Efficient Assembly of Molecular Complexity Enabled by Palladium‐Catalyzed Heck Coupling/C(sp²)−H Activation/ C(sp³)−H Activation Cascade

Abstract

A palladium‐catalyzed [2+2+1] annulation among 3‐iodochromones, benzyl bromides, and norbornene has been developed. This annulation consists of a domino sequence involving Heck coupling/C(sp2)−H activation/C(sp3)−H activation, affording a variety of complex chromone derivatives bearing five contiguous tertiary carbon centers in up to 94% yield and 99:1 dr. Interestingly, the diastereoselectivity could be switched by fine‐tuning the solvent, in which endo isomer and exo isomer were obtained using mesitylene/CH3CN and mesitylene, respectively.

Diversity‐Oriented Synthesis of Flavones and Isoflavones via Palladium/Norbornene Cooperative Catalysis

“…Although this strategy is mechanistically feasible, multiple challenges are foreseeable. First, as revealed by the groups of Han/Chen [ 38‐41 ] and Tang/Wu, [ 42 ] 3‐iodochromones are very challenging substrates to realize the Catellani‐type transformations under the conventional Pd/NBE cooperative catalysis conditions (Figure 1C). Second, several potential side reactions, e.g ., cyclopropanation, [ 35‐37 ] direct coupling with the terminating reagents and norbornene‐involved transformations, [ 38‐42 ] will be competitive pathways.…”

“…First, as revealed by the groups of Han/Chen [ 38‐41 ] and Tang/Wu, [ 42 ] 3‐iodochromones are very challenging substrates to realize the Catellani‐type transformations under the conventional Pd/NBE cooperative catalysis conditions (Figure 1C). Second, several potential side reactions, e.g ., cyclopropanation, [ 35‐37 ] direct coupling with the terminating reagents and norbornene‐involved transformations, [ 38‐42 ] will be competitive pathways. Third, a suitable NBE‐type mediator needs to be identified, [ 32‐34 ] to promote the alkenyl Catellani‐type transformations and prevent the competing side reactions.…”

“…Third, a suitable NBE‐type mediator needs to be identified, [ 32‐34 ] to promote the alkenyl Catellani‐type transformations and prevent the competing side reactions. [ 35‐42 ]…”

Recent Advances in Transition Metal‐Catalyzed Domino‐Cyclization Strategies for Functionalized Heterocyclic/Carbocyclic Compounds

“…Chromones are structurally privileged scaffolds found in many natural products and biologically active synthetic compounds. [73] This reaction involves the sequential Pd-catalyzed three components [2 + 2 + 1] Heck reaction/C(Sp 2 )-H activation and C(Sp 3 )-H activation of 3-iodochromone 184, benzyl bromides 185, and norbornenes 186 to give a variety of chromone derivatives 187 with tertiary carbon centers in good yields and diastereoselectivity. Under the optimized reaction condition 3-iodochromone 184, benzyl bromides 185, and norbornenes 186 were treated with Pd-(OAc) 2 (10 mol %), P(o-tol) 3 (20 mol %), K 3 PO 4 (2 eq.)…”

“…have also disclosed palladium‐catalyzed domino [2+2+1] annulation for the synthesis of a variety of chromone‐containing polycyclic compounds from 3‐iodochromones 184 , benzyl bromides, and norbornene 186 (Scheme 38). Chromones are structurally privileged scaffolds found in many natural products and biologically active synthetic compounds [73] . This reaction involves the sequential Pd‐catalyzed three components [2+2+1] Heck reaction/C(Sp 2 )‐H activation and C(Sp 3 )‐H activation of 3‐iodochromone 184 , benzyl bromides 185 , and norbornenes 186 to give a variety of chromone derivatives 187 with tertiary carbon centers in good yields and diastereoselectivity.…”