Nickel‐Catalyzed Regioselective Three Component Coupling Reaction of Alkyl Halides, Butadienes, and Ar‐M (M=MgX, ZnX)

Abstract

A new method for the regioselective three component cross-coupling reaction of alkyl halides, 1,3-butadienes, and aryl-Grignard reagents has been developed by the use of a nickel catalyst. This reaction proceeds efficiently at 25 8C using (dppf) NiCl 2 as a catalyst. Alkyl chlorides, bromides, and iodides can be used as suitable alkylating reagents. The reaction also proceeds when arylzinc halides are used instead of Grignard reagents. Competitive reactions of a mixture of primary, secondary, and tertiary alkyl bromides showed that the reactivities of the halides increase in the order primary < secondary < tertiary. A possible reaction pathway involving single electron transfer from a nickelate complex to alkyl halides is proposed.Keywords: alkyl halides; butadiene; C À C bond formation; cross-coupling; Grignard reagents; multicomponent reactions; nickelThe transition metal catalyzed coupling reaction of organic halides with organometallic reagents or alkenes has been extensively studied and employed in wide areas of organic synthesis.[1] These types of reactions are initiated generally by the oxidative addition of halides to low-valent metals such as Ni 0 and Pd 0 and the scope of the halides as substrates has been limited to aryl, vinyl, allyl, and benzyl halides, [2,3] partly, due to the slow oxidative addition of alkyl halides to metal complexes. Facile b-elimination from the alkylmetal intermediates also restricted the application of alkyl halides. In pursuit of finding novel uses for alkyl halides in transition metal catalyzed reaction, we have recently developed a new type of Ni [4] or Pd [5] catalyzed crosscoupling reaction of alkyl halides with Grignard reagents in the presence of 1,3-butadiene where bisallylmetalate complexes play important roles as active catalytic species. When we examined this reaction using [(dppf)NiCl 2 ], we found an unprecedented three component coupling reaction of alkyl halides, 1,3-butadienes, and arylmagnesium or arylzinc reagents [Eq. (1)]. ð1ÞFor example, into a mixture of isopropyl bromide (1.2 mmol), 2,3-dimethyl-1,3-butadiene (1 mmol), and [(dppf)NiCl 2 ] (0.08 mmol) was added a THF solution of PhMgBr (1.5 mmol, 1.5 mL). The solution was stirred at 25 8C for 24 h. Usual work-up and NMR analysis of the crude mixture indicated the formation of a coupling product 4b (R ¼ i-Pr, R' ¼ Me, R'' ¼ H, Ar ¼ Ph) bearing isopropyl and phenyl groups at the terminal carbons of the 1,3-butadiene unit in 99% yield by NMR (E/Z ¼ 67/33) ( Table 1, run 2). The product was obtained in pure form in 91% yield by recycling preparative HPLC using CHCl 3 as an eluent. Neither regioisomers of 4b nor isopropylbenzene (direct coupling product of i-PrBr with PhMgBr) were formed. The elongation of reaction time did not lead to isomerization of the double bond of the product.

Ni-Catalyzed Cascade Formation of C(sp3)C(sp3) Bonds by Cyclization and Cross-Coupling Reactions of Iodoalkanes with Alkyl Zinc Halides

“…More recently, Fu and co‐workers reported nickel‐catalyzed alkyl–alkyl coupling reactions of alkyl zinc halides with secondary iodides and bromides,8 as well as the first catalytic asymmetric cross‐coupling reaction of alkyl electrophiles 9. Three‐component coupling reactions of alkyl halides, dienes, and organomagnesium or organozinc reagents have also been reported 10. Alkyl–alkyl Negishi cross‐coupling reactions can also be catalyzed by palladium complexes with heterocyclic carbene ligands 11…”

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

“…These successful results prompted us to examine the chemical behavior of the ate complexes of late transition-metal catalysts, and we developed a regioselective three-component coupling reaction of alkyl halides, 1,3-butadienes, and Ar-M (M ¼ MgX and ZnX) by the aid of Ni catalyst. 24 For example, into a mixture of 2,3-dimethyl-1,3-butadiene (1 mmol), isopropyl bromide (1.2 molar amounts), and (dppf)-NiCl 2 (0.08 molar amount) was added a THF solution of PhMgBr (1.5 molar amounts) and the solution was stirred at 25 C for 24 h. The coupling product 41, bearing isopropyl and phenyl groups at the terminal carbons of the 1,3-butadiene unit, was obtained in 91% yield [E=Z ¼ 67=33] (Eq. 18).…”

Ni‐Catalyzed Cascade Formation of C(sp3)C(sp3) Bonds by Cyclization and Cross‐Coupling Reactions of Iodoalkanes with Alkyl Zinc Halides

“…[9] Three-component coupling reactions of alkyl halides, dienes, and organomagnesium or organozinc reagents have also been reported. [10] Alkyl-alkyl Negishi cross-coupling reactions can also be catalyzed by palladium complexes with heterocyclic carbene ligands. [11] Certain cross-coupling reactions of alkyl electrophiles with alkyl zinc halides seem to follow a radical pathway.…”