Investigations on the operation of stereochemical drift in the Wittig reaction by NMR and variable-temperature NMR spectroscopy of oxaphosphetane intermediates and their quench products

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Byrne, Peter A.
Muldoon, Jimmy
Ortin, Yannick
Mueller-Bunz, Helge
Gilheany, Declan G.
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Within the currently accepted mechanism of the Li‐salt‐free Wittig reaction, the phenomenon of stereochemical drift remains the one remaining “loose end” in an otherwise internally consistent explanation of a large body of diverse observations. The term describes the nonstereospecific decomposition of the oxaphosphetane (OPA) intermediate in reactions of certain alkylides with certain aldehydes. In this paper, it is shown that the previous examples in which drift occurs are not merely isolated aberrations from the observed norm, but rather that there is a general phenomenon in reactions of ethylides with benzaldehydes. Variable‐temperature NMR (VTNMR) spectroscopy was used to establish that the amount and diastereomeric ratio of the OPA intermediates do not change below a certain temperature. At and above the temperature at which OPA decomposition to alkene and phosphine oxide begins to occur, the alkene shows a different diastereomeric ratio to the OPA, which indicates the occurrence of stereochemical drift. In one example, owing to an apparent remarkable coincidence of rates, the diastereomeric ratio of the OPA does not change above the decomposition temperature, even though stereochemical drift occurs in the formation of the alkene product. An alternative mechanism for drift involving its catalysis by aldehyde was not confirmed. Drift was also shown not to occur in similar Wittig reactions of structurally related longer‐chain alkylides by stereospecific decomposition of OPA intermediates generated from β‐hydroxyphosphonium salts (β‐HPSs). The extremely useful (and generally applicable) NMR techniques, 1H–31P HMBC and selective 1H{31P}, which we have utilised to establish kinetic diastereomeric ratios, are described in full for the first time. Details of the determination of the relative stereochemistry of two β‐HPSs (derived from acid quenching of OPAs) by X‐ray crystallography are also given.
Wittig reactions , Stereochemical drift , NMR spectroscopy , Reaction mechanisms , Diastereomeric ratios , Mechanism , Selectivity , Phosphorus , Ylides , Decomposition , Rearrangement , Substituents , Esters , Origin
Byrne, P. A., Muldoon, J., Ortin, Y., Müller-Bunz, H. and Gilheany, D. G. (2014) 'Investigations on the Operation of Stereochemical Drift in the Wittig Reaction by NMR and Variable-Temperature NMR Spectroscopy of Oxaphosphetane Intermediates and Their Quench Products', European Journal of Organic Chemistry, 2014(1), pp. 86-98. doi: 10.1002/ejoc.201301103
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the pre peer reviewed version of the following article: Byrne, P. A., Muldoon, J. , Ortin, Y. , Müller‐Bunz, H. and Gilheany, D. G. (2014), Investigations on the Operation of Stereochemical Drift in the Wittig Reaction by NMR and Variable‐Temperature NMR Spectroscopy of Oxaphosphetane Intermediates and Their Quench Products. Eur. J. Org. Chem., 2014: 86-98, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."