The Diels–Alder Reaction of 4,6‐Dinitrobenzofuroxan with 1‐Trimethylsilyloxybuta‐1,3‐diene: A Case Example of a Stepwise Cycloaddition

The reaction of 4,6‐dinitrobenzofuroxan (DNBF) with 1‐trimethylsilyloxybuta‐1,3‐diene ( 8 ) is shown to afford a mixture of [2+4] diastereomeric cycloadducts ( 10 , 11 ) through stepwise addition–cyclization pathways. Zwitterionic intermediate σ‐adduct 9 , which is involved in the processes, has been successfully characterized by ¹H and ¹³C NMR spectroscopy and UV/visible spectrophotometry in acetonitrile. A kinetic study has been carried out in this solvent that revealed that the rate of formation of 9 nicely fits the three‐parameter equation log k=s(E+N) developed by Mayr to describe the feasibility of nucleophile–electrophile combinations. This significantly adds to the NMR spectroscopic evidence that the overall cycloadditions take place through a stepwise mechanism. The reaction has also been studied in dichloromethane and toluene. In these less polar solvents, the stability of 9 is not sufficient to allow direct characterization by spectroscopic methods, but a kinetic investigation supports the view that stepwise processes are still operating. An informative comparison of our reaction with previous interactions firmly identified as prototype stepwise cycloadditions is made on the basis of the global electrophilicity index, ω, defined by Parr within the density functional theory, and highlighted by Domingo et al. as a powerful tool for understanding Diels–Alder reactions.     

Superelectrophilicity of the nitroolefinic fragment of 4-nitrobenzodifuroxan in Michael-type reactions with indoles: a kinetic study in acetonitrile

The kinetics of the coupling of 4-nitrobenzodifuroxan (NBDF) with a series of indoles 8 a-e to give the expected Michael-type adducts 9 a-e have been investigated in acetonitrile solution. No significant influence of the nature of the isotopic substitution at C-3 of the indole ring has been found, indicating that the NBDF addition step is the rate limiting step of the SEAr substitution of the indole moiety. This implies that the measured second-order rate constants (k) for the reactions are identical to the second order rate constants (k1NBDF) associated to the C--C coupling step. By using the known N and s parameters characterizing the nucleophilicity of indoles, the k1NBDF rate constants are found to fit nicely to the three parameters equation logk1=s(N+E) introduced by Mayr to describe the feasibility of nucleophilic-electrophilic combinations. Based on this, the electrophilicity parameter E of NBDF could be determined as E=-6.15. This corresponds to a positioning of the reactivity of the nitroactivated double bond of NBDF in the domain of superelectrophilicity previously defined for nitrobenzofuroxans, in accord with the finding that the rates of coupling of 8 a-e with NBDF are only one order of magnitude lower than those for the coupling of these indoles with 4,6-dinitrobenzofuroxan (DNBF). The theoretical scale of electrophilicity introduced by Domingo et al. on the basis of the global electrophilicity index omega defined by Parr is also a very useful tool to discuss the relative reactivities of NBDF, DNBF, and a number of differently activated C==C double bonds.     

The stepwise Diels-Alder reaction of 4-nitrobenzodifuroxan with Danishefsky's diene

The Diels–Alder reaction of 4‐nitrobenzodifuroxan (NBDF) with 1‐methoxy‐3‐trimethylsilyloxy‐1,3‐butadiene has been investigated experimentally and theoretically. Treatment of NBDF with excess diene in chloroform at room temperature was found to afford a single product that contained a carbonyl functionality. Based on an X‐ray structure and NMR spectroscopic data, the product appeared to be a result of the hydrolysis of the OSiMe₃ moiety of the thermodynamically more stable endo [2+4] cycloadduct, characterized by a cis arrangement of the MeO and NO₂ functionalities. In situ NMR investigations of the interaction were carried out at room temperature in CDCl₃ and at ?40 °C in deuterated acetonitrile. Calculations at the B3LYP/6‐31G* level in the gas phase and in acetonitrile were carried out under the assumption that the most stable cis conformation of the diene is also the most reactive in the interaction. The analysis revealed the NBDF/cis diene interaction involves the formation of a zwitterionic intermediate. Importantly, this intermediate is formed in two preferred conformations, which correspond to the endo and exo modes of approach of the reagents. Cyclization of these two identified conformations afforded the experimentally characterized endo and exo [2+4] cycloadducts. According to the calculations, the interconversion of the two conformers can either take place through a return to the pre‐reaction complexes or it can occur by rotation through an intermediate conformation of lesser stability. In view of the stepwise character of the interaction, the possibility that the intermediate zwitterion is the result of the interaction between NBDF and the trans diene could not be excluded. Calculations carried out with the most stable and more populated s‐trans conformer confirmed this idea and supported the role of the zwitterion in the overall interaction.