The Catellani Reaction, (+) LINOXEPIN

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 The Catellani Reaction, a superb C-H Activation reaction. This recent review http://bit.ly/1LMNaKM outlines the challenges and future opportunities. Enjoy! #organichemistry #catellanireaction #CHactivation


LINK
http://urlaa.com/Catellani-Reaction-Perspective.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715096/
 lignan (+)-linoxepin 1 using domino C–H functionalization with an overall yield of 30 %. This synthesis is the first reported application of the palladium-catalyzed Catellani reaction in the synthesis of a complex natural product. We note that the optical rotation of the synthetic material is higher (+90.0; c=0.25, CHCl₃) than the reported value (+23.0; c=0.93, CHCl₃). All of the spectroscopic data of the final product are in complete agreement with the published data from the isolated material. It is noteworthy that Tietze and co-workers observed a higher optical rotation in their resolved material than was found in the isolated material (+96.1; c=0.61, CHCl₃).⁵ X-ray crystallographic analysis unambiguously confirms the reported structure of linoxepin (1). We are continuing to investigate the origin of the change in regioselectivity in the final Mizoroki Heck reaction and will provide further details as they become available.

Synthesis of (+)-linoxepin (1). a) PdCl₂ (20 mol %), PPh₃ (44 mol %), CsOAc (10.0 equiv), DMF, 75 °C, 4 h, 76 %.

 


 

ACADEMIC........................




The Catellani reaction was devised by Marta Catellani. It is Norbornene-mediated Ortho C-H functionalization consisting series of reaction.^[1] Norbornene acts as a catalyst in this reaction.^[2]

Reaction mechanism

Catellani reaction consist of a series of reaction and Norbornene acts as the catalyst in this reaction along with Palladium.^[3] Rhodium can also be used as a catalyst along with Norbornene instead of Palladium.^[4]

Different Steps of catellani reaction: 1. Oxidative addition 2. Carbopalledation with Norbornene 3. Palladocycle formation 4. Oxidative addition 5. Reductive elimination 6. Norbornene extrusion 7. Termination

Uses

Catellani reaction is used for polyfunctionalization of aromatic molecule. It has been used as a key step for synthesis of novel lignan (+)- linoxepin.^[5] It can also be used for synthesis of Rhazinal.^[6]

References

1. 
   

Catellani; et al. (1997). "Regioselektive Synthese o,o′-disubstituierter Vinylarene über einen komplexen Katalysecyclus". Angewandte Chemie 109 (1-2). doi:10.1002/ange.19971090146. Retrieved 26 December 2014.

Catellani; et al. (1997). "Regioselektive Synthese o,o′-disubstituierter Vinylarene über einen komplexen Katalysecyclus". Angewandte Chemie 109 (1-2). doi:10.1002/ange.19971090146. Retrieved 26 December 2014.

Catellani; et al. (1997). "Regioselektive Synthese o,o′-disubstituierter Vinylarene über einen komplexen Katalysecyclus". Angewandte Chemie 109 (1-2). doi:10.1002/ange.19971090146. Retrieved 26 December 2014.

Wu; et al. (2013). "An efficient method for the Heck–Catellani reaction of aryl halides". Chem. Commun. 49. doi:10.1039/C3CC46381H.

Weinstabl; et al. (16 Apr 2013). "Total Synthesis of (+)-Linoxepin by Utilizing the Catellani Reaction". Angewandte Chemie International Edition 52 (20). doi:10.1002/anie.201302327. Retrieved 26 December 2014.

6. Sui; et al. (June 2013). "Pd-Catalyzed Chemoselective Catellani Ortho-Arylation of Iodopyrroles: Rapid Total Synthesis of Rhazinal". J. Am. Chem. Soc 135 (25): 9318–9321. doi:10.1021/ja404494u. Retrieved 26 December 2014.

External links

• Total Synthesis of (+)-Linoxepin by Utilizing the Catellani Reaction

MORE........

