Dynamic Resolution of Boronic Esters: A Powerful Strategy for Asymmetric Atropisomer Synthesis

在有机化学中，阿托异构体是一类不寻常的分子，因为它们从平面分子片段中传递出明确的三维形状。异构化是由于空间碰撞导致单键旋转受阻而产生的，从而使分离单个异构体成为可能。从自然界和药物中提取的大量重要分子都表现出异构性，然而针对这些化合物的立体选择性合成方法仍然非常具有挑战性。我们已经开发出一种方法来高选择性地获得特定的阿托异构体，这涉及到容易制备的立体异构体混合物的平衡。这种方法的基础是硼的化学，它既可以控制阿托品的立体化学，又可以作为进一步化学修饰的把手。我们才刚刚开始了解这一过程的范围，但我们相信它将代表着制备这些重要化合物的一般方法。所申请的赠款将使我们能够展示该方法的潜力，并将表明我们可以使用它来获得非常广泛的高价值化学品。

Atropisomers are an unusual class of molecules in organic chemistry as they convey a defined three-dimensional shape from flat molecular fragments. Atropisomerism arises from hindrance of bond rotation about single bonds due to steric clashes, thereby making the isolation of the individual isomers possible. There are a large number of prominent molecules derived from nature as well as pharmaceuticals that exhibit atropisomerism, however stereoselective synthetic methods towards these compounds remain very challenging. We have developed a way to access specific atropisomers with high selectivity that involves the equilibration of an easily prepared stereoisomeric mixture. This method is underpinned by the chemistry of boron, which serves to both control atropisomer stereochemistry, while acting as a handle for further chemical modifications. We are only just beginning to understand the scope of this process, but we believe that it will represent a general method for preparing these important compounds. The requested grant will allow us to demonstrate the potential of the methodology, and will show that we can use it to access a very broad range of high value chemicals.