Coupling reactions copper® iodide

The most common application of transition metals in organic synthesis, however, is in cross-coupling reactions. Copper plays an important role in this field, as does palladium. An interesting example of the latter was recently published by the group of Tautens [39]. They performed a Catellani reaction that combined aryl iodide 138, alkyl iodide 139, and tert-butyl acrylate 140 under formation of linoxepin precursor 148. The precursor was then transformed to the desired product under optimized conditions in a three-step sequence that harbored another Heck-type coupling (Scheme 14.18). 

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-... 

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)... 

The analogous trifluoromethylseleno and pentafluorophenylseleno copper compounds are prepared via reaction of the corresponding diselenide with copper metal [265, 269] Coupling with aryl iodides gives the arylselenium denvative [265] (equation 185)... 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

Cyclohexene, purification of, 41, 74 reaction with zinc-copper couple and methylene iodide, 41, 73 2-CyclohEXENONE, 40,14 Cydohexylamine, reaction with ethyl formate, 41, 14... 

In 1988, Linstrumelle and Huynh used an all-palladium route to construct PAM 4 [21]. Reaction of 1,2-dibromobenzene with 2-methyl-3-butyn-2-ol in triethylamine at 60 °C afforded the monosubstituted product in 63 % yield along with 3% of the disubstituted material (Scheme 6). Alcohol 15 was then treated with aqueous sodium hydroxide and tetrakis(triphenylphosphine)palladium-copper(I) iodide catalysts under phase-transfer conditions, generating the terminal phenylacetylene in situ, which cyclotrimerized in 36% yield. Although there was no mention of the formation of higher cyclooligomers, it is likely that this reaction did produce these larger species, as is typically seen in Stephens-Castro coupling reactions [22]. 

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

Unsymmetrical 3,4-dihalo-l,2,5-thiadiazoles 118 and 119 were prepared from 3-amino-4-chloro-l,2,5-thiadiazole 117 via a Sandmeyer-like reaction involving successively tert-butyl nitrite and either copper bromide or copper iodide in anhydrous acetonitrile (Scheme 17) <2003H(60)29>. The bromo and iodo thiadiazoles 118 and 119 undergo selective Stille and Suzuki C-C coupling chemistry (see Section 5.09.7.6). 

The coupling with alkynyl iodides in the presence of CuCl and DMPU proceeds quite differently from that with alkynyl bromides. Although the first step of the coupling is the same, the subsequent Cu/I exchange reaction of the intermediate is different. As the final product, iododienyne 54 is obtained in high yields, as shown in Eq. 2.37 [35]. In the case of alkynyl bromides, Cu/Br exchange does not proceed. Therefore, the alkenyl copper moiety couples with the second alkynyl bromide molecule. 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

Previously published methods for the synthesis of dimethylzinc, a useful alkylating agent, include the reaction of dimethylmercury with metallic zinc,1 the reaction of a zinc-copper couple with methyl iodide,2 and the Grignard method.3 The reaction of trimethylaluminum with zinc(II) halides or alkoxides can be used,4 but it is more convenient to use zinc(ll) acetate, which is very readily obtained by dehydrating the commercial dihydrate with boiling acetic anhydride or by the reaction5 ... 

Furthermore, this copper system was interesting, since it changed the selectivity of the coupling reaction with 29. Thus, by application of the copper(I) iodide... 

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