Nickel-and palladium-catalyzed cross-coupling reactions of organic halides with organometallic reagents is one of the most versatile carbon±carbon bond-forming reactions in organic synthesis. [1] In most cases, aryl and vinyl halides are employed as organic halides, yielding sp 2 ±sp, sp 2 ±sp 2 , and sp 2 ± sp 3 linkages. The connection of two sp 3 carbon atoms under transition metal catalysis is also important, and a variety of retrosynthetic analyses are conceivable in which an arbitrary carbon±carbon bond in an alkyl chain is cleaved. However, coupling with alkyl halides is difficult for two main reasons: 1) Oxidative addition of alkyl halides is much slower than that of aryl and vinyl halides. 2) b-Hydride elimination of the alkylpalladium and -nickel compound is problematic. Thus, novel and efficient methods for alkyl±alkyl coupling are currently under intense investigation. [2, 3] We are interested in cobalt-catalyzed reactions [4,5] and report herein the cobalt-catalyzed cross-coupling reaction of alkyl halides with allylic Grignard reagents. Allylation of various alkyl halides proceeds smoothly, and even quaternary carbon atoms have become readily accessible by transitionmetal-catalyzed coupling reactions.
Allylmagnesium chloride (1.0 m solution in THF, 1.5 mmol) was added to a solution of 2-bromo-2-methyldecane (1 a; 0.50 mmol) in THF in the presence of [CoCl 2 (dppp)] (0.05 mmol) at À20 8C (Scheme 1; dppp ¼ 1,3-bis(diphenylphosphanyl)propane). Stirring for 2 h at À20 8C provided the allylated product 2 a, which contains a quaternary carbon center (90 % yield), and 3 a (8 %). No allylated product was obtained when the [CoCl 2 (dppp)] catalyst was omitted. The yield of 2 a was lower when 1,4-bis(diphenylphosphanyl)butane (DPPB), 1,2-bis(diphenylphosphanyl)ethane (DPPE), and bis(diphenylphosphanyl)methane (DPPM) were employed in place of DPPP. Reaction at À40 8C led to recovery of 1 a, whereas reaction at 0 8C resulted in a lower ratio of 2 a/ 3a (82:18).
Allylation of a variety of alkyl halides proceeded smoothly, although tuning of reaction conditions was necessary for the different substrates (Table 1). Benzylic allylation of 1 d required DPPE in place of DPPP to attain a satisfactory result. Primary and secondary bromides were less reactive. Instead, use of alkyl iodides such as 1 g-I led to high yields at À40 8C. It is worth noting that halides 1 h, 1 h-I, and 1 i-I, which have alkoxy groups at the b position to the halide atom, participated in the allylation.
Other allylic Grignard reagents were available for this reaction (Scheme 2). Regioselective coupling was observed to yield methyl-branched product 5 b upon treatment of 1 g-I with crotyl Grignard reagent. Unfortunately, reaction of prenyl Grignard reagent was unsuccessful.
Substrates having proper carbon±carbon double bonds were then subjected to the cobalt-catalyzed allylation (Scheme 3). Consequently, tandem cyclization/allylation occurred, thereby affording 3-butenyl-substituted lactones after Jones oxidation of the cyclic acetals. For example, iodoacetal 7 c was converted to lactone 9 c bearing a quaternary center, and cyclization of 7 d provided the trans isomer 9 d exclusively.
Interestingly, treatment of 7 e with the allyl Grignard reagent CH 2 ¼CHCH 2 MgCl in the presence of [CoCl 2 (dppp)] furnished the ring-opening product 9 e (Scheme 4). Given that intramolecular carbocobaltation proceeds to yield cyclopropylmethylcobalt species, b-carbon elimination would provide a route to 9 e. However, b-carbon elimination seems unlikely COMMUNICATIONS