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

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
× 10–4 and 9.62 × 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 (Δδ 1.0 ppm) in its 1H NMR, compared
to those without a nearby phenyl, indicating a strong CH-π 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 (pKa = 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.