A New Deprotection Procedure of MTM Ether

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.

Key words

MTM - protective group - deprotection - Pummerer rearrangement

• References and Notes

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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, CCH_A H_BOAc of acetoxy sulfide), 4.14 (1.64 H, s, CCH₂OAc of acetoxy acetal), 4.22 (0.18 H, d, J = 12 Hz, CCH_A H_B OAc of acetoxy sulfide), 4.50 (0.18 H, d, J = 10 Hz, OCH_A H_BS), 4.64 (0.18 H, d, J = 10 Hz, OCH_A H_B S), 5.22 (0.82 H, d, J = 7 Hz, OCH_A H_BOAc), 5.24 (0.36 H, s, SCH₂OAc), 5.35 (0.82 H, d, J = 7 Hz, OCH_A H_B 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, OCH_A H_BOTFA), 5.84 (1 H, d, J = 6 Hz, OCH_A H_B 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.
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