Aryl aldehydes, Betti reaction

The multicomponent reaction between 2-naphthol (1), aryl aldehydes and amines is known as the Betti reaction. ... 

Either ammonia or a variety of amine substrates can be used to prepare the product 2, widely called a Betti base. Various substitution patterns are tolerated on both the naphthol and aryl aldehyde component. While the reaction was classically performed in ethanol, a variety of solvents, and using the substrates neat are also possible. Increased rates have been observed using acid catalysis. The reaction results in a product 2 with a benzylic chiral center, which as such can be resolved into its enantiomers. Alternatively, chiral amines can be used to control the stereoselectivity of the process. Enantiomerically pure Betti bases have shown potential as chiral auxiliaries and as ligands in asymmetric reactions. ... 

A number of studies have also been reported using enantiopure Betti base derivatives as chiral ligands in asymmetric reactions. For example, Chan et al. reported that Betti base 33 was a useful ligand for the additional of diethyl zinc to aryl aldehydes, with excellent enantiomeric excesses... 

The multicomponent reaction between 2-naphthol, aryl aldehydes and ammonia or amines yields aminobenzylnaphthols in a process known as the Betti reaction, which was first uncovered at the beginning of the 20th century. The aminobenzylnaphthols could be easily resolved into their enantiomers. After a long silenee, the results of our research a decade ago on this useful reaction and on the chiral materials produced has stimulated further work in a number of other laboratories. As a result, novel applications of the Betti reaction to produce new chiral aminobenzylnaphthols were reported together with the evaluation of these chiral bases in asymmetric s5mthesis. 

The marked temperature dependence of the enantioselective addition of diethylz-inc to aryl aldehydes catalysed by (S)-2-(3-methyl-2-pyridyl)-3,5-di-r-butylphenol displays an inversion temperature which is affected by the para-substituent of the aldehyde. Enantioselectivities of up to 78% ee for addition of diethylzinc to ben-zaldehyde have been achieved using (15, 45)-2,5-diazabicyclo[2.2.1]heptane derivatives as catalysts however, a study of chiral compounds related to the Betti base (51a) has identified r-aminonaphthol (51b) as a much more effective catalyst (99% ee) for this reaction. The catalytic efficiency of chiral pyrrolidine derivatives and (25)-3-eJt -(dimethylamino)isobomeol have also been explored. 

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