 

 http://www.rsc.org/suppdata/cc/c3/c3cc46381h/c3cc46381h_2.pdf

[PDF]Catellani reaction experimental revised - Royal Society of ...

www.rsc.org/suppdata/cc/c3/c3cc46381h/c3cc46381h_2.pdf

Product isolation of Heck-Catellani Reaction of aryl chlorides and iodides ... 13C NMR spectra were obtained at 100 MHz on 400 MHz or 75 MHz on 300 MHz.



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OXOBOROLE COMPOUND

Preparation of

Preparation of 3-bromo-2-formylthiophene
Ref Acta Chem Scand 22 (1968) 4.1354
2,3-dibromothiophene (14 parts, 0.058 M ex Lancaster
Chemicals) was weighed into a reaction vessel equipped with a rubber septum. Dry diethyl ether (112 mis) was added by syringe through under a nitrogen blanket and cooled to -70°C. n-Butyl lithium (26.8 mis of 2.5 M solution in hexanes ex Aldrich) was slowly added over 20 mins. After stirring at -70°C for M hour, dimethylformamide (6.3 parts) in diethyl ether was added over 5 mins. The reactants were allowed to warm to 20°C, then 100 mis water was added with stirring. The ether solution was then washed with N hydrochloric acid, aqueous bicarbonate and water. The ether solution was then dried over magnesium sulphate and the ether evaporated to leave an orange/brown oil (12.32 parts). This oil was distilled at 0.05 mm Hg and 68°C to give a straw-coloured oil (4.5 parts). This oil was dissolved in dichloromethane and evaporated onto silica. This silica was formed into a column and the product separated by flash chromatography. The silica column was developed by washing with hexane containing increasing amounts of dichloromethane. The product was eluted in fractions containing from 10-30% dichloromethane in hexane.
Yield = 4.05 parts.
Elemental Analysis
Found 32.0% C, 1.8% H, 16.7% S
Theory 31.4% C, 1.6% H, 16.8% S

b) Preparation of 2-(3-bromo-2-thienyl)-1,3-dioxolane
3-bromo-2-formylthiophene (3.89 parts, 0.02 M) was heated at reflux with dry ethyleneglycol (1.6 parts) toluene (25 parts) and p-toluene sulphonic acid (0.1 parts) in a vessel equipped with a Dean and Stark separator for 16 hours. The reactants were then cooled and evaporated into silica. The silica was formed into a column which was then developed by elution with hexane containing increasing amounts of dichloromethane. The product was obtained from fractions containing 10- 60% dichloromethane as a pale straw-coloured oil (4.42 parts).
Elemental Analysis
Found 35.6% C, 3.1% H, 13.6% S
Theory 35.8% C, 3.0% H, 13.7% S c)

Preparation of 2-formyl-3-thiopheneboronic acid
Butyl lithium (7.9 ml of 2.5 M solution in hexanes ex
Aldrich) was slowly added to a solution of the dioxolane from (b) (4.28 parts, 0.018 M) in dry diethylether with stirring at -70°C under a nitrogen blanket. After stirring for 15 mins butyl borate (6 mis ex Aldrich) dissolved in ethylether (20ml) was slowly added at -70°C. The reactants were stirred for a further 4 hours at -70°C and then warmed to 20°C. 25 ml N hydrochloric acid was added and the reactants stirred for 1 hour at 20°C. The ether layer was then separated and extracted with N aqueous sodium carbonate solution (3 x 10ml). This aqueous carbonate solution was slowly acidified whereupon the product separated and was filtered and dried. Yield = 0.89 parts. Elemental Analysis
Found 36.6% C, 3.0% H, 19.6% S
Theory 38.5% C, 3.2% H, 20.5% S d)

Preparation of title compound
The boronic acid from (c) (0.5 parts, 0.0032 M) was dissolved in ethanol and sodium borohydride (30 mg ex Aldrich) added with stirring at 20°C. After 30 mins the reaction mass was evaporated onto silica which was formed into a column and developed with hexane containing increasing amounts of dichloromethane and then dichloromethane
containing increasing amounts of methanol. The product was obtained from fractions of dichloromethane containing 3-4% methanol. After evaporating the solvent, the product was recrystallised from toluene. Yield = 0.13 part mp 203-4°C.
Elemental Analysis
Found 45.5% C, 3.2% H, 23.3% S
Theory 45.8% C, 3.1% H, 26.4% S




