Org. Synth. 2000, 77, 45
DOI: 10.15227/orgsyn.077.0045
[ 1,2-Ethanediol, 1,1,2-triphenyl-, 2-acetate, (R)- ]
Submitted by John Macor, Anthony J. Sampognaro, Patrick R. Verhoest, and Robert A. Mack1 .
Checked by Christoph Gaul and Stephen F. Martin.
1. Procedure
(R)-(+)-2-Hydroxy-1,2,2-triphenylethyl acetate [(R)-HYTRA]. To a mechanically stirred solution of (R)-(+)-1,1,2-triphenyl-1,2-ethanediol (35.0 g, 0.121 mol, (Note 1)) and acetic anhydride (17.1 mL, 0.181 mol, 1.5 eq, (Note 2)) in anhydrous acetonitrile (500 mL, (Note 3)) at room temperature under nitrogen is added a solution of scandium(III) trifluoromethanesulfonate (1.23 g, 2.5 mmol, 2 mol%, (Note 4)) in anhydrous acetonitrile (125 mL) over approximately 35 min (Note 5). After about 8 min a white precipitate begins to appear, and the resulting mixture is stirred at room temperature under nitrogen for a total of 3 hr. The solid is filtered, washed with acetonitrile (2 × 25 mL), and dried under vacuum at 40°C overnight to afford (R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate (35.42 g, 0.107 mol, 88%) as a white solid (Note 6).
2. Notes
1. Commercially available 1,1,2-triphenyl-1,2-ethanediol in either antipode can be used. The checkers used (R)-(+)-1,1,2-triphenyl-1,2-ethanediol from Aldrich Chemical Company, Inc. , ([α] D 20 +210° (C2H5OH, c 1). Alternatively, 1,1,2-triphenyl-1,2-ethanediol can be prepared via the procedure in Organic Syntheses.2
2. Acetic anhydride was purchased from Aldrich Chemical Company, Inc., (99+% purity) , and used without additional purification. A 50% excess of acetic anhydride is needed for the reaction to be complete in a reasonably short period of time. Greater than a 50% excess of acetic anhydride does not appreciably improve the reaction time to completion.
3. Acetonitrile was purchased from Aldrich Chemical Company, Inc., (anhydrous, 99.8% purity in SureSealTM bottles) and used without additional purification.
4. Scandium(III) trifluoromethanesulfonate [Sc(OTf)3] was purchased from Aldrich Chemical Company, Inc., (99% purity) and used without additional purification.
5. The order of addition of the reagents has a significant effect on the yield of the reaction. The optimal order of addition of reagents is described above (i.e., addition of Sc[III](OTf)3 slowly, last). Continual addition of the scandium(III) triflate during the course of the reaction maintained the pace of the process. Bolus addition of the catalyst resulted in a reaction that slowed down or stopped part way, resulting in lower yields. Premixing the Sc[III](OTf)3 with the diol and adding the acetic anhydride last led to reproducibly lower yields of (R)-HYTRA and a longer time to precipitation of (R)-HYTRA. Absolutely seminal to the reaction was the choice of solvent since all starting materials were soluble in acetonitrile, whereas the product acetate was not, thus allowing purification by simple filtration.
6. Spectral data are as follows: mp 198-200°C (crude product); [α] D 22 +196° ( pyridine , crude product, c 1); mp 213-221°C ( benzene );3 4 5 2 [α] D 22 +201° (pyridine, c 1); 1H NMR (CDCl3, 300 MHz) δ: 1.97 (s, 3 H), 2.80 (s, 1 H), 6.66 (s, 1 H), 7.01-7.16 (m, 10 H), 7.24-7.38 (m, 3 H), 7.52-7.56 (m, 2 H) ; 13C NMR (CDCl3, 125 MHz) δ: 21.1, 78.5, 80.3, 126.2, 126.3, 127.0, 127.3, 127.5, 127.8, 127.9, 128.4, 128.5, 135.9, 142.7, 144.8, 169.7 ; IR (CHCl3) cm−1: 3064, 3024, 1737, 1495, 1372, 1239, 1168, 779 ; HRMS calcd for C22H19O2 ([MH+]-H2O), m/z 315.1385, found 315.1386 .
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
The (R)- and (S)-HYTRA (2-Hydroxy-1,2,2-Triphenylethyl Acetate) esters have been used in the diastereoselective addition of a chiral acetate to chiral and prochiral electrophiles, usually aldehydes.6 The generality of this reaction led to the commercialization of these agents and the precursor 1,1,2-triphenyl-1,2-ethanediols. Furthermore, Braun, Gräf, and Herzog had previously detailed a 100-plus-g synthesis.2 However, the HYTRA esters are costly,7 and the synthesis previously reported was straightforward until the final step, in which acetyl chloride reacted with the 1,1,2-triphenyl-1,2-ethanediol to produce the HYTRA ester.2 In this procedure, the HYTRA acetate was prepared in 92% yield (108 g), but the reaction work up was tedious and time consuming. To purify the HYTRA ester in this procedure, the reaction mixture is quenched with water, reaction solvent (CH2Cl2 ) is removed by evaporation under reduced pressure, and the resulting solids are filtered, washed with water, and then transferred to a flask with toluene . Water is removed from the solid by an azeotropic distillation using toluene. The product is finally filtered from toluene to yield the acetate.
Yamamoto and co-workers reported the use of scandium(III) triflate as an esterification catalyst when acetic anhydride was used as the acetate source.8,9 While they only reported on monoalcohols (1°, 2°, and 3°) on a small scale, the submitters modified the Yamamoto procedure to suit the submitters' reaction with the 1,1,2-triphenyl-1,2-ethanediol. As detailed above, the current procedure provides a yield of the HYTRA acetate that is comparable to the procedure reported by Braun and co-workers,2 but via simple, direct filtration for the reaction mixture.

