Nickel‐Catalyzed Cross‐Coupling Reaction of Alkyl Halides with Organozinc and Grignard Reagents with 1,3,8,10‐Tetraenes as Additives

Abstract

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...

Transition Metal-Catalyzed C–C Bond Formation Reactions Using Alkyl Halides

“…However, the cross-coupling reaction of alkyl halides with organometallic reagents has extensively been studied during the past several years 27 and alkyl halides as well as sulfonates have now become promising candidates as reagents in transition metal-catalyzed crosscoupling reactions. We could contribute to the progress of this field by providing a novel catalytic system where Ni 13,15,28 or Pd 29 catalyzes the cross-coupling reaction of alkyl fluorides, chlorides, bromides, and tosylates with Grignard reagents in the presence of 1,3-butadiene as an additive. These results include the first examples of a cross-coupling reaction using inactivated alkyl fluorides 15,28 and chlorides.…”

“…We could contribute to the progress of this field by providing a novel catalytic system where Ni 13,15,28 or Pd 29 catalyzes the cross-coupling reaction of alkyl fluorides, chlorides, bromides, and tosylates with Grignard reagents in the presence of 1,3-butadiene as an additive. These results include the first examples of a cross-coupling reaction using inactivated alkyl fluorides 15,28 and chlorides. 13 The reaction of decyl bromide (1 mmol) with n-BuMgCl (1.3 molar amounts) proceeded efficiently in the presence of isoprene (1.0 molar amounts) and NiCl 2 (0.03 molar amount) in THF at 25 C to give tetradecane in 92% yield along with trace amounts of decane (<1%) and decenes (2%) (Eq.…”

Carbon-carbon bond-forming reactions using alkyl fluorides

“…We could solve this problem by employing tetraene 4 that constructs a bis-π-allyl Ni structure with the Ni 0 species exclusively [11]. When 0.01 molar amount of NiCl 2 and 0.15 molar amount of the tetraene 4 as an additive was employed, undecane was obtained in 93 % yield with complete suppression of formation of octane and octenes (entry 15) [12].…”

Transition Metal Catalyzed Alkylation at sp3-, sp2-, and sp-Carbons

“…5). 12 This catalytic system tolerates a wide variety of functional groups, including nitriles, ketones, amides, and esters. 13 A plausible reaction pathway for this Ni catalyzed cross coupling is depicted in Scheme 2.…”

“…12 However, one drawback to this procedure is that only one of the alkyl groups on Zn can be transferred efciently (Scheme 3).…”