Various α‐Oxygen Functionalizations of β‐Dicarbonyl Compounds Mediated by the Hypervalent Iodine(III) Reagent p‐Iodotoluene Difluoride with Different Oxygen‐Containing Nucleophiles

Abstract

p-Iodotoluene difluoride (p-Tol-IF 2 ) has been found to be a general reagent for the effective introduction of various oxygen-containing functionalities including tosyloxy, mesyloxy, acetoxy, phosphoryloxy, methoxy, ethoxy and isopropoxy at the a-position of b-dicarbonyl compounds. These transformations can be readily realized by the use of the combined reagent of p-iodotoluene difluoride and various oxygen-containing nucleophilic compounds such as p-toluenesulfonic acid, methanesulfonic acid, acetic acid, diphenyl phosphate, methanol, ethanol and propan-2-ol under mild conditions, respectively. And, the in situ generated hypervalent iodineA C H T U N G T R E N N U N G (III) species via ligand exchange between p-iodotoluene difluoride and the respective oxygen-containing nucleophiles are believed to be the real oxidizing agents in such transformations.

α-Functionalization of Carbonyl Compounds Using Hypervalent Iodine Reagents

“…[29] Zhang and co-workers recently published a detailed study on the α-oxygenation of β-dicarbonyls mediated by TolIF 2 using a range of oxygen-containing nucleophiles, including TsOH, MsOH, AcOH, diphenyl phosphate, MeOH, EtOH and i PrOH. [30] A ligand exchange mechanism to form the necessary iodine(III) species in situ was postulated (Scheme 7), supported by NMR evidence. It is noteworthy that in most cases, these reactions proceed at room temperature in dichloromethane, as opposed to the standard conditions of reflux in acetonitrile.…”

Hypervalent iodine(III)-induced methylene acetoxylation of 3-oxo-N-substituted butanamides

“…The reaction initiates with the attack of the lone-pair electrons of the carbamoyl nitrogen [39–41] or carbonyl oxygen [42–45] on the iodine(III) of DIB, forming intermediates 3 and 5 , respectively. Alternatively, DIB attacks the C–C double bond of the enol derived from 1a and forms intermediate 6 [46–47]. The subsequent N–I, O–I and C–I bond cleavage along with the nucleophilic attack of the acetate ion on the C–N or C–C double bond of the intermediate 4 , 5 or 6 affords the final product 2a .…”

7.07 α-Oxygenation of Carbonyl Compounds

“…130,136 4-Iodotoluene difluoride is an efficient a-oxygenation reagent in the presence of oxygen-containing nucleophiles like TsOH, MsOH, AcOH, diphenyl phosphate, MeOH, EtOH, and i PrOH (Scheme 51(a)). 137 The active oxygenation reagent is believed to form in situ, and the reaction conditions are much milder than the standard ones. Cyclic hypervalent iodine reagents, called iodoxolones, can also be utilized in the preparation of a-tosyloxyketones, and fluorinated versions of the reagent increased the conversion.…”