Efficient Synthesis of Hydroxyl Isoindolones by a Pd‐Mediated CH Activation/Annulation Reaction

Abstract

Radical reaction: A convenient synthesis of hydroxyl isoindolones by a Pd-catalyzed CH activation/annulation reaction with near "click chemistry" efficiency is presented (see scheme; TBHP=tert-butyl hydrogen peroxide). This methodology features short reaction times (10-30 min), high atom economy, wide substrate scope (22 examples), and good reaction yields (up to 93 %).

Transition-Metal-Catalyzed C–H Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds

“…36 In contrast to an earlier report using Rh(III) catalysis where oxidative couplings to aromatic aldehydes were achieved using stoichiometric Ag 2 CO 3 , the Pd-catalyzed conditions allowed the authors to expand the scope of this chemistry to include C–H acylation with alkyl aldehydes using relatively inexpensive and abundant TBHP as the internal oxidant.…”

“…An analogous method was also developed later that featured a Pd(II) catalyst system (See Section 2.4.1, Scheme 21). 36 …”

Palladium Catalyzed Cross‐Dehydrogenative Coupling/Annulation Reaction: A Practical and Efficient Approach to Hydroxyisoindolo[1,2‐b]quinazolinone

“…On the basis of the previous reports, [11,28,29] a plausible mechanism pathway is proposed and depicted in Scheme 3. The reaction is probably initiated by chelate-assisted orthoselective cyclometalation of 2-phenylquinazolin-4(3H)-one (1a) by Pd(OAc) 2 and generates a five-membered cyclopalladated intermediate (A).…”

C–H Bond Activation for Arylations

“…Yu et al [45] have developed a Pd-catalyzed oxidative C-H activation/annulation reaction that affords hydroxyl isoindolones in very good yields (Figure 4.21).…”

“…21 A cross-section of results for the Pd-catalyzed C-H activation/annulation reaction leading to hydroxyl isoindolones as described by Yu et al[45]. .…”