Functional Group Manipulations

Abstract

CBr4–Ph3P is very straightforward and widely used. Workup and purification can be messy at times because of the by-product, Ph3PO. To a mixture of the alcohol (0.800 g, 3.36 mmol) and carbon tetrabromide (1.337 g, 4.03 mmol) in CH2Cl2 at 0 ºC was added a solution of PPh3 (1.319 g, 5.03 mmol) in CH2Cl2 (3 mL). The reaction mixture was stirred at room temperature for 1 h, concentrated under reduced pressure, and purified by column chromatography to afford the bromide (0.941 g, 93% yield). Reference: Hu, T.-S.; Yu, Q.; Wu, Y.-L.; Wu, Y. J. Org. Chem. 2001, 66, 853–861. A two-step sequence consisting of mesylate formation followed by treatment with LiBr can also be used. This procedure involves two steps, but workup and purification are very straightforward. The bromide can be carried out to the next step without further purification in many cases. To a solution of 5-hydroxymethyl-1-methylcyclopentene (3.8 g, 34 mmol) in CH2 Cl2 (50 mL) at 0 ºC was added triethylamine (5.2 mL, 37 mmol) followed by methanesulfonyl chloride (2.9 mL, 37 mmol). The mixture was stirred at 0 ºC for 5 h and then water was added. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic extracts were dried over MgSO4 and the solvent was removed under reduced pressure to give 6.4 g (98%) of (2-methylcyclopent-2- enyl)methyl methanesulfonate, which was used in the next step without further purification. A solution containing the mesylate (6.4 g, 34 mmol) in acetone (70 mL) was treated with lithium bromide (8.89 g, 102 mmol). The mixture was heated at reflux for 6 h, cooled to room temperature, diluted with water, extracted with ether, and the combined ethereal extracts were dried over MgSO4. Removal of the solvent under reduced pressure gave 4.6 g (78%) of 5-bromomethyl-1-methylcyclopentene, which was used in the next step without further purification.