A DFT computational study on the molecular mechanism of reaction between pyridinium salts and pi-deficient ethylenes: Why furan derivatives are formed instead of feasible cyclopropane derivatives and [3+2] cycloadducts?

作者：Emamian Saeedreza^*; Jasinski Radomir

来源：Computational and Theoretical Chemistry, 2017, 1114: 87-100.

DOI：10.1016/j.comptc.2017.05.019

• Pyridinium salt
• Kinetically- and thermodynamically-controlled conditions
• Regio- and stereoselectivity
• Non-covalent interactions analysis
• Parr functions
• ELF quantum topological analysis

The reaction between 1-(2-amino-2-oxoethyl)pyridinium ylide 4 (PY4) and 1-methylene-3,4-dihydro naphthalen-2(1H)-one 5 (MDN5) in the presence of acetonitrile (CH3CN) was theoretically studied at the M06-2X/6-31G(d,p) computational level. Calculated relative Gibbs free energies indicate that encounters between PY4 and MDN5 in the reaction mixture result in the formation of the highly zwitterionic betaine-like intermediate IM1ca in an entirely C1-C5 regio- and a cisoid-anti stereoselective manner over the course of a Michael addition reaction through a very low barrier (4.2 kcal/mol) and a highly exergonic (24.7 kcal/mol) pathway. While C1-C5 regioselectivity can be rationalized via the analysis of the computed nucleophilic and electrophilic Parr functions at the reactive sites of reagents, the cisoid-anti stere-oselectivity predominance over the cisoid-syn one can nicely be portrayed within the non-covalent interactions (NCIs) analysis at the cisoid-anti transition state TS1ca and cisoid-syn transition state TS1cs involved in the Michael addition reaction. The electron-localization ELF) quantum topological analysis obviously demonstrates that the C1 carbon atom in PY4 exhibits a pseudoradical character indicating the high reactivity of PY4 toward C5 electrophilic attack of MDN5 which is characterized with a very low barrier associated with the C1-C5 single bond formation along the Michael addition step. Upon formation of IM1ca, in excellent agreement with the experimental outcomes, an S(N)i-like reaction converts IM1ca into trans-furan derivative 8 together with pyridine via a high barrier (23.9 kcal/mol) but a highly irreversible pathway making compound 8 as the only reachable product under "thermodyna mically-controlled" conditions (refluxing over 8 h). In other words, neither [3 + 2] cycloadduct 6 (as the kinetically most favourable but thermodynamically most unfavourable product) nor cyclopropane derivative 7 (as both kinetically and thermodynamically most undesirable product) can be obtained under the reaction conditions. From the molecular mechanism point of view, the ELF analyses indicate that while C1-C5 single bond formation within the Michael addition reaction takes place via a C- to - C coupling of two pseudoradical C1 and C5 centers, formation of C1-O8 single bond accompanied with the C1-N15 single bond breaking at the generated IM1ca to afford compound 8 is a direct consequence of donation of some electron density of O8 oxygen lone electron pairs to the C1 carbon atom.

• 出版日期2017-8-15