Iodolactone 842 Subject

Reactants with internal nucleophiles are also subject to cyclization by electrophilic sulfur reagents, a reaction known as sulfenylcyclization.92 As for iodolactonization, unsaturated carboxylic acids give products that result from anti addition.93... 

It has been found that when 8,e-enolates bearing (3-siloxy substiments are subject to iodolactonization, the substituent directs the stereochemistry of cyclization in a manner opposite to an alkyl substituent. Suggest a TS structure that would account for this difference. 

The 4-hydroxy-(S)-proline-derived acid (232) was subjected to electrophilic lactoni-zation either with J2-KJ-NaHC03 to yield the iodolactone (233a), or benzeneselenyl chloride to give the phenylselenolactone (23b). Reductive removal of X from these products was achieved with tri-n-butyl- or triphenyltin hydride, followed by hydro-genolysis to yield (234) with at least 99% optical purity 231 j). 

The more obvious way to make this epoxide would be by epoxidation of the ester of the original unsaturated acid. However, the stereoselectivity in that reaction is nowhere near as good as in the iodolactonization. We shall return to this subject when we discuss reactions in acyclic systems in the next chapter. 

The C27-C38 segment 208 was prepared from D-galactal 227 (O Scheme 26). The silyl ether, prepared from 227, was selectively benzylated, and the resulting C3-alcohol was desilylated and propanoylated to afford 228. After the Ireland-Claisen rearrangement of 228, carboxylic acid 229 was subjected to iodolactonization followed by reductive removal of iodine to give y-lactone 230. This was converted to the C27-C38 segment 208. 

During the total synthesis of the pentacyclic sesquiterpene dilactone (+)-merrilactone A by S.J. Danishefsky et al., a two-carbon unit was introduced at C9 by a Johnson-Claisen rearrangement. This high yielding transformation was carried out in the presence of catalytic 2,2-dimethyl propanoic acid at 135 °C using mesitylene as the solvent. A mixture of diastereomeric esters were formed, which were later hydrolyzed and subjected to iodolactonization to form the second lactone ring present in merrilactone A. The natural product was synthesized in 20 steps with an overall yield of 10.7%. 

Formylpolystyrene 3a (Table 3) [130] has been used in reactions with nitro-methane to give a resin-bound nitrophenylethanol that could be dehydrated and subjected to cycloaddition reactions. The resulting adducts released tetrahydrofuran derivatives into solution by iodolactonization [131,132]. The... 

The aldol reaction with the lactate derivative was applied to the synthesis of citreoviral 78 (Scheme 8.12). The enolate of 72 was reacted with unsaturated aldehyde 73 to yield a,(3-dihydroxy-7,8-unsaturated imide 74 in a stereoselective manner. Adduct 74 was subjected to iodolactonization to accompany the removal of the chiral auxiliary to give 75 as a single isomer. Debenzylation was followed by etherification with the tertiary alcohol to provide the highly substituted furan 77 having all the chiral centers of the target molecule. The additional four-step sequence afforded citreoviral 78. 

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