[95061-46-4]  · C20H18O2  · 1,1,2-Triphenyl-1,2-ethanediol  · (MW 290.38)

(derived chiral monoesters undergo stereoselective aldol additions; formation of O-silyl orthoesters and cyclic phosphonates)

Physical Data: mp 126 °C. (R): [a]25D +214° (c = 1, ethanol), +220° (c = 1, 95% ethanol); (S): [a]25D -217° (c = 1, ethanol).

Solubility: sol dichloromethane, chloroform, THF, ethanol; insol hexane.

Form Supplied in: white solid; the (R)-form is commercially available.

Preparative Methods: (R)-1,1,2-triphenylethane-1,2-diol [(R)-(1)] is easily available from commercial (R)-Mandelic Acid, which is first esterified to give methyl mandelate and then treated with Phenylmagnesium Bromide (3.5 equiv). In an analogous way, (S)-(1) is accessible from (S)-mandelic acid, which is also commercially available (eq 1).2

anti-Selective and Diastereofacially Selective Aldol Additions.

2-Trimethylsilyloxy-1,2,2-triphenylethyl propionate, which is prepared from (R)-(1) by esterification with propionyl chloride and subsequent silylation of the tertiary hydroxy group, reacts in a highly stereoselective manner upon deprotonation, transmetalation with Dichlorobis(cyclopentadienyl)zirconium, and addition to 2-methylpropanal. The diastereoselectivity is 96:4, which is the ratio of the major product to the sum of all other diastereomers. Subsequent reduction with Lithium Aluminum Hydride affords (2S,3R)-2,4-dimethyl-1,3-pentanediol in 95% ee (eq 2).3 anti-Selective aldol additions which deliver chiral nonracemic products have been a longstanding problem of asymmetric synthesis.4 Doubly deprotonated 2-hydroxy-1,2,2-triphenylethyl propionate has been applied in a total synthesis of dolastatin.5

When 1,1,2-triphenylethane-1,2-diol-derived esters are submitted to a monodeprotonation and subsequently treated with Chlorotrimethylsilane, the formation of 2-trimethylsilyloxy-1,3-dioxolanes results. The orthoester moiety thus obtained serves as a protecting group for carboxylic acids (eq 3); it is stable towards alkyllithium reagents and can be cleaved under nonacidic conditions by alkaline hydrolysis.6

Methanephosphonyl dichloride reacts with (R)-(1) to give 2-methyl-4,4,5-triphenyl-2-oxo-1,3,2-dioxaphospholane (eq 4); the (RP,RC) diastereomer forms predominantly (9:1).7

A series of enantiomerically pure 1,1-diaryl-2-phenylethane-1,2-diols is available from methyl mandelate by addition of the corresponding substituted arylmagnesium bromides or aryllithium reagents.2b,8

Related Reagents.

10,2-Camphorsultam; (R)-2-t-Butyl-6-methyl-4H-1,3-dioxin-4-one; (R)-(+)-t-Butyl 2-(p-Tolylsulfinyl)propionate; Chloro(cyclopentadienyl)bis[3-O-(1,2:5,6-di-O-isopropylidene-a-D-glucofuranosyl)]titanium; 10-Dicyclohexylsulfonamidoisoborneol; Diisopinocampheylboron Trifluoromethanesulfonate; (R,R)-2,5-Dimethylborolane; 2-Hydroxy-1,2,2-triphenylethyl Acetate; a-Methyltoluene-2,a-sultam; (S)-4-Benzyl-2-oxazolidinone; 3-Propionylthiazolidine-2-thione; (R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis[3,5-bis(trifluoromethyl)benzenesulfonamide]; trans-2,5-Bis(methoxymethyl)pyrrolidine.

1. (a) McKenzie, A.; Wren, H. JCS 1910, 97, 473. (b) Roger, R.; McKay, W. B. JCS 1931, 2229.
2. (a) Braun, M.; Devant, R. TL 1984, 25, 5031. (b) Devant, R.; Mahler, U.; Braun, M. CB 1988, 121, 397. (c) Braun, M.; Gräf, S.; Herzog, S. OS 1993, 72, 32.
3. (a) Braun, M.; Sacha, H. AG 1991, 103, 1369; AG(E) 1991, 30, 1318. (b) Sacha, H.; Waldmüller, D.; Braun, M. CB 1994, 127, 1959.
4. For reviews, see: (a) Braun, M. In Advances in Carbanion Chemistry; Snieckus, V., Ed.; JAI: Greenwich, CT, 1992; Vol. 1, pp 177-247; (b) Braun, M.; Sacha, H. JPR 1993, 653.
5. (a) Pettit, G. R.; Singh, S. B. U.S. Patent 4 978 744, 1990, (CA 1991, 114, 164 824v). (b) Pettit, G. R.; Singh, S. B.; Herald, D. L.; Lloyd-Williams, P.; Kantoci, D.; Burkett, D. D.; Barkóczy, J.; Hogan, F.; Wardlaw, T. R. JOC 1994, 59, 6287.
6. Waldmüller, D.; Braun, M.; Steigel, A. SL 1991, 160.
7. Brodesser, B.; Braun, M. PS 1989, 44, 217.
8. Prasad, K.; Chen, K.-M.; Repic, O.; Hardtmann, G. E. TA 1990, 1, 703.

Manfred Braun

Heinrich-Heine-Universität, Düsseldorf, Germany

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