Di 4-chlorobutyl ketone

Stage 2 A 50 mL three-necked flask was charged with CoBr2 (218 mg, I mmol) in NMP (4mL) and ether (2mL). The reaction mixture was cooled to — 10°C and n-octanoyl chloride (1.62g, lOmmol) was added, followed by / (4-pivaloxybutyl)zinc (4mL of the prepared solution in Stage 1, 10 mmol). The resulting deep-blue solution was stirred for 0.5 h at — 10°C and worked up as usual. After evaporation of the solvents, the crude residue was purified by flash chromatography (hexane/ether, 95 5) providing the ketone 65 (2.2 g, 78% yield) as a colorless oil. 

A 20 mL three-necked flask was charged with MnBr2 (53 mg, 0.25 mmol), CuCl (15 mg, 0.15mmol), and DMPU (4.5mL). Diethylzinc (l.OmL, 10mmol) was added at 25°C, resulting in the formation of a black solution. The bromoketone 67 (1.1 g, 5 mmol) was added and the reaction mixture was heated to 60 °C for 0.5 h. The reaction mixture was cooled back to 25 °C and worked up as usual, affording after purification by flash chromatography (hexane/AcOEt, 9 1) the desired bicyclic alcohol 66 as a clear oil (575 mg, 82% yield). 

Cross-coupling is the reaction of an organometallic reagent R-M with an organic compound R -X (X is a leaving group) to give a product R-R and is often catalyzed by a complex of a transition metal such as nickel or palladium fEq.(l)] [1]. 

M= Li (Murahashi), Mg (Kumada-Tamao, Corriu), Zn (Negishi, Normant), B (Suzuki-Miyaura), A1 (Nozaki-Oshima, Negishi), Zr (Negishi), 

Because a C-Si bond is much less polarized than the C-metal bonds of the above organometallic reagents, the cross-coupling reaction using organosilicon compounds was not studied until 1988. 

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