芳基酰胺或芳胺基甲酸酯（主要是N-Boc衍生物）通過和叔丁基鋰【Katritzky AR, Org Prep Proced Int.,1987, 19, 263】或仲丁基鋰【Snieckus V, Chem Rev., 1990, 90, 879】進行鄰位拔氫鋰化後進行烷基化的反應。反應中加入LiCl可以加速反應【Collum DB, J Org Chem., 2009, 74, 2231】。

反應操作

2-n-Butylbenzanilide (6). To benzanilide 1 (1.97 g. 10 mmol) in THF (28.5 mL) and HMPA (1.5 mL) was added 2.5 M BuLi (4 mL) dropwise at -70 ℃. The mixture was warmed to r.t. and CO2 was passed through for 5 min. After removal of the solvent under vacuum, THF (30 mL) was added under Ar and 1.7 M t-butyllithium (6.5 mL) was added slowly at -70 ℃. The mixture was

maintained for 20 min at -20℃ and recooled to -70 ℃. n-Butyl bromide 5 (1.37 g, 10 mmol) was added. The mixture was stirred at r.t. for a few hours. The solvent was removed and 2N HCl was added to the residue at 0 ℃. The precipitate was recrystallized to give 1.85 g of 6 (73%), mp 72–73℃.

【Katritzky AR, Org Prep Proced Int.,1987, 19, 263】

1 Hauser CR J Heterocycl Chem 1969 6 475

2 Beak P J Org Chem 1977 42 1823

3 Hauser CR J Chem Eng Data 1978 23 183

4 Beak P Acc Chem Res 1982 15 306

5 Katritzky AR Org Prep Proced Int 1987 19 263

6 Schlosser M Tet Lett 1988 29 4277

7 Snieckus V Chem Rev 1990 90 879

8 Hassner A Tet Asymm 2001 12 2269

9 Florio S Org Lett 2005 7 3749

10 Hassine BB Tet Lett 2006 47 6405

11 Collum DB J Org Chem 2009 74 2231

編譯自：Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 206-207.

鄰位金屬化反應（Directed ortho Metalation）