Download Free Oxidative Palladiumii Catalyzed Arene C H Bond Functionalization And Progress Towards The Total Synthesis Of 6 Deoxyerythronolide B Book in PDF and EPUB Free Download. You can read online Oxidative Palladiumii Catalyzed Arene C H Bond Functionalization And Progress Towards The Total Synthesis Of 6 Deoxyerythronolide B and write the review.

Strategies for Palladium-Catalyzed Non-directed and Directed C-H Bond Functionalization portrays the complete scope of these two aspects of C-H bond functionalization in a single volume for the first time. Featured topics include the influence of palladacyclic systems in C-H bond functionalization (need for newer catalytic systems for better efficiency), mechanistic aspect of the functionalization strategies leading to better systems, and applications of these methodologies to natural product synthesis and material synthesis. Addresses the involvement of catalytic systems (palladacycles) for better functionalization of (hetero)arenes to emphasize the need for developing better, more selective systems Covers the use of powerful mechanistic tools for understanding and assisting the development of better functionalization strategies Discusses the finer aspects of C-H bond functionalization, such as control of regioselectivity with or without directing groups Includes a chapter detailing the synthesis of naturally occurring molecules or functional molecules via both pathways for assessing the applicability of the functionalization strategies
Kyle A. Grice, Margaret L. Scheuermann and Karen I. Goldberg: Five-Coordinate Platinum(IV) Complexes.- Jay A. Labinger and John E. Bercaw: The Role of Higher Oxidation State Species in Platinum-Mediated C-H Bond Activation and Functionalization.- Joy M. Racowski and Melanie S. Sanford: Carbon-Heteroatom Bond-Forming Reductive Elimination from Palladium(IV) Complexes.- Helena C. Malinakova: Palladium(IV) Complexes as Intermediates in Catalytic and Stoichiometric Cascade Sequences Providing Complex Carbocycles and Heterocycles.- Allan J. Canty and Manab Sharma: h1-Alkynyl Chemistry for the Higher Oxidation States of Palladium and Platinum.- David C. Powers and Tobias Ritter: Palladium(III) in Synthesis and Catalysis.- Marc-Etienne Moret: Organometallic Platinum(II) and Palladium(II) Complexes as Donor Ligands for Lewis-Acidic d10 and s2 Centers.
Achieving direct and selective functionalization of carbon-hydrogen (C-H) bonds to give carbon-carbon (C-C) or carbon-heteroatom (C-Y) bonds is a significant and long-standing goal in chemistry. C-H bonds are attractive reaction partners because they are ubiquitous in organic molecules. Thus, C-H functionalization methods could potentially expedite the synthesis of target molecules by providing new disconnections in retrosynthetic analysis. Among the numerous methods to affect this transformation, palladium-catalyzed C-H functionalization is one of most promising methods to construct C-C and C-Y bonds in term of versatile reactivity. The major challenges of palladium-catalyzed C-H functionalization are developing reactions that work with common and useful structural motifs and discovering new transformation, such as C-N or C-F bond formation. This thesis explores palladium-catalyzed C-H bond functionalization with substrates containing simple functional groups such as carboxylic acids and triflamides, which direct C-H cleavage through weak coordination with the metal catalyst. Chapter one introduces different types of C-H bond functionalization and focuses on Pd(II)/Pd(IV) catalysis. Chapter two covers Pd-catalyzed C-H iodination of arene carboxylic acids enabled by the discovery of coutercation-promoted C-H activation. Weak coordination has also been found to enable versatile reactivity of simple arene carboxylic acids. Chapter three focuses on the development of practical and useful C-H fluorination using triflamide as a weakly coordinating directing group that can be easily manipulated to a wide range of useful and common aryl halides. Chapter four describes applications of bystanding F+ oxidants to promote selective C-N reductive elimination in Pd(II)/Pd(IV) catalysis.
