Syntheses of Chroman-2-ones and α-Amino Acids through a Diastereoselective Domino Reaction

5 years ago

Syntheses of Chroman-2-ones and α-Amino Acids through a Diastereoselective Domino Reaction

D. Balaji Chandrasekhar, Shwu-Chen Tsay, Jih Ru Hwu, Tapan K. Pradhan

Many 3-aminochroman-2-ones and β,β-diarylalanines exhibit significant biological activities. A new method was thus developed for the syntheses of these compounds with high efficiency and diastereoselectivity. First, treatment of various phenols with Erlenmeyer–Plochl (Z)-azlactones and AlCl₃ in toluene produced the desired cis-3-aminochroman-2-ones in 65–90% yields under kinetic control. This coupling reaction involved a domino process of Friedel–Crafts alkylation, 1,4-AlCl₃ shift, transesterification, and protodealumination in a “single-flask.” The corresponding products, however, were not generated by replacement of AlCl₃ with a protonic acid. Second, hydrolysis of the resultant 3-amino-4-arylchroman-2-ones by NaHCO₃ in a mixture of THF and water gave α-(N-benzoyl)amino acids. Further deprotection of these isolated compounds by use of hydrochloric acid (12 N) in methanol afforded the desired free amino acids in 80–88% yields. Under these optimized conditions, epimerization did not occur at the α carbons of α-(N-benzoyl)- and free α-amino acids. These new findings provide a convenient way to generate 3,4-disubtituted chroman-2-ones and β,β-diarylalanine derivatives with very high stereoselectivity.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00260

DOI: 10.1021/acs.joc.7b00260