Selective Removal of Aminoquinoline Auxiliary by IBX Oxidation

Abstract

8-Aminoquinoline (AQ) is a widely used bidentate auxiliary in metal-catalyzed directed C−H functionalization reactions. Herein, we report an efficient and chemoselective method to convert various N-quinolyl carboxamides to primary amides with the treatment of a stoichiometric amount of 2-iodoxybenzoic acid oxidant or the combination of a catalytic amount of 2-iodobenzoic acid and Oxone co-oxidant in mixed solvents of H 2 O and HFIP. Its unique compatibility with the Phth-protected α-amino acid (αAA) substrates enhances the overall synthetic utility of the AQ-directed palladium-catalyzed C−H functionalization strategy for synthesis of complex αAAs.Recently, we demonstrated that reactions of N-aryl carboxamides featuring relatively electron-rich arenes with IBX in hexafluoro-2-propanol (HFIP) and water at room temperature undergo C(aryl)−N cleavage to give primary amides in good yield and selectivity. 8 Notably, the mechanism of the C(aryl)−

A Guide to Directing Group Removal: 8‐Aminoquinoline

“…Zhang, Zhang and Chen recently reported the IBX‐mediated oxidative cleavage of AQ from α‐amino acid derivatives (Scheme 43). [180] Oxidative dearomatization of 8‐aminoquinoline is proposed to form an o ‐iminoquinone ( 292 ) which is highly susceptible to hydrolysis. Aromatic and aliphatic AQ‐amides are thus transformed to primary amides at 60–70 °C with only a slight erosion of ee (from >99 % to 96 % for 293 ).…”

“… Oxidative removal of AQ from α‐amino acid derivatives ( ee values not reported) [180] . [a] Complex mixture.…”

Palladium-Catalyzed sp3 C–H Benzoxylation of Alanine Derivatives Using Aldehydes under Ambient Conditions

“…2). 20 In conclusion, we achieved a palladium-catalyzed sp 3 C-H bond benzoxylation reaction of alanine derivatives with aldehydes under ambient conditions. The reaction provides a variety of benzoate derivatives in 26-68% isolated yields.…”

Stereoselective Palladium-Catalyzed C(sp3)–H Mono-Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group

“…Acid 21 was converted to primary amide 22 by anhydride formation with isobutyl chloroformate, followed by treatment with aqueous NH4OH. 32 Notably, conversion of 2a to the primary amide 22 using IBX 33 or ozonolysis 34 conditions was unsuccessful due to alternative oxidation of the electron-rich PMP substituent. A Pd-catalyzed dehydration of amide 22 gave the corresponding nitrile in 77% yield.…”