- One-Pot Enzymatic-Chemical Cascade Route for Synthesizing Aromatic α-Hydroxy Ketones
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2-Hydroxyacetophenone (2-HAP) is an important building block for the production of a series of natural products and pharmaceuticals; however, there is no safe, efficient, and economical method for 2-HAP synthesis. Here, a one-pot enzymatic-chemical cascade route was designed for synthesizing 2-HAP based on retrosynthetic analysis. First, a spontaneous proton-transfer reaction was designed using a computational simulation that enabled 2-HAP synthesis from the isomer 2-hydroxy-2-phenylacetaldehyde. A route for 2-hydroxy-2-phenylacetaldehyde synthesis was then constructed by introducing the unnatural substrate glyoxylic acid into a C-C ligation reaction catalyzed by Candida tropicalis pyruvate decarboxylase. Assembly and optimization of this enzymatic-chemical cascade route resulted in a final yield of 92.7%. Furthermore, stereospecific carbonyl reductases were introduced to construct a synthetic application platform that enabled further transformation of 2-HAP into (S)- and (R)-1-phenyl-1,2-ethanediol. This method of cascading spontaneous chemical and enzymatic reactions to synthesize chemicals offers insight into avenues for synthesizing other valuable chemicals.
- Wang, Lei,Song, Wei,Wang, Binju,Zhang, Yan,Xu, Xin,Wu, Jing,Gao, Cong,Liu, Jia,Chen, Xiulai,Chen, Jinghua,Liu, Liming
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p. 2808 - 2818
(2021/03/15)
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- Palladium-Catalyzed [5 + 2] Annulation of Vinylethylene Carbonates with Barbiturate-Derived Alkenes
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A palladium/XantPhos-catalyzed [5 + 2] annulation of VECs with electron-deficient alkenes having an isolated carbon-carbon double bond has been developed to afford spirobarbiturate-tetrahydrooxepines. This study provides an expedient assembly of biologically interesting spirobarbiturate-tetrahydrooxepines. The easy scalability and versatile transformability of the reaction products were also exhibited.
- Chen, Yuehua,Deng, Hao,Gao, Xing,Guo, Hongchao,Jiang, Feng,Wang, Wei,Wu, Yongjun,Zhu, Dongyu
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supporting information
p. 7158 - 7163
(2020/10/02)
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- Spiro[indene-1,4′-oxa-zolidinones] Synthesis via Rh(III)-Catalyzed Coupling of 4-Phenyl-1,3-oxazol-2(3 H)-ones with Alkynes: A Redox-Neutral Approach
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Transition-metal-catalyzed C-H activation synthesis of heterocyclic spiro[4,4]nonanes has persistently witnessed the use of additional stoichiometric transition-metal oxidant when employing C=C bond as the spiro ring closure site. Herein, we have addressed the issue by reporting a redox-neutral strategy for spiro[indene-1,4′-oxa-zolidinones] synthesis via Rh(III)-catalyzed coupling of 4-phenyl-1,3-oxazol-2(3H)-ones with alkynes. The synthesis features a broad substrate scope and high regiospecificity.
- Liu, Zhongsu,Zhang, Wenjing,Guo, Shan,Zhu, Jin
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p. 11945 - 11957
(2019/10/02)
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- Palladium-Catalyzed (Z)-Selective Allylation of Nitroalkanes: Access to Highly Functionalized Homoallylic Scaffolds
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Nitroalkanes undergo decarboxylative allylation in the presence of vinyl-substituted cyclic carbonates, providing a wide variety of functionalized homoallylated compounds with exquisite stereocontrol. This Pd-mediated procedure features operational simplicity, versatile substrate combinations, and also allows for the sequential introduction of different allyl groups in the nitroalkane scaffolds with high levels of stereocontrol through the intermediacy of a (Z)-configured palladacyclic intermediate. As far as we know, the developed protocol is the first general Pd-mediated methodology toward (Z)-configured homoallylic nitroalkanes with attractive functional group diversity.
- Cristòfol, àlex,Escudero-Adán, Eduardo C.,Kleij, Arjan W.
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p. 9978 - 9990
(2018/09/06)
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- Enantioselective Silver-Catalyzed Cascade Synthesis of Fused Lactone and Lactam Oxazolines
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A new and highly stereoselective cascade reaction between isocyanoacetate esters and α-hydroxy and α-amino ketones has been developed. A cinchona alkaloid derived aminophosphine/silver(I) catalyst complex promoted the reaction and enabled the ready synthesis of fused bicyclic γ-lactone and γ-lactam oxazolines with high enantiocontrol (up to 99% ee).
- De La Campa, Raquel,Manzano, Rubén,Calleja, Paul,Ellis, Sam R.,Dixon, Darren J.
