Ylide formation parameters

Over the last 15 years, Padwa et al. (73,74) have been heavily involved with the study and application of carbonyl ylides as cycloaddition precursors in synthesis. Their work has helped make the tandem ylide formation-dipolar cycloaddition process a synthetically accessible transformation. Much of Padwa s early work focused on determining the extent and limitations of this methodology. Many of the early systems were carbocyclic in nature and helped define basic parameters such as... 

The rates of H-D exchange at the a-positions have been determined for a series of N- substituted pyridinium salts and pyridine 1-oxides in D20 at 75 °C (Scheme 197) (70JA7547). The rates give a good correlation with the Taft inductive parameter <77 pi = 15). The positively charged nitrogen in a ring has been estimated to activate the a-position towards deprotonation and ylide formation by a factor of 1014 16. 

The rates of HD exchange at the -positions for a series of N-substituted pyridinium cations and pyridine 1-oxide derivatives in D20 at 75 C (Figure 2) <1970JA7547> correlate well with the Tafts inductive parameter ] ( = 15). A positively charged nitrogen in a ring is estimated to activate the -position toward deprotonation and ylide formation by a factor of 101S. 

Once this was understood, we were able to track down the critical process parameters affecting the ylide formation. Ultimately, we eliminated many operational suspects (agitation, reagent addition rates, hot spots, and others) and discovered that differences in the potassium t-butoxide were responsible for differences in ylide reaction rates. Operationally, the NIR is utilized to decide whether to proceed with a particular ylide batch or to discard it and make a new one. The net impact was much-improved robustness and product quality. 

The spectral parameters of 15a and other silicon-organophosphorus betaines described henceforth in Section 2.2.2 allowed us to show reliably that the reaction of phosphorus ylides with thiocarbonyl compounds, unlike the classical Wittig reaction, occurs through the intermediate formation of betaines (17)11 (Scheme 9). Erker and coworkers performed a more detailed... 

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