A general get‐together: The Cu‐catalyzed cross‐coupling reaction of primary‐alkyl halides with primary‐, secondary‐, and tertiary‐alkyl and phenyl Grignard reagents proceeds efficiently in THF under reflux in the presence of 1‐phenylpropyne (see scheme). The reaction is also applicable to alkyl mesylates (OMs) and tosylates (OTs). The reactivities of alkylX with a Grignard reagent increase in the order X=Cl

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...

Gelungene Verbindung: Die Cu‐katalysierte Kreuzkupplung zwischen primären Alkylhalogeniden und primären, sekundären und tertiären Alkyl‐ sowie Phenyl‐Grignard‐Reagentien verläuft in THF unter Rückfluss in Gegenwart von 1‐Phenylpropin effizient (siehe Schema). Die Reaktion gelingt auch mit Alkylmesylaten (OMs) und ‐tosylaten (OTs). Die Alkyl‐X‐Reaktivitäten gegenüber dem Grignard‐Reagens nehmen in der Reihenfolge X=Cl

The carbomagnesiation of dienes and enynes with sec- and tert-alkyl Grignard reagents has been achieved by using copper salts as catalysts.

This account summarizes our recent results on C-C bond formation reactions using alkyl fluorides mostly focusing on the transition-metal-catalyzed reactions. These reactions proceed efficiently under mild conditions by the combined use of Grignard reagents and transition-metal catalysts, such as Ni, Cu, and Zr. It is proposed that ate complex intermediates formed by the reaction of these transition metals with Grignard reagents play important roles as the active catalytic species. Organoaluminun reagents react directly with alkyl fluorides in nonpolar solvents at room temperature to form C-C bonds. These studies demonstrate the practical usefulness of alkyl fluorides in C-C bond formation reactions and provide a promising method for the construction of carbon frameworks employing alkyl fluorides. The scope and limitations, as well as reaction pathways, are discussed.