Two novel domino NHC-catalyzed spirocyclizations are described herein, enabling the rapid construction of three new carbon-carbon bonds and a quaternary center with high diastereoselectivity. A variety of spiro bis-indane structures are assembled in a single step from simple o-phthaldialdehyde derivatives.

The synthesis of spiro bis-indanes by means of N-heterocyclic carbene (NHC) catalysis is reported. The dimerization of various o-formylchalcone substrates or their combination with phthaldialdehyde derivatives under the catalysis of thiazoliumderived carbenes afforded Stetter-aldol-Michael products and Stetter-aldol-aldol products, respectively. The use of poor Michael acceptors in conjunction with an N-alkyltriazolium-derived catalyst furnished a variety of dibenzo[8]annulene products. This work highlights the interplay of a variety of factors affecting competing pathways in NHC-catalyzed domino reactions.In recent years, N-heterocyclic carbene (NHC)-catalyzed reactions have been the subject of intensive research. 1 In 2009, our group reported the diastereoselective synthesis of indanes via a domino 2 Stetter-Michael reaction. 3,4 We proposed that this reaction proceeds through the addition of an acyl anion equivalent derived from 1 onto an electron-poor olefin 2, which generates an enolate intermediate 3 in situ. Subsequently, the enolate in 3 is trapped intramolecularly by a second electron-poor olefin to furnish the desired indane 4 (Scheme 1).Following the success of this indane synthesis, we became interested in the application of this concept towards the synthesis of benzo[b]furans 7 via a domino acyloin-oxaMichael reaction and isoindolines 8 via a domino azaacyloin-aza-Michael reaction (Scheme 2a). 5 At the outset of our studies, we investigated both domino processes by employing furfural (5) and o-formylchalcone 6a. Unfortunately, neither product 7 nor 8 were obtained. More interestingly, we obtained a complex spirocyclic structure 9a, which is derived from two equivalents of 6a. This exciting discovery allows the formation of three new carbon-carbon bonds and a quaternary center in one synthetic operation. The postulated mechanistic rationale for the formation of 9a is similar to that of the synthesis of indanes (Scheme 2b). Once the acyl anion equivalent I is generated, 6 it attacks the electron-poor olefin portion of a second equivalent of 6a leading to the formation of the enolate intermediate II. An aldol reaction then takes place, 7 along with elimination of the catalyst to furnish intermediate III. Under the basic reaction conditions, ketone III is deprotonated to form enolate intermediate IV, which cyclizes to 10a. Finally, dehydration of this intermediate affords the spiro bis-indane product 9a.In late 2010, we disclosed this highly efficient synthesis of spiro bis-indanes. 8 This work began with studies aimed at finding the optimal reaction conditions and scope of the Stetter-aldol-Michael (SAM) reaction (Table 1). The first step consisted in screening the main families of NHCs (not shown), of which thiazolium salt 11 gave the best results at 30 mol% loading. In order to achieve the best yield and diastereocontrol in this transformation, we surveyed various bases and found 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to be optimum (Table 1, entries 1-5). Using this base, the catalyst loading could ...

Various NHC‐catalyzed domino transformations involving dimerization of o‐formylchalcone substrates or their combination with dialdehyde derivatives (IV) are investigated.

NHC-Catalyzed Spiro Bis-Indane Formation via Domino Stetter-Aldol--Michael and Stetter-Aldol-Aldol Reactions. -(SANCHEZ-LARIOS, E.; HOLMES, J. M.; DASCHNER, C. L.; GRAVEL*, M.; Org. Lett. 12 (2010) 24, 5772-5775, http://dx.doi.org/10.1021/ol102685u ; Dep. Chem., Univ. Saskatchewan, Saskatoon, Sask. S7N 5C9, Can.; Eng.) -Klein