Triphenyl-1,2-ethanediol

Douglas M. Krein Todd L. Lowary The Ohio State University, Columbus, Ohio, USA 

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

Form Supplied in white solid the (f )-form is commercially available. 

Preparative Methods (7 )-l,l,2-triphenylethane-l,2-diol [(7 )-(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)-(l) is accessible from (S)-mandelic acid, which is also commercially available (eq 1).  

When l,l,2-triphenylethane-l,2-diol-derived esters are submitted to a monodeprotonation and subsequently treated with Chlorotrimethylsilane, the formation of 2-trimethylsilyloxy-l,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.  

---

Alkaline hydrolysis of the crude adduct formed with benzaldehyde, followed by treatment with diazomethane and column chromatography, affords methyl (2R,3S)-3-hydroxy-2-methyl-3-phenylpropanoate in 96% ee. Reduction of the crude products formed in the reactions with 2-inethylpropanal and 2,2-dimethylpropanal leads to the corresponding 1,3-diols with >96% ee. In both the hydrolysis and the reduction procedures, the chiral auxiliary reagent, 1,1,2-triphenyl-1,2-ethanediol, can be recovered and reused72. 

The cyclic phosphonate 41 was formed in the reaction of (/ )-l,l,2-triphenyl-1,2-ethanediol (40) with methanephosphonyl dichloride in a highly diastereoselective manner (dr=9 l) (Scheme 14) [31]. 

R)-(+)-1,1,2-Triphenyl-1,2-ethanediol is available from methyl3 and ethyl4 (R)-(-)-mandelate by treatment with phenylmagnesium bromide. The synthesis of (R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate [(R)-HYTRA] has been reported previously by the submitters.5 6 (S)-(-)-2-Hydroxy-1,2,2-triphenylethyl acetate is available according to this procedure starting from the enantiomeric methyl (S)-(+)-mandelate or (S)-(+)-... 

The addition of doubly deprotonated HYTRA to achiral4 5 as well as to enantiomerically pure aldehydes enables one to obtain non-racemic (3-hydroxycarboxylic acids. Thus, the method provides a practical solution for the stereoselective aldoi addition of a-unsubstituted enolates, a long-standing synthetic problem.7 As opposed to some other chiral acetate reagents,7 both enantiomers of HYTRA are readily available. Furthermore, the chiral auxiliary reagent, 1,1,2-triphenyl-1,2-ethanediol, can be recovered easily. Aldol additions of HYTRA have been used in syntheses of natural products and biological active compounds, and some of those applications are given in Table I. (The chiral center, introduced by a stereoselective aldol addition with HYTRA, is marked by an asterisk.)... 

Colorless, crystalline, optically pure (R)-(4-)-1,1,2-triphenyl-1,2-ethanediol can be recovered in >95% yield after recrystallization from methanol as described in... 

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(lll) 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 x 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). 

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... 

Yamamoto and co-workers reported the use of scandium(lll) triflate as an esterification catalyst when acetic anhydride was used as the acetate source.5 6 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 coworkers,2 1 but via simple, direct filtration for the reaction mixture. 

P-Hydroxy carboxylic acids (12,3).2 This acetate on double deprotonation with LDA undergoes diastereoselective aldol reactions with aldehydes. The adducts are easily hydrolyzed to optically active P-hydroxycarboxylic acids with release of (R)-(+)-1,1,2-triphenyl-1,2-ethanediol, the precursor to 1. Optically pure acids can be obtained by crystallization of the salt with an optically active amine such as (S)-(—)-1 -pheny lethylamine. 

Dicyclohexylsulfonamidoisobomeol Diisopinocampheyl-boron Trifluoromethanesulfonate a-Methyltoluene-2,a-sultam 1,1,2-Triphenyl-1,2-ethanediol. 

Related Reagents. (S)-4-Benzyl-2-oxazolidinone 10,2-Camphorsultam (/ )-(+)-f-Butyl 2-(p-Tolylsulfinyl)propionate 10-Dicyclohexylsulfonamidoisobomeol Diisopinocampheyl-boron Trifluoromethanesulfonate (R,R)-2,5-Dimethylborolane 2,6-Dimethylphenyl Propionate Ethyl 2-(Methyldiphenylsilyl)-propanoate a-Methyltoluene-2,a-sultam 3-Propionylthiazoli-dine-2-thione (/ ,/ )-1,2-Diphenyl-1,2-diaminoethane iV,iV -Bis-[3,5-bis(trifluoromethyl)benzenesulfonamide] 1,1,2-Triphenyl-1,2-ethanediol. 

---