Asymmetric synthesis of isoquinoline alkaloids

The asymmetric synthesis of isoquinoline alkaloids is usually performed using either of two synthetic strategies, specifically, the stereochemical modification of the traditional, classical methods, and introduction of nucleophilic or electrophilic carbon units into the C-1 position of isoquinoline derivatives. The former strategy involves the use of the sequential Bischler-Napieralski cyclization/reduction, the Pictet-Spengler, and various Pomeranz-Fritsch cyclizations, whereas the latter concerns the use of the C1-Cα connectivity approach. Among these methods, the traditional Bischler-Napieralski cyclization/reduction and Pictet-Spengler syntheses as well as the addition of carbon nucleophiles to the isoquinoline C=N double bond are the most often explored. Although these methods readily synthesize 1-substituted tetrahydroisoquinoline alkaloids, they suffer from various limitations. Thus, there is still a need for a general method that would secure preparation of all types of isoquinoline alkaloids with high optical purity.