- Efficient synthesis of an apremilast precursor and chiral β-hydroxy sulfones via ketoreductase-catalyzed asymmetric reduction
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Ketoreductase (KRED)-catalyzed asymmetric reduction of prochiral ketones is an attractive method to synthesize chiral alcohols. Herein, two KREDs LfSDR1-V186A/E141I and CgKR1-F92I with complementary stereopreference were identified towards reduction of apremilast prochiral ketone intermediate 1a. LfSDR1-V186A/E141I exhibited >99% conversion and 99.2% ee yielding an apremilast chiral alcohol intermediate ((R)-2a) at 50 g L?1 substrate loading. Furthermore, we investigated the substrate scope of β-keto sulfones by using LfSDR1-V186A/E141I and CgKR1-F92I to produce both enantiomers of the corresponding β-hydroxy sulfones, with good-to-excellent conversion (up to >99%) and enantioselectivity (up to 99.9% ee) being obtained in most cases. Finally, the gram-scale synthesis of (R)-2a was performed by employing the crude enzyme of LfSDR1-V186A/E141I and BsGDH to afford the desired enantiomer with >99% conversion, 85.9% isolated yield and 99.2% ee. This study presents a biocatalytic strategy to synthesize chiral β-hydroxy sulfones.
- Gao, Xiao,Guo, Jiyang,Jia, Xian,Qian, Dong,Qin, Bin,Wang, Huibin,You, Song,Zhang, Wenhe
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supporting information
p. 2081 - 2085
(2022/03/31)
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- Synthesis of β-hydroxy sulfones via opening of hydrophilic epoxides with zinc sulfinates in aqueous media
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Reaction of hydrophilic epoxides (ethylene oxide and propylene oxide) with readily accessible zinc sulfinates in aqueous solution under essentially neutral conditions afforded β-hydroxy sulfones in good yields. This method avoids the need for organic solvents and produces ZnO as the only major reaction byproduct. 2-(Methylsulfonyl)ethanol, a common reagent for the protection of various functional groups, was obtained by this methodology from ethylene oxide in 78% yield. Reaction of various simple zinc alkane- and benzenesulfinates with propylene oxide proceeded regioselectively in 63-67% yield. The corresponding opening of these epoxides with zinc 1,3-butadiene-1-sulfinate afforded 1-butadienyl β-hydroxyalkyl sulfones in 30% yield. Mechanistic studies revealed that the yields of these products were limited by their consumption in competing intra- and intermolecular Michael addition processes.
- Chumachenko, Nataliya,Sampson, Paul
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p. 4540 - 4548
(2007/10/03)
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- Lipase-promoted dynamic kinetic resolution of racemic β-hydroxyalkyl sulfones
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A series of racemic aryl β-hydroxyalkyl sulfones have been successfully transformed into the corresponding optically active O-acetyl derivatives in high yields (up to 80%) with enantiomeric excesses more than 99% using a dynamic kinetic resolution procedure, in which a lipase-promoted kinetic resolution is combined with a concomitant ruthenium-catalysed racemization of the substrates.
- Kielbasinski, Piotr,Rachwalski, Michal,Mikolajczyk, Marian,Moelands, Marcel A. H.,Zwanenburg, Binne,Rutjes, Floris P. J. T.
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p. 2157 - 2160
(2007/10/03)
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- Diastereoselective oxidation of β-hydroxysulfides with TBHP: A comparative study of titanocenes and Ti(Oi-Pr)4 as catalysts
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Titanocene dichlorides and Ti(Oi-Pr)4 have been used as catalysts for the oxidation with t-butyl hydroperoxide of racemic β-hydroxysulfides having a stereogenic carbon centre in α- or β- position with respect to the sulfur atom. β-Hydroxysulfides were oxidized in high yields to the corresponding sulfoxides, titanocenes being more chemo- and generally more diastereoselective than Ti(Oi-Pr)4. A divergent stereochemical outcome has been observed when using titanocenes or Ti(Oi-Pr)4 in the oxidation of protected β-hydroxy sulfides.
- Sala, Giorgio Della,Labano, Stefania,Lattanzi, Alessandra,Scettri, Arrigo
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p. 6679 - 6683
(2007/10/03)
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- Sulfone Directed Rhodium Catalysed Hydroboration: Regiochemistry in Acyclic System
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Rhodium catalysed hydroboration of allyl sulfones gave rise to Markownikoff product with high regioselectivity.
- Hou, Xue-Long,Hong, Dao-Guang,Rong, Guo-Bin,Guo, Yang-Long,Dai, Li-Xin
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p. 8513 - 8516
(2007/10/02)
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- SULFINATES AS NUCLEOPHILES FOR THE RING-OPENING OF EPOXIDES: A CONVENIENT ROUTE TO β-HYDROXYSULFONES
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It has been found that the nucleophilic ring-opening of epoxides by arenesulfinates, in the presence of magnmesium nitrate as a Lewis acid catalyst, provides a preparatively useful, convenient route to β-hydroxysulfones.
- Still, Ian W. J.,Ablenas, Fred J.
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p. 1103 - 1110
(2007/10/02)
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