Iodine catalysis, cyclization

Enol lactones with a halogen at the vinylic position have been synthesized as potential mechanism-based inactivators of serine hydrolyases <81JA5459). 5-Hexynoic acids (181) can be cyclized with mercury(II) ion catalysis to y-methylenebutyrolactones (182) (Scheme 41). Cyclization of the 6-bromo and 6-chloro analogues leads stereospecifically to the (Z)-haloenol lactones (trans addition) but is quite slow. Cyclization of unsubstituted or 6-methyl or 6-trimethylsilyl substituted 5-hexynoic acids is more rapid but alkene isomerization occurs during the reaction. Direct halolactonization of the 5-hexynoic acids with bromine or iodine in a two-phase system with phase transfer catalysis was successful in the preparation of various 5-halomethylene- or 5-haloethylidene-2-phenylbutyrolactones and 6-bromo-and iodo-methylenevalerolactones (Scheme 42). 

The extension of this method to heterocyclic products took advantage of nickel catalysis for the iodine-zinc exchange, for example, of iodoacetals 22, and the organozinc intermediates 23 formed by radical cyclization were again transmetallated to the corresponding copper species which could be reacted with the usual Michael acceptors to afford the products 24 with high diastereoselectivity (Scheme 6).33>33a... 

Treatment of -lonone (13) in Water. Traditional methods for the dehydration of a- and p-ionones to give ionene (14) have involved catalysis by hydriodic acid along with small amounts of phosphorus, or distillative heating in the presence of 0.5% iodine (18). This latter procedure is now known to co-produce about 10% 1,1,6-trimethyl-1,2-dihydronaphthalene (19). However, we have found that the cyclization could be effected by merely heating p-ionone in water at 250 °C for twenty minutes in the MBR. The microwave-assisted reaction was not optimized, and proceeded with only moderate conversion. Unlike in the literature method (18), however, the work-up did not require exhaustive washing procedures. 

In the area of oxidation catalysis, several interesting reactions have been developed by Waser using a Koser-type hypervalent iodine 71 with an incorporated acetylene ligand (Scheme 16.17). Under catalysis with palladium hexafluoroacetylacetonate, nucleopalladation with both a phenol (e.g., 70) and an acid (e.g., 73) followed by oxidative C(sp )-C(sp) coupling led to new products 72 and 74. Initially, this reaction was developed for cyclization of alcohols or acids, respectively. Both five-and six-membered ring cyclization were successfully employed, and a total of 20 examples with 34-82% yield demonstrate the broad scope of this approach [58]. 

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