Reaksi Kopling Merupakan Reaksi Penggabungan Rantai Karbon

Reaksi kopling merupakan reaksi penggabungan rantai karbon-karbon atau bukan karbon dengan menggunakan katalis (Negishi, 2002 dalam Aldes Lesbani, 2013). Katalis-katalis yang biasa digunakan dalam reaksi kopling merupakan katalis logam blok d pada umumnya termasuk senyawaan dan kompleks logam blok d. Akan tetapi ada juga beberapa unsur-unsur di blok s dan p yang dapat digunakan sebagai katalis dalam reaksi kopling (Hegedus, 2002 dalam Aldes Lesbani 2013).

Pengembangan reaksi kopling sangat pesat seiring dengan perkembangan sintesis dalam industri farmasi, industri pertanian, maupun industri makanan guna mencari senyawa-senyawa baru yang potensial dengan sifat yang unik (Hegedus, 2002 dalam Aldes Lebani). Disamping itu reaksi kopling juga ditujukan bagi

pengembangan sintesis senyawa dengan rute sintesis yang pendek dan waktu yang relatif singkat karena penggunaan katalis dalam reaksinya (Negishi, 2002).

Coupling reaction

From Wikipedia, the free encyclopedia

A coupling reaction in organic chemistry is a general term for a variety of reactions where two hydrocarbon fragments are coupled with the aid of a metal catalyst. In one important reaction type a main group organometallic compound of the type RM (R = organic fragment, M = main group centre) reacts with an organic halide of the type R'X with formation of a new carbon-carbon bond in the product R-R' [1][2]

Contributions to coupling reactions by Ei-ichi Negishi and Akira Suzuki were recognized with the 2010 Nobel Prize in Chemistry, which was shared with Richard F. Heck.[3][4]

Broadly speaking, two types of coupling reactions are recognized:

 cross couplings involve reactions between two different partners, for example bromobenzene (PhBr) and vinyl chloride to give styrene (PhCH=CH2).  homocouplings couple two identical partners, for example, the conversion

of iodobenzene (PhI) to biphenyl (Ph-Ph).

Contents [hide]  1 Mechanism o 1.1 Catalysts o 1.2 Leaving groups o 1.3 Operating conditions  2 Coupling types

 3 Miscellaneous reactions  4 Applications

 5 References

Mechanism

[

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]

The reaction mechanism usually begins with oxidative addition of one organic halide to the catalyst. Subsequently, the second partner undergoes transmetallation, which places both coupling partners on the same metal centre. The final step is reductive elimination of the two coupling fragments to regenerate the catalyst and give the organic product. Unsaturated organic groups couple more easily in part because they add readily. The intermediates are also less prone to beta-hydride elimination.[5]

In one computational study, unsaturated organic groups were shown to undergo much easier coupling reaction on the metal center.[6] _{The rates for reductive elimination followed the following}

order: vinyl-vinyl > phenyl-phenyl > alkynyl-alkynyl > alkyl-alkyl. The activation barriers and the reaction energies for unsymmetrical R-R′ couplings were found to be close to the averages of the corresponding values of the symmetrical R-R and R′-R′ coupling reactions; for example: vinyl-vinyl > vinyl-alkyl > alkyl-alkyl. Another mechanistic approach proposes that specifically in aqueous

solutions, coupling actually occurs via a radical mechanism rather than a metal-assisted one.[7]

Catalysts[

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]

Further information: Palladium-catalyzed coupling reactions

The most popular metal catalyst is palladium, but some processes often use nickel and copper. A common catalyst is tetrakis(triphenylphosphine)palladium(0). Palladium catalysed reactions have several advantages including functional group tolerance, low sensitivity

of organopalladium compounds towards water and air.

Reviews have been written for example on cobalt,[8] _palladium [9][10][11][12][13] _{and nickel} [14] _mediated

reactions and on applications [15][16]

Leaving groups[

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]

The leaving group X in the organic partner is usually bromide, iodide or triflate. Ideal leaving groups are chloride, since organic chlorides are cheaper than related compounds. The main group metal in the organometallic partner usually is tin, zinc, or boron.

