polarity; c) the vinyl group migrates ca. 200 times faster than an ethyl group in the dienone system7; d) the ester migrates much faster in a dienone system (4-methoxy-4-substitutient-2,5- cyclohexadienone) which forces more positive charge density on the migrating group than it does in a system where the charge is more distributed over the rest of the system and is thus less on the ester, demonstrating that the p bond can donate more stabilization in systems where it is more necessary for it to do so8, and e) more recent ab-initio MO calculations of acyl group migration in a rigid 7-oxabicyclo[2.2.1] heptyl cationic system are in experimental agreement with migrational ability and are attributed to a favorable hyperconjugative interaction of the carbonyl group11.
Based upon these principles, we predicted that other electron-withdrawing groups similar to the ester would migrate at substantially different rates in the same migrating system. The current work reports an attempt to verify this prediction experimentally. Comparison of the transition states for ester, 5a, thioester, 5b, and amide, 5c suggests that if the substituent X is more electron-donating, it should donate more electron density by resonance to the carbonyl group. This would decrease the effect of the p bond in back-donating electron density to the rest of the system, decreasing the over-all stability of the rearrangement transition state. This predicts that the order of rate of rearrangement, as measured by MT values, should be in the order: 5b>5a>5c, i.e. the order of rearrangement rates should be thioester > ester > amide.
Similar rearrangement studies have been carried out in an epoxide system. Using BF3OEt2 as the catalyst, qualitative observations suggested that the thioester group12,13 migrated substantially faster than the ester in that system, but the amide was very sluggish and refused to rearrange at all except for a small amount in one compound14.
The 4-methyl-4-substituent-2,5-cyclohexadienone system, 6, was chosen for this study, since this is the parent system for the dienone-phenol rearrangement, and the ester has already been substantially studied in this system. More importantly, quantitative studies to measure the MT values of the amide and thioester substituents could then be done.
OCH3 a. X = OEtb. X = SEtc. X = NEt2COX6
Figure 3. Compounds used for the rearrangement studies.
