Pentamethylphenyl (Ph*) and Related Derivatives as Useful Acyl Protecting Groups for Organic Synthesis: A Preliminary Study

Abstract

A study of acyl protecting groups derived from the Ph* motif is reported. While initial studies indicated that a variety of functional groups were not compatible with the Br₂-mediated cleavage conditions required to release the Ph* group, strategies involving the use of different reagents or a modification of Ph* itself (Ph*OH) were investigated to solve this problem.

Key words

protecting group - oxidative cleavage - acylium ion - HFIP - deprotection

Publication History

Received: 13 July 2020

Accepted after revision: 31 August 2020

Article published online:
22 September 2020

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• 18 Typical Procedure for CAN-Mediated Cleavage: Synthesis of 16 To a solution of phenol 14 (28.2 mg, 0.10 mmol) in MeOH (1.0 mL) was titrated a solution of CAN (272 mg, 0.50 mmol) in MeOH (0.5 mL) at RT in the open atmosphere until the color of the CAN solution persisted (orange, typically 4–5 equiv). The reaction mixture was diluted with H₂O (3 mL) and stirred for 5–10 min, then further diluted with CH₂Cl₂ (2 mL), and saturated with NaCl. The layers were separated, the aqueous layer extracted with CH₂Cl₂ (5 × 1.5 mL), the combined organics dried (Na₂SO₄) and concentrated in vacuo. Purification by flash column chromatography (SiO₂, eluent: pentane–Et₂O, 99:1) afforded ester 16 (10.1 mg, 61%) as a volatile colorless oil. IR (film): ν_max = 3087, 3064, 3028, 3002, 2952, 1735, 1604, 1497, 1454, 1436, 1365, 1293, 1255, 1195, 1161, 1079, 1029, 986, 950, 896, 837, 771, 750, 699 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.38–7.26 (2 H, m, Ph), 7.25–7.17 (3 H, m, Ph), 3.68 (3 H, s, OCH₃), 3.05–2.90 (2 H, m, CH₂Ph), 2.68–2.58 (2 H, m, CH₂COOCH₃). ¹³C NMR (126 MHz, CDCl₃): δ = 173.5 (C=O), 140.6 (ArC), 128.6 (2 C, 2 × ArCH), 128.4 (2 C, 2 × ArCH), 126.4 (ArCH), 51.8 (OCH₃), 35.8 (CH₂COOCH₃), 31.1 (CH₂Ph).
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