Acyl azolium, unsaturated

The Scheidt group reported a highly diastereo- and enantioselective NHC-catalyzed reaction of a,p-unsaturated aldehydes with nitrones to afford y-amino esters. It is postulated that a rare six-membered heterocycle is generated as the initial product of the reaction, which gives the final y-amino ester product upon the addition of an alcohol. The mechanism for this reaction involves the addition of the homoenolate equivalent to the nitrone as the stereochemical-determining step, and catalyst turnover is promoted by an intramolecular acylation after the tautomerization of enol to acyl azolium (Scheme 7.60). 

The Bode group documented detailed research on the asymmetric NHC-catalyzed annulation reaction of ynals and stable enols (kojic acid) to afford enantioenriched dihydropyranone products in excellent yields. Mechanistically, the key a,p-unsaturated acyl azolium intermediate was accessible via an NHC-catalyzed redox neutral reaction of ynals. The annulation occurs via... 

The Biju group developed a highly enantioselective NHC-catalyzed lac-tonization of 2-bromoenals with enolizable aldehydes proceeding via the chiral a,p-unsaturated acyl azolium intermediates. The reaction offers a new approach for the asymmetric synthesis of synthetically important 4,5-disubstituted dihydropyranones. Mild reaction conditions, relatively low... 

Recently, the Biju group demonstrated a highly enantioselective NHC-eatalyzed synthesis of functionalized cyclopentenes via o,p-unsaturated acyl azolium intermediates. This organo cascade reaetion of modified enals with malonic ester derivatives having a y-benzoyl group involves the Michael/ intramolecular aldol/p-lactonization/decarboxylation sequence to deliver functionalized cyclopentenes in good yields and excellent ee values (up to 85% yield and >99% ee) (Scheme 7.105). 

As their continued work on the development of a practical NHC-catalyzed stereoselective cascade reaction based on a,p-unsaturated acyl azolium... 

The Bode group disclosed NHC-catalyzed highly enantioselective annulations of a,P,P -trisubstituted enals with cyclic sulfonylimines. Mechanistically, it is proposed that the combination of enal and free NHC leads to the formation of the Breslow intermediate, which is oxidized to form the key a,p-unsaturated acyl azolium. Tautomerization between the imine and the enamine occurs readily in the presence of base, and the enamine is intercepted by the key a,p-unsaturated acyl azolium to form a hemiaminal which further engages in a Stork-Hickmott-Stille-type annulation via a tight-ion-pair/aza-Claisen type transition state. Lactam formation follows the protonation of enolate and brings about catalyst turnover to complete the catalytic cycle (Scheme 7.113). 

In 2013, the Chi group realized an NHC-catalyzed asymmetric p-functional-ization reaction of aldehydes via the transformation of saturated aldehydes to formal Michael acceptors via double oxidation. By using the catalyst derived from the chiral amino indanol triazolium salt in combination with quinone as the oxidant, the p-aryl substituted saturated aldehydes were converted to the o,p-unsaturated acyl azolium intermediates which further reacted with 1,3-dicarbonyl compounds or p-keto esters to generate the corresponding 5-lactones. It was found the use of LiCl and 4 A MS as additives was beneficial to improve the ee s of the products. Notably, the p-alkyl substituted saturated aldehydes were not viable substrates, probably due to the reduced acidity of the p-C—H bonds (Scheme 7.118). 

Ynals have also been substrates for similar reactions via the intermediacy of a,p-unsaturated acyl azoliums (126) generated by the base-mediated reaction between ynals (125) and acyl azolium (124). All derivatives have been unambiguously characterized by spectroscopic means (Scheme 15), and hemiacetals of (126) have been demonstrated to be the kinetically important intermediates not only in the annulation reactions but also in the acylation reactions of (125). 

SCHEME 5.46 Catalytic generation of a,P-unsaturated acyl azolium 151. 

Mahatthananchai J, Zheng P, Bode JW (2011) Observation and mechanistic investigation of a,P-unsaturated acyl azoliums liom N-heterocyclic carbene catalyzed reactions. Angew Chem Int Ed 50 1673-1677... 

Acyl azoliums generated from enals have been converted to cyclopropyl carboxylic esters with ee < 99% by reaction with sulfur ylides. Some FLPs have been found to i react by conjugate P/B addition to unsaturated ketones and esters, whereas 1,2-addition to corresponding aldehydes is usual. ... 

Reaction of a chiral A-heterocyclic carbene catalyst and a,/ -unsaturated aldehyde gives , -unsaturated acyl azolium that participates in enantioselective annulation via a Coates-Claisen rearrangement that invokes the formation of a hemiacetal before a sigmatropic rearrangement to give dihydropyranone products (Scheme 14)7 ... 

Building on the formal redox esterification of ynals discovered by Zeitler [104], the group of Bode showed that the unsaturated acyl azolium intermediate could be trapped by enols to yield dihydropyranones 128 enantioselectively (Scheme 18.24) [11a]. Mechanistically, the enol 127 could perform a 1,4-addition on the acyl azolium followed by a lactonization. Instead, the authors postulate a 1,2-addition/ Coates-Claisen rearrangement pathway that is supported by kinetic and computational studies [105]. Another notable finding was a strong counterion dependence on the reaction rate in the absence of added base. The data presented is consistent with the chloride ion in 74 effectively playing the role of base to deprotonate the triazoUum cation. 

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