Asymmetric continuous oxidation in microreactor driven by visible light

doi:10.11949/0438-1157.20190189

Abstract

Abstract:

Photocatalysis, asymmetric synthesis and molecular oxygen oxidation are combined with continuous reaction. Using a glass microreactor, a continuous reaction for asymmetric α-hydroxylation of β-keto ester compound is oxidized by ¹O₂ under visible light. The reaction is catalyzed by cinchona alkaloid phase transfer catalyst in gas-liquid-liquid heterogeneous system. The desired product is obtained in high yield (95%) and good enantio selectivity (87.0%) in microreactor. Compared with the batch reaction, continuous reaction greatly reduces reaction residence time from 30 min to 1.08 min and maintains high stereo selectivity. The method has the advantages of fast, low energy consumption, continuous and high efficiency, and has good industrialization prospects.

Key words: photochemistry, asymmetric organic catalysis, molecular oxygen oxidation, heterogeneous reaction, molecular synthesis, microreactor

摘要：

将可见光催化、不对称合成、分子氧氧化和连续化集成，创新性地用玻璃微通道反应器实现可见光活化分子氧氧化的β-酮酸酯类化合物的不对称α-羟基化反应的连续工艺。用金鸡纳碱衍生的相转移有机催化剂在气-液-液多相体系内实现可见光催化，分子氧不对称氧化连续反应。在心形微通道反应器内，1-茚酮-2-甲酸金刚酯底物完全氧化为(S)-2-羟基-1-茚酮-2-甲酸金刚酯，产物收率95%，对映选择性87.0%。与间歇反应相比，采用微反应器的连续反应在保持产物高立体选择性基础上将30 min反应停留时间缩短至1.08 min。该方法具有快速、低能耗、连续、高效等优势，具有良好的工业化前景。

关键词: 光化学, 不对称有机催化, 分子氧氧化, 多相反应, 分子合成, 微反应器

CLC Number:

TQ 460.31

Shihao FENG, Xiaofei TANG, Jian DU, Qingwei MENG. Asymmetric continuous oxidation in microreactor driven by visible light[J]. CIESC Journal, 2019, 70(8): 3202-3209.

冯世豪, 唐晓飞, 都健, 孟庆伟. 用微反应器实现可见光驱动的不对称氧化连续化反应[J]. 化工学报, 2019, 70(8): 3202-3209.

