Elucidation of the reaction mechanisms and diastereoselectivities of phosphine-catalyzed [4 + 2] annulations between allenoates and ketones or aldimines.
The phosphine-catalyzed [4 + 2] annulations between allenoates and electron-poor trifluoromethyl ketones or N-tosylbenzaldimine dipolarophiles have been investigated in continuum solvation using density functional theory (DFT) calculations. The detailed reaction mechanisms as well as the high cis-diastereoselectivities of the reactions have been firstly clarified. Our calculated results reveal that the whole catalytic process is presumably initiated with the nucleophilic attack of phosphine catalyst at the allenoate to produce the zwitterionic intermediate , which subsequently undergoes γ-addition to the electron-poor C=O (or C=N) dipolarophile to form another intermediate . The following [1,3] hydrogen shift of is demonstrated to proceed via two consecutive proton transfer steps without the assistance of protic solvent: the anionic O6 (or N6) of first acts as a base catalyst to abstract a proton from C1 to produce the intermediate , and then the OH (or NH) group can donate the acidic proton to C3 to complete the [1,3] hydrogen shift and generate the intermediate . Finally, the intramolecular Michael-type addition followed by the elimination of catalyst furnishes the final product. High cis-diastereoselectivities are also predicted for both the two reactions, which is in good agreement with the experimental observations. For the reaction of allenoates with trifluoromethyl ketones, the first proton transfer is found to be the diastereoselectivity-determining step. The cumulative effects of the steric repulsion, electrostatic interaction as well as other weak interactions appear to contribute to the relative energies of transition states leading to the diastereomeric products. On the contrary, in the case of N-tosylbenzaldimines, the Michael-type addition is found to be the diastereoselectivity-determining step. Similarly, steric repulsion, as well as electrostatic interaction is also identified to be the dominant factors in controlling the high cis-diastereoselectivity of this reaction.
State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Zhongshan Road 457, Dalian 116023, P.R. China.
Yan
Y
Qiao
Ke-Li
KL
Han
D000466:Alkadienes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism
D000466:Alkadienes; D007097:Imines; D007659:Ketones; D010720:Phosphines; C044646:phosphine