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
Reduction O 0220Zr(Ot-Bu) 4 -Catalyzed Tishchenko Reduction of β-Hydroxy Ketones. -Zr(Ot-Bu)4 is used as an effective catalyst for the Tishchenko reduction of β-hydroxy ketones to afford 1,3-anti-diol monoesters. Treatment of (IV) with isobutyraldehyde results in formation of a mixture of Tishchenko products; the ratio depends on the reaction temperature. For the anti-aldol educt (VII), a ratio of nearly 1:1 is observed due to epimerization. -(SCHNEIDER*, C.; KLAPA, K.; HANSCH, M.; Synlett 2005, 1, 91-94; Inst. Org. Chem., Univ. Leipzig, D-04103 Leipzig, Germany; Eng.) -S. Adam 22-048
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.