Wharton fragmentation

The Wharton fragmentation was used as a key step in an approach toward the total synthesis of xenicanes by H. Pfander et al. ° Two optically active substituted frans-cyclononenes were synthesized starting from (-)-Hajos-Parrish ketone. First, the bicyclic 1,3-diol was protected regioselectively on the less sterically hindered hydroxyl group with p-toluenesulfonyl chloride in quantitative yield. Next, the monosulfonate ester was exposed to dimsylsodium in DMSO, which is a strong base, to initiate the desired heterolytic fragmentation. 

Research by S. Arseniyadis and co-workers showed that the aldol-annelation-fragmentation strategy could be used for the synthesis of complex structures, which are precursors of a variety of taxoid natural products.This strategy allows the preparation of the twenty-carbon framework of taxanes from inexpensive and simple starting materials. 

The stereocontrolled synthesis of 5 -substituted kainic acids was achieved by A. Rubio et a. The C3 and C4 substituents were introduced by the Wharton fragmentation of a bicyclic monotosylated 1,3-diol. When this secondary alcohol was exposed to KOf-Bu, the corresponding fragmentation product was obtained in moderate yield. Jones oxidation of the aldehyde to the carboxylic acid followed by hydrolysis of the ester and removal of the Boc group resulted in the desired substituted kainic acid. 

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Table 13. Cycloheptenones by Grob- Wharton Fragmentation of Bicyclo[3.2.0]heptan-l-ol Derivatives...

A base-catalyzed Grob-Wharton fragmentation of a hydroxybicyclo[5.4.0]nonyl sulfone 3 yielded a cyclononenone derivative 4.193 The reaction is initiated by lactone cleavage with powdered potassium hydroxide in methanol, whereas sodium methoxide was not successful. 

Methoxide promoted lactone cleavage in a tricyclic sulfone initiated a Grob-Wharton fragmentation which gave a cycloundecadienone derivative 1 in refluxing methanol.210... 

This reaction type is called a Grob as well as a Wharton fragmentation [1] [2]. 

The great utility of fragmentations, especially those of 1,3-diol monosulfonates, for the construction of functionalized, medium-sized cycloalkenes was developed by Wharton, by applying previous results. In recognition of his important contributions to the chemistry of heterolytic fragmentations of cyclic 1,3-diol derivatives, this reaction type has been referred to in a recent review as the Wharton fragmentation . ... 

Wharton fragmentation Base-induced formation of medium-sized cyclic alkenes from 1,3-diol monosulfonates. 480... 

Related reactions Eschenmoser-Tanabe fragmentation, Wharton fragmentation ... 

Caine, D. Wharton fragmentations of cyclic 1,3-diol derivatives. A review. Org. Prep. Proced. Int. 1988, 20, 1-51. 

Although both are associated with P. S. Wharton, the Wharton fragmentation is a completely different transformation than the Wharton reaction (also called the Wharton transposition, rearrangement, or reduction). For a review of the Wharton reaction, see Li, J. J. In Name Reactions for Functional Group Transformations, Li, J. J., Ed. Wiley Hoboken, New Jersey, 2007 pp 152-158. 

Starting from (R)-carvone, the trienes 171 and 172 were prepared and RCM provided decalines 173 and 174, respectively (Scheme 1.29). Selective conversion of the secondary alcohols in 173 and 174 to the corresponding mesylates and Wharton fragmentation [39] led to (Z,Z)- and ( , Z)-germacratrienes 177 and 178. The more substituted germacrenes 179-182 were also prepared using this strategy [38]. 

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