2-Acetoxyisobutyryl Chloride

[40635-66-3]  · C6H9ClO3  · 2-Acetoxyisobutyryl Chloride  · (MW 164.592)

(useful for converting cis-diols to trans-chloroacetates1 followed by epoxide formation2)

Alternate Name: Moffatt reagent.

Physical Data: bp 55-56 °C/6 mmHg; d 2.236 g cm-3.

Form Supplied in: liquid of 95% purity commercially available.

Preparative Methods: can be prepared by the acylation of 2-hydroxyisobutyric acid (Acetyl Chloride, Acetic Acid) followed by reaction with Thionyl Chloride.1,3

Handling, Storage, and Precautions: corrosive and a lachrymator and should be handled accordingly.

2-Acetoxyisobutyryl chloride has been used to convert cis-diols to trans-chloroacetates (eq 1).1 trans-Diols give many products due to their inability to form the cyclic acetoxonium ion intermediate. Nucleophilic attack occurs primarily at the acetoxy carbonyl group due to the bulky substituents a to the acid chloride carbonyl.

Ribonucleosides also react smoothly with 2-acetoxyisobutyryl chloride. In this case, a chloroacetate compound was obtained but with retention of configuration due to participation of the C-2 carbonyl group of the uracil ring (eq 2).1,4

Recently, the Moffatt reagent has been used in the total synthesis of complex natural products.5 The chloroacetate compound is easily converted into an epoxide in excellent yield and on a large scale (eq 3).2 2-Acetoxyisobutyryl bromide has been employed similarly in natural product synthesis.6

1. Greenberg, S.; Moffatt, J. G. JACS 1973, 95, 4016.
2. Schreiber, S. L.; Sammakia, T.; Uehling, D. E. JOC 1989, 54, 15. Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L. JACS 1990, 112, 5583.
3. Friary, R. JHC 1978, 15, 63.
4. Russell, A. F.; Greenberg, S.; Moffatt, J. G. JACS 1973, 95, 4025. Jain, T. C.; Russell, A. F.; Moffatt, J. G. JOC 1973, 38, 3179. Jain, T. C.; Jenkins, I. D.; Russell, A. F.; Verheyden, J. P. H.; Moffatt, J. G. JOC 1974, 39, 30. Russell, A. F.; Prystasz, M.; Hamamura, E. K.; Verheyden, J. P. H.; Moffatt, J. G. JOC 1974, 39, 2182.
5. Ghosh, A. K.; McKee, S. P.; Thompson, W. J. TL 1991, 32, 5729. Jackson, P. F. W.; Raphael, R. A. TL 1983, 24, 2117.
6. Kim, G.; Chu-Moyer, M. Y.; Danishefsky, S. J.; Schulte, G. K. JACS 1993, 115, 30.

Regina Zibuck

Wayne State University, Detroit, MI, USA

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