Operating conditions[

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]

While many coupling reactions involve reagents that are extremely susceptible to presence of water or oxygen, it is unreasonable to assume that all coupling reactions need to be performed with strict exclusion of water. It is possible to perform palladium-based coupling reactions in aqueous solutions using the water-soluble sulfonated phosphines made by the reaction of triphenyl

phosphine with sulfuric acid. Another example of coupling in aqueous media, with the main reacting agent being trimolybdenum-alkylidyne clusters, is that of Bogoslavsky et al.[7] _{In general,}

the oxygen in the air is more able to disrupt coupling reactions, because many of these reactions occur via unsaturated metal complexes that do not have 18 valence electrons. For example, in nickel and palladium cross couplings, a zerovalent complex with two vacant sites (or labile ligands) reacts with the carbon halogen bond to form a metal halogen and a metal carbon bond. Such a zerovalent complex with labile ligands or empty coordination sites is normally very reactive toward oxygen.

Some catalysts might be easily poisoned by heterocycles under prolonged reaction at elevated temperature. To avoid this, chemists often use pressure reactors to accelerate reactions at high temperature and pressure. Q-Tube and microwave synthesizer are available safe pressure reactors.

Coupling types

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]

Coupling reactions include (not exhaustive):

Reaction

Yea

_r

Reactant

_A

Reactant B

Homo/Cr

_oss

Cataly

_st

Remark

Wurtz

reaction

185

5

R-X

sp

³

R-X

sp

³

homo

Na as

reducing

agent

Glaser

coupling

186

9

RC≡C

H

sp RC≡CH sp homo

Cu

O

2

as

H-acceptor

Ullmann

reaction

190

1

Ar-X

sp

²

Ar-X

sp

²

homo

Cu

high

temperatures

Gomberg-Bachmann

reaction

192

4

Ar-H

sp

²

Ar-N

2

X

sp

²

homo

requires base

Cadiot-Chodkiewicz

coupling

195

7

RC≡C

H

sp RC≡CX sp cross

Cu

requires base

Pinacol

coupling

reaction

|

Castro-Stephens

coupling

196

3

RC≡C

H

sp Ar-X

sp

²

cross

Cu

Gilman

reagent

coupli

ng

196

7

R

2

CuL

i

R-X

cross

Cassar

reaction

197

0

Alken

e

sp

²

R-X

sp

³

cross

Pd

requires

base

Kumada

coupling

197

2

Ar-MgBr

sp

²,

sp

³

Ar-X

sp

_²

cross

Pd or

Ni or

Fe

Heck reaction

197

₂

alkene

sp

_²

R-X

sp

_²

cross

Pd or

_Ni

requires

_base

Sonogashira

coupling

197

5

RC≡C

H

sp R-X

sp

³

sp

²

Negishi

coupling

197

7

R-Zn-X

sp

³,

sp

²,

sp

R-X

sp

³

sp

²

cross

Pd or

_Ni

Stille cross

coupling

197

8

R-SnR

3

sp

³,

sp

²,

sp

R-X

sp

³

sp

²

cross

Pd

Suzuki

reaction

197

9

R-B(OR)

2

sp

²

R-X

sp

³

sp

²

cross

Pd or

_Ni

requires

_base

Hiyama

coupling

198

8

R-SiR

3

sp

²

R-X

sp

³

sp

²

cross

Pd

requires

base

Buchwald-Hartwig

reaction

199

4

R

2

N-H sp R-X

sp

²

cross

Pd

N-C

coupling,

second

generation

free amine

Fukuyama

coupling

199

8

R-Zn-I

sp

3

RCO(S

Et)

sp

2

cross

Pd

Liebeskind–

Srogl

coupling

200

0

R-B(OR)

2

sp

3

,

sp

2

RCO(S

Et)

