Intramolecular reactions crossed-benzoin condensation

Unfortunately, the chiral bicyclic triazolium salt that had been found to be an excellent catalyst for the enantioselective intermolecular benzoin condensation proved to be ineffective in the intramolecular reaction. In searching for alternative catalysts, we synthesized the novel triazolium salts 19 and 20, starting from easily accessible enantiopure polycyclic y-lactams (Schemes 9.4 and 9.5) that finally delivered good results in the enantioselective intramolecular cross-benzoin condensation [35]. 

The substrates of the enantioselective intramolecular crossed benzoin condensation were varied to widen the scope of the reaction. Promising results were... 

A review of the asymmetric Stetter and asymmetric benzoin reactions focuses mainly on two classes of highly successful catalysts NHCs and metallophosphites. A new NHC, pyrido[l,2-a]-2-ethyl[l,2,4]triazol-3-ylidene (99), is a powerful catalyst of benzoin condensation in the presence of potassium f-butoxide. A DFT study of the mechanism suggests that the f-butanol solvent is explicitly involved. o-Phthalaldehyde chalcones (100) undergo intramolecular aldehyde-ketone crossed-benzoin condensation to naphthalenone tertiary alcohols (101) in yields up to 94%, in 20 min, using NHC catalysis. ... 

Modified benzoin condensations in which the acyl acceptor is not an aldehyde constitute a variation of the classical cross-benzoin condensation. Aldehydes and ketones can be coupled in an intramolecular annulation reaction to give tertiary a-hydroxyketones. The selective cross-coupling of... 

Later, the same group expanded this chemistry further by developing a cascade Michael addition/cross-benzoin condensation sequence of enolizable aldehydes 43 and activated enones 44 [27]. The reaction proceeded by means of enamine activation of aliphatic aldehydes to induce an asymmetric Michael addition to activated enones followed by an intramolecular cross-benzoin condensation (Scheme 9.30). Compared with their previous work, complex cyclopentanones with complementary substitution patterns were observed. Screening of the reaction parameters revealed that the chiral triazolium catalyst was necessary to ensure a satisfactory stereochemical outcome. Further mechanistic insights indicated that the high diasteroselectivity observed attributed to the secondary amine-induced epimerizing of the a-position of intermediate aldehyde 89. 

In contrast to the previously described intermolecular condensation reaction, intramolecular crossed benzoin reactions have been developed much less for a long time (Cookson and Lane 1976). 

Enders D, Kallfass U (2002) An efficient nucleophilic carbene catalyst for the asymmetric benzoin condensation. Angew Chem Int Ed 41 1743-1745 Enders D, Niemeier O (2004) Thiazol-2-ylidene catalysis in intramolecular crossed aldehyde-ketone benzoin reactions. Synlett 2004 2111-2114 Enders D, Niemeier O, Balensiefer T (2006) Asymmetric intramolecular crossed-benzoin reactions by N-heterocyclic carbene catalysis. Angew Chem Int Ed 45 1463-1467... 

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