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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 32268
Title Through-bound interactions in monosulfonated 1,4- and 1,5-diols and their application in natural product synthesis
Author(s) Bastiaansen, P.M.F.M.
Source Agricultural University. Promotor(en): Æ. de Groot; J.P.B.A. Wijnberg. - S.l. : S.n. - ISBN 9789054856108 - 147
Department(s) Organic Chemistry
Publication type Dissertation, internally prepared
Publication year 1996
Keyword(s) synthese - natuurlijke producten - synthesis - natural products
Categories Organic Chemistry
This thesis deals with the reaction behavior of 1,4- and 1,5-diol monosulfonate esters upon basic treatment in apolar solvents and the Through-Bond Interactions (TBI) which are playing a role in these reactions. Furthermore, the influence of TBI on the rate of desilylation of silyl ethers of 1,4-diol monosulfonate esters is shown. Finally, the application of the base-induced homofragmentation is illustrated by the synthesis of a natural product.

In Chapter 1 the historical background of the base-induced reactions of 1,4-diol monosulfonate esters is given. From previous work, it is known that the sulfonate ester bond of 1,4-diol monosulfonates can undergo a facile heterolysis upon treatment with a non- nucleophilic base -sodium tert -amylate- in refluxing benzene or toluene. TBI between the oxygen anion, generated by deprotonation of the hydroxyl group, and the sulfonate ester bond are thought to play a dominant role in this heterolysis proces. In this thesis all the typical reaction behaviors of the base-treated diol monosulfonates are explained with the concepts of TBI. Furthermore, some examples of chemical consequences of TBI are briefly discussed (Chapter 1).

The studies on the sulfonates 1-3 (Chapter 2) reveal that the magnitude of TBI strongly depends on the geometry of the σ-relay, as is reflected in the rate of heterolysis of the sulfonate ester bond and in the product outcome. For sulfonate ester 1 no reaction via heterolysis of the sulfonate ester bond has been found, whereas 2 shows a slow and 3 a fast homofragmentation reaction. The reactivity of these compounds perfectly parallels the increased TBI between two functionalities due to changing the geometry of the relaying σ-bonds from a U-, to a sickle-, and finally, to a W-shape. Though both 2 and 3 show homofragmentation only 3 affords nortricyclene ( 4 ) in high yields. The stereochemical and stereoelectronic requirements for the homofragmentation can be rationalized similarly to the Grob fragmentation.

Through-4-bond interactions are not strong enough to split off primary sulfonate esters, as can be concluded from studies on 5 . However, after the introduction of a methyl group at C(8), a selective homofragmentation of 6 to aldehyde 8 has been observed, indicating that the reluctance of the primary sulfonate to heterolyse is most likely due to the instability of the intermediate primary carbocation. The sulfonate ester 7 gives rise to four different products with aldehyde 9 as the main product. The product ratio can be rationalized by using the Curtin-Hammett principle.

In Chapter 3 a simplified Molecular Orbital (MO) description of TBI between an alkoxide function and an (incipient) carbocationic center is given. This description accounts for most of the experimental results obtained from the base-induced heterolyses of 1,4-diol monosulfonate esters. For example, it explains why a "W-shaped" σ-relay between an alkoxide and a sulfonate group results in a relatively facile formation of a carbocation. It also provides insight in the indirect transfer of negative charge from the alkoxide to the (incipient) carbocation center.

Upon desilylation, the negative charge developed on oxygen of Si-O bonds can be stabilized by remote electron-withdrawing groups (Chapter 4). Desilylation experiments on the silyl ethers of 1-3 and 5-7 demonstrate that the stabilization depends on the strength of the electron-withdrawing group (sulfonate ester vs methyl ether), but also, even to a greater extent, on the geometry of the relaying σ-bonds between the silyl ether and the electron- withdrawing group. The desilylation rate increases upon changing the cr-relay from a U- to a W-shape.

In contrast to 1,4-diol monosulfonate esters with an all-trans σ-relay, their 1,5 analogs 10-12 only exhibit fragmentation as a minor side reaction (Chapter 5).

Dependent on the degree of methyl-substitution no fragmentation product at all ( 10 ), a trace amount ( 11 ), or a 20% yield of the seven-center fragmentation product (12--->13) was obtained. It will be clear that the fragmentation of 1,5-diol monosulfonate esters can not effectively be applied in organic syntheses.

Monosulfonated 1,4-diols, on the other hand, react highly predictably and selectively, and consequently they can be applied as intermediates in total synthesis. Previous work on perhydroazulene sesquiterpenes (see Chapter 1) and the work on α-santalene sesquiterpenes described in this thesis (Chapter 6) nicely demonstrates this potential.

The homofragmentation reaction of monosulfonated 1,4-diols has been used as the key step in the enantiospecific synthesis of an a-santalane. The precursor for this α-santalane, mesylate 14 , was obtained from commercially available ( R )-(-)carvone. With this "Carvone ---> α-Santalane-route", the homofragmentation reaction has proven its utility in natural product synthesis.

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