# Revealing the Mechanism of TEMPO-Hypervalent Iodine(III) Oxidation of Alcohols

## TL;DR

This paper investigates how alcohols are oxidized to carbonyl compounds using TEMPO and a hypervalent iodine reagent, revealing a new dual catalytic mechanism.

## Contribution

The study proposes a revised dual catalytic mechanism involving hypervalent iodine and water, supported by experimental and computational evidence.

## Key findings

- A dual catalytic system involving alcohol, hypervalent iodine, and water is proposed.
- TEMPO is involved both before and after the rate-determining step.
- An iodine(V) species is likely formed during the oxidation process.

## Abstract

Experimental and computational studies on the mechanism
of a well-known
procedure for the oxidation of alcohols to carbonyl compounds using
TEMPO and the hypervalent iodine­(III) reagent (diacetoxyiodo)­benzene
(PIDA) are reported. Kinetic data show that the assumed classical
oxoammonium–hydroxylamine mechanism requires modification due
to zero-order behavior observed in TEMPO. Instead, a dual catalytic
system is proposed featuring two rate-determining steps involving
a combination of alcohol, hypervalent iodine species, and water, which
is typically present in adventitious quantities and is necessary for
the reaction to proceed. The use of different alcohols implies the
mechanism to be general. Intramolecular radical trap probes rule out
a radical mechanism, while an investigation of TEMPO derivatives suggests
that TEMPO is involved prior to the rate-determining step. Kinetic
isotope effect studies demonstrate that TEMPO is also involved after
the rate-determining step. Electrochemical studies find that the oxoammonium
form of TEMPO is reduced by PIDA, likely oxidizing iodine­(III) to
an iodine­(V) species. Theoretical investigations support the feasibility
of a pathway involving an iodine­(V) species, demonstrate good agreement
with the experimentally derived kinetics, and support an updated mechanism.
Finally, the demonstration of oxidative kinetic resolution of a secondary
alcohol using a chiral iodine­(III) reagent rationally extends the
reactivity of this system to new chemistry and lends further support
toward our mechanistic proposals.