Overcoming naphthoquinone deactivation: rhodium-catalyzed C-5 selective C–H iodination as a gateway to functionalized derivatives

Abstract

Rh-catalyzed C-5 selective C–H iodination of naphthoquinones provides a gateway to previously inaccessible A-ring analogues. C-2 selective processes can be achieved under related conditions.

Weakly-coordinating N-oxide and carbonyl groups for metal-catalyzed C–H activation: the case of A-ring functionalization

“…In 2016, the da Silva Júnior and Bower groups reported a rhodium(III) catalytic system for direct C-H activation at the C-5 position of the naphthoquinoidal system providing an access to A-ring substituted analogues. 42 The methodology made the synthesis of C-5 halogenated naphthoquinones possible in good yields and high regioselectivity and functional group tolerance, being considered an important method for direct naphthoquinoidal functionalization. The reaction consisted of the combination of [RhCp*Cl 2 ] 2 /AgNTf 2 as the catalytic system, stoichiometric amounts of Cu(OAc) 2 as the oxidant and NIS as the source of iodine, allied with microwave conditions to increase yields and lower the reaction time.…”

“…The insertion of a versatile atom like iodine opened way for the modification of the naphthoquinoidal moiety, as shown by da Silva Júnior and Bower in different works. 42,43 Use of palladium cross-coupling reactions proved to be an efficient tool to access novel C-5 functionalized naphthoquinoidal scaffolds with remarkable trypanocidal activity (Scheme 15).…”

Synthesis of Quinone‐Based N‐Sulfonyl‐1,2,3‐triazoles: Chemical Reactivity of Rh(II) Azavinyl Carbenes and Antitumor Activity

“…Recently, we broadened our research interests to rhodium‐catalyzed C−H functionalization of quinones for the regioselective synthesis of bioactive functionalized derivatives. We have reported the Rh‐catalyzed C‐5 selective C−H iodinations of naphthoquinones using an electrophilic iodine source . The C‐2 selective iodination, bromination and phenylselenation of benzoquinones were achieved under Rh‐catalyzed conditions and the relevant “chemistry” was reported by us very recently …”

Group 9 Transition Metal‐Catalyzed C−H Halogenations

“…In 2016, the groups of da Silva Júnior and Bower reported the Rh(III)‐catalyzed iodination of naphthoquinone (Scheme ) . This work overcomes the inherent reactivity of naphthoquinones and selectively functionalizes the C‐5 position at the A‐ring and hence opens a pathway to previously inaccessible analogues.…”