The participation of 2H-pyran-2-ones in [4+2] cycloadditions: An experimental and computational study

Abstract

Experimental and computational DFT studies of the Diels-Alder (DA) reaction mechanism for the series of 2H-pyran-2-ones 1 and non-symmetrically substituted alkynes 2, 10, and 11 were undertaken. Several 2H-pyran-2-ones 1 were treated with N,N-diethylpropynamine (2). The results point toward a polar and asynchronous two-step mechanism that is in line with the characteristics of a polar Diels-Alder (P-DA) reaction mechanism.5 Unexpected formation of minor products 4a-d during the reaction of 1 with 2 can be rationalized by considering the easily passable torsion barrier around the newly formed C-C bond that enables two different cyclization modes. The charge transfer (CT) and global reactivity indices analyses demonstrated that in these reactions 2H-pyran-2-ones act as electrophiles and N,N-diethylpropynamine (2) acts as a nucleophile reaction partner. The introduction of electron-withdrawing carboxylic substituents on the dienophiles 10 and 11 shifts the DA reaction with 2H-pyran-2-ones to a less polar and more synchronous concerted reaction mechanism. Calculated CT as well as values of the global electrophilicity and nucleophilicity N indexes revealed that 2H-pyran-2-ones act in this case as nucleophiles and reacting dienophiles 10 and 11 as electrophiles. The results are consistent with the experimental data and kinetic analyses, thus providing valuable insights into 2H-pyran-2-one chemistry and paving the way for an efficient synthesis of highly functionalized benzene derivatives as well as broadening the mechanistic understanding of these highly versatile reactions. A comprehensive study of the Diels-Alder reaction mechanism of 2H-pyran-2-ones and non-symmetrically substituted electron-rich and electron-pure alkynes using both experimental and computational approaches is presented. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.