////////http://www.google.com/patents/WO1995033754A1

1- formyl (3-chloro-2-carboxaldehyde-phenyl-1 -) - -4- piperazine

1- formyl (3-chloro-2-carboxaldehyde-phenyl-1 -) - -4- piperazine

Reference Example 2

1- formyl (3-chloro-2-carboxaldehyde-phenyl-1 -) - -4- piperazine

A mixture of 2-chloro-6-fluorobenzaldehyde (500mg, 3.15mmol), 1- formyl piperazine (396mg, 3.47mmol) was dissolved in DMF (5mL), and under nitrogen at room temperature was added potassium carbonate (2.18g, 15.77mmol). The mixture was stirred for 4 hours at 80 ℃, cooled water (20mL), ethyl acetate (3 × 5mL) was extracted, dried over anhydrous sodium sulfate, and concentrated to give a solid with petroleum ether (50mL) After beating 1h, filtered to give a pale yellow solid (588mg, yield 70%).

¹ HNMR (400 MHz, CDCl ₃ ): [delta] 10.45 (s, 1H), 8.13 (s, 1H), 7.44 (t, 1H), 7.18 (d, 1H), 7.02 (d, 1H), 3.80 (s, 2H), 36.4 (s, 2H), 3.10 (m, 4H) ESI: [M + 1] ⁺ = 253.1.

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=D842B4D68D66F641E505E9690CF876D0.wapp2nB?docId=WO2015054976&recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=FullText






 Saraqib, SYRIA

 



 

 

 

 
 

 

 

 
 

 

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1- formyl-4- (2-ethoxycarbonyl phenyl and thien-4-yl) - piperazine

Example 6

1- formyl-4- (2-ethoxycarbonyl phenyl and thien-4-yl) - piperazine 

Synthesis

1- formyl (3-chloro-2-carboxaldehyde-phenyl-1 -) - -4- piperazine

ethyl thioglycolate

In N ₂ protected, at room temperature was added the product of Reference Example 2[1- formyl (3-chloro-2-carboxaldehyde-phenyl-1 -) - -4- piperazine] to DMF (5mL) inside (1.0g, 3.7mmol), ethyl thioglycolate (410mg, 3.80mmol), potassium carbonate (1.38g, 10mmol), the mixture 80 ℃ stirred for 4 hours. Cooling water was added (20mL), ethyl acetate (3 × 5mL) was extracted, dried over anhydrous sodium sulfate, and concentrated to give a solid with petroleum ether (50mL) After beating 1h, filtered to give a pale yellow solid (1.0 g, yield 83%).

¹ HNMR (400 MHz, CDCl3): [delta] 8.15 (d, 2H), 7.59 (d, 1H), 7.41 (t, 1H), 6.94 (d, 1H), 4.44 (q, 2H), 3.85 (t, 2H ), 3.68 (t, 2H), 3.21-3.15 (m, 4H), 1.44 (t, 3H) ESI: [M + 1] ⁺ = 319.1.

REFERENCE

• WO2015054976 NEW

IDLIB, SYRIA


 
 

 
 

 

 


 

 


 
 Syrian internally displaced people walk in the Atme camp, along the Turkish border in the northwestern Syrian province of Idlib, on March 19, 2013. The conflict in Syria between rebel forces and pro-government troops has killed at least 70,000 people, and forced more than one million Syrians to seek refuge abroad. AFP PHOTO/BULENT KILIC (Photo credit should read BULENT KILIC/AFP/Getty Images)


 


 





 
 
 

 

سهل الروج في ريف إدلب وخلفه مدينة إدلب | Sahl al-Rouge (al-Rouge Plain) in the suburbs of Idlib with Idlib city visible in the background

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