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supporting information
p. 6033 - 6036
(2018/09/27)
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- Direct Aerobic Oxidative Reactions of 2-Hydroxyacetophenones
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Valuable and direct aerobic oxidation reactions of 2-hydroxyacetophenones were explored. The concept was based on the in situ treatment of small quantities of aerobically formed α-keto aldehydes that drove the reactions to the corresponding products. This new strategy was applied for a variety of oxidative reactions of 2-hydroxyacetophenones, and valuable products such as phthalides, quinoxalines, and α-keto amides were obtained in good to high yields.
- Sahoo, Subas Chandra,Nath, Utpal,Pan, Subhas Chandra
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supporting information
p. 4434 - 4438
(2017/08/23)
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- Copper-Mediated SN2′ Allyl-Alkyl and Allyl-Boryl Couplings of Vinyl Cyclic Carbonates
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A method for the copper-catalyzed borylmethylation and borylation of vinyl cyclic carbonates through an SN2′ mechanism is reported. These singular reactions involve selective SN2′ allylic substitutions with concomitant ring opening of the cyclic carbonate and with extrusion of CO2 and formation of a useful hydroxyl functionality in a single step. The stereoselectivity of the homoallylic borylation and allylic borylation processes can be controlled, and synthetically useful unsaturated (E)-pent-2-ene-1,5-diols and (E)-but-2-ene-1,4-diols are accessed.
- Miralles, Núria,Gómez, José Enrique,Kleij, Arjan W.,Fernández, Elena
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supporting information
p. 6096 - 6099
(2017/11/27)
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- Preparation method of indazole and application of indazole in medicine synthesis
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The invention belongs to the field of chemicals, and relates to a preparation method of indazole and an application of the indazole in medicine synthesis. The invention discloses a preparation method of indazole and an application of the indazole in synthesizing 1H-indazole-3-carboxylic acid, lonidamine, a compound 8, a compound 9, a compound 10, axitinib, YD-3, YC-1 and similar substances thereof.
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Paragraph 0087; 0088; 0093; 0094
(2017/04/21)
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- Stereoselective and Versatile Preparation of Tri- and Tetrasubstituted Allylic Amine Scaffolds under Mild Conditions
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Significant progress has been observed in recent years in the synthesis of allylic amines, which are important building blocks in synthetic chemistry. Most of these processes are effective toward the preparation of allylic amines, with limited potential to introduce three or four different substituents on the olefinic unit in a stereocontrolled fashion. Therefore, the discovery of a mild and operationally simple protocol allowing such challenging stereoselective synthesis of multisubstituted allylic amines remains an inspiring target. Herein, we report the first general and practical methodology for the stereoselective synthesis of tri- and tetrasubstituted allylic amines based on Pd-catalyzed conversion of allyl surrogates readily obtained from cyclic vinyl carbonates. These rare conversions are characterized by excellent stereoselectivity, operational simplicity, mild reaction conditions, and wide scope in reaction partners. DFT studies were performed to rationalize the stereocontrol in these allylic amine formation reactions, and evidence is provided that the formation of a six-membered palladacyclic intermediate leads toward the formation of (Z)-configured allylic amine products.
- Guo, Wusheng,Martínez-Rodríguez, Luis,Kuniyil, Rositha,Martin, Eddy,Escudero-Adán, Eduardo C.,Maseras, Feliu,Kleij, Arjan W.
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supporting information
p. 11970 - 11978
(2016/10/07)
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- Green organocatalytic α-hydroxylation of ketones
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An efficient and green method for the α-hydroxylation of substituted ketones has been developed. This method includes the in situ conversion of various ketones into the corresponding silyl enol ethers and their oxidation to the corresponding α-hydroxy ketones. Two protocols have been established leading either to protected α-hydroxy carbonyls or free α-hydroxy ketones. Both procedures are easy to follow and lead to good to high yields for a variety of ketones.
- Voutyritsa, Errika,Theodorou, Alexis,Kokotos, Christoforos G.
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p. 5708 - 5713
(2016/07/06)
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- Copper(I) Oxide-Mediated Cyclization of o-Haloaryl N-Tosylhydrazones: Efficient Synthesis of Indazoles
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An efficient synthesis of indazoles from readily accessible E/Z mixtures of o-haloaryl N-tosylhydrazones has been developed. The thermo-induced isomerization of N-tosylhydrazones is discussed. A series of valuable indazole derivatives are prepared in good yields, and the method has been successfully applied to the synthesis of the bioactive compounds, lonidamine, AF-2785, axitinib, YC-1 and YD-3.
- Tang, Meng,Kong, Yuanfang,Chu, Bingjie,Feng, Dan
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supporting information
p. 926 - 939
(2016/04/05)
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- Synthesis of α-hydroxyacetophenones
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A general method for the preparation of α-hydroxyacetophenones is presented. Functionalized arylmagnesium species are transmetalated to the corresponding arylzinc intermediates, which undergo Cu(I)-catalyzed reaction with acetoxyacetyl chloride. Acidic hy
- McLaughlin, Mark,Belyk, Kevin M.,Qian, Gang,Reamer, Robert A.,Chen, Cheng-Yi
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experimental part
p. 5144 - 5148
(2012/07/03)
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