Figures/Tables 7

References 32

1	Romero N A , Nicewicz D A . Organic photoredox catalysis[J]. Chem. Review, 2016, 116: 10075-10166.
2	Narayanam J M R , Stephenson C R J . Visible light photoredox catalysis: applications in organic synthesis[J]. Chemical Society Reviews, 2010, 40(1): 102-113.
3	Heggo D , Ookawara S . Multiphase photocatalytic microreactors[J]. Chemical Engineering Science, 2017, 196: 67-77.
4	Higuchi T , Heide C , Ullmann K , et al . Light-field-driven currents in graphene[J]. Nature, 2017, 550(7675): 224-228.
5	Seo H , Katcher M H , Jamison T F . Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow[J]. Nature Chemistry, 2016, 9(5): 453-456.
6	Huang H , Li X , Yu C , et al . Visible-light-promoted nickel- and organic-dye‐cocatalyzed formylation reaction of aryl halides and triflates and vinyl bromides with diethoxyacetic acid as a formyl equivalent[J]. Angewandte Chemie, 2017, 56(6): 1500-1505.
7	Nicewicz D A , Nguyen T M . Cheminform abstract: recent applications of organic dyes as photoredox catalysts in organic synthesis[J]. ChemInform, 2014, 4(1): 355-360.
8	丁奎岭 . 不对称催化新概念与新方法[M]. 北京：化学工业出版社, 2009.
	Ding K L . New Concepts and Methods: Asymmetric Catalysis[M]. Beijing: Chemical Industry Press, 2009.
9	Sim S B D , Wang M , Zhao Y . Phase-transfer-catalyzed enantioselective α-hydroxylation of acyclic and cyclic ketones with oxygen[J]. ACS Catalysis, 2015, 5(6): 3609-3612.
10	Liang Y F , Jiao N . Highly efficient C—H hydroxylation of carbonyl compounds with oxygen under mild conditions[J]. Angewandte Chemie, 2014, 126(2): 558-562.
11	Piera J , Backvall J E . Catalytic oxidation of organic substrates by molecular oxygen and hydrogen peroxide by multistep electron transfer—a biomimetic approach[J]. Angewandte Chemie (International ed. in English), 2008, 47(19): 3506-3523.
12	Lee D S , Amara Z , Clark C A , et al . Continuous photo-oxidation in a vortex reactor: efficient operations using air drawn from the laboratory[J]. Organic Process Research & Development, 2017, 21(7): 1042-1050.
13	Kockmann N , Gottsponer M , Zimmermann B , et al . ChemInform abstract: enabling continuous-flow chemistry in microstructured devices for pharmaceutical and fine-chemical production[J]. Chemistry — A European Journal, 2010, 14(25): 7470-7477.
14	Loubière K , Oelgemöller M , Aillet T , et al . Continuous-flow photochemistry: a need for chemical engineering[J]. Chemical Engineering & Processing Process Intensification, 2016, 104(6): 120-132.
15	Hejda S , Drhova M , Kristal J , et al . Microreactor as efficient tool for light induced oxidation reactions[J]. Chemical Engineering Journal, 2014, 255(7): 178-184.
16	Colmenares J C , Varma R S , Nair V , et al . Selective photocatalysis of lignin-inspired chemicals by integrating hybrid nanocatalysis in microfluidic reactors[J]. Chemical Society Reviews, 2017, 46(22): 6675-6686.
17	Cambié D , Zhao F , Hessel V , et al . A leaf-inspired luminescent solar concentrator for energy-efficient continuous-flow photochemistry[J]. Angewandte Chemie International Edition, 2017, 56(4): 1050-1054.
18	Emmanuel N , Mendoza C , Winter M , et al . Scalable photocatalytic oxidation of methionine under continuous-flow conditions[J]. Organic Process Research & Development, 2017, 21(9): 1435-1438.
19	Yoshida J , Kim H , Nagaki A . Green and sustainable chemical synthesis using flow microreactors[J]. ChemSusChem, 2011, 4(3): 331-340.
20	骆广生, 王凯, 王佩坚, 等 . 微反应器内聚合物合成研究进展[J]. 化工学报, 2014, 65(7): 2563-2573.
	Luo G S , Wang K , Wang P J , et al . Advances in polymer synthesis in microreactors[J]. CIESC Journal, 2014, 65(7): 2563-2573.
21	Gilmore K , Seeberger P H . Continuous flow photochemistry[J]. Chemical Record, 2014, 14(3): 410-418.
22	Fanelli F , Parisi G , Degennaro L , et al . Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis[J]. Beilstein Journal of Organic Chemistry, 2017, 13(1): 520-542.
23	Ding W , Xiao W J . Bifunctional photocatalysts for enantioselective aerobic oxidation of β-ketoesters[J]. Journal of the American Chemical Society, 2016, 139(1): 63-66.
24	Liu J , Ding W , Zhou Q Q ， et al . Enantioselective di-/perfluoroalkylation of β-ketoesters enabled by cooperative photoredox/nickel catalysis[J]. Organic Letters, 2018, 20(2): 461-464.
25	Tang X F , Feng S H , Wang Y K , et al . Bifunctional metal-free photo-organocatalysts for enantioselective aerobic oxidation of β-dicarbonyl compounds[J]. Tetrahedron, 2018, 74(27): 3391-3780.
26	Lian M , Meng Q , Gao Z , et al . Enantioselective photooxygenation of β-keto esters by chiral phase-transfer catalysis using molecular oxygen[J]. Cheminform, 2012, 7(9): 2019-2023.
27	孟庆伟, 赵静喃, 王亚坤, 等 . 有机催化β-酮酸酯不对称α-羟基化反应研究进展[J]. 化工进展, 2016, 35(Z2): 2563-2573.
	Meng Q W , Zhao J N , Wang Y K , et al . Review on enantioselective α-hydroxylation of β-keto ester[J]. Chemical Industry and Engineering Progress, 2016, 35(Z2): 2563-2573.
28	Wang Y , Hang Y , Meng Q W , et al . A series of cinchona-derived N-oxide phase-transfer catalysts: application to the photo-organocatalytic enantioselective alpha-hydroxylation of β-dicarbonyl compounds[J]. Journal of Organic Chemistry, 2016, 81(16): 7042-7050.
29	Wang Y K , Zheng Z D , Meng Q W , et al . Photo-organocatalytic enantioselective α-hydroxylation of β-keto esters and β-keto amides with oxygen under phase transfer catalysis[J]. Green Chem., 2016, 18(20): 5493-5499.
30	Coley C W , Abolhasani M , Lin H K , et al . Material-efficient microfluidic platform for exploratory studies of visible-light photoredox catalysis[J]. Angewandte Chemie, 2017, 56(33): 9847-9850.
31	Zou Y Q , Chen J R , Xiao W J , et al . Highly efficient aerobic oxidative hydroxylation of arylboronic acids: photoredox catalysis using visible light[J]. Angewandte Chemie, 2012, 124(3): 808-812.
32	Pieber B , Shalom M , Antonietti M , et al . Continuous heterogeneous photocatalysis in serial micro-batch reactors[J]. Angew. Chem. Int. Ed. Engl., 2018, 57(31): 9976-9979.

