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. Author manuscript; available in PMC: 2016 Apr 22.
Published in final edited form as: Tetrahedron Lett. 2015 Apr 22;56(17):2269–2271. doi: 10.1016/j.tetlet.2015.03.038

Oxidative conversion of δ-sultones to γ-lactones

Duminda S Liyanage a, Christian S Jungong a, Alexei V Novikov a,*
PMCID: PMC4465188  NIHMSID: NIHMS674463  PMID: 26085691

Abstract

Delta-sultones, prepared by C-H insertion, can be oxidatively converted to gamma-lactones by treatment with t-BuOK/t-BuOOH. An intermediate in the synthesis of (−)-eburnamonin was prepared using this approach.

Sultones are cyclic sulfonates, sulfonic ester analogs of lactones.1 δ-Sultones, particularly, can be conveniently prepared by C-H insertion from alkyl diazosulfonates.2,3 This reaction effectively permits fuctionalization of alcohols at the γ-position relative to the hydroxyl group, contrasted with β-functionalization that occurs with a more common ester tether (Scheme 1).4

Scheme 1.

Scheme 1

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C-H insertion of diazosulfonates

Since the discovery of this reaction we have been working on development of synthetically useful transformation of the obtained δ-sultones. Earlier, we reported a conversion of these compounds to δ-lactones via reductive desulfonation by treatment with samarium(II) iodide/DMPU in THF.5 After obtaining this result, we contemplated developing a method for conversion of δ-sultones to γ-lactones, a common structural fragment in many natural compounds. This transformation would require an oxidative conversion of the C2 carbon of the sultone to a carboxylate, along with removal of the ester carbon, possibly via a sort of oxidative decarboxylation process.

Du Bois has earlier demonstrated C2 oxidation of potassium anions of δ-sultones by Davis oxazaridine.3 Guided by this finding, we surveyed several oxidizing agents. We found that treatment of δ-sultones by t-butyl hydroperoxide in presence of potassium t-butoxide produced the desired γ-lactones.10 Good to excellent yields of the lactones were obtained for a range of δ-sultones (Table 1). The structures of lactones 2a and 2b, obtained from sultones 1a and 1b, were confirmed by comparison of their spectral data to the literature reports.6

Table 1.

Oxidative preparation of γ-lactones from δ-sultones

graphic file with name nihms674463t1.jpg
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We propose the following mechanism for this transformation (Scheme 2). Deprotonation of the sultone would produce enolate 3. This would be followed by an oxidation of the carbanion by t-butyl hydroperoxide anion, as known in some examples.7 The collapse of the produced alkoxide would produce α-ketoester 5, the product that was observed by Du Bois in the Davis oxazaridine oxidation.3 In presence of t-butylhydroperoxide, however, further oxidation may occur. t-Butylhydroperoxide anion could add to the ketone carbonyl, producing tetrahedral intermediate 6, then 3-membered intermediate 7 via an intramolecular attack on the ester carbonyl. The resulting intermediate would fragment with the expulsion of t-butoxide to form anhydride 8. Alternatively, 6 could form directly from 8 via a Bayer-Villiger type acyl shift. Extrusion of SO2 (either in the course of the reaction or during the work-up) would liberate the alcohol functionality that would close onto the anhydride to form the γ-lactone ring.

Scheme 2.

Scheme 2

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Proposed mechanism of the transformation

Using the sequence of sulfonate C-H insertion and this oxidative conversion to γ-lactone we prepared a key intermediate in the synthesis of (−)-eburnamonin. For this purpose enantiomerically enriched alcohol 10 was prepared via enantioselective addition of ethylmagnesium cuprate to α,β-unsaturated ester 9, catalyzed by tol-BINAP,8 followed by LAH reduction of the obtained ester. This alcohol was converted to diazosulfonate 11 using previously developed methods.2 C-H insertion of this diazosulfonate proceeded as expected under Rh2(esp)2 catalysis to produce δ-sultone 12 in good yield (Scheme 3).

Scheme 3.

Scheme 3

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Synthesis of the key intermediate for (−)-eburnamonin

Oxidative desulfonation of this sultone to lactone 13 proceeded in a 75% yield using the general procedure, effectively achieving a “remote carboxylation” of alcohol 10 at the tertiary position. Removal of the benzyl protecting group produced from lactone 13 provided intermediate 14 that was previously diastereoselectively converted to (−)-eburnamonin. 9

Thus, a δ-sultones can be converted to γ-lactones by treatment with t-butylhydroperoxide and potassium t-butoxide. In combination with C-H insertion to prepare δ-sultones this provides a method for “remote carboxylation” of alcohols at C3, leading to γ-lactones. An intermediate in the synthesis of (−)-eburnamonin was prepared using this approach.

Supplementary Material

Acknowledgements

This work was supported by National Institutes of Health under grant No. GM085645. We thank Alena Kubatova for HRMS analyses. The work on TOF MS was supported by the National Foundation under grant No. CHE-0216038.

Footnotes

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Supplementary data

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/.

References and Notes

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  • 10.General procedure for oxidative conversion of sultones to lactones:To a solution of the corresponding δ-sultone (1 equiv) in THF (2.5 mL) at rt was added a solution of tert-butyl hydroperoxide in decane (5M, 5 equiv), followed by a dropwise addition of a solution potassium tert-butoxide in THF (1M, 6 equiv). After stirring at rt for 16 h, sodium sulfite was added and the resulting suspension stirred for 15 min. 20 mL of 1N hydrochloric acid solution was added and the resulting mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate and evaporated to afford a crude product, which was purified by flash chromatography.

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Supplementary Materials

NIHMS674463-supplement.pdf (863.9KB, pdf)

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