Catalyst-free three-component synthesis of highly functionalized 2,3-dihydropyrroles

Catalyst-free three-component synthesis of highly functionalized 2,3-dihydropyrroles

Dong Wang,a  Linna Li,a  Hairong Feng,a  Hua Sun,a  Fabrice Almeida-Veloso,b  Marine Charavin,b Peng Yua  and  Laurent Désaubry*abc 

 Author affiliations

*Corresponding authors

aSino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
E-mail: desaubry@unistra.fr

bLaboratory of Therapeutic Innovation (UMR 7200), University of Strasbourg-CNRS, Faculty of Pharmacy, 67400 Illkirch, France

cLaboratory of Biomolecules (UMR7203), Sorbonne University – CNRS, 4 place Jussieu, 75005 Paris, France

Abstract

An efficient synthesis of fully substituted 2,3-dihydropyrroles has been achieved in one step through the three-component reaction of amines, aromatic aldehydes and α-ketoamides. This atom-economical and catalyst-free reaction is highly stereoselective and generates underexplored heterocycles in a single step. These compounds were examined in an enzymatic assay that led to the identification of potent α-glucosidase inhibitors, thereby demonstrating the utility of this novel methodology in medicinal chemistry.

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C8GC00987B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

N-(4-Chlorophenyl)-2-oxopropanamide (3a) Cl H N O O 3a Using 4-chloroaniline (1.0 g, 7.8 mmol), in accordance with General Procedure A, the title compound 3a was obtained (810 mg, 52% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.1, 157.6, 135.0, 130.6, 129.5, 121.1, 24.2. HRMS (ESI-TOF) m/z calcd. for C9H7NO2Cl- [M-H]- : 196.0171, found 196.0170

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Tert-butyl (N-[3-[(3S,4R)-3-amino-4-fluoro-4-(hydroxymethyl)tetrahydrofuran-3-yl]-4-fluorophenyl]acetamide)

tert-butyl (N-[3-[(3S,4R)-3-amino-4-fluoro-4-(hydroxymethyl)tetrahydrofuran-3-yl]-4-fluorophenyl]acetamide)

1H-NMR (500 MHz, DMSO-d6): 1.31 (s, 9H), 2.02 (s, 3H), 3.21 (m, 1H), 3.88 (m, 1H), 3.94 (m, 1H), 4.03 (m, 1H), 4.13 (m, 1H), 4.74 (m, 1H), 5.07 (m, 1H), 7.08 (m, 1H), 7.43 (bs, 1H), 7.63 (m, 1H), 7.67 (m, 1H), 10.03 (s, 1H) .

13C-NMR (125 MHz, DMSO-d6): 24.3, 28.5, 60.8, 65.1, 72.6, 78.1, 78.9, 105.8, 116.4, 119.7, 120.8, 127.2, 136.2, 155.2, 156.4, 168.7.

19F-NMR (470.6 MHz, DMSO-d6): -164.77, -117.26.

 

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Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00069

Chemical Names:	Cyclopentadienebenzoquinone; 1200-89-1; 1,4,4a,8a-Tetrahydro-1,4-methanonaphthalene-5,8-dione; 1,4-Methanonaphthalene-5,8-dione, 1,4,4a,8a-tetrahydro-; NSC 25329; 1,4,4a,8a-Tetrahydro-endo-1,4-methanonaphthalene-5,8-dione
Molecular Formula:	C11H10O2
Molecular Weight:	174.199 g/mol

1H NMR (CDCl3, 400 MHz) δ = 1.41 (dt, J = 8.8, 1.5 Hz, 1H), 1.52 (dt, J = 8.8, 1.8 Hz, 1H), 3.20 (dd, J = 2.5, 1.5 Hz, 2H), 3.52 (m, 2H), 6.04 (t, J = 1.9 Hz, 2H), 6.54 (s, 2H).

13C NMR (CDCl3, 100 MHz) δ = 48.4 (2 × CH), 48.8 (CH), 48.9 (2 × CH), 135.4 (2 × CH), 142.1 (2 × CH), 199.5 (2 × CO)

O=C3C=CC(=O)C2C3C1C=CC2C1

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00037

We report the use of a simple rotary evaporator as a semi-continuous UV photochemical reactor. By generation of a thin film from the rotation of a flask, better light penetration is achieved, and in this work we used high-power Hg lamps to enable the direct irradiation of molecules with UV light. The intramolecular [2 + 2] photocycloaddition of Cookson’s dione and the intermolecular [2 + 2] photocycloaddition of maleimide with 1-hexyne were used as test reactions to examine the effectiveness of this reactor. High productivities, equivalent to 210 g h–1, were obtained for the simple intramolecular reaction, demonstrating the scalability of the reactor. The effects of flask size, reaction mixture volume, and use of borosilicate or quartz glassware were also investigated.

 

 

Cookson’s Dione

CAS No.: 2958-72-7

1H NMR (CDCl3, 300 MHz) δ = 1.86 (d, J = 11.3, 1H), 2.02 (d, J = 11.3, 1H), 2.68 (m, 2H), 2.79 (m, 2H), 2.90 (m, 2H), 3.15 (m, 2H).

