Synlett 2014; 25(17): 2498-2502
DOI: 10.1055/s-0034-1379027
letter
© Georg Thieme Verlag Stuttgart · New York

A New Deprotection Procedure of MTM Ether

Masaatsu Adachi
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan   Fax: +81(52)7894111   Email: nisikawa@agr.nagoya-u.ac.jp
,
Honoka Hashimoto
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan   Fax: +81(52)7894111   Email: nisikawa@agr.nagoya-u.ac.jp
,
Ryo Sakakibara
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan   Fax: +81(52)7894111   Email: nisikawa@agr.nagoya-u.ac.jp
,
Takuya Imazu
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan   Fax: +81(52)7894111   Email: nisikawa@agr.nagoya-u.ac.jp
,
Toshio Nishikawa*
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan   Fax: +81(52)7894111   Email: nisikawa@agr.nagoya-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 10 July 2014

Accepted after revision: 05 August 2014

Publication Date:
15 September 2014 (online)


Abstract

A new deprotection procedure of methylthiomethyl (MTM) ether, a protective group for the hydroxy group, was developed. MTM was oxidized with MCPBA or Oxone, and the resulting sulfoxide was treated under conditions of the Pummerer rearrangement, to give acetoxy sulfide and/or acetoxy acetal. Alkaline hydrolysis of the products provided the unprotected alcohols in good yields. Details of the reactions using several different substrates are described.

Supporting Information

 
  • References and Notes

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  • 6 The similar cyclic methylene acetal formation in deprotection of MTM was reported: Wachter MP, Adams RE. Synth. Commun. 1980; 10: 111

    • For reviews of Pummerer rearrangement, see:
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  • 8 The model compound 8 was prepared from d-pinene through diol 12 in two steps. For details, see the Supporting Information.
  • 9 1H NMR Data of Acetoxy Sulfide 10a and Acetoxy Acetal 10b (ca. 1:4.6 Inseparable Mixture) 1H NMR (300 MHz, CDCl3): δ = 0.96 (3 H, s, CH3), 1.26 (3 H, s, CH3), 1.40–1.52 (1 H, m), 1.80–1.98 (5 H, m), 2.02 (3 H, s, CH3 of Ac), 2.08 (3 H, s, CH3 of Ac), 2.13–2.24 (2 H, m), 4.12 (0.18 H, d, J = 12 Hz, CCHA HBOAc of acetoxy sulfide), 4.14 (1.64 H, s, CCH2OAc of acetoxy acetal), 4.22 (0.18 H, d, J = 12 Hz, CCHA HB OAc of acetoxy sulfide), 4.50 (0.18 H, d, J = 10 Hz, OCHA HBS), 4.64 (0.18 H, d, J = 10 Hz, OCHA HB S), 5.22 (0.82 H, d, J = 7 Hz, OCHA HBOAc), 5.24 (0.36 H, s, SCH2OAc), 5.35 (0.82 H, d, J = 7 Hz, OCHA HB OAc).
  • 10 1H NMR spectra of the crude products of the Pummerer reaction indicated the presence of cyclic methylene acetal 13, which might be formed from 11a and/or 11b during the workup (concentration). Therefore, the reaction mixture was directly poured into an aq ammonia, resulting in exclusive formation of 12. For details, see the Supporting Information.
  • 11 TLC analysis indicated that the primary alcohol of 9 was first acetylated and then acetylation of the sulfoxide occurred to a mixture of the product 10a and 10b.

    • The related reactions involving oxonium intermediates generated from the sulfoxides of S,O-thioacetals with Tf2O or TFAA, and subsequent transformation were reported. For examples, see:
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  • 13 As it turned out later, the similar reactions giving acetoxy sulfides from the sulfoxides of MTM were reported: Antonsen Q, Benneche T, Undheim K. Acta Chem. Scand., Ser. B 1988; 42: 515
  • 14 For details regarding preparation of the substrates, see the Supporting Information.
  • 15 1H NMR Data of the Trifluoroacetoxy Acetal Derived from 16 1H NMR (300 MHz, CDCl3): δ = 0.19 (9 H, s, CH3 of TMS), 0.83 (3 H, s, CH3), 0.84–2.42 (18 H, m), 1.02 (3 H, s, CH3), 3.37 (3 H, s, CH 3OCH2O), 5.26 (1 H, br d, J = 5 Hz, C=CH), 5.76 (1 H, d, J = 6 Hz, OCHA HBOTFA), 5.84 (1 H, d, J = 6 Hz, OCHA HB OTFA).
  • 16 The structure of 21 was identified by analysis of NMR and MS spectra. For details, see the Supporting Information.
  • 17 The mechanism of formation for 20 is unclear.
  • 18 Ueda M. Chem. Lett. 2012; 41: 658