Deformative Transition of the Menschutkin Reaction and Helical Atropisomers in a Congested Polyheterocyclic System

Abstract

A 4,7-phenanthroline polycyclic 1A designed for probing the limits of the Menschutkin reaction was synthesized in a six-step sequence. The rotational barrier of the phenyl ring nearby the N-methyl group in rac-2A was estimated to be >= 18.1 kcal/mol from VT-NMR experiments, making them a new type of helical atropisomer. The methylation rate constants of 9 and 1A with MeI was found to be 2.22 x 10 (4) and 9.62 x 10 (6) s(1) mol(1) L, respectively; thus, the formation rate of (P/M)-2A is one of the slowest rates ever reported for a Menschutkin reaction. The N-methyl protons in (P/M)-2A exhibit a significant upfield shift (Delta delta 1.0 ppm) in its H-1 NMR, compared to those without a nearby phenyl, indicating a strong CH-pi interaction is involved. Conformational flexibility in dipyridylethene 9 is clearly shown by its complexation with BH3 to form helical atropisomers (P,P/M,M)-10. The pKa values of the conjugate acids of 1A and 9 in acetonitrile were determined to be 4.65 and 5.07, respectively, which are much smaller compared to that of pyridine 14a (pK(a) = 12.33), implying that the basicity, nucleophilicity, and amine alkylation rates of 1A and 9 are markedly decreased by the severe steric hindrance of the flanking phenyl rings in the polyheterocycles.