1.3- dipolar cycloaddition reactions synchronicity

The [3 + 2]-cycloaddition reactions of allenes with 1,3-dipoles are useful for the construction of a variety of five-membered heterocycles with a high degree of regio- and stereochemical control [67]. Generally, the dipolar cycloaddition reactions are concerted and synchronous processes with a relatively early transition state. The stereoselectivities and regiochemistries are accounted for by the FMO theory The reaction pathway is favored when maximal HOMO-LUMO overlap is achieved. 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

The position of the critical point on the concerted synchronous pathway for the 2s+2s reaction occurs at a position which is also a critical point in -T and in Q (the values of 3Q/3R and -3T/3R in Table 1 are both almost zero). Since Q is very flat this is the only possibility. Thus the maximum in -T coincides approximately with the local maximum on the energy surface shown in Fig. 2. The position of the critical point with respect to r for the 1,3 dpolar cycloaddition reaction occurs just before the minimum in Q (ie on the attractive part of Q) while -T is still decreasing in magnitude. Thus for the 1,3 dipolar cycloaddition reaction the transition state occurs only just before the critical... 

From the preceding discussion we see that, while the general shapes of the Q and T surfaces for the 3 reactions are similar, the condition for a critical point (slopes of Q and -T opposite or equal to zero) and the nature of the critical point (transition state or local maximum) are delicately intertwined and yield a very different topology on the surface that corresponds to the total energy. The critical points on the concerted synchronous pathway for the 2s+2s reaction and the 1,3 dipolar cycloaddition reaction... 

Figure 22-3 Overlapping Ji-electron atomic orbitals for 1,3 dipolar cycloaddition reaction.and the electronic reorganization is assumed to proceed according to structures (24) —(25). A concerted mechanism is concomitant with this valence-bond description, with the new C-C and C-N bonds being formed synchronously.

A review of recent developments in 1,3-dipolar cycloaddition of nitrones with sila-, thia-, phospha-, and halo-substituted alkenes has been reported. A DFT study of solvent effects on the intermolecular 3-l-2-cycloaddition reaction of norbornadiene with 3,4-dihydroisoquinoline A(-oxide at 398.15 K indicated that the reaction proceeds via a synchronous concerted mechanism. Chiral imidazolidinone salts, in the absence of water, promote the 1,3-dipolar cycloaddition reaction of alanine-derived ketonitrones... 

Such a conclusion is, nevertheless, connected with the synchronous character of the mechanism. If a stepwise process is involved (nonsimultaneous formation of the two new bonds), as for unsymmetric dienes and/or dienophiles or in hetero Diels-Alder reactions, a specific microwave effect could intervene, because charges are developed in the transition state. This could certainly be so for several cycloadditions [47, 48] and particularly for 1,3-dipolar cycloadditions [49]. Such an assumption has... 

The gas-phase Diels-Alder reaction between butadiene and ethene follows a synchronous pathway, while the 1,3-dipolar cycloaddition of fulminic acid to ethyne proceeds in a concerted, almost synchronous fashion, in spite of the different nature of the two bonds closing the isoxazole cycle. 

We now turn to the gas-phase 1,3-dipolar cycloaddition of fulminic acid to ethyne. The concerted, almost synchronous nature of this reaction might create the impression that the electronic mechanism of this process should be very similar to that of the Diels-Alder reaction. Such an expectation is reinforced by frontier orbital theory, which treats both reactions in very much the same way (see Ref. 32). The only significant differences are related to the fact that the lowest unoccupied MO (LUMO) for a linear 1,3-dipole... 

In contrast to strongly solvent-dependent [2- -2]cycloaddition reactions, which proceed through a 1,4-dipolar zwitterionic intermediate by a two-step mechanism or through a dipolar activated complex by a one-step mechanism cf. Section 5.3.2, and Eqs. (5-33) to (5-35) [92, 94-107], [2- -2]cycloadditions are also known that exhibit concerted, nearly synchronous bond formation without significant charge separation on activation in the transition state. An example is given in Eq. (5-47). Since the rate constant for this diphenylketene/styrene addition is practically independent of solvent polarity [140], it can be classed as concerted. 

The thermal unimolecular cyclization of 3-diazoalkenes to pyrazoles appears to be an intramolecular 1,3-dipolar cycloaddition and the first-order rate coefficients of four substituted // art5-3-diazo-l-phenylpropenes fit the Hammett equation (p = — 0.40). The small value of p, indicating a lack of sensitivity of the cyclization rate to the electronic nature of the substituents supports the belief that the reaction involves a synchronous, cyclic electron shift. Table 11 lists the measured rate coefficients. 

Step is the addition of azide ion. While such a reaction may be possible in some cases, this mechanism also requires that cyclization proceeds in preference to protonation of the intermediate carbanion and this seems unlikely. A more probable mechanism is a synchronous 1,3-dipolar cycloaddition, and such reactions of covalent azides are well documented... 

High-level quantum-chemical calculations on the 3 + 2-cycloadditions of thioformaldehyde 5 -imides, S -methylide, S-oxide, and 5-sulfide have been reviewed. Theoretical studies on the 1,3-dipolar cycloaddition between thioketene 5-oxide and methyleneimine show that this reaction is concerted but non-synchronous. Adamantanethione 5-methylide reacts with thiocarbonyl compounds to produce 1,3-dithiolanes. A density-functional-theory study of the cycloaddition of the sulfine H2CSO predicts the 2 + 3-mechanism having the lowest pathway, with an activation barrier of 12.3kcalmoP. R The thermal and photochemical reactions of fluorenethione 5-oxide (69) with cyclooctyne (70) involves an initial 1,3-dipolar cycloaddition to produce the adduct (71), followed by an efficient sulfur transfer to cyclooctyne to produce the enone (72) and the dithiin (73) (Scheme 26). ° ... 

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