Squaramides catalysts derived from

The group of Aleman and Parra reported the AFC reaction of phenol with Z-bromonitroalkene followed by a nucleophilic substitution on the bromide carbon. With 10 mol% of squaramide catalyst 157, the chiral trans-dihydroarylfuran derivatives 158 were efficiently synthesized from Z-bromonitroalkene and naphthol or phenol derivatives with moderate to good yields (28-94%) and excellent enantioselectivity (66-98% ee). The key of this eat-alytic system is the neutralization of the generated HBr by a stoichiometrie eo-base (Scheme 6.73). 

In 2012, Maikov and coworkers reported a similar strategy for the synthesis of spirocyclopropanes bearing two quaternary centers. In this approach, 2-chloroacetoacetates (49) reacted with 17c via a Michael/a-alkylation domino reaction (Scheme 10.16) [22]. The reaction was catalyzed by bifunctional Brpnsted Acid-Lewis base X. The final spirocyclopropanes 50 were obtained under optimized conditions in good yields and excellent diastereo and enantioselectivities. A similar approach was developed by the same research group using 3-chlorooxindoles (51) instead of 2-chloroacetoacetates [23]. This time, the catalyst was a bifiinctional squaramide-tertiary amine XI derived from cinchona alkaloids, rendering the final spirocyclopropanes 52 in good yields and excellent enantioselectivities. 

A bifunctional squaramide catalyst (460) has been utilised in the efficient and highly regio- and stereoselective synthesis of optically active dihydropyran phosphonates (457) by dual activation of both substrates used in the reaction. Thus, the hetero-Diels-Alder reaction of aliphatic and aromatic a,p-unsaturated acyl phosphonates (455) and a,(3-unsaturated aldehydes (456) afforded dihydropyran derivatives (457) in good yields ranging from 52% to 84% and up to 92% ee. The potential of the reaction has been also demonstrated by transformation of the products (457) into valuable and complex synthons (458) and (459) bearing five stereogenic centers (Scheme 138). ... 

Song and coworkers further utilized squaramide 33 for methanolytic desym-metrization of meso-glutaric anhydrides (Scheme 10.35) [113, 114]. The authors attributed the high enantioselectivity to the fact that the cinchona-derived dimeric squaramide catalyst does not self-associate. The catalyst can be easily recovered from the reaction mixture after extractive acid/base work up. A thiourea-catalyzed version of this process had been reported by the same authors in 2008 [115]. 

In 2012, Sun et al. established an enantioselective construction of spirocyclopentane bioxindoles from methyleneindolinones 54b and 3-substituted oxindoles 171 via a Michael-alkylation sequence (Scheme 2.47). The chiral 1,2-diammocyclohexane-derived squaramide 172 was found to be the best choice of the catalyst, affording the desired products 173, containing three conhguous stereocenters in good stereoselectivihes [66]. 

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