A Simple, General, and Highly Chemoselective Acetylation of Alcohols Using Ethyl Acetate as the Acetyl Donor Catalyzed by a Tetranuclear Zinc Cluster

Abstract

In the presence of a Zn-cluster catalyst, alcohols are efficiently converted to the corresponding acetate just by refluxing in EtOAc. The mild reaction conditions enabled the reactions of various functionalized alcohols to proceed in good to excellent yield. Moreover, even when a large excess of the acetyl donor is used, the hydroxyl groups are selectively acetylated in the presence of highly nucleophilic aliphatic amino groups, approaching chemoselectivity to that of enzymatic system.

Key words

zinc clusters - catalysis - acetylations - transesterifications - green chemistry

References and Notes

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12

See Supporting Information for details.

14

In a similar way, acidic alcohols, such as 1,1,1,3,3,3-hexafluoropropan-2-ol (pK _a 9.3), did not participate in the acylation, see ref. 9c.

15

For primary aliphatic alcohol selective acetylation by catalytic transesterification, see ref. 5d,f,i,k,7d,g.

18

Yield of 9 was determined after N-Boc protection to simplify the analysis.

19

Typical Experimental Procedure for the Acetylation of Alcohol 2f
A mixture of Zn₄ (OCOCF₃)₆O (1, 36 mg, 0.038 mmol),
4-(triethylsiloxymethyl)benzyl alcohol (2f, 759 mg, 3.0 mmol), and EtOAc (5.0 mL) was refluxed for 18 h under an argon atmosphere. The resulting mixture was concentrated and purified by silica gel column chromatography (silica gel, hexane-EtOAc = 20:1 to 4:1) to provide the acetate 3f (790 mg, 89%) as a colorless oil together with unreacted substrate 2f (38 mg, 5%). IR (neat NaCl): 2955, 2876, 1744, 1517, 1458, 1415, 1379, 1362, 1228, 1092, 1019, 971, 820, 742 cm^-¹. ^¹H NMR (300 MHz, CDCl₃, 35 ˚C): δ = 0.65 (q, J = 7.5 Hz, 6 H, SiCH ₂CH₃), 0.98 (t, J = 7.5 Hz, 9 H, SiCH₂CH ₃), 2.08 (s, 3 H, COCH ₃), 4.73 (s, 2 H, ArCH ₂OSi), 5.09 (s, 2 H, ArCH ₂OAc), 7.32 (m, 4 H, Ar). ^¹³C NMR (75 MHz, CDCl₃, 35 ˚C): δ = 4.51, 6.70, 20.92, 64.39, 66.13, 126.32, 128.21, 134.62, 141.54, 170.76. MS (EI): m/z (%) = 294 (1) [M⁺], 265 (62), 145 (100), 103 (39), 75 (20). HRMS (EI): m/z calcd for C₁₆H₂₆O₃Si: 294.1651; found: 294.1646.