Catalytic, Enantioselective β-Protonation through a Cooperative Activation Strategy

Abstract

The NHC-catalyzed transformation of unsaturated aldehydes into saturated esters through an organocatalytic homoenolate process has been thoroughly studied. Leveraging a unique "Umpolung"-mediated β-protonation, this process has evolved from a test bed for homoenolate reactivity to a broader platform for asymmetric catalysis. Inspired by our success in using the β-protonation process to generate enals from ynals with good E/Z selectivity, our early studies found that an asymmetric variation of this reaction was not only feasible, but also adaptable to a kinetic resolution of secondary alcohols through NHC-catalyzed acylation. In-depth analysis of this process determined that careful catalyst and solvent pairing is critical for optimal yield and selectivity; proper choice of nonpolar solvent provided improved yield through suppression of an oxidative side reaction, while employment of a cooperative catalytic approach through inclusion of a hydrogen bond donor cocatalyst significantly improved enantioselectivity.

Poly(imidazolium) Carbosilane Dendrimers: Synthesis, Catalytic Activity in Redox Esterification of α,β-Unsaturated Aldehydes and Recycling via Organic Solvent Nanofiltration

“…All model imidazolium salts were tested as precatalysts of redox esterification of cinnamaldehyde and benzyl alcohol (Table 1). This reaction is often used as a benchmark allowing facile evaluation of the catalytic performance of newly prepared compounds [43,44]. Preliminary experiments were performed at 100 • C in toluene, with 10 mol% catalyst loading and 10 mol% of the base (DBU); dioctyl phthalate was added as an inert standard to enable accurate quantification of GC-FID data.…”

N‐Heterocyclic Carbene Organocatalysis: Activation Modes and Typical Reactive Intermediates

“…This cooperative catalytic system could improve both of the reaction yield and stereoselectivity when compared with the single NHC-catalyzed processes. [71] Scheme 43 Enantioselective β-protonation via NHC/HBD cooperative catalysis strategy Glorius has demonstrated in 2016 that transition-metal catalysis can be combined with NHC organocatalysis in cooperative fashion (Scheme 44). Asymmetric induction can be realized through the cooperative activation by a chiral NHC with palladium co-catalyst.…”

Kinetic Resolution, Dynamic Kinetic Resolution and Asymmetric Desymmetrization by N-Heterocyclic Carbene Catalysis

“…NHC-catalyzed O-acylative KR, DKR and asymmetric desymmetrization have been reported based on the use of aldehydes as acyl donors. [12][13][14][15] Scheidt and co-workers were able to resolve racemic 1phenylethanol by reaction with cinnamaldehyde in the presence of the NHC derived from chiral 1,3-bis(1-phenylethyl)imidazolium iodide (Scheme 2). 12,13 Sequential protonation of homoenolate 2 and tautomerization produces the chiral acyl azolium 3, which preferentially reacts with the (R)-enantiomer of 1-phenylethanol.…”