This book presents Pd- and Ni-catalyzed transformations generating functionalized heterocycles. Transition metal catalysis is at the forefront of synthetic organic chemistry since it offers new and powerful methods to forge carbon–carbon bonds in high atom- and step-economy. In Chapter 1, the author describes a Pd- and Ni-catalyzed cycloisomerization of aryl iodides to alkyl iodides, known as carboiodination. In the context of the Pd-catalyzed variant, the chapter explores the production of enantioenriched carboxamides through diastereoselective Pd-catalyzed carboiodination. It then discusses Ni-catalyzed reactions to generate oxindoles and an enantioselective variant employing a dual ligand system. Chapter 2 introduces readers to a Pd-catalyzed diastereoselective anion-capture cascade. It also examines diastereoselective Pd-catalyzed aryl cyanation to synthesize alkyl nitriles, a method that generates high yields of borylated chromans as a single diastereomer, and highlights its synthetic utility. Lastly, Chapter 3 presents a Pd-catalyzed domino process harnessing carbopalladation, C–H activation and π-system insertion (benzynes and alkynes) to generate spirocycles. It also describes the mechanistic studies performed on these reactions.
Transition metal-catalyzed transformations of allenes are underexplored compared to other unsaturated functional groups. However, the consecutive, orthogonal double bonds of allenes represent an extremely valuable functional handle that can be manipulated to rapidly build molecular complexity. The first section of this work (Chapter 2) describes how targeted changes to the reaction conditions enable control over the mechanism of Pd-catalyzed allene cross-coupling/cyclization and cycloisomerization, irrespective of the allene substitution pattern. Both enantioenriched cyclopropanes and cyclopentenes can be obtained through axis-to-center chirality transfer from the allene precursor at room temperature. The next section (Chapter 4) demonstrates a highly stereoselective Pd-catalyzed Heck-type reaction of allenes to form 1,3-dienes in which the stereochemistry of both olefins is set simultaneously. The stereodetermining factors and a plausible mechanism for this work are proposed and both inter- and intramolecular trapping of the Ï0-allyl intermediate with an oxygen nucleophile are demonstrated. The final portion of this work will be focused on progress towards the total synthesis of Nogalamycin (NOG) (Chapter 6). NOG is a member of the glycosidic anthracyclines and shows a unique dumbbell type binding to DNA. Toxicity and relatively low antineoplastic activity have prevented NOG from clinical use, but semisynthetically accessed derivatives have shown great potential, leading to the need for a highly modular synthetic approach to access new analogs and further probe SARs. A complex bicyclic aminosugar motif creates a significant challenge for the synthesis of NOG, as there are no reliable synthetic methods to install the C℗Ơaryl-Cglycoside bond late stage. In this section, we propose a late-stage chemoenzymatic installation of the C℗Ơaryl-Cglycoside bond inspired by the biosynthetic pathway. The synthesis of the tetracyclic anthracycline core includes a key boron-directed cycloaddition, a novel SmI2 mediated ring opening of an oxanorbornadiene, and a proposed Ni-catalyzed cross electrophile coupling.
Transition metal-catalyzed transformations of allenes are underexplored compared to other unsaturated functional groups. However, the consecutive, orthogonal double bonds of allenes represent an extremely valuable functional handle that can be manipulated to rapidly build molecular complexity. The first section of this work (Chapter 2) describes how targeted changes to the reaction conditions enable control over the mechanism of Pd-catalyzed allene cross-coupling/cyclization and cycloisomerization, irrespective of the allene substitution pattern. Both enantioenriched cyclopropanes and cyclopentenes can be obtained through axis-to-center chirality transfer from the allene precursor at room temperature. The next section (Chapter 4) demonstrates a highly stereoselective Pd-catalyzed Heck-type reaction of allenes to form 1,3-dienes in which the stereochemistry of both olefins is set simultaneously. The stereodetermining factors and a plausible mechanism for this work are proposed and both inter- and intramolecular trapping of the Ï0-allyl intermediate with an oxygen nucleophile are demonstrated. The final portion of this work will be focused on progress towards the total synthesis of Nogalamycin (NOG) (Chapter 6). NOG is a member of the glycosidic anthracyclines and shows a unique dumbbell type binding to DNA. Toxicity and relatively low antineoplastic activity have prevented NOG from clinical use, but semisynthetically accessed derivatives have shown great potential, leading to the need for a highly modular synthetic approach to access new analogs and further probe SARs. A complex bicyclic aminosugar motif creates a significant challenge for the synthesis of NOG, as there are no reliable synthetic methods to install the C℗Ơaryl-Cglycoside bond late stage. In this section, we propose a late-stage chemoenzymatic installation of the C℗Ơaryl-Cglycoside bond inspired by the biosynthetic pathway. The synthesis of the tetracyclic anthracycline core includes a key boron-directed cycloaddition, a novel SmI2 mediated ring opening of an oxanorbornadiene, and a proposed Ni-catalyzed cross electrophile coupling.
