Rhodium‐Catalyzed Direct C–H Phosphorylation of (Hetero)arenes Suitable for Late‐Stage Functionalization

Abstract

Efficient rhodium-catalyzed direct C-H phosphorylation of (hetero)arenes was developed. Va riousd irecting groups andawide range of substrates,i ncluding heterocycles,c an be utilized in this C-H phosphorylation process,a llowing for the rapid installation of the phosphonate group into medicinally and biologicallyi mportantp rivileged scaffolds. Thee fficienta nd straightforward method could serve as an ew tool to streamlinel ate-stage C-H functionalization for preparing aryl phosphonates, which are important structural motif in synthetic and medicinalc hemistry.

Scalable Rhodium(III)‐Catalyzed Aryl C−H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination

“…Although transition metal catalyzed C−H phosphorylation is a straightforward and attractive approach for the construction of C−P bonds, it is difficult to execute in practice because of the strong propensity of phosphorus reagents to induce catalyst poisoning through coordination . Deactivation can be avoided by either adding the phosphorus reagent slowly to the reaction mixture (Scheme a) or employing α‐hydroxyalkylphosphonate as a masked, slow‐releasing phosphonating reactant (Scheme b,c) . In addition, the installation of a chelating directing group on benzoic acid derived substrates has been shown to enable the use of H‐phosphonates directly in Cu‐catalyzed reactions (Scheme d) .…”

Copper‐Catalyzed C2 and C3 Phosphonation of Benzofuran and Benzothiophene with Trialkyl Phosphites

“…The C3 phosphonation of benzofuran (benzothiophene), to the best of our knowledge, has only been studied by Hong and co‐workers. They realized C3 phosphonation through the rhodium‐catalyzed oxidative coupling of pyridine‐directing benzofuran and α‐hydroxyalkyl phosphonates . Despite this important advance, limitations on the substrate remain, and a noble‐metal catalyst was necessary.…”

“…According to the above mechanistic studies and earlier literature reports, a plausible reaction pathway for phosphonation is depicted in Scheme . Initially, Cu II is oxidized by K 2 S 2 O 8 to form Cu III and SO 4 .− .…”

Scalable Rhodium(III)‐Catalyzed Aryl C−H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination

“…[1] Although transition metal catalyzed C À Hp hosphorylation is astraightforward and attractive approach for the construction of C À Pbonds,itis difficult to execute in practice because of the strong propensity of phosphorus reagents to induce catalyst poisoning through coordination. [4,5] In addition, the installation of achelating directing group on benzoic acid derived substrates has been shown to enable the use of H-phosphonates directly in Cu-catalyzed reactions (Scheme 1d). [4,5] In addition, the installation of achelating directing group on benzoic acid derived substrates has been shown to enable the use of H-phosphonates directly in Cu-catalyzed reactions (Scheme 1d).…”

“…[10] Recently,m any elegant examples of electrochemically driven transition metal catalyzed C À Hf unctionalizations have been reported, [11,12] including aPd-catalyzed C À H phosphorylation reaction [11l] and af ew Rh III -catalyzed CÀC cross-coupling reactions. [5] We began our studies by first optimizing electrochemical conditions for the phosphorylation of N-(2-pyridyl)aniline (1) with diphenylphosphine oxide (2), ar eaction which has not been reported previously.T he electrosynthesis was performed in an undivided cell (a three-necked round-bottomed flask) equipped with ar eticulated vitreous carbon (RVC) anode and aplatinum plate cathode.The optimal results were obtained at reflux (65 8 8C) and ac onstant current of 3mA, with areaction mixture consisting of Cp*Rh(OAc) 2 (5 mol %) as the catalyst, KPF 6 (1 equiv) as the supporting salt, and MeOH as the solvent (Table 1). [5] We began our studies by first optimizing electrochemical conditions for the phosphorylation of N-(2-pyridyl)aniline (1) with diphenylphosphine oxide (2), ar eaction which has not been reported previously.T he electrosynthesis was performed in an undivided cell (a three-necked round-bottomed flask) equipped with ar eticulated vitreous carbon (RVC) anode and aplatinum plate cathode.The optimal results were obtained at reflux (65 8 8C) and ac onstant current of 3mA, with areaction mixture consisting of Cp*Rh(OAc) 2 (5 mol %) as the catalyst, KPF 6 (1 equiv) as the supporting salt, and MeOH as the solvent (Table 1).…”