Methyl (2RS,4RS)-4-hydroxy-4-isopropyl-1,2,3,4-tetrahydronaphthalene-2-carboxylate

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Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, Germany

 Corresponding author email     hreissig@chemie.fu-berlin.de

This article is part of the Thematic Series "Organometallic chemistry" and is dedicated to the memory of Professor Peter Hofmann.

Guest Editor: B. F. Straub

Beilstein J. Org. Chem. 2016, 12, 1236–1242.

doi:10.3762/bjoc.12.118

Jakub Saadi, Christoph Bentz, Kai Redies, Dieter Lentz, Reinhold Zimmer, Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242. published 16 Jun 2016

Abstract

Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine.

For our systematic studies on samarium diiodide promoted cyclizations leading to benzannulated medium-sized rings [1-4] we required starting materials such as alkenyl-substituted compounds B (Scheme 1). Obvious precursors for B are aryl iodides A that smoothly undergo palladium-catalyzed coupling reactions to provide the desired products. However, in one case [A: R¹–R² = (CH₂)₄] typical Heck reaction conditions employing styrene as olefin component not only led to the desired styrene derivative B but mainly to the cyclized product C. If the reaction was performed without the olefin it provided only the tertiary alcohol C in reasonable yield [5]. Similar C–C bond forming reactions of aryl halides that involve an insertion of the intermediate aryl palladium species into a carbonyl group are relatively rare (see discussion below). Therefore this serendipitous discovery led us to investigate the reaction in more detail.

Scheme 1: Planned Heck reaction of A to compound B and serendipitous discovery of the palladium-catalyzed cyclization to products C.

Conclusion

We have found new examples of intramolecular palladium-catalyzed nucleophilic additions of aryl iodides to alkyl ketones. These additions proceed in the presence of only 2–5 mol % Pd(PPh₃)₄ and afford bi- and tricyclic compounds with excellent stereoselectivity and in moderate to very good efficacy. The low mass balance observed in several cases may be due to subsequent reactions such as simple de-iodination of the precursor compounds or elimination of water in the products. However, in general none of these byproducts has been isolated. For compound 2 the bulky isopropyl group slows down the addition to the carbonyl group and an enolate arylation was observed instead as major reaction pathway. Although the scope of the discovered aryl iodide addition to carbonyl groups may be limited it is attractive since only low catalyst loadings are required and interesting products are formed with high stereoselectivity.

Methyl (2RS,4RS)-4-hydroxy-4-isopropyl-1,2,3,4-tetrahydronaphthalene-2-carboxylate

Methyl (2RS,4RS)-4-hydroxy-4-isopropyl-1,2,3,4-tetrahydronaphthalene-2-carboxylate (8): According to the GP1: compound 2 (200 mg, 0.535 mmol), Pd(PPh3)4 (30 mg, 27 µmol), NEt3 (18 mg, 1.78 mmol), DMF (4 mL), 90 °C, 3 d. Column chromatography (silica gel, hexanes/ethyl acetate 4:1 to 1:1) provided 14 mg (11%) of 8, 33 mg (25%) of 9 and 82 mg (62%) of 10 as colorless oils. 

1H NMR (CDCl3, 500 MHz): δ = 0.60, 1.13 (2 d, J = 6.9 Hz, 2 × 3 H, CHMe2), 1.84 (dd, J = 13.9, 12.3 Hz, 1 H, 3-H), 1.95 (s, 1 H, OH), 2.17 (ddd, J = 13.9, 2.7, 2.4 Hz, 1 H, 3-H), 2.47 (sept, J = 6.9 Hz, 1 H, CHMe2), 2.81 (dd, J = 14.5, 12.7 Hz, 1 H, 1-H), 2.88 (dddd, J = 12.7, 12.3, 2.7, 2.6 Hz, 1 H, 2-H), 2.98 (ddd, J = 14.5, 2.6, 2.4 Hz, 1 H, 1-H), 3.73 (s, 3 H, CO2Me), 7.10-7.25, 7.48-7.49 (2 m, 3 H, 1 H, Ar) ppm. 

13C NMR (CDCl3, 126 MHz): δ = 16.3, 18.6 (2 q, CHMe2), 33.2, 33.3 (2 t, C-1, C-3), 36.6 (d, C-2), 37.9 (d, CHMe2), 75.0 (s, C-4), 125.8, 127.2, 127.5, 129.2, 135.9, 140.4 (4 d, 2 s, Ar), 51.9, 176.1 (q, s, CO2Me) ppm. 

IR (neat): ν̃= 3490 (br, O-H), 3060-2845 (=C-H, C-H), 1735 (C=O) cm-1 . 

MS (EI = 70 eV): m/z (%) = 248 (1) [M]+ , 217 (4), 242 (6), 205 (100), 173 (32), 145 (62). 

