Synthesis of Tricyclic Phosphonopyrrolidines via IMDAF: Experimental and Theoretical Investigation of the Observed Stereoselectivity.
作者
Claeys, Diederica D.;Moonen, Kristof;Roman, Bart I.;Nemykin, Victor N.;Zhdankin, Viktor V.;Waroquier, Michel;Van Speybroeck, Veronique;Stevens, Christian V.;
[摘要]：During the synthesis of tricyclic phosphonopyrrolidines via intramol. Diels-Alder reactions of 1-acylamino(furan-2-yl)methyl phosphonates, two isomers are formed in most cases. The presence of a short three-atom tether together with spectroscopic data, including difference NOE, revealed that the cycloaddn. occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via x-ray anal. A thermodn. preference for the product with the phosphonate function in the endo position was obsd. exptl. and was confirmed theor. D. functional theory methods and several high-level post Hartree-Fock procedures were used to rationalize the obsd. isomer ratio of the IMDAF-reactions. This was done for two different types of reagents: with the activating carbonyl group in the tether or as a substituent on the tether. For the 1st type of mols. there is a large steric hindrance of the bulky tether substituents that disfavors the exo-isomer. In the latter case, there was a very small energy difference between the transition states causing a mixt. of epimers being formed.
