Alkylzinc bromide cross-coupling

Scheme 8.9 Hayashi s cross coupling of sec-alkylzincs with aryl bromides.

All of the alkyl electrophiles shown in Schemes 73-78 are primary alkyl derivatives. On the other hand, cross-coupling of primary alkylzincs with secondary alkyl iodides and bromides was shown to be feasible with 4% Ni(COD)2, 8% s-Bu-Pybox (3) and DMA(N,N-Dimethylacetamide)88k (Scheme 79). More recently, a modification of this procedure through the use of -Pr-Pybox and 7 1 DMI/THF, where DMI is 1,3-dimethyl-2-imidazolidinone, in place of v-Bu-Pybox (3) and DMA has been shown to permit enantioselective alkylation of racemic secondary a-bromoamides with organozincs210 (Scheme 79). 

The first examples of microwave-assisted cross-couplings with organo-zinc compounds were reported in 2001, as shown in Scheme 70. Aryl- as well as alkylzinc bromides were effectively coupled with short reaction times [155]. 

Palladium catalysed cross-coupling of an alkylzinc bromide with an aryl iodide preparation of ethyl 4-(p-chlorophenyl)butanoate43... 

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. 

Cross-coupling of RMgX with organic halides (9, 147). This complex is the most active and selective known catalyst for coupling of n- and sec-butylmagnesium chloride or the corresponding alkylzinc reagents with aryl and vinyl bromides.1... 

Scheme 14.5 Ni-catalysed enantioselective cross-couplings of benzylic bromides and secondary alkylzinc reagents.

In addition to the above-mentioned allylic alkylation reactions, catalytic-in-copper C(sp )-C(sp ) cross-coupling reactions with alkylzincs can be achieved with some other specific electrophiles. For instance, the benzylzinc reagent 127, prepared in the presence of LiCl, undergoes coupling with the benzyl bromide 128 in the presence of only 0.4mol% CuCN-2 LiCl, with a yield of 89% (Scheme 4.29) [112, 113]. 

Furthermore, homobimetallic dimers derived from phosphinous acids [134] or phosphine chlorides [239], palladium nanoparticles stabilized by wBu4NBr [142], as well as the catalyst derived from [Pd(C3H5)Cl]2 as well as the tetraphosphine ligand Tedicyp (l,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane) [240] are also systems with high catalytic activity that enable the cross-coupling of primary alkylzincs and aryl bromides or iodides with good generality. 

Catalysts derived from NHC ligands have proved very efHcient in this context. Primary alkyl bromides can be cross-coupled with primary alkylzincs in good... 

Scheme 4.96 Enantioselective Ni-catalyzed cross-coupling of alkylzinc bromides with sec-onda7 alkyl halides in the presence of tridentate nitrogen ligands [294-296].

Scheme 3.8 Cross-coupling of secondary aryl bromides with secondary alkylzinc reagents.

Fu et al. reported Ni-catalyzed alkyl-alkyl cross-couphng reactions of diverse alkylzinc reagents with unactivated secondary alkyl halides under very mild conditions. Ni(cyclooctadiene)2 and sBu-pyridine-bis(oxazohne) (Pybox) catalyzed the Negishi coupling of various functional alkyl bromides and iodides at room... 

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