Ar-SMe

sp

2

cross

Pd

requires

Cu

TC

Coupling reaction overview. For references consult satellite pages

Miscellaneous reactions

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In one study, an unusual coupling reaction was described in which

an organomolybdenum compound, [Mo3(CCH3)2(OAc)6(H2O)3](CF3SO3)2 not only sat on a shelf for 30 years without any sign of degradation but also decomposed in water to generate 2-butyne, which is the coupling adduct of its two ethylidyneligands. This, according to the researchers, opens another way for aqueous organometallic chemistry.[17]

One method for palladium-catalyzed cross-coupling reactions of aryl halides with fluorinated arenes was reported by Keith Fagnou and co-workers. It is unusual in that it involvesC-H functionalisation at an electron deficient arene.[18]

Applications

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Many coupling reactions have found their way into pharmaceutical industry [19] _{and into conjugated}

organic materials [20]

References

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1. Jump up ^ Organic Synthesis using Transition Metals Rod Bates ISBN 978-1-84127-107-1

2. Jump up ^ New Trends in Cross-Coupling: Theory and Applications Thomas Colacot

(Editor) 2014ISBN 978-1-84973-896-5

3. Jump up ^ "The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki". NobelPrize.org. 2010-10-06. Retrieved 2010-10-06.

4. Jump up ^ Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to

the 2010 Nobel Prize Dr. Carin C. C. Johansson Seechurn, Dr. Matthew O. Kitching, Dr. Thomas   J. Colacot, Prof. Victor Snieckus Angew. Chem. Int. Ed. 2012, 51,

5062-5085.doi:10.1002/anie.201107017

5. Jump up ^ Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 1-891389-53-X

6. Jump up ^ V. P. Ananikov, D. G. Musaev, K. Morokuma, “Theoretical Insight into the C-C Coupling Reactions of the Vinyl, Phenyl, Ethynyl, and Methyl Complexes of Palladium and Platinum” Organometallics 2005, 24, 715. doi:10.1021/om0490841

7. ^ Jump up to:ab _{Benny Bogoslavsky, Ophir Levy, Anna Kotlyar, Miri Salem, Faina Gelman} and Avi Bino (2012). "Do Carbyne Radicals Really Exist in Aqueous Solution?". Angewandte Chemie International Edition 51 (1): 90–94. doi:10.1002/anie.201103652.PMID 22031005.

8. Jump up ^ Cobalt-Catalyzed Cross-Coupling Reactions Grard Cahiez and Alban Moyeux

Chem. Rev., 2010, 110 (3), pp 1435–1462 Publication Date (Web): February 11, 2010 (Review)doi:10.1021/cr9000786

9. Jump up ^ Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium

CatalystsLunxiang Yin and Jürgen Liebscher Chem. Rev., 2007, 107 (1), pp 133–173 Publication

Date (Web): December 21, 2006 (Article) doi:10.1021/cr0505674

10. Jump up ^ Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions

Using Alkyl-organometallics as Reaction Partners Ranjan Jana, Tejas P. Pathak, and Matthew S.

11. Jump up ^ Efficient, Selective, and Recyclable Palladium Catalysts in Carbon−Carbon

Coupling Reactions rpd Molnr Chem. Rev., 2011, 111 (3), pp 2251–2320 doi:10.1021/cr100355b

12. Jump up ^ Palladium-Catalyzed Cross-Coupling Reactions of Organoboron

Compounds Norio. Miyaura, Akira. Suzuki Chem. Rev., 1995, 95 (7), pp 2457–

2483 doi:10.1021/cr00039a007

13. Jump up ^ Diazonium Salts as Substrates in Palladium-Catalyzed Cross-Coupling

Reactions Anna Roglans, Anna Pla-Quintana, and Marcial Moreno-Mañas Chem. Rev., 2006,

