A Novel Method for the Synthesis of Thioacetates Using Benzyltriethyl­ammonium Tetrathiomolybdate and Acetic Anhydride

Abstract

Herein we report a simple and efficient methodology for the synthesis of thioacetates using benzyltriethylammonium tetrathiomolybdate and acetic anhydride as the key reagents, starting from alkyl halides in a multistep, tandem reaction process. Its application in the synthesis of orthogonally protected cysteine and anomeric β-thioglycosides has also been demonstrated.

Key words

benzyltriethylammonium tetrathiomolybdate - acetic anhydride - thioacetates

References and Notes

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23

General Procedure for the Synthesis of Thioacetates - Synthesis of 4a
To the solution of alkyl halide 5a (0.169 g, 1 mmol,) in MeCN (5 mL), tetrathiomolybdate 1 (0.37 g, 2.2 equiv) was added and the reaction mixture was stirred for 1 h. To this solution, Ac₂O (0.408 g, 4.0 equiv) was added and the reaction mixture was stirred further for 1.5 h. The solvent was removed under vacuum, the solid residue was extracted with CH₂Cl₂-Et₂O (3:7) 5 × 10 mL, filtered through Celite and concentrated. The crude product was purified by silica gel (100-200 mesh) column chromatography; EtOAc-hexane (19:1); gummy liquid, yield 94%. IR (neat): 3030 (w), 2924 (m), 1692 (s), 1353 (w), 1133 (m), 627 (m) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.27 (s, 5 H), 4.09 (s, 2 H), 2.31 (s, 3 H). ^¹³C (75 MHz, CDCl₃): δ = 194.8, 137.4, 128.6, 128.4, 127.1, 33.2, 30.1. HRMS: m/z calcd for C₉H₁₀OS: 189.030 [M + Na]; found: 189.0358.
Compound 4d: oily liquid, yield 96%. IR: 2988 (w), 1676 (s), 1416 (m), 1176 (s), 625 (m) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.88 (d, J = 8.1 Hz, 2 H), 7.30 (d, J = 8.1 Hz,
2 H), 4.13 (s, 2 H), 2.57 (s, 3 H), 2.35 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 197.4, 194.5.
Compound 4l: oily liquid, yield 80%. IR (neat): 2903 (m), 2863 (w), 1732 (s), 1462 (m), 1110 (s) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.71 (m, 1 H), 2.37 (s, 3 H), 1.70-1.30 (m, 8 H), 1.00 (t, J = 7.2 Hz, 3 H), 0.91 (t, J = 7.2 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 195.4, 54.4, 33.0, 26.7, 22.5, 13.8, 11.0. HRMS: m/z calcd for C₉H₁₈OS: 197.0976 [M + Na]; found: 197.0970.
Compound 8: white solid, mp 77 ˚C, yield 80%; [α]_D ^²8 -48 (c 1, CHCl₃). IR (neat): 3351 (br), 2951 (w), 1698 (s), 1517 (m), 1212 (m) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.33 (m, 5 H), 5.55 (d, J = 7.2 Hz, 1 H), 5.11 (s, 2 H), 4.50-4.60 (m, 1 H), 3.75 (s, 3 H), 3.42 (dd, J = 14.0, 4.8 Hz, 1 H), 3.40 (dd, J = 14.0, 4.8 Hz, 1 H), 2.32 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 194.8, 170.5, 155.6, 136.0, 128.4, 128.1, 128.0, 67.0, 53.4, 52.7, 31.1, 30.3. HRMS: m/z calcd for C₁₄H₁₇O₅S: 334.0725 [M + Na]; found 334.0710.
Compound 11: gummy solid, yield 78%; [α]_D ^²8 +8.7 (c 1, CHCl₃). IR (neat): 3318 (br), 2965 (m), 2930 (m), 1736 (s), 1695 (s), 1682 (s), 1635 (m), 1262 (m), 1213 (m), 1139 (m) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.34 (s, 5 H), 6.92 (d, J = 8.0 Hz, 1 H), 5.67 (d, J = 8.0 Hz, 1 H), 5.12 (s, 2 H), 4.52 (dd, J = 8.6, 4.8 Hz 1 H), 4.40 (m, 1 H), 3.35 (dd, J = 16.0, 4.0 Hz, 1 H), 3.12 (dd, J = 16.0, 8.0 Hz, 1 H), 2.30 (s, 3 H), 1.90-1.86 (m, 1 H), 1.44-1.36 (m, 1 H), 1.18-1.12 (m, 1 H), 0.90-0.86 (m, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 196.6, 171.8,169.6, 156.3, 136.0, 128.4, 128.1, 128.0, 67.7, 56.6, 55.0, 52.1, 37.6, 31.4, 30.4, 25.0, 15.3, 11.2. HRMS: m/z calcd for C₂₀H₂₈N₂O₈S: 447.1506 [M + Na]; found: 447.1563.

24

To a solution of dipeptide 9 (1.0 mmol, 0.366 g) and pyridine (5 mmol, 0.395 g) in CH₂Cl₂ (10 mL) at -10 ˚C MsCl (1.2 mmol, 0.136 g) was added and the reaction mixture was stirred for 6 h. The reaction was quenched with H₂O and extracted with CH₂Cl₂ (3 × 15 mL). The organic extract was washed with brine, dried over Na₂SO₄, and concentrated. The crude product was purified by column chromatography on silica gel (100-200 mesh), white solid, mp 119 ˚C, yield 95%; [α]_D ^²8 +15.7 (c 1, CHCl₃). IR (neat): 3334 (br), 2964 (m), 1731 (s), 1674 (s), 1529 (m), 1361 (m), 1170 (m) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.31 (s, 5 H), 6.95 (d, J = 7.5 Hz, 1 H), 5.68 (d, J = 7.2 Hz, 1 H), 5.14 (s, 2 H), 4.61-4.53 (m, 3 H), 4.35 (dd, J = 9.0, 7.2 Hz, 1 H), 3.80 (s, 3 H), 3.00 (s, 3 H), 1.93-1.84 (m, 1 H), 1.45-1.33 (m, 1 H), 1.25-1.00 (m, 1 H), 0.92-0.86 (m, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 171.7, 167.7, 155.9, 135.6, 128.54, 128.3, 128.1, 68.3, 67.5, 56.7, 53.6, 52.2, 37.6, 37.2, 24.9, 15.3, 11.4. HRMS: m/z calcd for C₁₉H₂₈N₂O₈S: 467.1467 [M + Na]; found: 467.1451.

25

Compound 11 was obtained in optically pure form and there was no racemization or formation of diastereomer.