Regioselective access of alkylidendibenzo[c,f]oxocine framework via cyclocarbopalladation/cross-coupling cascade reactions and reductive Heck strategy

Regioselective access of alkylidendibenzo[c,f]oxocine framework via cyclocarbopalladation/cross-coupling cascade reactions and reductive Heck strategy

New J. Chem., 2017, Advance Article
DOI: 10.1039/C6NJ03825E, Paper

Tapas Ghosha  

a

Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
E-mail: tapas.ghosh@uni-wuerzburg.de,tapasghosh.chem@gmail.com
Tel: +49-931-31-81629

New J. Chem., 2017, Advance Article

DOI: 10.1039/C6NJ03825E
Palladium-catalyzed dual strategies of cascade cyclocarbopalladation/cross-coupling of alkynes and a reductive Heck reaction have been developed to construct dibenzo[c,f]oxocine frameworks with tri- and tetra-substituted exo-cyclic alkenes with high stereo- and regio-control.

Palladium-catalyzed dual strategies of cascade cyclocarbopalladation/cross-coupling of alkynes and a reductive Heck reaction have been developed to construct dibenzo[c,f]oxocine frameworks with tri- and tetra-substituted exo-cyclic alkenes with high stereo- and regio-control. The success of this efficient methodology has been demonstrated by the synthesis of a number of dibenzoxocines in moderate to good yields and in sufficient quantities to support their further development.

 

http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C6NJ03825E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FNJ+%28RSC+-+New+J.+Chem.+latest+articles%29#!divAbstract

 

12-benzylidene-7,12-dihydro-5H-dibenzo[c,f]oxocine (8a): The material obtained after workup was subjected to column chromatography on silica gel with petroleum ether/EtOAc (19:1) as eluent to deliver pure 8a. Off white solid, yield = 82%,

 

mp. 134-136 oC,

 

IR (KBr): 2861, 1623, 1602 cm-1 , 1H NMR (400 MHz, CDCl3): δH = 7.47 (d, 1H, J = 7.2 Hz), 7.19-7.34 (m, 5H), 7.05-7.15 (m, 5H), 6.94-6.96 (m, 2H), 6.64 (s, 1H), 4.87 (s, 2H), 4.75 (s, 2H).

 

13C NMR (100 MHz, CDCl3): δC = 144.6, 142.1, 138.3, 137.4, 136.9, 129.9, 129.1, 128.9, 128.6, 128.3, 128.1, 127.9, 127.4, 127.0, 126.7, 73.0, 70.3.

 

HRMS (ESI [M+Na]+ ): for C22H18O calcd 321.1255; found 321.1245.

 

 

 

///////Regioselective, alkylidendibenzo[c,f]oxocine, cyclocarbopalladation/cross-coupling cascade reactions, reductive Heck strategy

Asymmetric total synthesis of (-)-δ-lycorane

1H NMR

13C NMR

Org. Chem. Front., 2017, Advance Article
DOI: 10.1039/C7QO00021A, Research Article

Junliang Wang, Jianneng Li, Xianwang Shen, Cong Dong, Jun Lin, Kun Wei
A first asymmetric synthesis of (-)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction is reported.

Asymmetric total synthesis of (−)-δ-lycorane

Junliang Wang,ab   Jianneng Li,a   Xianwang Shen,a  Cong Dong,a   Jun Lin*ab and   Kun Wei*a  

*Corresponding authors

aSchool of Chemical Science and Technology, Yunnan University, P. R. China

bSchool of Chemical Science and Technology, Yunnan University, Key Laboratory of Medicinal Chemistry for Natural Resource (Ministry of Education), Kunming, P. R. China
E-mail: weikun@ynu.edu.cn, linjun@ynu.edu.cn
Fax: +86871 65031633
Tel: +86871 65031633

Org. Chem. Front., 2017, Advance Article

DOI: 10.1039/C7QO00021A

A first asymmetric synthesis of the lycorine-type Amaryllidaceae alkaloid (−)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction as a powerful tool to construct the skeleton of the alkaloid on the basis of unsaturated β-ketoester and nitroalkene is reported. The sequence afforded a highly functionalized intermediate with three stereogenic centres with high diastereoselectivity (>20:1 dr) and high enantioselectivity (92% ee) in one step, which was converted into (−)-δ-lycorane in eight steps.

