Oxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases

Abstract

Oxoammonium salt oxidations (using 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) of alcohols containing a β-oxygen atom in the presence of pyridine yield dimeric esters, while in the presence of 2,6-lutidine the product is a simple aldehyde. The formation of a betaine between pyridine and an aldehyde is presented to explain this disparity in reactivity. The betaine is oxidized by the oxoammonium salt to give an N-acylpyridinium ion that serves as an acylating agent for ester formation. Steric effects deter the formation of such a betaine with 2,6-disubstituted pyridines. A series of alcohols containing a β-oxygen substituent were oxidized to aldehydes in the presence of 2,6-lutidine, and a short study of the relative reactivity of various alcohols is given. An overall mechanism for oxoammonium cation oxidations is suggested, premised on nucleophilic additions to the oxygen atom of the positively charged nitrogen-oxygen double bond. Possible mechanisms for both dimeric oxidations and simple oxidations are given.

Toward a Unified Mechanism for Oxoammonium Salt-Mediated Oxidation Reactions: A Theoretical and Experimental Study Using a Hydride Transfer Model

“…8 We then assumed the likely reversible formation of a dipole-stabilized preoxidation complex. Not surprisingly, the overall change in energy to reach this even more entropically demanding state (ΔS complex = −0.037 kcal mol −1 K −1 ) was higher as compared to the unassisted mechanism (7.8 kcal mol −1 for ΔG complex in the unassisted mechanism vs 8.9 kcal mol −1 for ΔG complex from the hydrogen-bonded complex).…”

“…8 From this standpoint, a mechanism originally ruled out by Semmelhack becomes far more viable, namely, one involving a hydride transfer from an activated C−H bond to the electrophilic oxygen of the oxoammonium cation.…”

Probing the Effect of Counterions on the Oxidation of Alcohols Using Oxoammonium Salts

“…[1] In the realm of stoichiometric oxidation, oxoammonium salts have attracted particular interest. It has been employed not only for oxidation of alcohols to aldehydes and ketones, [3][4][5][6][7] but also for a range of oxidative functionalization reactions such as oxidative esterification with hexafluoroisopropanol to form hexafluoroisopropyl esters, [8] conversion of aldehydes to nitriles using hexamethyldisilazane as the nitrogen source, [9] and for the cleavage of ethers. The most commonly used oxoammonium salt used is 4-acetamido-2,2,6,6-tetramethylpiperidin-1-oxoammonium tetrafluoroborate salt (1c).…”

Access to Nitriles from Aldehydes Mediated by an Oxoammonium Salt

“…Given the advantages of oxoammonium salt oxidants, namely that they are environmentally benign, recyclable, and metal-free species which can facilitate oxidation under extremely mild reaction conditions, and our interest in enhancing the profile of oxoammonium saltbased transformations, we elected to advance this unusual outcome into a general methodology for the direct synthesis of nitriles from aldehydes. [10] To understand our unexpected result better, we systematically examined the role of each of the reaction components. This study also served as an opportunity to optimize reaction conditions.…”