Eighteen rutaecarpine derivatives were synthesized through Cp*IrCl 2 2 ‐catalyzed cyclization of indole‐quinazoline precursors with ethylene glycol in 43%–83% isolated yields. Structural characterization was performed using 1 H & 13 C NMR spectroscopy, high‐resolution electrospray ionization mass spectrometry (HRESI‐MS), and X‐ray diffraction (XRD) analysis, with data corroborated by literature comparisons. Mechanistic investigations revealed a hydrogen‐borrowing cascade facilitating sequential C‐alkylation and N‐alkylation, wherein regioselectivity was governed by an iridium‐chelated intermediate. Density functional theory (DFT) calculations provided further validation of the proposed mechanism. This methodology establishes an environmentally benign approach for synthesizing bioactive alkaloids while elucidating fundamental mechanistic aspects of transition‐metal‐mediated heterocycle fusion.
Feng et al. (Tue,) studied this question.