Zr(OtBu) 4 was found to catalyze the Tishchenko reduction of b-hydroxy ketones giving rise to differentiated 1,3-anti-diol monoesters in high yields and excellent stereoselectivity.The diastereoselective reduction of b-hydroxy ketones is a fundamental synthetic operation in the stereoselective synthesis of 1,3-dioxygenated compounds such as polyacetate-or polypropionate-derived natural products. 1 A large number of methods have been developed for the selective synthesis of either 1,3-syn-or 1,3-anti-diols. 2 Most prominent among the syn-selective methods is the Narasaka-Prasad protocol employing NaBH 4 /Et 2 BOMe, 3 which is based upon an external hydride delivery onto a preformed boron chelate and furnishes 1,3-syn-diols typically with >96% de. In addition, Zn(BH 4 ) 2 , 4 DIBALH 5 and combinations of TiCl 4 and various reductants 6 have also been shown to reduce b-hydroxy ketones to 1,3-syndiols, albeit with occasionally diminished diastereoselectivity. The most widely employed method to obtain 1,3-anti-diols was developed by Evans et al. and involves the use of Me 4 NBH(OAc) 3 , which delivers the hydride intramolecularly with anti/syn ratios of 95:5 or better. 7 Alternatively, a samarium-catalyzed Tishchenko reduction has been developed by Evans et al. which gives rise to 1,3-anti-diol monoesters with exceptional levels of diastereoselectivity (>98% de) and furnishes monoprotected and thus differentiated 1,3-diols in one step. 8 A binuclear aluminum alkoxide, 9 a zirconocene complex, 10 and Sc(OTf) 3 11 have also been reported as catalysts for this reaction. Apart from hydride reagents one-electron reducing agents such as SmI 2 have been employed in conjunction with proton sources to effect the highly anti-diastereoselective reduction of b-hydroxy ketones. 12 We have recently shown that Zr(Ot-Bu) 4 is a powerful catalyst for the aldol-Tishchenko reaction of ketone aldols such as diacetone alcohol (Scheme 1). 13 The reaction presumably proceeds via retro-aldol cleavage of the thermodynamically unstable ketone aldol, furnishing a zirconium enolate which then undergoes the aldol-Tishchenko reaction in good yield and excellent diastereoselectivity. These observations suggested that Zr(Ot-Bu) 4 may be employed as catalyst solely for the Tishchenko step of this sequence starting directly from b-hydroxy ketones. Accordingly, a systematic investigation was undertaken to devise optimal conditions for the Zr(Ot-Bu) 4 -catalyzed Tishchenko reduction of b-hydroxy ketones.Scheme 1