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

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.