[reaction: see text] The association of lipase-catalyzed enzymatic resolution with in situ racemization mediated with the thiyl radical enables the dynamic kinetic resolution of non-benzylic amines. It leads to (R)-amides with high enantioselectivities. It can be applied either to the conversion of racemic mixtures or to the inversion of (S)-enantiomers.

The racemization of nonactivated aliphatic amines has been mediated with alkanethiols and with methyl thioglycolate in the presence of AIBN. The process involves reversible H-abstraction at the chiral center, in a position alpha relative to nitrogen, by thiyl radical. The knowledge of the reaction enthalpy is critical to select the appropriate thiol. In the absence of experimental values, theoretical calculations of the alpha-C-H BDEs and the S-H BDE provide a useful guide.

The aim of this article is to provide an updated review on the various methodologies that allow allylic C–N bonds (and by extension propargylic C–N bonds) to be cleaved. Since selectivity is crucial for synthetic planning, as far as possible, the relative reactivity of the various allylic groups is examined, and the discrimination between O‐allyl and N‐allyl derivatives is discussed. A special development is devoted to reactions leading to enamines through a 1,3‐hydrogen shift, even though some of these reactions were not originally performed for the purpose of cleaving the N‐allyl bond. Some selected applications are discussed. In addition to preparative deprotection methods, reactions such as the enzyme‐mediated cleavage of allylic C–N bonds are also mentioned, although these reactions may not have any practical synthetic interest at the moment. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Thiyl radical mediated reversible H abstraction from the stereogenic center α to the nitrogen atom is a mild method to racemize benzylic amines. Owing to the sensitivity of atom‐transfer reactions to enthalpic effects, a knowledge of both the S–H and the α‐C–H bond dissociation energies is fundamental to select the thiol that is appropriate to abstract the hydrogen atom from a given amine. In the absence of experimental data, theoretical calculations supply a useful predictive tool. The experiments described here are helpful in delineating the optimal conditions that have to be fulfilled for the racemization to proceed in a reasonable time in the presence of either a stoichiometric or a catalytic amount of thiol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Thiols mediate the radical isomerization of allylic amines into enamines. The reaction results in the cleavage of the allylic C-N bond, after treatment with aqueous HCl. The mechanism involves the abstraction of an allylic hydrogen alpha to nitrogen by thiyl radical, followed by a return hydrogen transfer from the thiol to the carbon gamma to nitrogen in the intermediate allylic radical. The scope and limitations of the reaction with respect to the nature of the thiol, to the structure of the allylic chain, and to the nature of the substituents at nitrogen were investigated. The experimental results were interpreted on the ground of DFT calculations of the C-Halpha BDE in the starting allylic amines, and of the C-Hgamma BDE in the resulting enamines. The efficiency of the initial hydrogen transfer is the first requirement for the reaction to proceed. A balance must be found between the S-H BDE and the two above-mentioned C-H BDEs. The incidence of stereoelectronic factors was analyzed through NBO calculations performed on the optimized geometries of the starting allylic amines. Additional calculations of the transition structures and subsequent tracing of the reaction profiles were performed for the abstraction of Halpha from both the allyl and the prenyl derivatives by p-TolS(*). The latter allowed us to estimate the rate constant for the abstraction of hydrogen by thiyl radical from an N-prenylamine and an N-allylamine.