Lipase/aluminum-catalyzed dynamic kinetic resolution of secondary alcohols
Lipase/aluminum-catalyzed dynamic kinetic resolution of secondary alcohols
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DOI：
10.1002/anie.200600379
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Mueller, Thomas N.
中科院分区：
文献类型：
--
作者：
Berkessel, Albrecht;Sebastian-Ibarz, M. Luisa;Mueller, Thomas N.
The combination of enzymatic kinetic resolution with a metal-catalyzed racemization by reversible hydrogen transfer was reported by Williams and co-workers for the preparation of enantiomerically pure secondary alcohols. In this early work, the rhodium catalyst [Rh2 (OAc) 4] and a lipase effected dynamic kinetic resolution (DKR) with 60% conversion and 98% ee.[1] The research groups of Bäckvall,[2–5] Kim, and Park [6–8] have devised related protocols using rutheniumbased racemization catalysts originally developed by Shvo and Menashe [9] in combination with an immobilized lipase from Candida antarctica (CALB, commercially available as Novozym435). In general, high yields and enantiomeric excesses were obtained. As shown by Jacobs etal., the DKR of secondary benzylic alcohols can also be achieved by combining an acidic zeolite as the racemization catalyst with a lipase in a biphasic system.[10, 11] We considered using aluminum-based catalysts, which are easily obtainable and inexpensive. The Meerwein–Ponndorf–Verley–Oppenauer (MPVO) reaction can be exploited for the racemization of alcohols:[1, 12–14] Oppenauer oxidation of the alcohol is followed by nonstereoselective reduction of the resulting ketone by the Meerwein–Pondorf–Verley reaction. In general, preformed aluminum alkoxide catalysts such as commercially available Al (iPrO) 3 are less active than Rubased systems.[1] As a consequence, relatively high temperatures and prolonged reaction times are usually required. However, much higher reactivities for MPV reductions have recently been reported for dinuclear AlIII complexes [15–17] and for AlIII alkoxides generated in situ.[18] With this in mind, we set out to investigate the activity of aluminum alkoxides prepared in situ for the racemization of chiral secondary alcohols and in particular their utility for the DKR of these substrates in the presence of lipases and acylating agents. We first generated several aluminum species by reaction of ClAlMe2 or AlMe3 with the bidentate ligands (R)-and (S)-1, 1’-bi-2-naphthol (binol), in different ratios, and examined their ability to racemize (S)-1-phenylethanol ((S)-1). Acetophenone (2, 0.5 equiv) was employed as a hydrogen acceptor (Scheme 1).AlMe3/binol (1: 1) proved to be a very effective catalyst: At room temperature, 10 mol% of the Al catalyst sufficed to racemize the substrate completely within three hours. The aluminum catalysts generated from (R)-and (S)-binol showed virtually identical activity. On the basis of these findings, we developed a method for the DKR of 1-phenylethanol (rac-1). We chose 1-phenylvinyl acetate (3) as the acylating agent. The commonly used 2-propenyl acetate (4) gives acetone as the by-product, which acts as a hydrogen acceptor and oxidizes 1-phenylethanol (1) to acetophenone (2). 1-Phenylvinyl acetate (3) is easily synthesized (Scheme2; see the Supporting
