The effects of change of solvent and reaction time, of addition of Li+-chelating agent, and, in some instances, of change of temperature and metallating agent, on the metallation of 2-(2-furyl)-and 2-(N-methylpyrrol-2-yl)oxazolines by alkyl-lithium reagents are explored. Conditions are thereby established for high-yielding syntheses of lithio-intermediates and for control of regioselectivity of metallation. Syntheses of pure samples of 2-(3hydroxyphenylmethyl-2-furyl) -, 2-(5-hydroxyphenylmethyl-2-furyl) -, 2-(3-carboxy-N-methylpyrrol-2-yl)and 2-(5-carboxy-N-methylpyrrol-2-yl) -4,4-dimethyloxazolines, based on the results of these investigations, are reported.FURAN, thiophen, and N-alkylpyrroles undergo electrophilic substitution and metallation predominantly at apositions. This reactivity pattern makes the syntheses of the p-substituted derivatives a challenging problem and any new methodology in this connection is therefore valuable. The bias towards a-electrophilic substitution may sometimes be overcome by the introduction of an electron-withdrawing group at one a-position : 2,4disubstituted derivatives have been prepared by this approach, in favourable cases, but regioselectivity is frequently poor. A second strategy, applicable to pyrroles, requires the use of a bulky N-substituent to restrict access to the a-positions: success is achievable, but only with very large substituents (e.g. t-butyl) and large electrophiles as in the Vilsmeier reaction.2 In 1977, Vecchia and Vlattas recognised that the oxazolino group at an a-position in thiophen could be used to direct metallation into the adjacent @-position with high regioselectivity (Scheme 1) thus providing a new route4 '1. R = 4,4-dimethyloxazolin -2 -y l SCHEME 1 Vlattas' procedure with the 2-(2-thienyl)oxazoline Reageiils: i, BunLi, Et,O, -70-25 " C ; ii, PhCHO
