Detailed rate studies on the Wittig reaction of nonstabilized phosphorus ylides via phosphorus-31, proton, carbon-13 NMR spectroscopy. Insight into kinetic vs. thermodynamic control of stereochemistry

The modern interpretation of the Wittig reaction mechanism

“…This may provide an explanation for the observation of stereochemical drift in certain reactions of alkylidenetriphenylphosphoranes -in particular those with aromatic aldehydes. 65,92 Non-stabilised ylides for which one or more of the P-phenyl 85 groups are replaced by alkyl group(s) show much lower Zselectivity than alkylidenetriphenylphosphoranes; 4 in the context of the cycloaddition mechanism this is explained by decreased 1-3 interactions and thus a to lower propensity to cycloaddition TS puckering.…”

“…The cis-OPA is believed to undergo reversal to ylide and aldehydes, while the trans-OPA does not. 68,92 and thus trans-…”

“…98 25 There is also a small and well-defined set of Wittig reactionsall involving non-stabilised ylides -that exhibit stereochemical drift under Li salt-free conditions ("Li + -free stereochemical drift"). Li + -free stereochemical drift and has been observed only for the OPAs produced in the reactions of trialkylphosphonium 30 alkylides with tertiary or aromatic aldehydes, 68,69,92 and in reactions of aromatic aldehydes with the ethylides of triphenylphosphine, 38,65 ethyldiphenylphosphine 38 and P-phenyl-5H-dibenzophosphole. 38 In the first two cases, the augmentation of trans-OPA at the expense of the cis-isomer occurred at 35 temperatures below which OPA cycloreversion to alkene and phosphine oxide could not occur, and thus it could be monitored by NM R. These experiments represent the only examples in which stereochemical drift has been observed in action.…”

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

“…This was the result of a discontinuous uncovering of the operation of several different factors that can have a bearing on the mechanism and, especially, on the stereoselectivity of the reaction. Only in hindsight can we see that the results of valid and well-constructed studies concerned with the involvement of betaines (salt-free or otherwise), 16,17,18 and the related issues of the effect of lithium cation 19,20,21,22 and reversible formation of intermediate(s) 23,24,25,26,27,28 led incorrectly to the twin hypotheses of the involvement of betaines and the operation of thermodynamic control in Wittig reactions. 29 That these ideas persist in the modern literature 30,31,32,33,34 perhaps may be attributed to their simplicity.…”

“…26,35 It is significant (and ironic) that the very limited number of cases in which genuine reversibility of OPA formation occurs involve non-stabilized ylides. 23,24,25,26 The present emerging consensus on the mechanism centers on [2+2] cycloaddition of the ylide and carbonyl to give oxapho sphetane (OPA) directly (Scheme 1). As developed by Vedejs and co-workers, 35,38 and modified for reactions of stabilized ylides by Aggarwal, Harvey and co-workers, 13 it is the mechanism that best accounts for experimental observations.…”