Npys-Mediated Elimination Reactions of Alcohols and Thiols: A Facile Route to Dehydroalanine and Dehydrobutyrine Building Blocks

Abstract

We report a new and rapid method for side-chain dehydration/dehydrothiolation of serine, threonine, and cysteine building blocks. The method relies on activation with 3-nitro-2-pyridinesulfenyl chloride (Npys-Cl) followed by treatment with base. It is possible to perform the sequence as a one-pot operation and due to the significant functional-group compatibility of Npys-Cl, this method may be compatible with multifunctional and complex substrates.

Key words

3-nitro-2-pyridinesulfenyl - Npys-Cl - dehydroalanine - elimination - amino acids

• References and Notes

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• 14 General Procedure for the Synthesis of Compound 4 To a 10 mL flame-dried flask was added 3 (125 μmol, 1.0 equiv) and dissolved in the given solvent (2.5 mL). To this solution was then added base (500 μmol, 4.0 equiv). The reaction course was monitored by TLC analysis at 2 min, 5 min, 10 min, and every 5 min thereafter until the reaction was complete. The reaction mixture was then concentrated directly before purification, except for the entries with DMF and DMSO which underwent aqueous workup; the reaction was diluted with 5% KHSO₄ (aq, 5 mL), extracted with Et₂O (3 × 10 mL), dried (Na₂SO₄), filtered, and concentrated. The resulting residue was purified by flash column chromatography (CH₂Cl₂), yielding 4 as a colorless oil. R_f = 0.48 (CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 7.01 (s, 1 H, NH), 6.14 (s, 1 H), 5.71 (d, J = 1.4 Hz, 1 H), 3.82 (s, 3 H), 1.47 (s, 9 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 164.6, 152.7, 131.4, 105.3, 80.8, 53.0, 28.4 ppm. HRMS (ES): m/z calcd for C₄H₈NO₂ ⁺ [M + H – C(O)OC(CH₃)₃]⁺: 102.0550; found: 102.0550. IR (neat): ν_max = 3429, 2985, 1736, 1635, 1508, 1442, 1395, 1369, 1324, 1245, 1204, 1155, 1065, 1001, 967, 887, 847, 808, 712, 599 cm^–1.

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