References and Notes
  1. Astra Zeneca, Three Biotech, One Innovation Drive, Worchester, MA 01605. Present address for J. M.: Bristol-Myers Squibb, Pharmaceutical Research Institute, P. O. Box 4000, Princeton, NJ 08543.
  2. 249-251°C (from toluene), Braun, M.; Gräf, S.; Herzog, S. Org. Synth., Coll. Vol. IX 1998, 507.
  3. Several different melting points are reported in literature: (a) m.p. 220-221°C (from diethyl ether), Polansky, O.; Schinzel, E.; Wessely, F. Monatsh. Chem. 1956, 87, 24-46;
  4. mp 220-220.5°C (from diethyl ether/CH2Cl2), Corey, E. J.; Casanova, J. J. Am. Chem. Soc. 1963, 85, 165-169;
  5. 224.5-225.5°C (from benzene), Ito, N.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc. Jpn. 1983, 56, 3527-3528;
  6. Braun, M.; Gräf, S. Org. Synth., Coll. Vol. IX 1998, 497, and references cited therein.
  7. (R)-HYTRA ester in the 1998-1999 Aldrich Chemical Company catalog (p. 1499, item 37,650-7) is $29.10/g.
  8. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1995, 117, 4413-4414.
  9. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Org. Chem. 1996, 61, 4560-4567.

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

(R)-(+)-2-Hydroxy-1,2,2-triphenylethyl acetate:
1,2-Ethanediol, 1,1,2-triphenyl-, 2-acetate, (R)- (11); (95061-47-5)

1,2-Ethanediol, 1,1,2-triphenyl-, (R)- (11); (95061-46-4)

Acetic anhydride (8);
Acetic acid anhydride (9); (108-24-7)

Acetonitrile: TOXIC: (8,9); (75-05-8)

Scandium(III) trifluoromethanesulfonate:
Methanesulfonic acid, trifluoro-, scandium (3+) salt (13); (144026-79-9)