Departamento de Química Orgánica I, Universidad del País Vasco UPV/EHU, Manuel Lardizabal 3, 20018, San Sebastián, Spain.
Chemistry. 2018 May 17;24(28):7217-7227. doi: 10.1002/chem.201800506. Epub 2018 Apr 30.
A new method for the enantioselective synthesis of 5,5-disubstituted (quaternary) hydantoins was developed on the basis of an organocatalytic Michael reaction approach involving the use of 2-benzylthio-3,5-dihydroimidazol-4-ones as key hydantoin surrogates. The method is general with respect to the substitution pattern at the hydantoin N (alkyl, aryl, acyl), N (aryl), and C (linear/branched alkyl, aryl) positions and affords essentially single diastereomeric products with enantioselectivities higher than 95 % ee in most cases. Among the bifunctional Brønsted base/H-bond catalysts examined, a known squaramide-tertiary amine catalyst and a newly prepared squaramide-tertiary amine catalyst provide the highest selectivity so far with either nitroolefins or vinyl ketones as the acceptor components. Kinetic measurements support a first-order rate dependence on both reaction partners, the donor template and the Michael acceptor, whereas competitive H NMR spectroscopy experiments reveal the high ability of the template for catalyst binding.
一种新的对映选择性合成 5,5-二取代（季碳）海因的方法是基于涉及使用 2-苄硫基-3,5-二氢咪唑-4-酮作为关键海因替代物的有机催化迈克尔反应方法开发的。该方法对海因的 N（烷基、芳基、酰基）、N（芳基）和 C（直链/支链烷基、芳基）位置的取代模式具有通用性，并在大多数情况下以高于 95%ee 的对映选择性提供基本上单一的非对映异构体产物。在所研究的双功能 Brønsted 碱/H-键催化剂中，一种已知的酰亚胺-叔胺催化剂和一种新制备的酰亚胺-叔胺催化剂在作为接受体组分的硝基烯烃或乙烯基酮的情况下提供了迄今为止最高的选择性。动力学测量支持对供体模板和迈克尔接受体的反应伙伴的一级速率依赖性，而竞争性 H NMR 光谱实验揭示了模板对催化剂结合的高能力。
