Wittig intermediates, stereochemical equilibration

V. Boundary Conditions for Stereochemical Equilibration of Wittig Intermediates... 

V. BOUNDARY CONDITIONS FOR STEREOCHEMICAL EQUILIBRATION OF WITTIG INTERMEDIATES... 

Methods A, D, and E suffer from the inherent limitation that they deliberately generate a betaine as the precursor of the oxaphosphetane. Since there is no assurance that the reaction of an ylide with an aldehyde would involve the same ionic intermediate (19,21) these control experiments may provide opportunities for stereochemical equilibration that may not be available to the corresponding Wittig reactions. If the oxaphosphetane generated by methods A or E is stable enough to observe directly, then it is usually possible to distinguish between oxaphosphetane equilibration, betaine equilibration, and other mechanisms for loss of stereochemistry (21 c). However, this is not possible for oxaphosphetanes that contain unsaturated substituents at Cj because oxaphosphetane decomposition is fast at — 78°C (21c). In these examples, method A (like method D or E) can only establish an upper limit for equilibration of all of the conceivable intermediates betaines, betaine lithium halide adducts, oxaphosphetanes, and so on. 

Tables 6 and 7 summarize results from stereochemical equilibration studies performed over the past decade by MaryanofT et al. (22,23), and Vedejs et al. (20, 21c, 39-42). A few other convincing examples are included to expand the scope of the systems covered. Table 6 lists those examples where control experiments establish at least 90% retention of stereochemistry from intermediates-to alkene products. As already discussed, the percentage of equilibration represents the upper limit for loss of stereochemistry from all possible pathways in the control experiments. No attempt has been made to determine whether the minor levels of stereochemical leakage in Table 6 occur at the stage of oxaphosphetanes, betaines, or other potential intermediates. Table 6 includes entries corresponding to all of the principal families of Wittig reagents nonstabilized ylides (entries 1-12, 24, 25, 29, and 30), benzylic ylides (entries 13-17 and 28), allylic ylides (entries 22, 23, 26, and 27), and ester-stabilized ylides (entries 18-21). The corresponding Wittig reactions must take place under dominant kinetic control.

There are also some examples where significant reversal and stereochemical equilibration of intermediates has been demonstrated in aldehyde Wittig reactions (Table 7, subset 1). Several additional examples of reversal from betaine generation experiments may also be relevant, depending on whether the same betaines play any role in the Wittig process (Table 7, subset 2). The following generalizations follow from the comparison of Tables 6 and 7. 

Several puzzling entries in Table 14 remain to be explained, including reactions where hydroxylic solvents or alkoxide bases are used (entries 11-14). Betaine reversal was demonstrated under hydroxylic conditions in the original Trippet-Jones experiment (Scheme 4) (13), and it is conceivable that interconversion between oxaphosphetanes and betaines could be fast enough in hydroxylic solvents to allow significant betaine reversal to the ylide and aldehyde in some cases. However, there is no clear evidence to implicate stereochemical equilibration of benzylide-derived Wittig intermediates in ether solvents. 

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