 

 

References 1. Clark, C. A.; Lee, D. S.; Pickering, S. J.; Poliakoff, M.; George, M. W. Org. Process Res. Dev. 2016, 20, 1792-1798. 2. Elliott, L. D.; Knowles, J. P.; Koovits, P. J.; Maskill, K. G.; Ralph, M. J.; Lejeune, G.; Edwards, L. J.; Robinson, R. I.; Clemens, I. R.; Cox, B.; Pascoe, D. D.; Koch, G.; Eberle, M.; Berry, M. B.; Booker-Milburn, K. I. Chem. Eur. J. 2014, 20, 15226-15232. 3. Marchand, A. P.; Allen, R. W. J. Org. Chem. 1974, 39, 1596-1596. 4. Elliott, L. D.; Berry, M.; Harji, B.; Klauber, D.; Leonard, J.; Booker-Milburn, K. I. Org. Process Res. Dev. 2016, 20, 1806-1811. 5. Hook, B. D. A.; Dohle, W.; Hirst, P. R.; Pickworth, M.; Berry, M. B.; Booker-Milburn, K. I. J Org Chem 2005, 70, 7558-7564.

ORGANIC SPECTROSCOPY INTERNATIONAL: Cookson's Dione

https://orgspectroscopyint.blogspot.com/search/label/Cookson’s%20Dione

 

Oct 3, 2016 - Cookson's Dione 125 W Batch Reaction A solution of Diels Alder adduct 3[3] (2.61 g, 15 mmol) in degassed EtOAc (150 ml) was irradiated with a pre-warmed 125 W medium pressure mercury lamp in a 150 ml batch reactor equipped with a. Pyrex immersion well for 15 min. The solvent was removed in ..

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4,4,5,5-tetramethyl-2-phenethyl-1,3,2-dioxaborolane

http://orgsyn.org/demo.aspx?prep=v94p0234

 4,4,5,5-Tetramethyl-2-phenethyl-1,3,2-dioxaborolane (1) has the following physical and spectroscopic properties: R_f = 0.47 (3:97, ethyl acetate:pentane), the checkers report the following values for 1: R_f = 0.09 (3:97 ethyl acetate:pentane); R_f = 0.52 (10% EtOAc in hexanes); Merck silica gel 60 F254 plate; mp 38-39 °C; 

¹H NMR pdf(CDCl₃, 400 MHz) δ: 1.18 (t, J = 8.4 Hz, 2H), 1.26 (s, 12H), 2.79 (t, J = 8.0 Hz, 2H), 7.16-7.22 (m, 1H), 7.23-7.32 (m, 4H); 

¹³C NMR pdf(CDCl₃, 151 MHz) d: 25.0, 30.1, 83.2, 125.6, 128.1, 128.3, 144.6 [N.B. the carbon attached to boron was not observed due to quadrupolar relaxation]; 

HRMS (ESI⁺) calculated for C₁₄H₂₂BO₂⁺ = 233.1707, mass found = 233.1710; 

IR (film): 3026, 2978, 2929, 1372, 1318, 1139, 848, 755, 703 cm^-1; 

Anal. calcd for C₁₄H₂₁BO₂: C, 72.44; H, 9.12. Found: C, 72.18; H, 9.28. 

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BRUSH UP YOUR NMR, 4-(3,5-Dichloropyridin-4-yl)morpholine

3,5-Dichloro-4-morpholinopyridine

Preparation of 4-(3,5-Dichloropyridin-4-yl)morpholine (5).(Pichowicz, M.; Crumpler, S.; McDonald, E.; Blagg, J. Tetrahedron 2010, 66, 2398, DOI: 10.1016/j.tet.2010.01.101)

 

 5 as a light-orange solid.

 

1H NMR (CDCl3, 400 MHz): δ = 8.35 (2H, s), 3.84 (4H, m), 3.37 (4H, m);

 

13C NMR (CDCl3, 101 MHz): δ = 150.8, 149.3, 128.4, 67.4, 50.4;

 

HRMS–ESI+: m/z [M + H]+ calcd for C9H11Cl2N2O+: 233.02429; found: 233.02446.

 

 

 

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00009

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Clc2cncc(Cl)c2N1CCOCC1

METHYL 2-(ACETYLTHIO)ACETATE

Methyl 2-(methylthio)acetate

• Molecular FormulaC4H8O2S
• Average mass120.170 Da
• 16630-66-3
• S-Methylthioglycolate

DOI: 10.1021/acs.oprd.7b00378

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This paper demonstrates an efficient, mild, and chemoselective synthesis of various thioesters via a HOTf-catalyzed S-acetylation of aromatic and aliphatic thiols using isopropenyl acetate as a cheap and convenient acetylating agent. During our tests, we also investigated the differences between the activities of metal triflates and triflic acid as catalysts in the acetylation of thiols. Finally, the potential of our concept has been increased by the implementation of Nafion as a heterogeneous catalyst for S-acetylation of thiols.

S-Acetylation of Thiols Mediated by Triflic Acid: A Novel Route to Thioesters

Krzysztof Kuciński*  and Grzegorz Hreczycho* 

Faculty of Chemistry, Adam Mickiewicz University in Poznań, ul. Umultowska 89b, 61-614 Poznań, Poland

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00378

Publication Date (Web): March 12, 2018

Copyright © 2018 American Chemical Society

*E-mail: kucinski.k@amu.edu.pl., *E-mail: g.h@amu.edu.pl. Web: http://ghgroup.home.amu.edu.pl.

 

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