The residue was purified by flash silica 8 Please do not adjust margins Please do not adjust margins Please do not adjust margins gel chromatography (DCM/MeOH = 10/1) to give (−)-δ-lycorane (9 mg, 72%) as a white solid.

m.p.: 125-126 °C; [α] = -51.9, (c = 0.1, CHCl3);

IR (thin film, ν cm -1): 3551, 3477, 3414 , 1637, 1617, 619, 473;

1H-NMR (500 MHz, CDCl3), δ (ppm): 6.79 (s, 1H), 6.68 (s, 1H), 5.93 (s, 2H), 4.29 (d, J = 14.5 Hz, 1H), 3.95 (dd, J = 11.0, 8.5 Hz, 1H), 3.68 (d, J = 14.5 Hz, 1H), 3.52 (dd, J = 11.5, 4.0 Hz, 1H), 3.25 (s, 1H), 2.50 (m, 1H), 2.41 (d, J = 2.0 Hz, 1H), 1.86 (m, 1H), 1.77 (m, 2H), 1.66 (d, J = 14.5 Hz, 1H), 1.59 (m, 2H), 1.37 (m, 2H);

13C-NMR (125 MHz, CDCl3) δ (ppm): 149.0, 146.5, 131.3, 120.5, 109.5, 106.9, 101.5, 66.3, 55.1, 50.7, 39.7, 34.5, 29.6, 29.0, 24.8, 20.4;

HRMS (ESI): m/z calcd for C16H20NO2 + [M + H]+ : 258.1489, found: 258.1488.

////(−)-δ-lycorane

4-Pentenoic acid, 5-(3,4-methylenedioxyphenyl)-3-oxo-, ethyl ester

4-Pentenoic acid, 5-(3,4-methylenedioxyphenyl)-3-oxo-, ethyl ester

cas 860547-52-0

MF C14 H14 O5

4-Pentenoic acid, 5-(1,3-benzodioxol-5-yl)-3-oxo-, ethyl ester

Molecular Weight, 262.26

Melting Point (Experimental)

Value: 58-60 °C

Purification of the residue by flash column chromatography (10% ethyl acetate in hexanes) afforded the β-keto ester (12.0 g, 90%) as a pale yellow oil. Compound 3

1H-NMR (400 MHz, CDCl3), δ (ppm):12.00 (s, 0.4 H, enol OH), 7.52 (d, 1H, J = 16.0 Hz, C5 keto ), 7.35 (t, J = 15.6, 1H, C6’ keto), 7.05 (complex, 1.4H, C2’ keto, C2’ enol ), 7.03 (d, J = 12.8, 1H, C5’ keto), 6.97 (d, J = 8.0 Hz, 0.5H, C5’ enol), 6.83-6.78 (m, 1.5H, C6’, C5 and C2 enol), 6.65 (d, J = 16.0 Hz, 1H, C4 keto), 6.27 (d, J = 16 Hz, 0.5H, C4 enol), 6.02 (s, 2H, C7’ keto), 5.98 (s, 1H, C7’ enol), 4.22 (complex, 3H, COOCH2CH3, keto and enol), 3.66 (s, 2H, C2 keto), 1.29 (complex, 4.7H, COOCH2CH3 keto and enol);

13C-NMR (100 MHz, CDCl3), δ (ppm): 191.7, 172.8, 169.4, 167.5, 150.2, 148.8, 148.4, 148.2, 144.4, 136.4, 129.8, 128.4, 125.4, 123.5, 123.2, 119.9, 108.6, 108.5, 106.6, 106.1, 101.7, 101.4, 91.3, 77.3, 77.0, 76.7, 61.4, 60.1, 47.6, 14.2, 14.1.