Chapter 1. A sequence of research projects beginning with studies in diastereoselective C-H bond functionalization applied to the synthesis of ( - )-incarvaillateine to the Rh(III) catalyzed arylation of imines, are described. Some theory and mechanistic considerations are discussed in relation to the genesis of these projects. Research directions are summarized and rationalized. Chapter 2. The synthesis of ( - )-incarvillateine utilizing a key C-H bond alkylation step is described as a means to highlight the synthetic utility of a newly reported olefinic C-H bond functionalization methodology. Elements of diastereoselectivity are also explored in the key step which allows for the concise, stereoselective synthesis of the natural product. Progress in the area of enantioselective C-H alkylations are also summarized as it applies to the synthesis of other natural products. Chapter 3. A method for the enantioselective cyclization of N-allylimidazoles is developed. The reaction is thought to proceed via a novel, reactive N-heterocyclic carbene. High enantioselectivities are achieved, which is unusual in view of the elevated temperatures of the reaction. Chapter 4. The first general method for the oxidative coupling of unactivated alkenes via C-H bond functionalization is reported using a methyl oxime directing group. A silver abstractor is important to obtain reactivity. Several functional groups are compatible with the reaction and no precautions to exclude air are required. Chapter 5. A rare example of C-H activation and intermolecular coupling to N-protected-imines is achieved using a cationic Rh(III) catalyst. The reaction is directed by pyridines and related heterocycles and produces a variety of aryl-branched amines. The reaction accommodates several reactive functional groups and is mild enough to even couple with sensitive alkyl N-sulfonyl-imines.
Transition metal-catalyzed functionalization of C-H bonds has been used as a powerful tool for the construction of C-C and C-heteroatom bonds. Within this dissertation, methods that allow functionalization of C-H bonds via iron and copper catalysis have been developed. Additionally, functionalization of sp3 C-H bonds in amino acid derivatives using auxiliary-assisted palladium-catalyzed methodology is also demonstrated. A method for iron-catalyzed alkylation of arenes and heterocycles containing acidic C-H bonds has been developed. Various heterocycles such as pyridine, furan, thiophene and electron deficient arenes can be coupled with both alkyl bromides and iodides. Magnesium amide base is required for the reaction. Similarly, the deprotonative dimerization of arenes and heterocycles can be effected in the presence of an iron catalyst. Thus, the method allows direct functionalization of arenes and heterocycles. Additionally, the use of an iron catalyst is an advantage compared with existing methods. Methods for copper-catalyzed direct sulfenylation and amination of sp2 C-H bonds have been developed. Using 8-aminoquinoline auxiliary and copper catalyst, ortho C-H bonds of benzoic acid amides can be sulfenylated by disulfides. The method provides an alternative, milder way for the preparation of aryl trifluoromethylsulfides. Furthermore, ortho C-H bonds of benzoic acid amides can be aminated by reaction with simple amines using 8-aminoquinoline directing group and a copper catalyst. Sulfenylation and amination of g-C-H bonds of benzyl amine derivatives using picolinic acid auxiliary were also demonstrated. Broad substrate scope, high regioselectivity, and good functional group tolerance were observed. The use of a copper catalyst and a removable directing group are significant improvements compared with the existing methods. Finally, a novel way for synthesis of non-natural amino acids via auxiliary-assisted, palladium-catalyzed C-H functionalization methodology was developed. Under palladium catalysis, 2-methyl thioaniline auxiliary allows the monoarylation of b-C-H bonds of alanine derivatives generating, after directing group removal, substituted phenylalanines. In contrast, using 8-aminoquinoline auxiliary, methylene groups in phenylalanine, leucine, and lysine derivatives can be arylated. Methods for alkylation and acetoxylation were also reported. The directing group can be removed without significant erosion of enantiomeric excess. The method provides a straight-forward way to synthesize non-natural amino acids from the chiral pool.