Intramolecular -proton shift

The sulfide derivative of furocoumarin based natural products can be synthesized by treatment of a thiadiazole 107 with KO-f-Bu and an organohalide in an one-pot operation. This process presumably involves the generation of a phenolate 108 and is followed by an intramolecular proton shift and a rearrangement to give an alkynethiolate 109, which undergoes a sequence of intramolecular proton shift, cyclization and alkylation to lead to the furocoumarin product. The thiadiazole, in turn, can be prepared by reaction of the corresponding acetyl precursor with carbethoxyhydrazine, followed by treatment with thionyl chloride . 

On the basis of distribution of products obtained in these reactions with the change of solvents, temperature and molar ratio of reactants, a mechanism has been suggested for the anomalous annulation which does not involve an initial attack of the tetrasub-stituted isomer of the enamine (equation 16)51. Alkylation of the more stable cis isomer of the enamine (80) with methyl vinyl ketone (MVK) would afford zwitterion 81 (attack by the other side of the enamine leads to strong steric interactions in the transition state). Reaction of the thermodynamically less favorable trans isomer 83 gives rise to zwitterions 84 and 89 (both without axial-axial interactions), and ion 84 is sterically able to undergo intramolecular proton shift to afford enamine 85. Zwitterionic intermediates 81 and 89 can be stabilized by conversion to dihydropyrans 82 and 90, or protonated to immonium ions. The pair 81-82 will lead to enamine 85, while the pair 89-90 will afford enamine 91. Then, cyclization of 85 or 91 will afford the enone expected from the normal enamine version of the Robinson annulation. 

Termination involving intramolecular proton shift or intermolecular proton transfer, both followed by elimination of a molecule of water has been reported for the high temperature cationic polymerization of lactams a) intramolecular ... 

The reaction of benzofuroxan with malononitrile and amine catalysis proceeds to give 3-amino-quinoxaline-2-carbonitrile 1,4-dioxide (6). In this case, the primary adduct is stabilized by an intramolecular proton shift rather than by an elimination rcaction. " - Benzimidazoles can also be formed through this reaction (see also Houbcn-Weyl, Vol. E8a, p 303). 

Nevertheless intramolecular proton shifts are competive with deprotonation under these conditions. The hydrocarbon products from the nitrous acid deamination of 1 -propylamine (628) consist of 10% cyclopropane and 90% propene. The 1-propanol (630) obtained from labeled (628) arises mainly by solvolytic displacement leading to isotopically unrearranged (630a) and partly from protonated cyclopropane with isotopic scrambling466. ... 

The methyl-bridged ions discussed so far have no reasonable chance for intramolecular proton shifts because the resultant isomers would be higher in energy, e.g. 

FIGURE 11.4. Tautomeric rearrangement of the protons in an A-T base pair (schematic) (a) after Watson and Crick (intramolecular proton shifts) and (b) after Lowdin (intermo-lecular shifts of the protons). 

The importance of catalysis of the keto-enol tautomerization is brought home by calculations of the energy of the hypothetical transition states for direct intramolecular proton shift between carbon and oxygen. For acetone, it is 53 kcal mol This would require temperatures of 500°C for the reaction to occur without a catalyst. 

---