Toward a Predictive Understanding of Phosphine-Catalyzed [3 + 2] Annulation of Allenoates with Acrylate or Imine

Abstract

Both theoretical and experimental studies were performed to explore the mechanism, regioselectivity, and enantioselectivity of phosphine-catalyzed [3 + 2] annulation between allenoates and acrylate or imine. Using density functional theory computations, we predicted that the enantioselective determining step is the nucleophilic addition of acrylate or imine to the catalyst-activated allenoate. In the key step, we proposed two hydrogen bonding interaction models (intermolecular H-bond model and intramolecular H-bond model). For acrylate substrates, the reaction proceeds via the intramolecular H-bond model and the strong noncovalent interactions between the 2-naphthyl ester moiety lead to the re-face attack pathway being more favorable. For imine substrates, the intermolecular H-bond model operates. In the annulation process, the bulky n-propyl oriented toward a crowded, sterically demanding environment plays a significant role in asymmetric induction. The theoretical calculation results agreed with experimental observations, and these results provide valuable insight into catalyst design and understanding of mechanisms of related reactions.

Phosphine-Catalyzed Stereoselective Dearomatization of 3-NO2-Indoles with Allenoates

“…Interestingly, the use of allenes in umpolung-type dearomatizations of indoles is still unknown. However, we thought that by switching from electron-rich to electron-deficient allenes (i.e., allenoates) we could match the intrinsic electrophilic character of nitro-indoles with the well-known nucleophilic activation of allenoates. − Eventually, an interesting [3 + 2]-type dearomative cycloaddition could occur, leading to densely functionalized C(2)/C(3)-fused polycyclic indoline derivatives 3 (Figure ). However, numerous regiochemical (α-addition vs γ-addition, 3 vs 3′ ) as well as stereochemical issues can theoretically challenge the process, making the design and optimization of both the catalytic systems and the reaction parameters a pivotal aspect of the whole methodology.…”

Dielectrophilic Allenic Ketone-Enabled [4 + 2] Annulation with 3,3’-Bisoxindoles: Enantioselective Creation of Two Contiguous Quaternary Stereogenic Centers

“…Finally, another intramolecular proton transfer followed by regeneration of the phosphine catalyst furnishes the desired [4 + 2] annulation product. To rationalize asymmetric induction, we believe that amide and carbamate moieties of the catalyst interact with the bisoxindole substrate through hydrogen bonding interactions and thus direct the addition of anionic bisoxindole to phosphonium intermediate I , leading to the formation of the observed stereoisomer …”

Control of Selectivity in Homogeneous Catalysis through Noncovalent Interactions

“…[78][79][80] According to the proposed mechanism, the negative charge-assisted intramolecular hydrogen bond stabilized phosphonium enolate intermediate, generated from the nucleophilic attack of the phosphine catalyst at the benzyl buta-2,3-dienoate, approaches the naphthalen-2-yl 2-phenylacrylate from its Re face to produce the major stereoisomer 3-benzyl 1-(naphthalen-2-yl) (S)-1phenylcyclo-pent-3-ene-1,3-dicarboxylate (yield 95 %, ee 74 %, Scheme 5). [78,80] In the case of (E/Z)-N-butylidene-P,P-diphenyl-phosphinic amide, the selectivity and rate determining step are controlled by the intermolecular hydrogen bonds between the bifunctional NÀ H donor centers of the catalyst and the O=P moiety of the substrate (Scheme 5). [79,80] In addition, due to the bulky n-propyl group the preferential orientation of the cis conformation of (E/Z)-N-butylidene-P,P-diphenyl-phosphinic amide supports a H-bonded intermediate and accelerates the intramolecular delivery of the phosphonium enolate to the imine (Scheme 5).…”

“…[78,80] In the case of (E/Z)-N-butylidene-P,P-diphenyl-phosphinic amide, the selectivity and rate determining step are controlled by the intermolecular hydrogen bonds between the bifunctional NÀ H donor centers of the catalyst and the O=P moiety of the substrate (Scheme 5). [79,80] In addition, due to the bulky n-propyl group the preferential orientation of the cis conformation of (E/Z)-N-butylidene-P,P-diphenyl-phosphinic amide supports a H-bonded intermediate and accelerates the intramolecular delivery of the phosphonium enolate to the imine (Scheme 5).…”