Wittig Reaction
We brought forward substantial experimental evidence securing the Wittig reaction as a [2+2] cycloaddition (Publications P5/P6), solving one of the long-standing controversies in mechanistic chemistry. The project grew out of some simple observations on anomalous and counterintuitive E/Z ratios of ortho-substituted stilbenes (Tet Lett. 2002, 43, 2449). However it required insight to see that the effect, based in the pentavalent pentacoordinated oxaphosphetane intermediate, might be generalisable to all ylide types, leading to a design for the needed substrates. In contrast to the Appel work, this project involved just myself and a talented co-worker – Dr. Peter Byrne, who subsequently won a von Humboldt Fellowship. An extra bonus: an easy work-up of the Wittig reaction (Org. Biomol. Chem. 2012, 10, 3531). In a follow up (P7), we detected for the first time the pentavalent intermediate of phosphonium salt/ylide hydrolysis & proposed a revised mechanism for the latter.
Selected publications:
Unequivocal Experimental Evidence for a Unified Lithium Salt-Free Wittig Reaction Mechanism for All Phosphonium Ylide Types: Reactions with β-Heteroatom-Substituted Aldehydes Are Consistently Selective for cis-Oxaphosphetane-Derived Products
The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism.
Peter A. Byrne, Declan G. Gilheany (2012) Journal of the American Chemical Society, 134 (22), 9225-9239 (link to paper)
The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism.
Peter A. Byrne, Declan G. Gilheany (2012) Journal of the American Chemical Society, 134 (22), 9225-9239 (link to paper)
First ever observation of the intermediate of phosphonium salt and ylide hydrolysis: P-hydroxytetraorganophosphorane
P-Hydroxytetraorganophosphorane, the long-postulated intermediate in phosphonium salt and ylide hydrolysis, has been observed and characterised by low temperature NMR, finally definitively establishing its involvement in these reactions. The results require modification of the previously accepted mechanism for ylide hydrolysis: P-hydroxytetraorganophosphorane is generated directly by 4-centre reaction of ylide with water.
Peter A. Byrne, Yannick Ortin, Declan G. Gilheany (2015) Chemical Communications, 51 (6), 1147-1150 (Link to paper)
P-Hydroxytetraorganophosphorane, the long-postulated intermediate in phosphonium salt and ylide hydrolysis, has been observed and characterised by low temperature NMR, finally definitively establishing its involvement in these reactions. The results require modification of the previously accepted mechanism for ylide hydrolysis: P-hydroxytetraorganophosphorane is generated directly by 4-centre reaction of ylide with water.
Peter A. Byrne, Yannick Ortin, Declan G. Gilheany (2015) Chemical Communications, 51 (6), 1147-1150 (Link to paper)