氨基催化酶选择性 [2 + 2] 循环添加 Bicyclo[1.1.0] 布坦和α,β-不和化物
René Slot Bitsch1, Enrico Marcantonio1, Erlaitz Basabe Obregón1
1Department of Chemistry, Aarhus University 8000 Aarhus C Denmark kaj@chem.au.dk.
这项研究引入了一种新型的氨基催化方法,通过对抗选择性 [2 + 2] 循环添加合成双环[2.1.1] . 这种反应有效地将双环[1.1.0]布坦与多种α,β不和化物结合在一起,形成有价值的化学支架.
科学领域:
- 有机化学
- 催化剂
- 医学化学
背景情况:
- 单环[1.1.0]布坦为合成新型分子支架提供独特的化学结构.
- 在药物发现中,自行车[2.1.1] 是有前途的整形和元基生物异构剂.
- 对于开发纯立体化学药物而言,酶选择性合成至关重要.
研究的目的:
- 开发了第一种氨基催化对双环[1.1.0]布坦与α,β-不和化物进行 [2 + 2]循环添加.
- 探索这种新合成方法的范围和局限性.
- 通过进一步的转换来证明由此产生的bicyclo[2.1.1]hexane支架的实用性.
主要方法:
- 使用二次氨基催化剂与Ytterbium triflate (Yb(OTf) 3一起作为一个易斯酸.
- 用于与各种α,β不和化物进行循环添加的活性双环[1.1.0].
- 使用奇拉分析来确定等离子比率 (e.r. ) 的情况.
主要成果:
- 达到了适度到良好的双环[2.1.1]hexane循环载荷管与甲 (高达96.5:3.5 e.r. ) 的情况.
- 获得的高产量和反选择性 (高达98.5:1.5 e.r.) 具有和功能的α,β不和化物.
- 对于广泛的基板的耐受性已被证明,并披露了bicyclo[2.1.1]hexane支架的后续功能.
结论:
- 建立了一种多功能和反选择性氨基催化方法来构建双环[2.1.1]hexanes.
- 开发的方法为药物化学应用提供了有价值的支架.
- 提出了一个反应机制来阐明催化循环.
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