Counterion-Enhanced Pd/Enamine Catalysis: Direct Asymmetric α-Allylation of Aldehydes with Allylic Alcohols by Chiral Amines and Achiral or Racemic Phosphoric Acids

Abstract

We report a straightforward and efficient Pd/enamine catalytic procedure for the direct asymmetric α-allylation of branched aldehydes. The use of simple chiral amines and easily prepared achiral or racemic phosphoric acids, together with a suitable Pd-source resulted in a highly active and enantioselective catalyst system for the allylation of various α-branched aldehydes with different allylic alcohols. The reported procedure could provide an easy access to both product antipodes. Furthermore, two possible orthogonal derivatizations of the enantioenriched aldehydes were performed without any decrease in enantioselectivity.

Recent DFT Calculations on the Mechanism of Transition‐Metal‐Catalyzed C−O Activation of Alcohols

“…In addition to the mechanism in Figure 24, we would also suggest the readers of this review paper pay attention to the chiral phosphonic acid‐assisted activation of allyl alcohols, which was proposed in some earlier experimental studies [78–80] …”

Synergistic Strategies in Aminocatalysis

“…The employ of phosphoric acid 103 could serve as counterion for this cationic metal species (Scheme 24). [48] …”

Linear Regression Model for Predicting Allyl Alcohol C–O Bond Activity under Palladium Catalysis

“…Therefore, numerous preactivation strategies of allyl alcohol have been developed, which usually convert hydroxyl groups into the electron-withdrawing ester or ether groups to weaken the C–O bonds (Scheme a) but inevitably bring about complicated operation procedures, inferior atomic utilization, and the other shortcomings. To overcome these problems, in situ activation strategies for allyl alcohols have been gradually developed, in which the electron-deficient species, including Lewis or Brønsted acids, are used to activate C–O bonds by forming hydrogen bonds or Lewis acid–base interaction with the hydroxyl groups of allyl alcohols, such as alkyl alcohols, phenol derivatives, alkyl carboxylic acids, benzoic acid derivatives, phosphonic acid, and some boron reagents (Scheme b). In this way, the transition metal catalyst is coordinated with the double bond of allyl alcohol ( INA ), and then, the activator is complexed with the hydroxyl group through the intermolecular interaction to form intermediate INB , which is then converted to the metal allyl zwitterion species INC via C–O bond cleavage for the subsequent transformation. , …”