Coupling reactions reagents

When carrying out coupling reactions, reagents and solvents should be carefully dried. Traces of water may compete with the acceptor for the donor molecule, and this may be disastrous because of the much lower molecular weight and much higher mobility of the water molecule. 

Acylation and Coupling Reactions. Reagents used for the preparation of unsymmetrical ketones by coupling alkyl halides with acid chlorides include activated nickel, prepared by the action of lithium and naphthalene on nickel(II) chloride in glyrae (Vol,8,... 

Regiocontrolled q- or / -alkenylation and arylation of cyclic enones are possible without protection of the ketone by applying the coupling reaction of the Q- or /3-halo enones 607 and 608 with aryl and alkenylzinc reagents[468,469]. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

The great reactivity of the sulfurane prepared by this procedure toward active hydrogen compounds, coupled with an indefinite shelf life in the absence of moisture, makes this compound a useful reagent for dehydrations,amide cleavage reactions, epoxide formation, sulfilimine syntheses, and certain oxidations and coupling reactions. 

Coupling reactions and related fluoroalkylations with polytTuoioalkyl halides are induced by vanous reagents, among them metals such as copper and zinc, or by an electrochemical cell. More recently, examples of carbon-carbon bond forma tion by coupling of unsaturated fluorides have been reported Both acyclic and cyclic fluoroolefins of the type (Rp)2C=CFRp undergo reducUve dimerization on treatment with phosphines [42] (equation 33) The reaction shown in equation 33 IS also accompbshed electrocheimcally but less cleanly [43]... 

These zinc reagents are useful precursors for stereocontrolled palladium-catalyzed cross-coupling reactions, as illustrated in equations 73-80 [100, 101, 102, 103, 104, 105, 106, 107, 108] This methodology has been used to prepare new fluorinated analogues of codlemone [I09. ... 

Perfluorovinyl iodides readily undergo stereospecific coupling with the tn-fluoroinethylcopper solution [224] (equation 151) prepared from dibromodifluo-romethane [210] With longer-chain perfluoroalkylcopper reagents, the coupling reaction is accompanied by some exchange processes [225] (equation 152)... 

The copper species formed depends on the solvent, and three different species were detected by F NMR, although the structure of each species was not elucidated [245 This copper reagent undergoes a variety of coupling reactions with aryl, alkenyl, allyl, and acetylenic halides [244, 245 (equation 162)... 

Reductive coupling reaction of fluonnated vinyl iodides or bromides has been used as a route to fluorinated dienes [246, 247, 248, 249, 250. Generally, the vinyl iodide is heated with copper metal in DMSO or DMF no 1 ntermediate perfluorovmy I-copper reagent is detected. Typical examples are shown m equations 163-165 [246, 247, 249. The X-ray crystal structure of perfluorotetracyclobutacyclooctatetraene, prepared via coupling of tetrafluoro-l,2-diiodocyclobutene with copper, is planar... 

The perfluoroacetylenic copper compounds undergo coupling reactions with aryl iodides and provide a useful synthetic route to the perfluoroalkyl aryl alkynes [147, 255] (equation 170) Coupling of these copper reagents with the 1-iodo-perfluoroalkynes gives the perfluorodiynes [747 255] (equation 171)... 

Copper(I) halide-catalyzed coupling reactions of perfluoro Gngnard reagents with allyl and propargyl halides have been reported [256], The acetylenic copper compound may be an intermediate in these reactions. 

An alumina-supported trifluoromethylthiocopper reagent gave improved yields of trifluoromethyl aryl sulfides in coupling reactions with this reagent [26 ] (equation 184). 

Aryl perfluoroalkylsulfonaies, readily available by the reaction of the corresponding phenols and acid anhydrides or chlorides, are used as reagents in or-ganometallic coupling reactions (for a recent review, see reference 69)... 

Similarly, aromadc Grignaid reagents undeiga free-radical self-coupling reactions when treated with MCI2 (M=Cr, Mn, Ft, Co, Ni), e.g. ... 

In addition to its uses in photography and medicine, iodine and its compounds have been much exploited in volumetric analysis (iodometry and iodimetry, p. 864). Organoiodine compounds have also played a notable part in the development of synthetic organic chemistry, being the first compounds used in A. W. von Hofmann s alkylation of amines (1850), A. W. Williamson s synthesis of ethers (1851), A. Wurtz s coupling reactions (1855) and V. Grignard s reagents (1900). 

Another type of Grignard reaction is the alkylation with alkyl halides. Upon treatment of a Grignard reagent RMgX with an alkyl halide 5, a Wwrtz-like coupling reaction takes place. 

---