序号	催化剂用量/%(mol)	碱(水溶液)	转化率/%	ee/%
1	2.5	1% K₂CO₃	100	78.0(S)
2	5	1% K₂CO₃	100	80.4(S)
3	7.5	1% K₂CO₃	100	82.3(S)
4	10	1% K₂CO₃	100	85.4(S)
5	15	1% K₂CO₃	100	85.4(S)
6	20	1% K₂CO₃	100	85.5(S)
7	10	20% K₂CO₃	100	85.4(S)
8	10	1% Na₂CO₃	100	84.9(S)
9	10	1% Cs₂CO₃	100	85.0(S)
10	10	1% K₂HPO_4、	100	83.0(SS)
11	10	20% K₂HPO₄	100	83.0(S)

序号	催化剂用量/%(mol)	碱(水溶液)	转化率/%	ee/%
1	2.5	1% K₂CO₃	100	78.0(S)
2	5	1% K₂CO₃	100	80.4(S)
3	7.5	1% K₂CO₃	100	82.3(S)
4	10	1% K₂CO₃	100	85.4(S)
5	15	1% K₂CO₃	100	85.4(S)
6	20	1% K₂CO₃	100	85.5(S)
7	10	20% K₂CO₃	100	85.4(S)
8	10	1% Na₂CO₃	100	84.9(S)
9	10	1% Cs₂CO₃	100	85.0(S)
10	10	1% K₂HPO_4、	100	83.0(SS)
11	10	20% K₂HPO₄	100	83.0(S)

序号	光敏剂	光源	转化率/%	ee/%
1	亚甲基蓝	白光	5	—
2	酞菁	白光	25	—
3	TPP	白光	100	85.0(S)
4	TPP	红光	100	84.4(S)
5	TPP	蓝光	100	80.3(S)
6	TPP	无光	未反应	—
7	TPP	50mW/cm²白光	60	83.7(S)

序号	光敏剂	光源	转化率/%	ee/%
1	亚甲基蓝	白光	5	—
2	酞菁	白光	25	—
3	TPP	白光	100	85.0(S)
4	TPP	红光	100	84.4(S)
5	TPP	蓝光	100	80.3(S)
6	TPP	无光	未反应	—
7	TPP	50mW/cm²白光	60	83.7(S)

序号	v _a/(ml/min)	v _b/ (ml/min)	v _c/ (ml/min)	p/MPa	T/℃	转化率/%	ee/%
1	1.5	1.5	5.0	0.5	0	100	85.6(S)
2	1.5	1.5	7.5	0.5	0	100	85.7(S)
3	1.5	1.5	10.0	0.5	0	100	87.2(S)
4	1.5	1.5	12.5	0.5	0	100	85.2(S)
5	1.5	1.5	15.0	0.5	0	100	86.4(S)
6	1.5	1.5	20.0	0.5	0	100	85.1(S)
7	1.5	1.5	25.0	0.5	0	100	86.3(S)
8	1.0	2.0	10.0	0.5	0	100	84.4(S)
9	2.0	1.0	10.0	0.5	0	100	85.5(S)
10	0.5	2.5	10.0	0.5	0	100	84.6(S)
11	2.5	0.5	10.0	0.5	0	100	84.8(S)
12	1.5	1.5	10.0	0	0	100	83.5(S)
13	1.5	1.5	10.0	0.8	0	100	84.5(S)
14	1.5	1.5	10.0	0.5	5	100	85.4(S)
15	1.5	1.5	10.0	0.5	10	100	84.7(S)
16	1.5	1.5	10.0	0.5	15	100	84.9(S)
17	1.5	1.5	10.0	0.5	20	100	84.8(S)
18	1.5	1.5	10.0	0.5	30	100	83.8(S)