Theoretical Study on Asymmetric [2 + 2] Cycloaddition of an Alkynone with a Cyclic Enol Silyl Ether Catalyzed by a Chiral N,N′-Dioxide-Zn(II) Complex

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The reaction mechanism and enantioselectivity of the asymmetric [2 + 2] cycloaddition between an alkynone (R1) and a cyclic enol silyl ether (R2) were studied theoretically by the DFT method at the B3LYP-D3(BJ)/6-311G**(CH2Cl2,SMD)//B3LYP-D3(BJ)/def2-SVP(CH2Cl2,SMD) theoretical level. The noncatalytic reaction occurred via a stepwise mechanism. The first C–C bond was constructed by coupling two pseudo radical centers generated at the most nucleophilic C2 atom in the cyclic enol silyl ether and the most electrophilic terminal Cβ atom in the alkynone, which was responsible for the regioselectivity of the reaction. The counterion NTf2– could stabilize the Zn(II) complex by coordinating to the center metal, forming a high-reactivity hexacoordinate Zn(II)-complex intermediate. The bulky CF3 group in the NTf2– ion adjusted the blocking effect of o-iPr in aniline of the ligand toward the reactive site (that is, the Cβ atom in the alkynone) and induced the si face of the cyclic enol silyl ether to approach the alkynone from its less hindered re face, achieving a high enanotioselectivity of products. The Pauli repulsion between the Zn(II)-associated moiety and cyclic enol silyl ether fragment was the main contributor to the stereodifference of the two competing pathways in chiral N,N′-dioxide-Zn(II)-catalyzed [2 + 2] cycloaddition. The unfavorable steric repulsion between the o-iPr group of aniline in the ligand and tert-butyldimethylsilyl (TBS) in the cyclic enol silyl ether along the re face path translated into a more destabilizing ΔEPauli value, leading to the predominant cycloaddition product (P-RR) observed in experiments. Variation of the linkage and chiral backbone could affect the repulsion among the o-iPr in the ligand, the counterion NTf2–, and substrates, leading to different stereochemical outcomes. These results are in good agreement with experimental observations.