Enyne carbodiimides

When in the enyne carbodiimide the N-phenyl terminus is blocked with methyl groups, as in 72, formation of the indoloquinoline 73 occurs upon photolysis with elimination of a methyl radical. ... 

The generation of heterocyclic enyne carbodiimides is more readily accomplished by reacting the enyne isocyanate derivative with suitable iminophosphoranes, followed by heating in refluxing p-xylene (see examples in Table 3.2). 

Table 3.2 Heterocyclic Compounds Obtained from Enyne Carbodiimides... 

Schmittel M et al (1998) Two novel thermal biradical cyclizations in theory and experiment new synthetic routes to 6H-indolo 2,3-b quinolines and 2-amino-quinolines frran enyne-carbodiimides. Angew Chem Int Ed 37 2371-2373... 

Thermolysis of the enyne carbodiimide gives them the potential to participate in the synthesis of pharmacologically important drugs. This stimulated an investigation of the influence of external effects (polar and nonpolar media) and the effects of internal groups (electron acceptor and electron donor) on the cyclization of systems for increasing the use of this reaction for combinatorial synthesis [425, 426]. 

Computer modeling of thermal C -C cyclization of enyne-carbodiimide 3.968b (Scheme 3.146, A = B = N) [424] showed that intermediate 3.970b (for A = B = N) to be a diradical, as for (A = B = C) [424]. However, subsequent kinetic study of the process including the influence of solvent and the nature of substitution showed that the intermediate 3.970b is either carbene (for the case of electron-withdrawing substituents) or a zwitterion (for electron-releasing substituents). 

Radical C -C Myers-Saito cyclization of enyne-allene, as well as the reaction of C -C cyclization do not depend on the donor properties of the solvent [427]. For enyne carbodiimides the situation is different, because the nitrogen atom is a potential donor center and is well known for the high electrophilicity of the central carbon atom of the car-bodiimide group. Indeed, the study of the thermolysis of carbodiimide 3.971a showed a strong dependence of the cyclization rate constant on the solvent properties. At 85°C, the reaction was seven times faster in dioxane k = 5.3 x 10 s ) and was nine times faster in acetonitrile K = 6.93 X 10 s ) than in benzene (k = 7.83 x 10 - s ). The rate constant of the thermal C -C cyclization of enyne-carbodiimides correlates better with the donor properties of the solvent rather than its dielectric constant, which is different from the reactions of enyne-allenes. Therefore, any discussion of the mechanism requires the consideration of alternative routes (Scheme 3.147) [424]. 

Figure 3.13 Summarized kinetic data of the enyne-carbodiimide 3.971a-l cycliza-tion at 120°C (k, s a, kcal/mol) [424],...

The nonlinearity of the correlation between log k/ko) and Hammett (Tp constant at the cyclization of compounds 3.971 suggests that there is a change in reaction mechanism of C -C cyclization of the enyne carbodiimide, possibly from carbene to polar intermediates. Electron donor substituents X and Y increase probability of formation of the high polar zwitterionic carbene intermediate (Scheme 3.147, structures B and C), whereas electron-withdrawing substituents lead to a less polar carbenes (Scheme 3.147, structure A). The mechanism of polar intermediate is supported by a noticeable increase of the reaction rate with increasing the donor properties of the solvent that was observed for carbodiimide 3.971a. However, more detailed study of conditions of the... 

There has been a mechanistic investigation of the possible intermediates in the thermal C -C cyclization of enyne-carbodiimides [424]. Kinetic studies of enyne-carbodiimides with electron-withdrawing substituents gave a nonlinear Hammett correlation. This supported a concerted/nonpolar mechanism to produce a carbene intermediate. However, when electron-donating substituents were present, the results indicated a polar cyclization mechanism giving a carbene with zwitte-rionic character. Earlier, theoretical investigations by density functional theory (DFT) and NBO analysis had supported a diradical intermediate. 

Li, H., Petersen, J.L. and Wang, K.K. (2003) Cascade cyclizations via N, 4-didehydro-2-(phenylamino)pyridine biradicals/zwitterions generated firom enyne-carbodiimides. Journal of Organic Chemistry, 68(14), 5512-5518. 

Schmittel, M., Steffen, J.R, Rodrigues, D., Engelen, B., Neumann, E. and Cinar, M.E. (2008) Thermal C -C cyclization of enyne-carbodiimides experimental evidence contradicts a diradical and suggests a carbene intermediate. Journal of Organic Chemistry, 73(8), 3005-3016. 

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