Hexadienyloxycarbonyl (Hdoc) - A Mild Acid Labile Protecting Group for Amines

Abstract

Hexadienyloxycarbonyl is an amine protecting group which can be cleaved with 1% TFA in CH₂Cl₂. It is stable to Pd(0) and basic conditions and is proposed as a useful alternative to the trityl and Bpoc protecting groups.

Key words

protecting groups - amines - amino acids - cleavage - protonations

References

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1

Current address: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Parma, Viale della Scienza, 43100 Parma, Italy.

3

2,4-E,E-Hexadien-1-ol (10 g, 98 mmol) was dissolved in CH₂Cl₂ (50 mL) and p-nitrophenylchloroformate (21 g, 105 mmol) was added. DIPEA (18.3 mL, 105 mmol) was added dropwise with cooling, and the solution was stirred for 16 hours at room temperature under N₂. The solvent was removed under vacuum and the residue was purified by flash chromatography on silica gel eluting with 5% EtOAc in hexane. The product was recrystallised from hexane/EtOAc to give a white solid. (17.4 g, 68%); δ_H (400 MHz, CDCl₃), 1.70-1.72 (d, J = 7 Hz, 3 H, CH ₃), 4.69-4.71 (d, J = 7 Hz,
2 H, CHCH ₂O), 5.58-5.65 (dq, J = 7 Hz, 12 Hz, 1 H, CH₃CHCH), 5.71-5.80 (dt, J = 7 Hz, 15 Hz, 1 H, CHCHCH₂), 5.98-6.05 (dd, J = 10 Hz, 12 Hz, 1 H, CH₃CHCH), 6.25-6.32 (dd, J = 10 Hz, 15 Hz, 1 H, CHCHCH₂), 7.29-7.32 (d, J = 9 Hz, 2 H, o-ArH), 8.19-8.21 (d, J = 9 Hz, 2 H, m-ArH); δ_C (101 MHz, CDCl₃), 18.6 (CH₃), 70.2 (CH₂), 122.0 (CH₃ CH), 122.2 (o-ArC), 125.7 (m-ArC), 130.5 (CH₃CHCH), 133.2 (CHCH₂), 137.4 (CHCHCH₂), 145.8 (p-ArC), 152.8 (C=O), 156.0 (i-ArC).