Cross-coupling reactions primary alkyl

Tamura and Kochi studied the cross-coupling reactions of alkyl halides with alkyl Grignard reagents catalyzed by silver compounds first [422, 426, 427]. The coupling of primary alkyl halides with primary Grignard reagents resulted in a mixture... 

In the initial study, which focused on palladium-catalyzed cross-couplings of primary alkyl bromides with vinylstannanes, use of P(t-Bu)2Me provided the best yields (solvent=THF) [27]. PCy3 was slightly less effective, whereas a variety of other ligands, including JV-heterocyclic carbenes, were essentially ineffective. The choice of activator (Me4NF) and the presence of molecular sieves were important for the success of these reactions. Some examples of Pd/P(t-Bu)2Me-catalyzed Stille couplings of alkyl bromides with vinylstannanes are provided in entries 1-3 of Table 6. 

Kumada-Murahashi cross-couplings of primary alkyl bromides and tos-ylates have been described by Kambe [34]. Pd(acac)2/butadiene was employed as the catalyst, and couplings of alkyl and aryl Grignard reagents were achieved. The reactions proceed in the presence of an aryl chloride, an aryl bromide, and a styrenyl group. A typical cross-coupling is illustrated in Eq. 13. 

During a study of Pd/P(t-Bu)2Me-catalyzed Suzuki cross-couplings of primary alkyl bromides with boronic acids, Fu examined the stoichiometric reaction of Pd(P(t-Bu)2Me)2 with an alkyl bromide (Eq. 16) [17]. Interestingly, not only was oxidative addition facile at 0 °C, but the adduct (4) could be isolated in excellent yield and even crystallographically characterized. 

Palladium-catalyzed cross-coupling reactions of alkyl bromides with arylboron reagents represent another breakthrough for the development of a general method for arylation of alkyl halides. Fu found that the palladiumprimary alkyl bromides with various arylboronic acids (Equation 5.6) [10]. An air-stable commercially available preligand, [HP(t-Bu)2Me]BF4 5, also worked well with a variety of arylboronic acids and gave the same products in comparable yields, as shown in the parentheses in Equation 5.6. 

Lithium dialkylcuprates and diarylcuprates (R2CuLi and Ar2CuLi) are prepared by the reaction of a copper(I) salt with two equivalents of the corresponding organolithium reagent and undergo cross-coupling with primary alkyl halides and aryl and vinylic halides. 

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

Transition metal-catalyzed cross-coupling reactions between vinyl organometallic compounds and unactivated alkyl halides that can be usually performed with palladium, nickel and cobalt are of particular synthetic interest [37-39]. Recently, the groups of Cahiez [48] and Cossy [49] concurrently reported the first iron-catalyzed reaction of alkenyl Grignard compounds with primary and secondary alkyl halides (X=Br, I) (Scheme 5.15). The two protocols basically differ in the iron source... 

Negishi-type cross-coupling reactions of primary and secondary alkyl iodides 1 and alkylzinc bromides 2 proceeded with 10 mol% of Ni(py)4Cl2/(sBu)-PyBOX 5a (entry 6) [48]. Based on calculations, an alkylNi(I)(PyBOX) complex is formed by initial SET reduction, which carries much of the spin density in the ligand, similar to Vicic s catalysts 9. Based on this result a Ni(I)-Ni(II)-Ni(III) catalytic cycle was proposed to operate. 

Lithiation of compound 560 with s-BuLi-TMEDA in THF at —78 °C following an inverse addition protocol provided the anion 561. It reacts with primary alkyl iodides and triflates, silyl chlorides, diphenyl disulfide, epoxides, aldehydes, ketones, imines, acyl chlorides, isocyanates and sulfonyl fluorides to yield the expected compounds 562 (Scheme 152). The transmetallation of compound 561 with ZnBr2 allowed the palladium-catalyzed cross-coupling reaction with aryl and vinyl bromides837. When the reaction was quenched with 1,2-dibromotetrafluoroethane, the corresponding bromide 562 (X = Br) is obtained838. 

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