 

1H NMR PREDICT

 

13C NMR PREDICT

 

/////////

Org. Chem. Front., 2017, Advance Article,
DOI: 10.1039/C7QO00021A

and

1. English, James, Jr.; Journal of the American Chemical Society 1943, V65, P2466-7 
2. (2) Borsche, W.; Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen 1933, V66B, P1792-801 

O=C(OCC)CC(=O)/C=C/c1ccc2OCOc2c1

1,3-Diphenylisoquinoline

1,3-Diphenylisoquinoline (3a). Pale-yellow solid (103.5 mg, 92%),

 mp 78-79 oC (lit.24,  73-74.5 oC). 24 J. D. Tovar and T. M. Swager, J. Org. Chem., 1999, 64, 6499

1H NMR (500 MHz, CDCl3) δ 8.25-8.23 (m, 2H), 8.15-8.14 (m, 1H), 8.09 (s, 1H), 7.95-7.93 (m, 1H), 7.84-7.83 (m, 2H), 7.70-7.67 (m, 1H), 7.59-7.50 (m, 6H), 7.44-7.40 (m, 1H);

13C NMR (125 MHz, CDCl3) δ 160.5, 150.3, 140.1, 139.8, 138.0, 130.4, 130.2, 128.8, 128.7, 128.6, 128.4, 127.7, 127.6, 127.2, 127.0, 126.0, 115.8.

Efficient synthesis of isoquinolines in water by a Pd-catalyzed tandem reaction of functionalized alkylnitriles with arylboronic acids

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC00267J, Paper

Kun Hu, Linjun Qi, Shuling Yu, Tianxing Cheng, Xiaodong Wang, Zhaojun Li, Yuanzhi Xia, Jiuxi Chen, Huayue Wu
Pd-catalyzed tandem reaction of functionalized alkylnitriles with arylboronic acids for the synthesis of diverse isoquinolines in water.

Efficient synthesis of isoquinolines in water by a Pd-catalyzed tandem reaction of functionalized alkylnitriles with arylboronic acids

Kun Hu,^a   Linjun Qi,^a   Shuling Yu,^a   Tianxing Cheng,^a  Xiaodong Wang,^a   Zhaojun Li,^b   Yuanzhi Xia,^a  Jiuxi Chen*^a and   Huayue Wu^a  

 

*Corresponding authors

^aCollege of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China
E-mail: jiuxichen@wzu.edu.cn

^bInstitute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Key Laboratory of Plant Nutrition and Fertilizer, Ministry of Agriculture, Beijing, China

Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC00267J, 

A palladium-catalyzed tandem reaction of 2-(cyanomethyl)benzonitriles or 2-(2-carbonylphenyl)acetonitriles with arylboronic acids in water has been developed for the first time. This reaction features good functional group tolerance and provides a new strategy for the synthesis of diverse isoquinolines under mild conditions. The use of water as the reaction medium makes the synthesis process environmentally benign. Preliminary mechanistic experiments indicate that the major reaction pathway involves carbopalladation of the C(sp³)–cyano group and subsequent intramolecular cyclization findings that were further supported by density functional theory (DFT) calculations.

1,3-Diphenylisoquinoline (3a). Pale-yellow solid (103.5 mg, 92%),

 mp 78-79 oC (lit.24,  73-74.5 oC). 24 J. D. Tovar and T. M. Swager, J. Org. Chem., 1999, 64, 6499

1H NMR (500 MHz, CDCl3) δ 8.25-8.23 (m, 2H), 8.15-8.14 (m, 1H), 8.09 (s, 1H), 7.95-7.93 (m, 1H), 7.84-7.83 (m, 2H), 7.70-7.67 (m, 1H), 7.59-7.50 (m, 6H), 7.44-7.40 (m, 1H); 

13C NMR (125 MHz, CDCl3) δ 160.5, 150.3, 140.1, 139.8, 138.0, 130.4, 130.2, 128.8, 128.7, 128.6, 128.4, 127.7, 127.6, 127.2, 127.0, 126.0, 115.8. 

//////// isoquinoline, pd-catalyzed, arylboronic acids

(E)-2-(fluoro(phenyl)methylene)cyclopentan-1-one

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC02656G, Communication

Qingshan Tian, Bin Chen, Guozhu Zhang
A stereoselective synthesis of [small beta]-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described.

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Qingshan Tian,^a   Bin Chen^a and   Guozhu Zhang*^a  

*

Corresponding authors

^a

State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China
E-mail: guozhuzhang@sioc.ac.cn

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02656G

A stereoselective synthesis of β-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described. A variety of 2-methylenecyclopentanones with fluoro, chloro and bromo functionalities are efficiently prepared from 1-alkynyl cyclobutanols. This method offers facile access to halogenated complex molecules which are not only useful chemicals but also valuable building blocks for further derivatizations.

