In 1972, Kumada's group and Corriu's group independently reported cross-coupling reaction of Grignard reagents with aryl and alkenyl halides catalyzed by nickel(II) halides. 1 The catalytic cycle, which involves oxidative addition, transmetalation, and reductive elimination steps, has become a prototype of a more practical Pdcatalyzed cross-coupling reaction. These reactions proceed smoothly using a variety of organometallic reagents containing B, Mg, Li, Sn, Al, and Zn as the metal connecting to alkyl, alkenyl, aryl, alkynyl, allyl, and benzyl groups as the organic part. 2 As for the coupling partner, however, the scope is generally limited to aryl and alkenyl moieties. The use of alkyl halides, triflates, or tosylates usually gives unsatisfactory results due mainly to the slow oxidative addition to transition metal catalysts and the facile -elimination from the alkylmetal intermediates. Thus, the alkyl-alkyl crosscoupling reaction catalyzed by transition metal complexes has remained as an interesting and challenging theme to be solved in this field. 3-7 Recently, we have developed regioselective monoand dialkylation of alkenes or dienes with alkyl halides or tosylates using titanocene 8 or zirconocene 9 catalysts. During the course of our study on transition metal catalyzed alkylation reactions, we have found that Ni catalyzes the cross-coupling reaction of alkyl chlorides, bromides, and tosylates with Grignard reagents in the presence of a 1,3-butadiene as an additive (eq 1).For example, a reaction of n-decyl bromide with n-butylmagnesium chloride (1.3 equiv) in the presence of isoprene (1.0 equiv) and NiCl 2 (0.03 equiv) at 25°C for 3 h gave tetradecane in 92% yield along with trace amounts of decane (<1%) and decenes (2%) ( Table 1, entry 1). In the absence of isoprene, tetradecane was obtained in only 2% yield and significant amounts of decane and decenes were formed (entry 2). The use of Ni(acac) 2 and Ni(COD) 2 also afforded tetradecane in high yields (entries 3 and 4). When nickel complexes bearing phosphine ligands, such as NiCl 2 (PPh 3 ) 2 and NiCl 2 (dppp), were used, tetradecane was obtained only in 45% and 22% yields, respectively. Under similar conditions, FeCl 3 and CoCl 2 (dppe) were ineffective, and PdCl 2 gave a moderate yield of tetradecane (entry 5). Next, we examined the effect of additives which are essential to promote the present coupling reaction. Unsubstituted 1,3-butadiene shows by far the highest activity for this cross-coupling reaction (entry 6). 2,3-Dimethyl-1,3-butadiene, COD, alkynes, and alkenes are far less effective under the same conditions (entries 7-10).Optimization of the reaction conditions using 1,3-butadiene revealed that use of only 1 mol % of NiCl 2 and 10 mol % of 1,3-butadiene (0.07 M in THF, 10 equiv to Ni catalyst) based on the halides at 0°C afforded coupling products quantitatively in the reaction of primary bromides with primary alkyl Grignard reagents (Table 2, entries 1 and 2). Interestingly, the bromo substituent on the aryl ring remained intact in this r...

n-Octyl fluoride underwent a cross-coupling reaction with n-propylmagnesium bromide in the presence of 1,3-butadiene using NiCl2 as a catalyst at room temperature to give undecane in moderate yields. This alkyl-alkyl cross-coupling proceeded more efficiently when CuCl2 was employed instead of NiCl2. Addition of 1,3-butadiene dramatically improved the yields of the coupling products from primary alkyl Grignard reagents in both Ni- and Cu-catalyzed reactions. Alkyl fluorides efficiently reacted with tertiary alkyl and phenyl Grignard reagents using CuCl2 in the absence of 1,3-butadiene to afford the coupling products in high yields. The competitive reaction of a mixture of alkyl halides (R-X; X = F, Cl, Br) with nC5H11MgBr showed that the reactivities of the halides increase in the order R-Cl < R-F < R-Br. In contrast, in the Cu-catalyzed reaction with PhMgBr, the reactivities increase in the order R-Cl < R-Br < R-F.

