Synthesis of tricyclic phosphonopyrrolidines via IMDAF: experimental and theoretical investigation of the observed stereoselectivity.
During the synthesis of tricyclic phosphonopyrrolidines via intramolecular 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 cycloaddition occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via X-ray analysis. A thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically. Density functional theory methods and several high-level post Hartree-Fock procedures were used to rationalize the observed 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 first type of molecules 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 mixture of epimers being formed.
Claeys
Diederica D
DD
Research Group SynBioC, Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
Moonen
Kristof
K
Roman
Bart I
BI
Nemykin
Victor N
VN
Zhdankin
Viktor V
VV
Waroquier
Michel
M
Van Speybroeck
Veronique
V
Stevens
Christian V
CV
D018360:Crystallography, X-Ray; D008958:Models, Molecular; D063065:Organophosphonates / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013816:Thermodynamics
D063065:Organophosphonates; D011759:Pyrrolidines