Mechanisms and consequences of oxygen transfer reactions*

The geometry about oxygen in the transition-state structures for oxygen transfers from a nitrone to phosphorous, from a percarboxylic acid to a carbon–carbon double bond, and from an N-sulfonyl oxaziridine to a carbon–carbon double bond have been evaluated by the endocyclic restriction test. The former can proceed at an oblique angle, while the latter two require a large angle between the entering and leaving groups on oxygen. This information is used to determine the mechanism of the aldehyde-dependent oxygen transfer from molecular oxygen to a carbon–carbon double bond. Many chemical reactions, when broken down to their elementary steps, are atom transfer processes. Proper descriptions of the pathways of these reactions require experimental determinations of the arrangement of atoms in transition-state structures. With this information in hand, an informed choice between alternative pathways may be made, and understanding of the mechanism can be developed. The endocyclic restriction test is based on work by Eschenmoser, who investigated nucleophilic substitution of carbon and Hogg and Vipond who investigated nucleophilic displacements at sulfur [1–3]. We have used this approach to evaluate the orientation of atoms in transition-state structures for reactions in which the atom Y is transferred from the leaving group L to a nucleophile N. The test determines whether the transfer of Y from L to N can occur in an endocyclic ring. The size of the ring restricts the bond angles available in a transition-state structure (2) [1]. Experimentally, the approach involves determination of whether reaction (2) is intramolecular or intermolecular. For example, if a nucleophile and leaving group are linked by three methylene groups, the atom transfer could occur intramolecularly or intermolecularly (3). An intramolecular reaction would be observed if N–Y–L bond angle of approximately 120° would be accessible in a transition-state structure. If that or a smaller bond angle were not possible for the transfer of atom Y, the reaction could proceed in an intermolecular mode. In order to obtain a sound mechanistic conclusion, evaluation of a dissociative reaction would be required. *Plenary lecture presented at the 15 International Conference on Physical Organic Chemistry (ICPOC 15), Göteborg, Sweden, 8–13 July 2000. Other presentations are published in this issue, pp. 2219–2358. †Corresponding author Experimental determination of the molecularity of the reaction can be achieved by an isotopic double labeling or by kinetic experiments. If these approaches are inadequate, alternatives, including competitive intramolecular transfers or the use of surrogate intermolecular reporter molecules may be employed. A notable feature of the endocyclic restriction test is its applicability to nonstereogenic atoms and its ability to afford definitive information, even for low-yielding reactions. The present report summarizes our investigations of the geometries of oxygen transfer reactions and shows how the information obtained from these studies allows the determination of a reaction mechanism of oxygen transfer in a case that was ambiguous. OXYGEN TRANSFER FROM A NITRONE TO A PHOSPHINE The transfer of oxygen from a nitrone to phosphorous has been investigated for the conversion of a nitrone phoshine to an imine phosphine oxide (4). This reaction was shown, by double labeling, to be intramolecular in a six-membered endocyclic ring. A pathway that allows a small bond angle between the entering and leaving groups on oxygen is available for the reaction. Substituent effects are most consistent with a six-membered ring transition structure with valance expansion at phosphorous (4) [4]. OXYGEN TRANSFER FROM A PERCARBOXYLIC ACID TO A DOUBLE BOND We have established by double-labeling experiments that the transfer of oxygen from a peroxycarboxylic acid to an olefin to provide an epoxide is an intermolecular reaction in an 8-membered endocyclic ring, but is intramolecular in a 16-membered endocyclic ring (5) [5]. This result is consistent with the transition structure proposed many years ago by P. D. Bartlett which has come to be known as the “butterfly mechanism” [6]. This experiment shows that a large bond angle between the double bond and the oxygen–oxygen bond is required in the transition-state structure (5). P. BEAK et al. © 2000 IUPAC, Pure and Applied Chemistry 72, 2259–2264 2260