Nitro-Substituted Benzaldehydes in the Generation of Azomethine Ylides and Retro-1,3-Dipolar Cycloadditions.

1,3-Dipolar cycloaddition of 2- and 3-nitrobenzaldehydes with 2-aminomethylpyridine and ethyl (2)-2-cyano-3-(4-nitrophenyl)prop-2-enoate yielded -cycloadducts as the sole products under various reaction conditions. Fortuitously, 4-nitrobenzaldehyde behaved differently in three- and four-component cascades to produce a mixture of - and '-cycloadducts. This reaction is solvent- and temperature-dependent, and consequently, both the - and '-cycloadducts were synthesized in an excellent regio-, stereo-, and chemoselective fashion. Retro-1,3-dipolar cycloadditions of the -cycloadducts were conducted under mild reaction conditions, and the generated -dipoles were stereomutated into -dipoles which recycloadded with the dipolarophiles to provide the '-cycloadducts. Mechanistic studies were carried out to support the proposed mechanisms. Unprecedentedly, particular arylidene scaffolds participated as aldehyde or activated methylene precursors. Density functional theory calculations were performed to shed light on the importance of AcOH in the generation and isomerization of dipoles and to explain the high selectivity and the possibility of retro-cycloaddition.