Possible Mechanisms And Origin Of Selectivities For Phosphine-Catalyzed [2+N] (N=3, 4) Annulations Of Saturated Amines And Delta-Acetoxy Allenoates

The density functional theory (DFT) calculations were performed to gain insights into possible reaction mechanisms and origin of selectivities on phosphine catalyzed [2+3] and [2+4] annulations of saturated amine with allenoate for the first time. The computed results reveal that allenoate prefers to serve as a C3 synthon rather than C4 synthon under phosphine catalysis, and the whole catalytic cycle generally undergoes through eight processes, i. e. (1) adsorption of catalyst, (2) dissociation of AcO- group, (3) deprotonation of saturated amine, (4) nucleophilic attack by the deprotonated amine anion to the electrophilic phosphonium diene intermediate, (5) [1,6]-proton shift, (6) ring closure of five-membered heterocycle, (7) [1,2]-proton shift, and (8) desorption of catalyst and the formation of 3-pyrroline. The fourth step was identified as both chemo- and stereo-selectivities determining step, and the pathway associated with R-isomer is energetically favorable pathway. Further non-covalent interaction (NCI) and Bader's atoms-in-molecules (AIM) analysis reveal that the C-H...O interaction has a significant contribution to the stability of R-configured transition state. The obtained insights should be valuable for understanding the general principle for the detailed mechanism and predicting the origin of the chemo- and stereo-selectivities on the phosphine catalyzed [2+3] and [2+4] annulations of saturated amine with allenoate.