Mechanism of Phosphine‐Catalyzed Allene Coupling Reactions: Advances in Theoretical Investigations

Abstract

Organocatalysis has emerged as an effective strategy for chemical synthesis. Within this area, phosphine-catalyzed coupling reactions have attracted considerable attention because of their versatility and wide range of applications in the construction of new C-C bonds. Recently, various experimental studies on the phosphine-catalyzed coupling reaction of allenes have been reported, and mechanistic and computational studies have also progressed considerably. As a nucleophile, phosphine can react with an allene to form a zwitterionic phosphoniopropenide intermediate. After stepwise cycloaddition and proton transfer, the phosphine catalyst can be regenerated by C-P bond cleavage. Alternatively, the zwitterionic phosphoniopropenide intermediate could also be protonated by a Brønsted acid to generate a phosphonium intermediate, which can be used to construct new C-C bonds by electrophilic addition. In this review, we have summarized details of mechanistic studies of phosphine-catalyzed allene coupling reactions that follow these two reaction modes. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of the phosphine-catalyzed allene coupling reaction are also discussed in this review.

Phosphine‐Promoted Amide Bond Formation Reactions from Carboxylic Acids and Tetraalkylthiuram Disulfides

“…Then, the anhydride intermediate undergo a decarboxylation (decarbonylsulfide, ‐COS) process leading to the desired amide product ,,, Further studies on the details of the mechanism and the related applications for this protocol are undergoing in our lab.…”

Unraveling the Selectivity Patterns in Phosphine-Catalyzed Annulations of Azomethine Imines and Allenoates

“…Therefore, the ambident nature of this reactive species introduces a challenging problem, namely, the control of regioselectivity in these processes. Previous calculations suggest that the regioselectivity of the overall process takes place in the Michael addition step as the α-attack is kinetically favored over the corresponding γ-addition. , For instance, the computed activation barrier difference ΔΔ G 298 ⧧ = 1.2 kcal/mol at the B3LYP/6-31+G* level for the PMe 3 -catalyzed reaction involving methyl acrylate and H 2 CCCH­(CO 2 Me) predicts an α/γ ratio of 79:21, a value close to the experimental ratio of 85:15 reported by Zhang and Lu …”

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

“…Subsequently, we demonstrated application of this powerful catalyst in asymmetric [3 + 2] annulation between imines and allenoates . Although the mechanisms of phosphine-catalyzed [3 + 2] annulations have been investigated experimentally and computationally in previous studies, elucidation of stereoselectivities of phosphine-promoted catalytic processes is still very limited. In our initial disclosures, we proposed that our bifunctional phosphine catalysts interact with substrates, e.g., acrylate or imine, through hydrogen bonding interactions, which were believed to be the key to the observed stereoselectivity.…”