A Practical Route to Regiospecifically Substituted (R)- and (S)-Oxazolylphenols

Abstract

New, diversely substituted phenolic oxazolines 14a−d and 15a−d were prepared by two complementary routes A and B, starting from salicylic derivatives 4−7 and various enantiomerically pure 1,2-amino alcohols 13a−d. In route A, the 1,2-amino alcohols 13a−d were directly condensed with the salicylic acids 5 and 7, using the Appel reaction, whereas in route B the amino alcohols 13b−d were treated with the 2-hydroxybenzonitriles 4 and 6, under Witte−Seeliger conditions. The latter route was advantageous for L-valinol 13b and L-tert-leucinol 13c, while route A was the method of choice for the new, sterically demanding amino alcohol 13a, prepared from D- and L-serine. The nitro group in the salicylic derivatives 5 and 6 was introduced by means of a regiospecific ipso substitution of a tert-butyl group by nitric acid. The structure of the nitro product 5 was unambiguously assigned by NOE spectroscopy on the basis of the recently developed DPFGSE-ROE pulse sequence.