Transition-metal-catalyzed cross-coupling reactions between organic halides and organometallic reagents is a powerful tool for constructing carbon skeletons.[1] Significant advances have been achieved in this field over the last decade that have enabled cross-coupling reactions to be effected between alkyl groups by using either a nickel or palladium catalyst.[2] We have contributed to this progress by developing a unique catalytic system that proceeds efficiently under mild conditions by using 1,3-butadiene as an additive in the absence of phosphane ligands, where bis-p-allylnickel or -palladium intermediates (1) are proposed to be involved [Eq. (1)]. [3] This system facilitates the cross-coupling of a wide variety of alkyl tosylates and halides, such as fluorides, chlorides, and bromides, with Grignard reagents. However, a drawback of this methodology is the range of functional groups that are tolerant to this system because of the high reactivity of the Grignard reagents. Herein, we reveal a solution to this problem by employing 1,3,8,10-tetraenes (2) that serve as extremely efficient ligands to promote the nickel-catalyzed cross-coupling reaction of alkyl halides with organozinc reagents [4][5][6] in a THF/N-methylpyrrolidone (NMP) mixed solvent containing magnesium bromide. It was also found that these tetraenes (2) were effective also for the nickel-catalyzed cross-coupling of alkyl fluorides with Grignard reagents.First we examined a cross-coupling reaction of alkyl halides with organozinc reagents that used 1,3-butadiene as the additive. For example, n-decyl bromide (1 mmol), diethylzinc (2 equivalents, 1m in hexane), NiCl 2 (0.03 equiv), and 1,3-butadiene (1 equivalent) were added sequentially to a solution of THF (8 mL) and NMP (4 mL) at À78 8C and the mixture stirred at 25 8C for 48 hours. However, this reaction gave only a trace amount of the cross-coupling product, ndodecane (< 1 %), as shown in Table 1 (entry 1). Addition of magnesium bromide increased the yield of n-dodecane to 45 %, but side reactions (reduction and HBr elimination) could not be suppressed (entry 2). Only a trace amount of dodecane was obtained without 1,3-butadiene even in the presence of magnesium bromide (entries 3 and 4). The salts Bu 4 NBr, Bu 4 NI, [5] and LiBr were also shown to be not effective as additives (entries 5-7). The yield of dodecane was increased up to 73 % by adding four equivalents of 1,3-butadiene; however, formation of by-products, n-decane and decenes, could not completely be suppressed (entries 8 and 9). Under similar conditions, [Ni(acac) 2 ] (acac = acetylacetanoate) afforded a slightly better yield of the product (entry 10), while nickel catalysts bearing phosphane ligands were less efficient (entries 11 and 12). PdCl 2 did not show a high catalytic activity (entry 13). The coupling products were obtained in yields of only 37 and 7 %, respectively (entries 14 and 15), when isoprene and p-fluorostyrene [5] were employed as additives under the same conditions as entry 10.It is noteworthy that this cross-c...

Ni0 reacts with 1,3-butadienes to form octadienediyl-nickel complexes, which play an important role as key intermediates in the oligomerization of butadienes. [1,2] This reaction demonstrates extreme synthetic utility as a straightforward method for the formation of C 8 building blocks in organic synthesis. The cycloaddition of butadienes is one of the most successful transformations of this type. [1d, 3] However, many attempts toward the synthesis of functionalized oligomers (i.e. telomerization) by using Ni catalysts resulted in the formation of mixtures of products. [1b, 4] We have recently developed new methods for the regioselective addition of silicon and/or carbon functionalities to alkenes or dienes in the presence of early-transition-metal catalysts, such as zirconium complexes [5] and titanium complexes. [6] During the course of these studies, we found that Ni catalyzes the dimerization and carbosilylation of butadienes in the presence of chlorosilanes and Grignard reagents to give rise to 1,6-dienes with high regio-and stereoselectivity [Eq. (1)].When a catalytic amount of [Ni(acac) 2 ] (0.05 mmol; acac = acetylacetone) was added to a solution of isoprene (2 mmol), chlorotriethylsilane (1 mmol), and nBuMgCl (1.2 mmol) in THF (1.3 mL) at À20 8C, and the resulting mixture was stirred for a further 18 hours at the same temperature, compound 1, with Et 3 Si and nBu groups at positions 3 and 8 of its dimerized isoprene skeleton, was isolated in 87 % yield (E/Z = 76:24) from the crude mixture by HPLC, with CHCl 3 as the eluent ( (dppp = propane-1,

Ni0 reacts with 1,3-butadienes to form octadienediyl-nickel complexes, which play an important role as key intermediates in the oligomerization of butadienes. [1,2] This reaction demonstrates extreme synthetic utility as a straightforward method for the formation of C 8 building blocks in organic synthesis. The cycloaddition of butadienes is one of the most successful transformations of this type. [1d, 3] However, many attempts toward the synthesis of functionalized oligomers (i.e. telomerization) by using Ni catalysts resulted in the formation of mixtures of products. [1b, 4] We have recently developed new methods for the regioselective addition of silicon and/or carbon functionalities to alkenes or dienes in the presence of early-transition-metal catalysts, such as zirconium complexes [5] and titanium complexes. [6] During the course of these studies, we found that Ni catalyzes the dimerization and carbosilylation of butadienes in the presence of chlorosilanes and Grignard reagents to give rise to 1,6-dienes with high regio-and stereoselectivity [Eq. (1)].When a catalytic amount of [Ni(acac) 2 ] (0.05 mmol; acac = acetylacetone) was added to a solution of isoprene (2 mmol), chlorotriethylsilane (1 mmol), and nBuMgCl (1.2 mmol) in THF (1.3 mL) at À20 8C, and the resulting mixture was stirred for a further 18 hours at the same temperature, compound 1, with Et 3 Si and nBu groups at positions 3 and 8 of its dimerized isoprene skeleton, was isolated in 87 % yield (E/Z = 76:24) from the crude mixture by HPLC, with CHCl 3 as the eluent ( (dppp = propane-1,