Easy Access to Enantiopure (S)‐ and (R)‐Aryl Alkyl Alcohols by a Combination of Gold(III)‐Catalyzed Alkyne Hydration and Enzymatic Reduction

Abstract

Chemoenzymatic one‐pot processes based on the combination of metal catalysis and biocatalysis open up highly attractive perspectives regarding the production of enantiopure compounds. By combining a gold‐catalyzed hydration reaction with an enzymatic reduction, we present a straightforward and atom‐economical chemoenzymatic method for the synthesis of secondary alcohols with excellent optical purity. Efficient cofactor recycling exploits the solvent of the metal‐catalyzed step as an auxiliary substrate for the enzymatic step.

Polydopamine‐Encapsulated Dendritic Organosilica Nanoparticles as Amphiphilic Platforms for Highly Efficient Heterogeneous Catalysis in Water

“…To initiate the study, we selected acetophenone as model substrate for the biotransformation, which was conducted in modified conditions developed by Mihovilovic (Table 3, Entry 1), [ 39 ] namely 50 mmol/L concentration of ketones, DON@ADH@PDA (50 mg, the loadings of ADH were calculated to be 9.8 wt%), Tris‐HCl buffer (pH 8.0), NADP + and i ‐PrOH (30% V / V ), 37 o C, 12 h reaction time. As expected, the desired chiral benzyl alcohol was obtained in 93% yield and 99% ee.…”

Chemoenzymatic Relay Reaction and Its Applications in Highly Efficient and Green Synthesis of High-Value Chiral Compounds

“…图式 12 一锅多步酶水解/金催化环化合成手性四氢呋喃衍生 物 [25] Scheme 12 Chemoenzymatic synthesis of chiral tetrahydrofuran derivatives via enzymatic hydrolysis/Au-catalyzed cyclization [25] 最近 Mihovilovic 课题组 [29] 通过将金催化的水合反 应与酶促还原相结合, 报道了一种简单且原子经济高适…”

“…由于在金催化步骤 中使用 i PrOH 作 Au(III)催化水合的溶剂, 反应中金属催 化步骤的反应混合物可用于随后的酶促还原反应. * 图式 13 金催化的水合反应与酶促还原相结合合成手性醇 [29] Scheme 13 Chemoenzymatic synthesis of chiral alcohols via enzymatic Au-catalyzed hydrolysis and enzymatic reduction [29] 1.5 酶催化与其他金属催化剂相结合 除了以上金属催化剂与酶催化相结合进行多步串 联反应外, 其他过渡金属, 如 Cu、Rh 等也用来催化不 对称转移氢化(ATH), 并与酶相结合合成光学活性化合 物. 2013 年, Lavandera 课题组 [30] 报道了在温和的反应条 件下, 在水性介质中通过组合单一醇脱氢酶(ADH)与 Cu 催化的"点击"反应的结合, 高收率、高对映选择性 图式 14 单一醇脱氢酶(ADH)与 Cu 催化的"点击"反应相结 合合成不同的手性 1,2,3-三唑衍生的二醇 [30] Scheme 14 Synthesis of different chiral 1,2,3-triazole-derived diols by combining a single alcohol dehydrogenase (ADH) with a Cu-catalyzed "click" reaction [30] 2017 年, 陈永正课题组 [31] 报道了一种新颖的不对 称"金属-生物催化体系", 反应将 Rh 催化的 ATH 过 程与全细胞介导的不对称羟基化相结合, 可得到一系列 有两个立体中心的手性 2-取代的-四氢喹啉-4-醇(47%的 产率, 99∶1 的 dr, ＞99% ee, Scheme 15).…”

Alcohol Dehydrogenases and N‐Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β‐Disubstituted Allylic Alcohols

“…Among them, the only stereoselective application was demonstrated by Asikainen and Krause, who reported the synthesis of optically active 2,5‐dihydrofurans through a tandem hydrolytic kinetic resolution/cycloisomerization employing Pseudomonas cepacia lipase and HAuCl 4 [51] . On the other hand, approaches involving gold catalysis and alcohol dehydrogenases (ADHs) have also been described, but through sequential transformations due to the incompatibility of individual catalytic systems and reaction conditions [54–56] . In this context, the one‐pot two‐step synthesis of chiral sec ‐alcohol derivatives in high conversions and enantiomeric excess was described via gold‐catalyzed hydration of terminal aryl‐ or alkyl acetylenes using either gold(III) chloride at 65 °C in a water/2‐propanol (2‐PrOH) mixture, [55] or HandaPhos‐gold(I) chloride, a silver salt and a surfactant in water that formed micelles under argon atmosphere, [56] both followed by the ketone intermediate bioreduction with external addition of the corresponding ADH and auxiliary reagents (Scheme 2, top).…”