Dimethyl L-Tartrate1

[608-68-4]  · C6H10O6  · Dimethyl L-Tartrate  · (MW 178.14)

(synthon for chiral auxiliary/ligand preparation; chiral ligand for asymmetric catalysis)

Physical Data: mp 57-60 °C (dec); bp 163 °C/23 mmHg; d 1.238 g cm-3; [a]23 +21° (c = 2.5, H2O).

Solubility: sol most organic solvents, water.

Form Supplied in: moist white crystals.

Handling, Storage, and Precautions: may cause irritation; store in a cool, dry place.

Synthon for Chiral Auxiliary/Ligand Preparation.

(R,R)-Dimethyl L-tartrate, a derivative of natural L-tartaric acid, is readily transformed into useful chiral auxiliaries and ligands for asymmetric synthesis.1 Many of these transformations involve initial acetalization of the 2,3-vicinal hydroxy groups.2-6 Thus a,a,a,a-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs) are prepared from the corresponding acetals of dimethyl L-tartrate (eq 1) and, as the TiIV complexes (see 2,2-Dimethyl-a,a,a,a-tetraphenyl-1,3-dioxolane-4,5-dimethanolatotitanium Diisopropoxide), are useful catalysts for enantioselective additions of dialkylzinc reagents to aldehydes,5 Diels-Alder reactions,6,7 asymmetric hydrocyanations of aldehydes,8 and others.9 The enolate of the acetonide of dimethyl L-tartrate alkylates with good selectivity to give, after acetonide hydrolysis, allyl- or benzylated derivatives (eq 2).10 Orthoesters are also prepared from dimethyl tartrate, and acylate silyl enol ethers in good yield and selectivity to give monoprotected 1,3-diketones (eq 3).11

In an industrial asymmetric synthesis en route to the antiinflammatory agent naproxen, the dimethyl L-tartrate acetals of ethyl aryl ketones are brominated in high yield and selectivity to give the corresponding a-bromo derivatives.12,13 Subsequent stereospecific AgI-promoted 1,2-aryl migration provides the 2-alkyl-2-arylacetic acid after hydrolysis of the tartrate auxiliary, which is recovered (e.g. eq 4).

The vicinal diol cyclic sulfate from dimethyl tartrate undergoes nucleophilic opening to give substituted malate esters.14,15 However, for this application diethyl and diisopropyl L-tartrates give superior yields and selectivities. The asymmetric cyclopropanation of the 1-alkenylboronic ester derived from dimethyl L-tartrate (eq 5) is another example where other tartaric acid derivatives surpass the performance of dimethyl tartrate.16

Chiral Ligand for Asymmetric Catalysis.

Dimethyl L-tartrate is a demonstrated chiral ligand for the TiIV-catalyzed asymmetric epoxidation of allylic alcohols (Sharpless epoxidation),17 and the ZnII-mediated asymmetric cyclopropanation of allylic alcohols (Simmons-Smith reaction), see Iodomethylzinc Iodide.18 Enantioselectivities in these reactions are, however, better with the use of diethyl L-tartrate as the chiral modifier.

1. Seebach, D.; Hungerbühler, E. Modern Synthetic Methods; Scheffold, R., Ed.; Salle-Sauerländer: Aarau, 1980; Vol. 2, pp 91-171.
2. Carmack, M.; Kelley, C. J. JOC 1968, 33, 2171.
3. Musich, J. A.; Rapoport, H. JACS 1978, 100, 4865.
4. Ott, J.; Ramos Tombo, G. M.; Schmid, B.; Venanzi, L. M.; Wang, G.; Ward, T. R. TL 1989, 30, 6151.
5. Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker, D.; Petter, W. HCA 1992, 75, 2171, and references cited therein.
6. Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.; Nakashima, M.; Sugimori, J. JACS 1989, 111, 5340.
7. Corey, E. J.; Matsumura, Y. TL 1991, 32, 6289.
8. Minamikawa, H.; Hayakawa, S.; Yamada, T.; Iwasawa, N.; Narasaka, K. BCJ 1988, 61, 4379.
9. Narasaka, K. S 1991, 1.
10. Naef, R.; Seebach, D. AG(E) 1981, 20, 1030.
11. Longobardo, L.; Mobbili, G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. T 1992, 48, 1299.
12. Castaldi, G.; Cavicchioli, S.; Giordano, C.; Uggeri, F. JOC 1987, 52, 3018.
13. Giordano, C.; Coppi, L.; Restelli, A. JOC 1990, 55, 5400.
14. Gao, Y.; Sharpless, K. B. JACS 1988, 110, 7538.
15. Gao, Y.; Zepp, C. M. TL 1991, 32, 3155.
16. Imai, T.; Mineta, H.; Nishida, S. JOC 1990, 55, 4986.
17. Review: Finn, M. G.; Sharpless, K. B. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: Orlando, 1985; Vol. 5, Chapter 8.
18. Ukaji, Y.; Nishimura, M.; Fujisawa, T. CL 1992, 61.

Bruce A. Barner

Union Carbide Corporation, South Charleston, WV, USA

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