106 (11), pp 4622–4643 doi:10.1021/cr0509861

14. Jump up ^ Nickel-Catalyzed Cross-Couplings Involving Carbon−Oxygen Bonds Brad M. Rosen, Kyle W. Quasdorf, Daniella A. Wilson, Na Zhang, Ana-Maria Resmerita, Neil K. Garg, and Virgil Percec Chem. Rev., 2011, 111 (3), pp 1346–1416 doi:10.1021/cr100259t

15. Jump up ^ Selected Patented Cross-Coupling Reaction Technologies Jean-Pierre Corbet and Gérard Mignani Chem. Rev., 2006, 106 (7), pp 2651–2710 2006

(Article)doi:10.1021/cr0505268

16. Jump up ^ Copper-Mediated Coupling Reactions and Their Applications in Natural

Products and Designed Biomolecules Synthesis Gwilherm Evano, Nicolas Blanchard and

Mathieu Toumi Chem. Rev., 2008, 108 (8), pp 3054–3131 doi:10.1021/cr8002505

17. Jump up ^ A. Bino, M. Ardon and E. Shirman (2005). "Formation of a Carbon-Carbon Triple Bond by Coupling Reactions In Aqueous Solution". Science 308 (5719): 234–

235.Bibcode:2005Sci...308..234B. doi:10.1126/science.1109965. PMID 15821086.

18. Jump up ^ M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou (2006). "Catalytic Intermolecular Direct Arylation of Perfluorobenzenes". J. Am. Chem. Soc. 128 (27): 8754– 8756.doi:10.1021/ja062509l. PMID 16819868.

19. Jump up ^ R.H. Crabtree, The Organometallic Chemistry of the Transition Metals 4th Ed. 20. Jump up ^ Organotransition Metal Chemistry: From Bonding to Catalysis John Hartwig

Reaksi kopling

Dari Wikipedia, ensiklopedia gratis

Reaksi kopling dalam kimia organik adalah istilah umum untuk berbagai reaksi di mana dua fragmen hidrokarbon yang digabungkan dengan bantuan katalis logam. Dalam satu reaksi penting ketik senyawa organologam kelompok utama dari jenis RM (R = fragmen organik, M = pusat kelompok utama) bereaksi dengan halida organik dari jenis R'X dengan pembentukan ikatan karbon-karbon baru di RR produk '[1] [2]

Kontribusi reaksi kopling dengan Ei-ichi Negishi dan Akira Suzuki diakui dengan 2010 Nobel Kimia, yang bersama dengan Richard F. Heck. [3] [4]

• lintas kopling melibatkan reaksi antara dua mitra yang berbeda, misalnya bromobenzene (PhBr) dan vinil klorida untuk memberikan styrene (PhCH = CH2). • beberapa dua mitra homocouplings identik, misalnya, konversi iodobenzene (PHI) ke bifenil (Ph-Ph). Isi [hide] • 1 Mekanisme o 1.1 Katalis o 1.2 kelompok Meninggalkan o 1,3 kondisi operasi • 2 jenis Coupling • 3 reaksi Miscellaneous • 4 Aplikasi • 5 Referensi Mekanisme [sunting]

Mekanisme reaksi biasanya dimulai dengan penambahan oksidatif satu halida organik untuk katalis. Selanjutnya, pasangan kedua mengalami transmetallation, yang menempatkan kedua pasangan kopling pada pusat logam yang sama. Langkah terakhir adalah eliminasi reduktif dari dua fragmen kopling untuk

regenerasi katalis dan memberikan produk organik. Tak jenuh beberapa kelompok organik lebih mudah sebagian karena mereka menambahkan mudah. Intermediet juga kurang rentan terhadap beta-hidrida eliminasi. [5]

