Carbon-Carbon bond forming reactions are very important in organic synthesis. Preparation of most of the leading drugs on the market involves at least one carbon-carbon bond forming transformation. However, use of preformed oganometallics for this purpose is neither atom economical nor cost effective. Thus, development of atom economical and environmentally benign carbon-carbon bond forming methods is highly desirable. Catalytic hydrogenation is one of the most widely used transformations in the pharmaceutical and chemical industry. However, for several years the catalytic hydrogenation was limited to the carbon-carbon bond forming processes such as alkene hydroformylation and the Fischer-Tropsch reactions. In 2004 Krische group demonstrated a novel reductive aldol cyclization under rhodium catalyzed hydrogenation conditions. Following this, a variety of reductive carbon-carbon bond forming reactions were developed under hydrogenation conditions. The first chapter of this dissertation summarizes the reductive couplings of π-unsaturates to imines. N-heterocyclic compounds are very valuble in pharmaceutical and agrochemical industries. In the second chapter a variety of hydrogen mediated reductive couplings to aromatic N-heterocycles have been described. Transfer hydrogenation represents another important class of reactions in organic chemistry. This process employs hydrogen sources other than gaseous dihydrogen, such as isopropanol. Very recently, the Krische group reported a number of novel C-C coupling reactions using the concept of transfer hydrogenation. Thus, in chapter 3 a very elegant ruthenium catalyzed allylation reaction has been described. Finally, chapter 4 focuses on the reactivity of zinc enolates toward less reactive electrophiles such as allylic carbonates in the absence of any transition metal catalyst. During this process a direct allylic substitution of allylic carbonates with diorganozinc reagents has been discovered. These two transformations are conceptually very interesting. / text

Carbon-carbon bond forming reactions are fundamental transformations for constructing structurally complex organic building blocks, especially in the realm of natural products synthesis. Classical protocols for forming a C-C bond typically require the use of stoichiometrically preformed organometallic reagents, constituting a major drawback for organic synthesis on process scale. Since the emergence of transition metal catalysis in hydrogenation and hydrogenative C-C coupling reactions, atom and step economy have become important considerations in the development of sustainable methods. In the Krische laboratory, our goal is to utilize abundant, renewable feedstocks, so that the reactions can proceed in an efficient and atom-economical manner. Our research focuses on developing new C-C bond forming protocols that transcend the use of stoichiometric, preformed organometallic reagents, in which [pi]-unsaturates can be employed as surrogates to discrete premetallated reagents. Under transition metal catalyzed transfer hydrogenation conditions, alcohols can engage in C-C coupling, avoiding unnecessary redox manipulations prior to carbonyl addition. Stereoselective variants of these reactions are also under extensive investigation to effect stereo-induction by way of chiral motifs found in ligands and counterions. The research presented in this dissertation represents the development of a new class of C-C bond forming transformations useful for constructing synthetic challenging molecules. Development of transfer hydrogenative C-C bond forming reactions in the form of carbonyl additions such as carbonyl allylation, carbonyl propargylation, carbonyl vinylation etc. are discussed in detail. Additionally, these methods avoid the use of stoichiometric chiral allenylmetal, propargylmetal or vinylmetal reagents, respectively, accessing diastereo- and enantioenriched products of carbonyl additions in the absence of stoichiometric organometallic byproducts. By exploiting the atom-economical transfer hydrogenative carbonyl addition protocols using ruthenium and iridium, preparations of important structural motifs that are abundant in natural products, such as allylic alcohols, homoallylic alcohols and homopropargylic alcohols, become more feasible and accessible. / text

Carbon-carbon bond formation is one the fundamental reactions in organic synthesis. The quest for the development of new and more efficient processes for the construction of this bond has been an ongoing focus for years. The transformations that permit the use of simple precursors to access complex structural architectures in the absence of stoichiometric quantities by-products are highly desirable. Hydrogen is a cheapest and cleanest reductant available to the mankind. The catalytic hydrogenation has been widely utilized in the industry, however the construction of the carbon-carbon bond under hydrogenative conditions has been achieved only for alkene hydroformylations and Fisher-Tropsh process and limited to the use of carbon monoxide. The extension of the hydrogenative carbon-carbon bond formations beyond aforementioned processes would be of a great significance to the synthetic community. The overview of allene use in the metal catalyzed reactions to achieve carbonyl and imine allylation and vinylation is presented in Chapter 1. The following chapter vii discusses the development of metal catalyzed hydrogenative and transfer hydrogenative coupling of allenes and carbonyl compounds to afford allylation products. These studies have resulted in the development of the first carbonyl allylation from the alcohol oxidation level. Chapter 3 discusses efforts towards achieving highly enantioselective hydrogenative coupling of alkynes to carbonyl compounds. / text

The focus of my graduate research in the Krische group has been the development of catalytic carbon-carbon bond forming reactions with an emphasis on controlling diastereo- and enatio-selectivity in transfer hydrogenative couplings. The broad goal of our research program has been the development and implementation of efficient green methods for carbonyl addition employing [pi]-unsaturates as surrogates to preformed organometallic reagents, thus enabling byproduct free variants of traditional carbanion chemistry. This dissertation shows the new reactions that I have developed toward this goal. These reactions includes new metal catalyzed approaches for carbonyl crotylation, aminoallylation, and vinylogous reformatsky aldol reactions. / text