Alkylzinc bromides

Either Cul or CuCN (10 mol %) in conjunction with BF3 and TMS-C1 catalyze addition of alkylzinc bromides to enones. 

An alternative protocol for treating alkylzinc bromides with primary and secondary alkyl bromides and iodides was described by Zhou and Fu.409 In the study, a combination of Ni(cod)2 and a chiral oxazoline ligand 306 was used as a catalytic system providing 62-88% yield of product 307 A,A-dimethylacetamide (DMA) was the reaction solvent (Scheme 156). 

When Knochel and his co-workers attempted to use [PdC CF CN ] and related palladium(n) complexes as catalysts in the reactions of dialkylzincs with alkyl iodides, they observed the formation of the halogen-zinc exchange405 or cyclization406 products only. A recent paper of Zhou and Fu demonstrated that palladium complexes can also be used in the coupling reactions of alkylzinc bromides with alkyl iodides, bromides, chlorides, and... 

Zinc was effectively activated from zinc chloride using lithium and a catalytic amount (10%) of naphthalene in order to prepare secondary or tertiary alkylzinc bromides 517 (starting from the corresponding aUcyl bromides 516). These reagents react with acyl chlorides or a,/3-unsaturated ketones to give the expected ketones 15 and 518 (Scheme 143). 

SCHEME 18. Mixed Mn/Cu-catalyzed alkylzinc bromides synthesis... 

Alkyl units, unactivated, functionalization, 10, 102 Alkylzinc bromides, preparation, 9, 84 Alkylzinc halides... 

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]. 

Add the alkylzinc bromide reagent dropwise to the cyclohexenone mixture over 20 min. Stir the heterogeneous reaction mixture for 3.5 h at -30°C. 

Add the solution of the alkylzinc bromide to the CuCN 2LiCI solution rapidly. Allow to warm to 0°C, stir for 10 min, and cool the resulting light green solution to -25°C. 

Copper catalysed allylation of a boron stabilized secondary alkylzinc bromide preparation of 2-butyl-1-decen-4-ol8... 

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

Confirm the alkylzinc bromide formation by performing an iodolysis and a hydrolysis as described in Protocol 1. 

Cool the alkylzinc bromide solution to -30°C and then slowly add the above prepared PdCI2(dppf) solution. 

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. 

Alkylzinc halides. The structural relationship of several alkyl bromides with reactivity toward Zn has been determined. With 1 equiv of Zn an aliphatic tertiary bromide can be converted to the alkylzinc bromide while retaining a primary bromide. However, 1-bromoadamantane is less reactive than 1-bromopentane. 

A related preparation of diethyl 3-oxoalkyIphosphonates uses a zinc-mediated approach from dietliyl 2-bromoethylphosphonate. Thus, treatment of diethyl 2-bromoethylphosphonate with zinc dust in THF at 30°C affords the corresponding alkylzinc bromide in 90% yield. The addition of the soluble CuCN2LiCl at 0°C transmetallates the intermediate zinc compound to the copper compound. This copper-zinc reagent reacts with acyl chlorides in THF at 0°C to provide the corresponding diethyl 3-oxoalkyIphosphonates in high yields (84-96%, Scheme 7.57). ... 

Alkylzinc iodides can also be prepared in good yield from the alkyl iodide and zinc powder in a strongly solvating solvent the accelerating action of the solvent increases in the order isooctane < dibutyl ether < diethylene glycol dimethyl ether (diglyme) < 1,2-dimethoxyethane < dimethylformamide, dimethyl sulfoxide. In such solvents alkyl bromides also react with the zinc-copper pair, giving the alkylzinc bromide in yields of up to 80% in dimethyl... 

Conjugate additions. In the presence of MCjSiCl and BF OEtj, secondary and tertiary alkylzinc bromides add to enones without a copper catalyst. Enhancement of yields and selectivity is also achieved by using MCjSiCI for the conjugate addition of stabilized organolithiums such as (PhSjjCLi. ... 

Ketones. Rieke zinc produced by the reduction of Zn(CN)j with Li naphthalenide reacts with alkyl halides, and the organozinc halides can be used to form ketones on treatment with CuCN and acid chlorides. Secondary and tertiary alkylzinc bromides are readily prepared in this direct manner." a-Chloromethyl ketones have been prepared by this method using chloroacetyl chloride in the coupling reaction. ... 

A versatile and regio- and stereoselective synthetic method of terpenoids containing 1,5-diene units has been developed by Negishi. Chemoselective coupling of the alkylzinc bromide 49 with the alkenyl iodide in 50 provided 51. The alkyl iodide in 51 was converted to alkylzinc bromide, which was coupled again with the alkenyl iodide 50 to provide 52. Coenzyme Qio (53) was synthesized in 26 % overall yield by repeating a similar sequence of the coupling reactions [61]. 

Unless otherwise mentioned, the reactions were carried out at 23 °C in DMF or DMF-THF using either 0.65 molar equiv of a dialkylzinc or 1.3 molar equiv of an alkylzinc bromide or iodide. 

Alkylmagnesium halides can also be used. Functionalized alkylzinc bromides [56] such as 30-33 (Scheme 4.7), as well as benzylzinc chlorides [55, 57], can be prepared starting from the corresponding organic halides through in situ reduction involving Mg(0) in the presence of Zn(II) salts. 

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].

The Formation and Chemistry of Secondary and Tertiary Alkylzinc Halides 45 Table 3.15 Formation and coupling reactions of sec- and f-alkylzinc bromides. 

Table 3.15, entries T-5,0.9 and 0.7 equiv benzoyl chloride, respectively). t-Butyl bromide easily reacted at rt in 1 h to form the zinc reagent. The tertiary alkylzinc bromides (Table 3.15, entries 7-9) couple slowly with benzoyl chloride (0.7 equiv), taking 4-8 h for completion. These results are significant, in that tertiary alkylzinc bromides can be formed readily from active zinc insertion in high yield, which would be difficult or impossible by other methodologies which do not tolerate functionality. 

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