the 6,5-open 1,2-methanofullerene (43) (106). On the other hand, photolysis produced a 4 3 mixture of 43 and the 6,6-closed methanofullerene (44) (108). The three isomeric pyrazolines obtained from the reaction of [70]fullerene and diazomethane behaved analogously (109). With all other diazo compounds so far explored, no pyrazoline ring was isolated and instead the methanofullerenes were obtained directly. As a typical example, the reaction of Cgo with ethyl diazoacetate yielded a mixture of two 6,5-open diastereoisomers 45 and 46 as well as the 6,6-closed adduct 47 (110). In contrast to the parent compound 43, the ester-substituted structures 45 and 46, which are formed under kinetic control, could be thermally isomerized into 47. The fomation of multiple CPh2 adducts from the reaction of Ceo and diazodiphenylmethane was also observed (111). The mechanistic pathway that involves the extrusion of N2 from pyrazolino-fused [60]fullerenes has been investigated using theoretical methods (112). 

Whereas 260 does not react with electron-rich dipolarophiles, the more delocalized isomiinchnone 261 does react with both electron-rich and -deficient dipolarophiles (154). A detailed FMO analysis is consistent with these observations and with the regiochemistry exhibited by diethyl ketene acetal and methyl vinyl ketone as shown in Scheme 10.36. The reaction of 261 with the ketene acetal to give 262 is LUMO-dipole HOMO-dipolarophile controlled (so-called lype III process). In contrast, the reaction of 261 with methyl vinyl ketone to give 263 is HOMO-dipole LUMO-dipolarophile controlled (so-called lype I process). In competition experiments using a mixture of A-phenylmaleimide and ketene acetal only a cycloadduct from the former was isolated. This result is consistent with a smaller energy gap for... 

Hydrazones have also been used as azomethine imine precursors to achieve cycloadditions.157 Proto-nated hydrazones act under suitable conditions as quasi-azomethine imines in polar [3+ + 2] cycloadditions. Thus, r.cetaldehyde phenylhydrazone (201) was found to react with styrene in the presence of sulfuric acid in a regiospecific manner to give pyrazolidine (203 Scheme 47) as a diastereomeric mixture.157 The most commonly used azomethine imine has a phenyl group attached to one end of the dipole and hence has a raised HOMO relative to the unsubstituted system. Because the coefficients at the terminal atoms of the dipole are smaller in the LUMO than they are in the HOMO, the phenyl group does not lower the energy of the LUMO as much as it raises the energy of the HOMO. With electron-deficient di-polarophiles like methyl acrylate, the reaction is dipole HOMO-controlled, and mixtures can be expected. In fact, a 1 1 mixture of regioisomers was obtained in the reaction of (201) with acrylonitrile (equation 9).157... 

The cycloaddition of azides to multiple -ir-bonds is an old and widely used reaction. Organic azides are well known to behave as 1,3-dipoles in thermal cycloaddition reactions.178 The first example of this reaction was observed by Michael in 1893.179 Since then the addition of azide to carbon-carbon double and triple bonds has become the most important synthetic route to 1,2,3-triazoles, -triazolines and their derivatives.180-184 The cycloadditions of simple organic azides with electron-rich dipolarophiles are LUMO controlled.3 Since the larger terminal coefficients are on the unsubstituted nitrogen in the azide and unsubstituted terminus in the dipolarophiles, the 5-substituted A2-triazolines are favored, in agreement with experiment.185-187 Reactions with electron-deficient dipolarophiles are HOMO controlled, and... 

Azide cycloaddition to electron-deficient dipolarophiles is normally HOMO-dipole LUMO-dipolaro-phile controlled, whereas the reverse is true for electron-rich dipolarophiles. Products with an electron-deficient group at the 5-position or an election-rich group at the 4-position are favored electronically in intramolecular cycloadditions, steric constraints can be expected to outweigh these considerations. 

However, this interaction should also be increased by alkyl substituents, which lower the alkene IP, or, equivalently, raise the alkene HOMO energy. Experimentally, there is either no change in rate, or a small decrease, as the IP of the alkene decreases. Thus, an apparent contradiction is revealed in these examples dipole LUMO-alkene HOMO control nicely accounts for regioselectivity and the nitrile oxide substituent effect, but does not explain the decrease in rate for increasing alkyl substitution. More potent electron-donors do, indeed, accelerate the reaction, but only feebly. For example, butyl vinyl ether reacts 2.1 times faster than ethylene with BNO at 0 °C, while styrene reacts only 1.2 times faster than ethylene with BNO, in spite of the low IP of styrene (8.48 eV)72. ... 

This reaction is therefore dipole-HO-controlled, and we can turn to the coefficients , the (eft)2 values, for the HOMO of the dipole from Table 6.1 and the coefficients of the LUMO of the dipolarophile from Fig. 6.22. Regioselectivity follows in the usual way from the large-large/small-small interaction 6.223, which has the carbon end of the dipole bonding to the ft carbon of the Z-substituted alkene, as observed. 

With Z-substituted dipolarophiles and phenyl azide, the situation is again delicately balanced and only just dipole-HO-controlled (9.5 eV against 10.7 eV). For the dipole-HO-controlled reaction, we should expect to get adducts oriented as in Fig. 6.36a. However, a phenyl group reduces the coefficient at the neighbouring atom both for the HOMO and for the LUMO, and this will reduce the polarisation of the HOMO. Conversely, it will increase the polarisation for the LUMO and hence increase the effectiveness of the interaction of the LUMO of the dipole with the HOMO of the dipolarophile, as in Fig. 6.36b. The difference in... 

Dipolarophiles with electronegative heteroatoms such as carbonyl groups, imines and cyano groups also show an orientation in agreement with frontier orbital theory. Because heterodienophiles all have low-energy LUMOs, their reactions will usually be dipole-HO-controlled. The reaction of diazomethane with an imine giving the triazoline 6.240 and the final step in the formation of an ozonide... 

Incorporation of perfluoroalkyl groups into 1,3-dipoles usually increases reactivity, i.a. by lowering the energies of the frontier orbitals and reducing the LUMO 1,3-dipole/HOMO dipolarophile energy gap. On the other hand, when perfluoroalkyl and partially fluorinated substituents are directly bonded to the dipolarophile skeleton, cycloaddition reactions occur preferentially under HOMO 1,3-dipole/LUMO dipolarophile control. Furthermore, perfluoroalkyl groups often stabilize the newly formed ring systems. 

The terms endo and exo have long been used to represent the stereochemical pathway of the HOMO(dipole)-LUMO (dipolarophile) interaction-controlled cycloadditions. However, on the basis of the stereochemical analysis of the cycloadducts alone, the approach (endo or exo) cannot be specified. There are two geometries possible for each of the anti- and syn-... 

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