Synthesis and optical resolution of axially dissymmetric pyrroles and pyrocolls: new catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes

Abstract

The novel axially dissymmetric pyrroles, 4-methyl-3-(2′-methoxy-1′-naphthyl)pyrrole-2-carboxylates 1 and 4-ethyl-3-(10′-methoxy-9′-phenanthryl)pyrrole-2-carboxylates 3 were synthesized from the corresponding nitroalkenes and ethyl isocyanoacetate. Optical resolution of compounds 1 was achieved via crystallization of a diastereoisomeric mixture of the (R)-1-phenylethyl esters 1d, while the antipodes of compound 3b spontaneously resolved upon crystallization of the racemate. The rotational barrier (ΔG‡) at 25 °C about the pyrrole–phenanthrene bond in compound 3b (160 kJ mol^–1) was 30 kJ mol^–1 higher than that about the pyrrole–naphthalene bond in compound 1b. The carboxylate 1b or 3b lost optical activity upon lactonization, while the resulting lactone 2 opened diastereoselectively by reaction with lithium (S)-1-phenylethylamide. The antipodes of compounds 1a and 3a were converted respectively without racemization into axially dissymmetric pyrocolls, 1,6-bis(2′-hydroxy-1′-naphthyl)-2,7-dimethylpyrocoll 5a and 2,7-diethyl-1,6-bis(10′-hydroxy-9′-phenanthryl)pyrocoll 6a, both of which effectively catalysed enantioselective addition of Et₂Zn to aromatic aldehydes.