✍ Scribed by Yuji Mori; Miki Kuhara; Akio Takeuchi; Makoto Suzuki
No coin nor oath required. For personal study only.
The diastereoselective reduction of acyclic B-alkoxy ketones with lithium aluminum hydride in the presence of lithium iodide has been studied and found to provide syn-1,3-diol derivatives with high diastereoselection. -The stereocontrolled formation of 1,3-diols is of great interest to synthetic chemists since the 1,3-polyhydroxylated chain forms the basic skeleton of polyene and polyol macrolide antibiotics. 1 In connection with our stereochemical study of sporaviridin,' a polyol macrolide, we needed an efficient method for preparing x-1,3-diols. Among the procedures developed for the synthesis of 1,3-diols, hydroxy-directed reduction of B-hydroxy ketones has proven to be highly valuable, with boron or zinc chelating intermediates playing an important role in determining the stereoselectivity. On the other hand, aluminum complex hydride methods have been of less interest due to their low selectivity.4 We have now developed a lithium aluminum hydride-lithium iodide reduction as a promising new method for our purposes.
In this letter we report our results on the 8-alkoxy-directed reduction of acyclic Balkoxy ketones using LiA1H4-LiI as the reducing agent (eq. 1).
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LiI t [ f&M ] LiAlH4_fKM (eq 1) A B C Diastereoselection 95:5 The 8-alkoxy-B'-hydroxy ketone 1 is a useful precursor for 1,3-polyol synthesis.5 Reduction of the ketone 1 with NaBH4 and LiAlH4 afforded 1,3-diols with moderate 1,3-x selectivity in nearly quantitative yields (Table I, entries 1,3,4). Considering the typically low selectivity observed in LiA1H4 reductions of Bhydroxy ketones, 4a these results suggested that 1,3-asymmetric induction from the B-alkoxy group in 1 was operative. The LiAlH4-LiI reduction of 8-alkoxy-8'-hydroxy and 6-alkoxy ketones with terminal 1,3dioxolane rings is a versatile and useful method for the diastereoselective formation of syn-1,3-diol derivatives. The highly w-selectivity arises from 8-chelation of both the ketone and ether oxygens with lithium cation to form an intermediate complex B (eq. 1). This locks the conformation of the 8-alkoxy ketone chain and hydride then attacks from less hindered side, resulting in the formation of the w-product C. Applications of the LiAlH4-LiI reduction were demonstrated in short and efficient syntheses of optically active (-)-endo-1,3-dimethyl-2,9-dioxabicyclo[3.3.l]nonane 15, a host specific substance for the ambrosia beetle which infests the Norwegian spruce,6 and a synthetic intermediate 20 of (+)-nonactic acid.' The starting ketones 10 and 16 were prepared from the acid 9, which was obtained from (S)-(-)-malic acid (95% ee),8 by the treatments of 4-pentenyllithium and methyllithium, respectively, in good yield. A highly a-selective reduction of 10 with LiA1H4 in the presence of LiI in ether at -78°C gave the w-alcohol 11, [a]~*+3.35" (c 1.0, CHC13), in 88% yield (w:anti=95:5). Deprotection of the acetonide group in 11 gave the trio1 12, [(x]i'+7.84' (c 0.5, CHC13) in 95% yield. Direct bicyclic acetal formation was achieved LiI indicated temperature and LiAlH4 (10 mmol) was added. The reaction mixture was stirred for 30 min. Workup in usual manner gave products. The reduction products may be purified by flash chromatography on silica gel. RE 1.
📜 SIMILAR VOLUMES
Chx 2 BCl-mediated syn-aldol reaction of the a-OTBS lactate-derived ketone 1 followed by in situ reduction of the resulting boron aldolate with LiBH 4 lead to complete stereoselectivity for the boronates 2 in 80-95% yields. Then, a very mild oxidative work-up of 2 (H 2 O 2 /NaOAc in THF-H 2 O) allow
## Abstract The anti‐diols are formed with <95% diastereoselectivity from hydroxyketones (I) using the known Zn(BH~4~)~2~ reagent.