Project Summary/Abstract Nitrogen-containing heterocycles are prevalent in bioactive natural products and pharmaceuticals, with piperidine serving as the most prevalent heterocycle found in drug scaffolds. Although largely understudied, strained azacyclic allenes have the potential to serve as building blocks for the construction of densely functionalized piperidines. The manipulation of azacyclic allenes in a controlled manner would offer new opportunities for making arrays of heterocycles with valuable applications in the pharmaceutical industry and in organic synthesis. The primary goal of this proposal is to develop a model for predicting the regioselectivities and steroselectivities of azacyclic allenes in Diels–Alder cycloadditions, thereby accelerating their application in the synthesis of highly functionalized nitrogen-containing heterocycles. The research environment in the Garg and Houk laboratories at UCLA is ideal for achieving this goal. The laboratories have a track record of collaboration at the interface of synthetic chemistry and mechanism. Both Professor Garg and Professor Houk are leaders in their respective fields and are also known to have excellent track records of mentoring graduate students and ensuring their success. Thus, the trainee would become an expert in both the fields of organic synthesis and computational chemistry. The proposal will be accomplished through two specific aims involving a combination of computations and experiments. In Aim 1, a predictive model for regioselective Diels–Alder cycloadditions with 3’ and 5’ substituted azacyclic allenes will be developed. This effort will involve high accuracy DFT calculations and experimental testing of computational predictions to confirm the reliability of the model. Aim 2 will involve the development of enantiospecific Diels–Alder cycloadditions of azacyclic allenes. The role of substituents in these reactions will be studied computationally, and a simple model to predict stereospecificity will be developed. Computational predictions will be tested experimentally and will establish the reliability of the predictive model for a variety of azacyclic allenes. This work would ultimately demonstrate the utility of strained cyclic allenes in asymmetric synthesis.