Hypervalent Iodine(III)-Promoted Radical Oxidative C–H Annulation of Arylamines with α-Keto Acids

Abstract

A novel catalyst-free radical oxidative C−H annulation reaction of arylamines with α-keto acids toward benzoxazin-2-ones synthesis under mild conditions was developed. This hypervalent iodine(III)-promoted process eliminated the use of a metal catalyst or additive with high levels of functional group tolerance. Hypervalent iodine(III) was both an oxidant and a radical initiator for this reaction. The synthetic utility of this method was confirmed by the synthesis of the natural product cephalandole A.

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles

“…Further, the utility of this protocol was extended to the synthesis of the natural product cephalandole (Scheme 38). 97…”

“…Further, the utility of this protocol was extended to the synthesis of the natural product cephalandole (Scheme 38). 97 In the proposed mechanism, the condensation of primary amine (61) with phenylglyoxylic acid generates an α-iminoacid intermediate (A). Next, an intermediate (B) is generated via transesterification of BI-OAc with α-iminoacids.…”

Engineering of Hydroxymandelate Oxidase and Cascade Reactions for High-Yielding Conversion of Racemic Mandelic Acids to Phenylglyoxylic Acids and (R)- and (S)-Phenylglycines

“…While racemic alcohols are easily available starting materials, ketones and enantiopure amines are often useful and valuable fine chemicals and pharmaceutical intermediates. , Conversions of racemic α-hydroxy acids to the corresponding α-keto acids and enantiopure α-amino acids are representative examples (Scheme a). For instance, oxidation of substituted mandelic acids (MAs) 1a–k could produce phenylglyoxylic acids (PGAs) 2a–k (Scheme b), which are important intermediates for the synthesis of key precursors in pharmaceutical production. − Chemical synthesis uses special oxidants, − or Oxone oxidation of sulfur ylides, giving low product yield, unwanted side products, and toxic chemical wastes such as metal catalysts and harmful solvents. ,,− On the other hand, amination of substituted MAs 1a–k could give ( S )- or ( R )-phenylglycines (PGs) 3a–k (Scheme b), which are an important class of non-natural amino acids with wide application in pharmaceutics. While ( R )-4-hydroxyphenylglycine 3a is a rare amino acid used in the production of vancomycin type antibiotics, , ( R )-2-fluorophenylglycine 3b and ( S )-2-chlorophenylglycine 3e are the building blocks of antiplatelet drugs prasugrel and clopidogrel, respectively. − Conventional methods of producing enantiopure PGs are based on the kinetic resolution of PGs with a maximum yield of 50% .…”

Bis(trifluoroacetoxy)iodo benzene (PIFA)-promoted transamidation of carboxamides and carboxylic acids with amines

“…[27][28] Remarkably, these novel substances show promising activity in oxidation or catalytic reactions. 29 However, PIFA has been considered to be an active and elegant reagent to promote several important organic reactions such as amination, sulfenylation, oxidative coupling, amidation, carboxylation, ring-rearrangement, cascade reaction, alkylarylation, and many others. [30][31][32][33] Particularly, hypervalent iodine (III) has been involved in the direct C-N bond formation and metal-free functionalization.…”