Palladium-Catalyzed Double C–H Functionalization of Arenes at the Positions <i>ortho</i> and <i>meta</i> to Their Directing Group: Concise Synthesis of Benzocyclobutenes

Abstract

The synthesis of benzocyclobutenes from simple arenes bearing a directing group was investigated via the palladium-catalyzed cyclization of norbornene derivatives. This approach allowed for the facile construction of benzocyclobutenes along with the double functionalization of the C-H bonds at the positions ortho and meta to the directing group. This result shows that the key palladacyclopentene intermediate in the Catellani reaction can be prepared by the directed double ortho C-H activation of the substrate. The results of this study also revealed that the combination of an N-protected amino acid with benzoquinone (BQ) was effective for this transformation.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…An alkylation in the broader sense was the synthesis of benzocyclobutenes via a Pd catalysed reaction with norbornenes ( Scheme 57C ). 314 Norbornene is a quite useful auxiliary in C–H activation chemistry, for example in the Catellani reaction. 11 , 315 However, in the present transformation, the norbornene was not an auxiliary but a reaction partner and remained in the final products.…”

Recent Advances in Retained and Dehydrogenative Dual Functionalization Chemistry

“…Takemoto and co-workers reported the synthesis of benzocyclobutenes (25) via a Pd-catalyzed cyclization of directing group substituted arenes (23) with norbornene derivatives (24), which involves a double functionalization of CÀ H bond at the ortho and meta positions (Scheme 7). [11] The directing group of 23 and (À )-Men-Val-OH coordinate to the divalent palladium catalyst to construct Pd(II) complexes (23-A) via cleavage of the ortho CÀ H bond. The subsequent insertion of 24 into intermediates (23-A) provides CÀ C bond formed Pd(II) complexes (23-B), and the following meta CÀ H activation of the benzene ring affords palladacycles (23-C).…”

Palladium(0)-Catalyzed Benzylic C(<i>sp</i>³)–H Functionalization for the Concise Synthesis of Heterocycles and Its Applications

“…In this review, we provide a summary of our recent research on the Pd(0)-catalyzed benzylic C(sp 3 )-H functionalization reaction and its application. [33][34][35][36][37][38][39][40][41][42][43] 2. Pd-Catalyzed Benzylic C(sp 3 …”