Catalyst-controlled stereoselective combinatorial synthesis.
Catalyst-controlled stereoselective combinatorial synthesis.
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催化剂控制的立体选择性组合合成。
DOI：
10.1002/anie.200351129
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发表时间：
2003
影响因子：
--
通讯作者：
G. Sekar
中科院分区：
文献类型：
--
作者：
L. Tietze;Nils Rackelmann;G. Sekar
[9] 使用对映体纯助剂的试剂控制反应同样是可能的。 [10] N. Uematsu、A. Fujii、S. Hashiguchi、T. Ikariya、R. Noyori、J. Am。化学。苏克。 1996, 118, 4916–4917. [11]将 2a 和 4a（27.6 g，70.2 mmol）的外消旋混合物在 CH3CN（650 mL）中的溶液在 78℃ 下用 KMnO4（23.3 g，147 mmol）分小份处理 15 分钟，然后在 58℃ 下搅拌 70 分钟。将反应混合物用冰冷的Et 2 O(2.5L)稀释，将有机相用饱和NaCl溶液洗涤直至溶液无色，并经Na 2 SO 4 干燥。减压除去溶剂，得到二氢异喹啉3，为浅黄色油状物，其无需进一步纯化即可使用（24.7g，90%）。 [12]将二聚二氯(对伞花烯)钌(ii)(403mg，0.66mmol)、1,2-(R,R)-N-甲苯磺酰基-1,2-二苯基乙二胺(530mg，1.45mmol)和NEt3(0.37mL，2.63mmol)在DMF(6.1mL)中的溶液在氩气下搅拌20分钟808°C 60 分钟。将温热的溶液添加至二氢异喹啉3(21.5g，55mmol)的DMF(103mL)溶液中，并将混合物冷却至08℃。然后滴加HCO 2 H和NEt 3 (5:2；27.5mL)的混合物，并将反应混合物在258℃搅拌2小时。通过添加饱和K 2 CO 3 溶液来处理反应，用H 2 O稀释混合物，用乙酸乙酯萃取水相，并用Na 2 SO 4 干燥合并的有机相。减压除去溶剂后，通过硅胶色谱法(AcOEt/NEt3，100:1)纯化棕色粗产物，得到黄色油状的2a(20.2g，93%，>95%ee)。 [13] a) LF Tietze，A. Modi，医学博士。资源。修订版 2000, 20, 304–322; b) L. F. Tietze、F. Haunert，《化学中的刺激概念》（Eds. F. Vögtle、JF Stoddart、M. Shibasaki、Wiley-VCH、Weinheim、
[9] Reagent-controlled reactions in which enantiomerically pure auxiliaries are used are likewise possible.[10] N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 4916–4917.[11] A solution of a racemic mixture of 2a and 4a (27.6 g, 70.2 mmol) in CH3CN (650 mL) was treated at À78C with KMnO4 (23.3 g, 147 mmol) in small portions over a period of 15 min and then stirred for 70 min at À58C. The reaction mixture was diluted with ice-cold Et2O (2.5 L), the organic phase was washed with saturated NaCl solution until the solution was colorless, and dried over Na2SO4. The solvent was removed under reduced pressure to yield the dihydroisoquinoline 3 as a pale yellow oil, which was used without further purification (24.7 g, 90%).[12] A solution of dimeric dichloro (p-cymene) ruthenium (ii)(403 mg, 0.66 mmol), 1, 2-(R, R)-N-tosyl-1, 2-diphenylethylenediamine (530 mg, 1.45 mmol), and NEt3 (0.37 mL, 2.63 mmol) in DMF (6.1 mL) was stirred under argon for 60 min at 808C. The warm solution was added to the dihydroisoquinoline 3 (21.5 g, 55 mmol) in DMF (103 mL) and the mixture was cooled to 08C. A mixture of HCO2H and NEt3 (5: 2; 27.5 mL) was then added dropwise, and the reaction mixture was stirred for 2 h at 258C. The reaction was worked up by the addition of a saturated solution of K2CO3, the mixture was diluted with H2O, the aqueous phase extracted with ethyl acetate, and the combined organic phases dried over Na2SO4. After removal of the solvent under reduced pressure, the brown crude product was purified by chromatography on silica gel (AcOEt/NEt3, 100: 1) to yield 2a as a yellow oil (20.2 g, 93%,> 95% ee).[13] a) LF Tietze, A. Modi, Med. Res. Rev. 2000, 20, 304–322; b) L. F. Tietze, F. Haunert in Stimulating Concepts in Chemistry (Eds. F. Vögtle, JF Stoddart, M. Shibasaki, Wiley-VCH, Weinheim,