Dalam satu studi komputasi, kelompok organik tak jenuh ditunjukkan untuk

menjalani kopling reaksi lebih mudah pada pusat logam [6] Harga untuk eliminasi reduktif mengikuti urutan berikut:. Vinyl-vinyl> fenil-fenil> alkunil-alkunil> alkil-alkil. Hambatan aktivasi dan energi reaksi untuk simetris RR 'kopling ditemukan untuk menjadi dekat dengan rata-rata dari nilai-nilai yang sesuai dari RR simetris dan R'-R' reaksi kopling; misalnya: vinyl-vinyl> vinil-alkil> alkil-alkil. Pendekatan mekanistik lain mengusulkan bahwa khusus dalam larutan air, kopling benar-benar terjadi melalui mekanisme radikal daripada satu logam-dibantu. [7]

Katalis [sunting]

Katalis logam yang paling populer adalah paladium, namun beberapa proses sering menggunakan nikel dan tembaga. Katalis yang umum adalah tetrakis

(trifenilfosfina) paladium (0). Palladium katalis reaksi memiliki beberapa keunggulan termasuk toleransi kelompok fungsional, sensitivitas rendah dari senyawa

organopalladium terhadap air dan udara.

Ulasan ini telah ditulis misalnya pada kobalt, [8] paladium [9] [10] [11] [12] [13] dan nikel [14] reaksi dimediasi dan pada aplikasi [15] [16]

Kelompok meninggalkan [sunting]

Kelompok meninggalkan X di mitra organik biasanya bromida, iodida atau triflat. Kelompok meninggalkan yang ideal adalah klorida, karena klorida organik lebih murah daripada senyawa terkait. Logam Kelompok utama di mitra organologam biasanya timah, seng, atau boron.

Kondisi operasi [sunting]

Sementara banyak reaksi kopling melibatkan reagen yang sangat rentan terhadap adanya air atau oksigen, itu tidak masuk akal untuk mengasumsikan bahwa semua reaksi kopling perlu dilakukan dengan pengecualian yang ketat air. Hal ini

dimungkinkan untuk melakukan reaksi kopling berbasis paladium dalam larutan air menggunakan phosphines tersulfonasi yang larut dalam air yang dibuat oleh reaksi dari trifenil fosfin dengan asam sulfat. Contoh lain dari kopling di media air, dengan agen bereaksi utama menjadi cluster trimolybdenum-alkylidyne, adalah bahwa dari Bogoslavsky et al. [7] Secara umum, oksigen di udara lebih mampu mengganggu reaksi kopling, karena banyak reaksi ini terjadi melalui kompleks logam tak jenuh yang tidak memiliki 18 elektron valensi. Misalnya, dalam nikel dan paladium lintas kopling, sebuah kompleks bervalensi-nol dengan dua situs kosong (atau ligan labil) bereaksi dengan ikatan halogen karbon untuk membentuk halogen logam dan ikatan karbon logam. Seperti kompleks bervalensi-nol dengan ligan labil atau situs koordinasi kosong biasanya sangat reaktif terhadap oksigen.

Beberapa katalis mungkin mudah diracuni oleh heterocycles bawah reaksi berkepanjangan pada suhu tinggi. Untuk menghindari hal ini, ahli kimia sering menggunakan reaktor tekanan untuk mempercepat reaksi pada suhu tinggi dan tekanan. Q-Tube dan microwave synthesizer yang reaktor tekanan aman tersedia.

Reaksi lain-lain [sunting]

Dalam sebuah penelitian, reaksi kopling biasa digambarkan dimana senyawa

organomolybdenum, [Mo3 (CCH3) 2 (OAc) 6 (H2O) 3] (CF3SO3) 2 tidak hanya duduk di rak selama 30 tahun tanpa tanda-tanda degradasi tetapi juga terurai dalam air untuk menghasilkan 2-butyne, yang merupakan adduct kopling dua ligan ethylidyne

nya. Ini, menurut para peneliti, membuka jalan lain untuk kimia organologam berair. [17]

Salah satu metode untuk reaksi cross-coupling paladium-katalis dari halida aril dengan arena fluorinated dilaporkan oleh Keith Fagnou dan rekan kerja. Hal ini tidak biasa dalam fungsionalisasi itu involvesC-H di sebuah elektron arena kekurangan. [18]