Methyl O-Methyllactate1

[17639-76-8]  · C5H10O3  · Methyl O-Methyllactate  · (MW 118.15)

(lithium enolate used in the stereoselective synthesis of 2-methoxy-3-hydroxypropionate derivatives3)

Physical Data: bp 130-131 °C.

Preparative Methods: by esterification of the known O-methyllactic acid.2,3a

The (Z)-lithium enolate (2), derived from reaction of methyl O-methyllactate (1) with Lithium Diisopropylamide, reacts with aldehydes to form (3) (l isomer) in preference to (4) (u isomer) (eq 1).3 The stereoselectivity is approximately 3:1 in reactions with straight-chain and aromatic aldehydes. Stereospecificity is achieved in reactions with aldehydes with branching at the a-carbon. Other ethers (e.g. benzyl or MEM) derived from methyl lactate exhibit the same trend in stereoselectivity, although the magnitude is lower.3 Stereoselectivity in favor of compounds of u relative stereochemistry, illustrated in (4), is obtained in reactions using the benzyl ether derivative of a hindered ester (e.g. 5).3 The stereoselectivity in aldol reactions of (2) has been used to set the relative stereochemistry at C-3 and C-4 in a synthesis of L-cladinose (6).4

Related Reagents.

(R,R)-2-t-Butyl-5-methyl-1,3-dioxolan-4-one; Ethyl Lithioacetate; Ethyl Mandelate; Phenoxyacetic Acid; Tris(trimethylsilyloxy)ethylene.

1. (a) Heathcock, C. H. Modern Synthetic Methods Scheffold, R. Ed.; VCH: Weinheim, 1992. (b) Heathcock, C. H. COS 1991, 2, Chapter 1.6. (c) Heathcock, C. H. Asymmetric Synthesis; Academic: New York, 1984; Vol. 3.
2. (a) Oki, M.; Hirota, M. BCJ 1963, 36, 290. (b) Petrov, A. A.; Gantseva, B. V.; Kiseleva, O. A. ZOB 1953, 23, 737.
3. (a) Heathcock, C. H.; Pirrung, M. C.; Young, S. D.; Hagen, J. P.; Jarvi, E. T.; Badertscher, U.; Marki, H.-P.; Montgomery, S. H. JACS 1984, 106, 8161. (b) Heathcock, C. H.; Hagen, J. P.; Jarvi, E. T.; Pirrung, M. C.; Young, S. D. JACS 1981, 103, 4972.
4. (a) Montgomery, S. H.; Pirrung, C. H.; Heathcock, C. H. Carbohydr. Res. 1990, 202, 13. (b) Heathcock, C. H.; Montgomery, S. H. TL 1985, 26, 1001.

William A. Kleschick

DowElanco, Indianapolis, IN, USA

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