**3.2 Intermolecular Stetter reaction**

The initial intermolecular reaction established by Endres et al. with chiral thiazolium catalyzed reaction of *n*-butanal with chalcones resulted in Stetter product with 40% ee [34, 35] (**Figure 10**).

Rovis et al. contributed in the asymmetric intermolecular Stetter reaction of glyoxamide derivatives as aldehyde component and alkylidene molecule as Michael acceptors [36, 37]. DiRocco and Rovis expanded the reaction of intermolecular

**Figure 9.**

*Some examples of intramolecular Stetter reaction.*

*N-Heterocyclic Carbene Mediated Organocatalysis Reactions DOI: http://dx.doi.org/10.5772/intechopen.100642*

**Figure 10.** *The first intermolecular Stetter reaction by Enders et al.*

#### **Figure 11.**

*Intermolecular Stetter reaction with α,β-unsaturated aldehyde and β-nitrostyrenes.*

Stetter reaction with α,β-unsaturated aldehyde as aldehyde component and β-nitrostyrenes using fluorinatedtriazolium salt (**Figure 11**) [38].

The synthesis of enantiomeric α-amino acid derivative was developed by Glorius et al. using N-alylamidoarylate as Michael accepter [39]. Biju co-workers reported the efficient enantioselective NHC catalyzed intermolecular Stetter reaction of aldehydes with α,β-unsaturated sulfones and vinyl phosphonates [40, 41].

### **3.3 Hydroacylation of enol ethers of double bonds and triple bonds**

Acyl anion reaction has been extended followed by the addition to electron neutral as carbon–carbon multiple bonds. She and Pan explained for the first time using alkyl tosylates (**Figure 12**) and found the selectivity changes when the native substrate with a phenyl group [42]. The reaction resulted in the formation of benzofuranone and the mechanism involving the addition of the Breslow intermediate to the C–C double bond of the enol ether [43].

A very important reaction for the synthesis of chromanones from the intermolecular cyclization of 2-allyloxy benzaldehydes using thiazolium NHCcatalyst by Glorious et al. for the first time [44] (**Figure 13**). Biju et al. showed the coupling of cyclopropenes using achiral triazolium with aryl aldehyde coupling partners (**Figure 14**) [45].

#### **3.4 Annulation reaction**

The extended Breslow intermediate has explored very well especially for the synthesis of heterocyclic compounds. Bode and Glorius reported NHC catalyzed homoenolate reactivity leading to synthesis of useful molecule from simple enal cascade. The reaction involved in the formation of extended Breslow intermediate from enal with carbene followed by 1,2-addition to aryl aldehyde which was then cyclized to deliver the γ-lactone product (**Figure 15**).

Several groups explored NHC catalyzed to synthesize enantioselective γ-lactone [46–48], spirocyclic γ-lactones [49, 50]. [3 + 4] Annulation reaction between enals

**Figure 12.** *Proposed mechanism of hydroacylation reaction of enol ether.*

**Figure 13.** *The intermolecular cyclization of 2-allyloxy benzaldehydes using thiazolium NHC-catalyst.*

**Figure 14.** *The coupling of cyclopropenes using achiral triazolium with aryl aldehyde.*

*N-Heterocyclic Carbene Mediated Organocatalysis Reactions DOI: http://dx.doi.org/10.5772/intechopen.100642*

and o-quinonemethides (**Figure 16**) was reported by Ye et al. in 2013 to obtain dioxolane fused-quinone methides [51].

The [8 + 3] annulation of enals and tropone *via* conjugate addition followed by cyclization afforded a lactone (**Figure 17**), reported by Nair et al. [52].

A number of nitrogen-containing heterocycles generated by homoenolate has explored largely. Synthesis of enantioselective cyclic sulfonyl ketamine annulation [53], β-lactam formation [54], synthesis of pyrazolidinones [55], isoxazolidinone formation [56] and mainly nitroso coupling reactions [57] and others have many

**Figure 16.** *[3 + 4] Annulation reaction between enals and o-quinonemethides.*

**Figure 17.** *[8 + 3] Annulation of enals and tropone.*

**Figure 18.** *The first NHC generated homoenolate in the formation of cyclopentenes.*

synthetic applications. The first NHC generated homoenolate further utilized in the formation of cyclopentenes was introduced by Nair et al. in 2006 [58, 59]. The homoenolate intermediate reacts with chalcones generates allyloxide, further cyclized 4-membered β-lactone which decarboxylate to provide cyclopentene (**Figure 18**).
