Tandem Transformation of Indazolones to Quinazolinones through Pd-Catalyzed Carbene Insertion into an N–N Bond

Abstract

Serendipitous and expedite transformation of 1-aryl- and 2-aryl-1,2-dihydro-3H-indazol-3-ones to 1,2-di(hetero)aryl- and 2,3-di(hetero)aryl-2,3-dihydroquinazolin-4(1H)-ones, respectively, was achieved in high efficiency by reacting them with aldehydic N-tosylhydrazones. The protocol proceeded through a cascade process involving base-mediated Pd-carbenoid generation by the decomposition of N-tosylhydrazones, nucleophilic attack of indazolone on the Pd-carbenoid complex, and intramolecular ring expansion via N–N bond cleavage. The utility of the strategy is demonstrated toward the synthesis of bioactive NPS 53574, a calcium receptor antagonist.

Recent Update on Alkylation of Indole and Its Derivatives Using N‐Tosylhydrazone

“…In pathway A, the ionization of 42 is facilitated by a Lewis acid, resulting in the formation of propargylic cation species A. This species then undergoes a reaction In the study conducted by Chikkagundagal K. Mahesha et al, [42] it was observed that the reaction between aldehydic Ntosylhydrazones 46 and 1-aryl-1,2-dihydro-3H-indazol-3-ones 45, as well as 2-aryl-1,2-dihydro-3H-indazol-3-ones 45', resulted in the unexpected and highly efficient formation of 1,2di(hetero)aryl-2,3-dihydroquinazolin-4(1H)-ones 47 and 2,3-di-(hetero)aryl-2,3-dihydroquinazolin-4(1H)-ones 48. This process involved a cascade sequence that started with the breakdown of N-tosylhydrazones, which directed to the construction of Pdcarbenoids mediated by a base.…”

Recent Progress in Pd-Catalyzed Tandem Processes

“…By the reaction with aldehydic N-tosylhydrazones, the treansformation of 1-aryl-and 2-aryl-1,2-dihydro-3H-indazol-3-ones into 1,2-di(hetero)aryl-and 2,3-di(hetero)aryl-2,3dihydroquinazolin-4(1H)-ones was carried out (Figure 40) [96]. The method involved a cascade process that included base-mediated Pd-carbenoid production via the decomposition of N-tosylhydrazones, a nucleophilic attack of indazolone on the Pd-carbenoid complex, and intramolecular ring expansion by N-N bond cleavage.…”

Dearomative spiroannulation of indoles enabled by the diaza-[1,2]-Wittig rearrangement

“…[48][49][50][51][52] Due to the relatively weak N-N bond, a reaction involving the diaza-[1,2]-Wittig rearrangement can be conducted under mild conditions. [53][54][55][56] For instance, Liu/Zhou reported a selective N-N bond activation/ [6 + 1] annulation cascade between pyrazolidinones and diazopyrazolones without a base for the synthesis of spiropyrazolone skeletons. 57 Inspired by these achievements, we envision that the diaza-[1,2]-Wittig rearrangementenabled DSA reaction of indoles is feasible (Scheme 2C).…”