Nitrene C–H Bond Insertion Approach to Carbazolones and Indolones. Formal Total Synthesis of (–)-Methyl N-Decarbomethoxychanofruticosinate, (–)-Aspidospermidine and (+)-Kopsihainanine A

A new, modular platform for access to 1,2,3,9-tetrahydro-4H-carbazol-4-ones (H4-carbazolones) and 3,4-dihydrocyclopenta[b]indol-1(2H)-ones (H2-indolones) is disclosed from readily accessed 2-arylcycloalkane-1,3-diones (6- and 5-membered). These precursors were prepared through a Cu-catalyzed arylation of 1,3-cyclohexanediones with aryl iodides or via a ring-expansion of aryl succinoin derivatives. Activation of a single carbonyl group in the diones, a highly regioselective reaction with unsymmetrical 2-arylcyclohexane-1,3-diones, and subsequent azidation gave 3-azido-2-aryl-cycloalk-2-en-1-ones. The regioselectivity was computationally assessed. Finally, a Rh-catalyzed nitrene/nitrenoid insertion into the ortho-C–H bond of the aryl moiety, gave the H4-carbazolones and H2-indolones, products that are of high synthetic value. One carbazolone synthesized was elaborated to a key intermediate for the formal total synthesis of N-decarbomethoxychanofruticosinate, (–)-aspidospermidine, (+)-kopsihainanine A. With 2-aryl-1,3-cycloheptanedione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was accomplished in a facile manner. However, the Rh-catalyzed reaction led to some unusual observations, with an azirine as a major product. DFT computations were performed in order to understand the differences in reactivities of the 5- and 6-membered -azido enones in comparison to the 7-membered analogue.