Intramolecular Anodic Olefin Coupling Reactions: Synthesis Of Nitrogen- And Oxygen-Heterocycles

Anodic oxidation has been shown to be a powerful method for initiating umpolung reactions that allow the coupling of two nucleophilic functional groups. Most of the work in this area concentrates on making carbon-carbon bond. Hence, the reactions are usually terminated with olefin nucleophiles. The use of heteroatom-based coupling partners to form carbon-heteroatom bond is less explored despite the wide occurrence of heterocyclic compounds as natural products, pharmaceuticals, and synthetic building blocks. Therefore, this thesis focuses on the application of heteroatom-based coupling partners in intramolecular anodic olefin coupling reactions for the synthesis of N- and O-heterocyclic compounds. First, a synthesis of: -)-crobarbatic acid was accomplished in 10 steps by employing as the key step anodic coupling of an alcohol and a ketene dithioacetal. The key to the success of the oxidative cyclization reaction is the use of lithium methoxide as a base instead of the commonly used weak base, 2,6-lutidine. The synthesis demonstrates that a vinyl substituted ketene dithioacetal is compatible with anodic cyclizations and that it is possible to reverse the stereochemistry of the newly formed stereogenenic center in the electrolysis product. Next, the anodic coupling of sulfonamides and electron-rich olefins was developed in order to build cyclic amino acid derivatives. Low yields were obtained under reaction conditions employing 2,6-lutidine as a base. However, with the use of a stronger base, LiOMe, a variety of electron-rich olefins such as enol ethers, vinyl sulfides, ketene dithioacetals, and allylsilanes, are compatible with the cyclizations affording proline and pipecolic acid derivatives in good to excellent yields and diastereoselectivity. The mechanism of the reactions under the basic reaction conditions was investigated using competition studies. The harsh reaction conditions associated with the removal of the tosyl group from the electrolysis products prompted us to study the use of primary amines as coupling partners. The oxidative coupling of unprotected amines with ketene dithioacetals afforded proline and pipecolic acid derivatives with alpha-tetrasubstituted carbon atoms despite the oxidation potential of the product being significantly lower than either functional group in the substrate. The competing oxidation of the product was avoided because the oxidation potential of the substrate is lowered by a fast cyclization. One of the limitations of the oxidative cyclization reactions is the failure to afford cyclic amino acids that do not have alpha-tetrasubstituted carbon atoms. Hence, a complementary method, base induced intramolecular hydroamination of ketene dithioacetals, was developed to address this issue. The catalytic cyclizations afforded both five and six-membered ring products with an aldehyde equivalent at C2 in excellent yield and diastereoselectivity. Amides such as O-benzyl hydroxamate and N-phenyl amides were employed successfully in intramolecular anodic olefin coupling reactions to provide lactams. This study demonstrates that amidyl radicals can be generated easily from N-H amides using anodic oxidation. Compared with established methods for the generation of amidyl radicals, which usually involve the fragmentation of amide derivatives under relative high temperatures, the electrochemical oxidation method generates amidyl radicals at room temperature and avoids the preparation of amide derivatives, which are usually unstable and hard to prepare. In addition to the synthesis of N-heterocycles, carboxylic acids were used as nucleophiles in anodic coupling reactions to provide lactones with a carbonyl equivalent at the C2 position. Such structures can be found in many natural products. The cyclizations afforded both gamma-butyro- and delta-valerolactones in good to excellent yields and diastereoselectivity

SLOPE ONE COLLABORATIVE FILTERING BASED ON USER SIMILARITY

To solve the problem of data sparsity in traditional collab-orative filtering algorithm and improve the accuracy of rec-ommendation algorithm, a Slope based on user similarity is proposed.One Filling Score Matrix Collaborative Filtering Algo-rithms. The algorithm first uses the basic cosine similarity to calculate the similarity between users and generates the user similarity matrix, then fills the original user similarity matrix with the score predicted value of Slope One algorithm as the backfill value of the first n neighbors, and finally recommends the filled similarity matrix according to the traditional item-based collaborative filtering algorithm. Slope One collabora-tive filtering algorithm based on user similarity takes full ac-count of the similarity between users when filling the matrix, which makes the score prediction more accurate. The new al-gorithm alleviates the problem of data sparsity to a certain extent and improves the accuracy of the algorithm. The im-proved algorithm, classical collaborative filtering algorithm and even-weighted Slope One algorithm are tested on Movie Lens dataset. The results show that the Slope One collabora-tive filtering algorithm based on user similarity effectively al-leviates the problem of data sparsity and has better recom-mendation effect

Efficient Multi-Task and Transfer Reinforcement Learning with Parameter-Compositional Framework

In this work, we investigate the potential of improving multi-task training and also leveraging it for transferring in the reinforcement learning setting. We identify several challenges towards this goal and propose a transferring approach with a parameter-compositional formulation. We investigate ways to improve the training of multi-task reinforcement learning which serves as the foundation for transferring. Then we conduct a number of transferring experiments on various manipulation tasks. Experimental results demonstrate that the proposed approach can have improved performance in the multi-task training stage, and further show effective transferring in terms of both sample efficiency and performance.Comment: 8 pages, accepted by IEEE Robotics and Automation Letters (RA-L

Firm Dynamics in News Driven Business Cycle: The Role of Endogenous Survival Rate

Our structural VAR shows that the new business formation in U.S. data has similar positive co-movement pattern as common aggregate variables in response to a favorable anticipated shock about technology. However, incorporating �firm dynamics into Jaimovich and Rebelo's (Jaimovich and Rebelo, 2009, American Economic Review) model cannot explain our empirical fi�nding. Even worse, the model predicts an aggregate recession instead of a boom. Then, we show that this problem can be resolved with a minor modification by introducing endogenous survival rate of the new entrants