1-(m-tolylethynyl)cyclobutan-1-ol (1b) Yield: 89%; Yellow oil;

1H NMR (400 MHz, CDCl3)

δ 7.25 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 2.51 (dt, J = 15.8, 6.3 Hz, 2H), 2.34 (t, J = 9.3 Hz, 2H), 2.30 (s, 3H), 1.85 (m, 2H);

13C NMR (100 MHz, CDCl3)

δ 137.94, 132.27, 129.19, 128.72, 128.17, 122.49, 92.16, 83.58, 68.31, 38.64, 21.20, 12.98; HRMS (EI+ , 70 eV): C13H14O [M]+ : calcd. 186.1045, found 186.1047

(E)-2-(fluoro(phenyl)methylene)cyclopentan-1-one (2a) Yield: 85%; Colorless oil;

1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 8.0, 1.5 Hz, 2H), 7.46-7.40 (m, 3H), 2.94 (td, J = 7.3, 3.3 Hz, 2H), 2.43 (td, J = 7.9, 1.2 Hz, 2H),1.99 (m, 2H);

13C NMR (100 MHz, CDCl3) δ 204.7 (d, J = 14.4 Hz), 162.4 (d, J = 270.7 Hz), 131.1, 130.0, 129.7, 128.7 (d, J = 7.0 Hz), 127.8, 117.3 (d, J = 19.4 Hz), 40.7 (d, J = 4.3 Hz), 27.6 (d, J = 3.9 Hz), 19.4;

19F (376 MHz, CDCl3) δ -76.9;

HRMS (EI+ , 70 eV): C12H11FO [M]+ : calcd. 190.0794, found 190.0795.

////////

1,2-bis((5-bromopyridine-2-yl)diazene oxide

 

1,2-bis((5-bromopyridine-2-yl)diazene oxide

1H NMR (DMSO): δ in ppm (integral, multiplicity, Hz) 8.83 (1H, dd, 0.56, 2.38) 8.82 (1H, dd, 0.64, 2.49) 8.48 (1H, dd, 2.40, 8.65) 8.28 (1H, dd, 0.60, 8.64) 8.02 (1H, dd, 0.67,8.69)

13C NMR (DMSO): δ in ppm (type of carbon) 150.33 (C-H), 149.48 (C-H), 142.74 (C-H), 140.86 (C-H), 119.60 (C-H), 119.46 (C-H)

LC/MS data (ESI) 358.8981 ([M+H]+ ), 380.8789 ([M+Na]+ )

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00433

///////////////

(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester, Ramipril intermediate

93779-31-8 cas

Cyclopenta[b]pyrrole-2-carboxylicacid, octahydro-, phenylmethyl ester, (2S,3aS,6aS)-

Formula:	C15H20ClNO2
Molecular Weight:	281.78

cas 93779-29-4

(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester

(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester, white solid. Yield 33.7 g (95%); mp 178–180 8C (lit.[6c] mp 180 8C); [a]D 20 ¼ 240.0 (c ¼ 1, H2O) [lit.[6c] [a]D 30 ¼ 238.4 (c ¼ 1, H2O)];

 1H NMR (400 MHz, CDCl3) d 1.36–1.42 (m, 1H), 1.58–1.75 (m, 2H), 1.82–2.01 (m, 3H), 2.32–2.37 (m, 1H), 2.58 (dt, J ¼ 13.2, 8.4 Hz, 1H), 2.83–2.88 (m, 1H), 4.31 (td, J ¼ 8.0, 3.6 Hz, 1H), 4.43 (t, J ¼ 8.4 Hz, 1H), 5.20 (AB q,J ¼ 12.0 Hz, 2H), 7.33–7.37 (m, 5H); 13C NMR (50 MHz, DMSO) d 24.07, 29.60, 31.02, 33.45, 41.37, 60.11, 63.81, 66.99, 128.11, 128.28, 128.43, 135.14, 167.32; FT IR (KBr disc) 1758 cm21; MS: m/e 246 (Mþ).

(c) Teetz, V.;
Geiger, R.; Gaul, H. Synthesis of unnatural amino acids: (S,S,S)-2-azabicyclo-
[3.3.0]-octane-3-carboxylic acid. Tetrahedron Lett. 1984, 25, 4479.