《有机合成经典反应 Heck 反应》由会员分享，可在线阅读，更多相关《有机合成经典反应 Heck 反应（20页珍藏版）》请在金锄头文库上搜索。
1、经典化学合成反应标准操作1.前言2. 分子内的Heck反应22.1生成烯基取代的反应22.1.1分子内Heck反应化生成环外双键示例32.2形成季碳中心的反应42.2.1分子内不对称Heck反应示例52.3多烯大环的合成52.2.1 Heck反应用于合成大环多烯示例63. 分子间的Heck反应7常规分子间Heck反应3.1.1Pd(OAc)2-P(o-tol)3体系用于不饱和梭酸酯的Heck反应标准操作三.83.23.33.1.23.1.33.1.43.1.53.1.6不饱和酮的Heck反应标准操作杂环芳香卤代物和不饱和段酸酯的Heck反应标准操作一杂环芳香卤代物和不饱和梭酸酯的Heck反应标
2、准操作二芳香卤代物和不饱和梭酸的Heck反应合成反式3.芳基不饱和酸示例.10非共巍双键Heck反应示例不对称分子间Heck反应1011格外用离去基团的 Heck 反应(Irina P. Beletskaya Chem. Rev. 2000, 100,3009-3066)113.3.1重氮盐参与的Heck反应示例123.1.2不饱和酮的Heck反应标准操作=/POT, DMF, DIEAxf xA mixture of 4-bromotoluene (10.0 mmol), Cyclohex-2-enone (10 mmol), palladium acetate(0.1 -0.5 mmol)
3、, tri(o-tolyl) (0.2-1 mmol,催化剂的 2-4 倍的量)and DIEA (30 mmol) inDMF (30 mL) was heated under N2 at 100 C for 6-12 h. The reaction mixture was cooled,diluted with 50 mL of water and extracted with ether (2 x 50 mL). The combined organicportion was washed with brine solution, dried over anhydrous magnesi
4、um sulfate and finallyfiltered. Evaporatation of the volatiles under reduced pressure purification with columnchromatography to give the product.Note:有时可以分别到双键还原的产物。3.1.3杂环芳香卤代物和不饱和梭酸酯的Heck反应标准操作一A suspension of ArBr (68.4 mmol), Pd(dppf)C12 (5 g, 6.84 mmol), tetrabutylammoniumiodide (30 g, 82 mmol)
5、 and K2CO3 (28 g, 205 mmol) in N,N-dimethylformide (130 mL)was degassed via three vacuum/nitrogen ingress cycle, and then added methyl acrylate (17.6 g,205 mmol), the mixture was stirred at 100 C overnight To the mixture was added water; theaqueous layer was extracted with EtzO (3x100 ml). The combi
6、ned organic phases werewashed by brine, dried over MgSO% filtered and concentrated. The residue was purified bycolumn chromatography to afford the product (, yield50%).3.1.4杂环芳香卤代物和不饱和梭酸酯的Heck反应标准操作二A suspension of ArBr (170mmol), Pd(OAc)2 (1.9g, 8.5mmol), tetrabutylammonium iodide(55.Og, 170mmol) a
7、nd KOAc (5.01g, 511mmol) in N,N-dimethylformide (200 mL) wasdegassed via three vacuum/nitrogen ingress cycle, and then added methyl acrylate (46.0mL,511 mmol), the mixture was stirred at 100 C overnight. To the mixture was added water; theaqueous layer was extracted with Et2。(3x300 mL). The combined
8、 organic phases werewashed by brine, dried over MgSO% filtered and concentrated. The residue was purified bycolumn chromatography to afford the product (15 g, yield 50%).Note: Pd(OAc)2的质量有时是试验成败的关键，3.1.5芳香卤代物和不饱和梭酸的Heck反应合成反式3.芳基不饱和酸示例Br+ base, benzene, 40 C1a: Ar = Ph (96% ee)1b: Ar = p-CIC6H4 (96%
9、 ee)1c: Ar = p-MeOC6H4 (87% ee)1d: Ar = 2-naphthyl (96% ee)Tamio Hayashi, Pure & AppL Chem., 1992, 64(3), 421-427碱对芳基花产物的对应选择性有肯定的影响。例如，用高位阻的强碱性1, 8-双若用2, 6-二甲基毗嚏作碱(N,N-二甲氨基)蔡时，其la的对应选择性超过96%ee。时，la的对应选择性为69%ee。(R)2(S)-3(R)BINAP【_yPd(OAc)22(R)BINAPArOTf + (O+ base, - base-HOTfin benzene1a: Ar = Ph (
10、96% ee)1b: Ar = p-CIC6H4 (96% ee)1c: Ar = m-CIC6H4 (96% ee)1d: Ar = o-CIC6H4 (92% ee)1e: Ar = p-AcC6H4 (96% ee)1f: Ar = p-NCC6H4 (96% ee)1g: Ar = p-MeOC6H4 (87% ee)1h: Ar = 2-naphthyl (96% ee)3.3 格外用离去基团的 Heck 反应(Irina P. Beletskaya Chem. Rev. 2000, 100, 3009-3066)Beller等人报道了重氮盐参与的Heck反应不需要麟催化剂和胺，条件温存，是很COOMe有用的芳基化反应。ArN2BF4 + JOOMe _5% P&C MeOH, 40-60 C ArBeller, M.; Kuehlein, K. Synlett. 1995, 441碘盐参与的Heck反应条件也比较温存，用水作溶剂反应较快，适用于一些惧怕激烈反应条件的底物。对于二芳基碘盐的Heck反应，一般常温下得到一取代的产物，回流条件下得到二取代产物。V/0H , Ph2rBF4 Pd(OAc)2(2md%)N一CH3CN/H2O(5:1), rtv一Kang, S.-K. J. Org. Chem. 1996, 61
