Abstract
A new and versatile synthesis of substituted isoquinolines: lithiated o-tolualdehyde tert-butylimines are shown to condense with nitriles to form eneamido anion intermediates that can be trapped in situ with various electrophiles, affording a diverse array of highly substituted isoquinolines, many of which are difficult to access by known methods. Further substitutional diversification can be achieved by modification of the work-up conditions and by subsequent transformations. This method should be useful for the preparation of biological active isoquinolines, such as analogs of the isoquinoline-containing natural product cortistatin A.