EA: C15H20O3 (248.3) calcd. (%): C 72.55, H 8.12; found (%): C 72.47, H 7.75. 

/////////1,2-addition,  aryl iodides,  ketones,  nucleophilic addition,  palladium catalysis, 

MALVANI FOOD, MAHARASHTRA, INDIA

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1,2,3-Trichloropropane

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 IR

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1,2,3-Trichloropropane(96-18-4)

 



 




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 Scheme 1.

(a) PPh₃, C₂Cl₆/TEA, toluene/reflux 2 h; (b) dry toluene, CS₂; (c) RCHO, ClCH₂COOH, fused CH₃COONa, reflux; (d) piperidine, THF, rt.

(Z)-2-Benzylidene-7-isocyano-3,6-dioxo-8-phenyl-3,6-dihydro-2H-thiazolo-[3′,2′:2,3][1,2,4]triazolo[1,5-a]pyridine-9-carbonitrile (4a)

White solid in a yield of 87%, mp 146–148 °C; IR (KBr, cm⁻¹): 3032 (Ar-H), 1730 (CO), 1590 (CN), ¹H NMR (300 MHz, DMSO-d₆): δ 8.20 (s, 1H, CH), 7.60–7.55 (m, 2H, Ar-H), 7.45–7.33 (m, 6H, Ar-H), 7.19–7.17 (m, 2H, Ar-H), LC–MS (m/z, %): 422 (M+1)⁺. Anal. Calcd for C₂₃H₁₁N₅O₂S: C, 64.25; H, 2.55; N, 16.57. Found: C, 65.55; H, 2.63; N, 16.62.

3-Hydroxy-7-isocyano-6-oxo-8-phenyl-2-(phenyl(piperidin-1-yl)methyl)-6H-thiazolo-[3′,2′:2,3][1,2,4]triazolo[1,5-a]pyridine-9-carbonitrile (5a)

Colorless crystals in a yield of 67%, mp 130–132 °C; IR (KBr, cm⁻¹): 3100 (O–H), 3030 (Ar-H), 2960 (C–H aliphatic), 1730 (CO), 1590 (CN), ¹H NMR (300 MHz, DMSO-d₆): 7.70–7.30 (m, 10H, Ar-H), 6.90 (s, 1H, CH), 3.7–3.22 (m, 4H, N(CH₂)₂), 1.7–1.4 (m, 6H, (CH₂)₃). LC–MS (m/z, %): 507 (M+1)⁺. Anal. Calcd for C₂₈H₂₂N₆O₂S: C, 66.93; H, 5.02; N, 16.95. Found: C, 66.39; H, 4.38; N, 16.59.

Arabian Journal of Chemistry

Volume 9, Issue 1, January 2016, Pages 136–142

Synthesis and pharmacological evaluation of novel 2H/6H-thiazolo-[3′,2′:2,3][1,2,4]triazolo[1,5-a]pyridine-9-carbonitrile derivatives

• Maddila Suresh,
• Palakondu Lavanya,
• Chunduri Venkata Rao^,

• Department of Chemistry, S.V. University, Tirupati 517502, India

doi:10.1016/j.arabjc.2011.02.004

 http://www.sciencedirect.com/science/article/pii/S1878535211000451

SURESH MADDILA

NRF-DST Innovation Post-Doctoral Research Scientist at University of KwaZulu Natal, West Ville Campus, Durban

 

NRF-DST Innovation Post-doctoral Research Scientist

University of Kwazulu Natal, WestVille Campus, Durban

January 2011 – Present (5 years 7 months)School of Chemistry & Physics., University of KwaZulu Natal, Durban

Currently, I am working as a NRF-DST Innovation Post-Doctoral Researcher at UKZN on temporary basis for a period of 1 month. I further extended my research by deriving the data from various syntheses of organic molecules, photocatalysis with ozone and synthesis of homogeneous & heterogeneous catalysts. The derived data has been compared and validated with the various spectroscopic techniques like 1H NMR, 13C NMR, MASS, IR spectroscopic data. In addition, I started my work towards middle homogeneous & heterogeneous photocatalysis and ozonation using different GC, XRD, SEM, TEM, BET, RAMAN, UV, UV-DRS, IR and spectrophotometers. The working group has been carried out under my investigation.

Teaching Assistant

Sri Venkateswara University, Tirupati, India.

August 2006 – October 2010 (4 years 3 months)

Inorganic, Organic Chemistry & Physical Chemistry, Spectroscopy and Environmental Science

 

 MOM WILL TEACH YOU NMR


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 Sinjar, Nineveh Province, Iraq
 SINJAR IRAQ

Sinjar

Town in Iraqi Kurdistan

Sindjar, also known as Shingal and formerly Sanjár, is a town in Sinjar District, Nineveh Province, Iraq near Mount Sinjar. Its population in 2013 was estimated at 88,023. Wikipedia

 

 

 

 

 
 
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