Mechanism and Origin of Stereoselectivity in Chiral Phosphoric Acid‐Catalyzed Aldol‐Type Reactions of Azlactones with Vinyl Ethers

Abstract

The precise mechanism of the chiral phosphoric acid‐catalyzed aldol‐type reaction of azlactones with vinyl ethers was investigated. DFT calculations suggested that the reaction proceeds through a Conia‐ene‐type transition state consisting of the vinyl ether and the enol tautomer of the azlactone, in which the catalyst protonates the nitrogen atom of the azlactone to promote enol tautomerization. In addition, the phosphoryl oxygen of the catalyst interacts with the vinyl proton of the vinyl ether. The favorable transition structure features dicoordinating hydrogen bonds. However, these hydrogen bonds are not involved in the bond recombination sequence and hence the catalyst functions as a template for binding substrates. From the results of theoretical studies and experimental supports, the high enantioselectivity is induced by the steric repulsion between the azlactone substituent and the binaphthyl backbone of the catalyst under the catalyst template effect.

Dynamic parallel kinetic resolution of α-ferrocenyl cation initiated by chiral Brønsted acid catalyst

“…Thus, TSs and TSr feature multi-coordinating hydrogen bonds, which are an essential interaction mode observed widely in CPA-catalysed reactions 5–7 and are beneficial for controlling the stereochemical outcome. 20,21 Among the interactions observed, it is noteworthy that the hydrogen bond is formed between the vinyl proton of cation A and the oxygen atom of chiral conjugate base ( R )- 2− in both transition states TSs and TSr .…”

Mechanism and Origin of Enantioselectivity in Bifunctional Squaramide‐Catalyzed α‐Thiolation of Azlactones

“…The main interactions during this proposal occur between the cinchona nitrogen and the azlactone enol hydrogen and hydrogen bonding interactions between the squaramide and the succinimide. The last proposal (Step 2C) consists of a less common proposal involving the formation of a key interaction between the azlactone enolate nitrogen atom and the ammonium salt of the catalyst, resulting in a Münchnone‐type activation [16–18] . This kind of activation mode has been proposed as the most plausible mechanism in recent studies involving azlactone ring transformations and has been attracting great interest in the literature [19,20] .…”

“…A second possibility (Step 2B) involves the acid-base reaction between the azlactone enolate and the ammonium salt of the catalyst, resulting in the formation of an enol tautomer intermediate, which is commonly evoked as a key intermediate during azlactone transformations. [16][17][18] The main interactions during this proposal occur between the cinchona nitrogen and the azlactone enol hydrogen and hydrogen bonding interactions between the squaramide and the succinimide. The last proposal (Step 2C) consists of a less common proposal involving the formation of a key interaction between the azlactone enolate nitrogen atom and the ammonium salt of the catalyst, resulting in a Münchnone-type activation.…”

Chiral phosphoric acid-catalyzed stereodivergent synthesis of trisubstituted allenes and computational mechanistic studies

“…4a ). Therefore, a Münchnone-type mode 59 , 60 , 66 ( mode B ) was proposed and the correct syn -addition outcomes were achieved depended on the achiral DMP catalyst (Fig. 4c ).…”

“…1b ). Herein, we report an enantioselective and diastereodivergent synthesis of trisubstituted allenes via asymmetric conjugate additions of activated 1,3-enynes by oxazolones 57 – 60 enabled by CPA catalysis, in which the diastereodivergent construction of the allenic axial chirality is realized by modifications of CPA catalysts (Fig. 1c ).…”