Abstract:
Malamides (diamide derivatives of malic acid) are prevalent in nature and of significant biological interest, yet only limited synthetic methods to access functionalised enantiopure derivatives have been established to date. Herein, an effective synthetic method to generate this molecular class is developed through in situ formation of spirocyclic β-lactone-oxindoles (employing a known enantioselective isothiourea-catalysed formal [2+2] cycloaddition of C(1)-ammonium enolates and isatin derivatives) followed by a subsequent dual ring-opening protocol (of the β-lactone and oxindole) with amine nucleophiles. The application of this protocol is demonstrated across twelve examples to give densely functionalised malamide derivatives with high enantio- and diastereo-selectivity (up to >95:5 dr and >99:1 er).
摘要:
苹果酸酰胺(苹果酸的二酰胺衍生物)在自然界中普遍存在,具有重要的生物学意义。然而,迄今为止,仅建立了有限的合成方法来获得官能化的对映体纯衍生物。在这里,一种有效的合成方法是通过原位形成螺环β-内酯-羟吲哚(采用已知的对映体选择性异硫脲催化的C(1)-烯醇化铵和Isatin衍生物的形式[22]环加成)来开发的。随后的双开环方案(β-内酯和羟吲哚)与胺亲核试剂。在十二个实施例中证明了该方案的应用,以得到具有高对映和非对映选择性(高达>95:5dr和>99:ler)的致密官能化的苹果酰胺衍生物。