Nitrogen-containing molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for the formation of these motifs is of great importance. Hydroamination, that is the addition of an N-H bond across an unsaturated carbon-carbon bond of an alkene or alkyne, stands out as a potential approach to obtain such molecules. To date, most research in this area relies on transition-metal catalysis to enable such reactivity. In efforts directed towards metal-free alternatives, we have developed a simple, metal-free hydroamination of alkenes using hydrazides. Further investigation into the corresponding reactivity of alkynes with hydrazides has provided access to novel azomethine imine products. In Chapter 2, expansion of the substrate scope with respect to the intramolecular hydroamination of alkenes using hydrazides, as well as studies directed towards elucidation of the mechanism of this reaction will be presented. The intramolecular hydroamination of alkynes using hydrazides and methods to access and isolate the azomethine imine products formed will be discussed in Chapter 3.

Zugl.: Stuttgart, Univ., Diss., 2009

A central tenant of organic synthesis is the construction of carbon-carbon bonds. One of the traditional methods for carrying out such transformations is that of carbonyl addition. Unfortunately, traditional carbonyl addition chemistry suffers various drawbacks: preactivation, moisture sensitivity, and the generation of stoichiometric organometallic waste. The research presented in this dissertation focuses on the development of methods that make use of nucleophile-electrophile pairs generated in situ via transfer hydrogenation, which allow the formation of carbonyl or imine addition products from the alcohol or amine oxidation level; streamlining the construction of complex molecules from simple, readily available starting materials. Additionally, studies toward the total synthesis of the fibrinogen receptor inhibitor tetrafibricin, utilizing the methods developed in catalytic carbon-carbon bond formation through the addition, transfer or removal of hydrogen, are presented. / text

Chiral molecules as with biological activity are plentiful in nature and the chemical literature; however they represent a smaller portion of the pharmaceutical drug market. As asymmetric methodologies grow more powerful, the tools are becoming available to synthesize chiral molecules in an enantioselective and efficient manner. Recent breakthroughs in our understanding of phosphoric acid now allow for Lewis acid catalysis via pairing with alkaline earth metals. Using alkaline earth metals with chiral phosphates is an emerging approach to asymmetric methodology, but already has an influential record. The development of new conditions for the phosphoric acid-catalyzed highly enantioselective ring-opening of meso-aziridines with a series of functionalized aromatic thiol nucleophiles is described in this thesis. This methodology utilizes commercially available aromatic thiols, a series of meso-aziridines, and a catalytic amount of VAPOL calcium phosphate to explore the substrate scope of this highly enantioselective reaction. Additionally, the development of new conditions for a catalytic asymmetric aza-Darzens aziridine synthesis mediated by a vaulted biphenanthrol (VAPOL) magnesium phosphate salt is described in this thesis. Using simple substrates, this methodology explores the scope and reactivity of a new magnesium catalyst for an aziridination reaction capable of building chirality and complexity simultaneously.

The allylic bromide functionality within brominated poly(isobutylene-co-isoprene), or BIIR, alkylates primary amines repeatedly to generate thermoset products at reaction rates that are too fast to support commercial rubber processing operations. The objective of this work was to assess the utility of latent N-nucleophiles as curatives and modification reagents for BIIR. Ideally, BIIR formulations containing these latent amines would not cure at standard compound mixing temperatures, but support high crosslinking rates and yields upon heating to conventional vulcanization temperatures. Carbon dioxide-derived salts of ammonia, including (NH4)2CO3, (NH4)HCO3 and (NH4)H2NCO2, can be mixed with BIIR without incurring crosslinking at temperatures below 100oC, but they generate adequate crosslink yields upon heating to 160oC. The corresponding CO2-derived salts of primary amines decompose below 100oC and, therefore, do not provide adequate scorch protection when mixed with BIIR. Latency was conferred on primary amines using imine derivatives, in particular N-alkylbenzaldimine and its substituted analogues. These latent curatives are activated by hydrolysis, thereby providing a means of controlling active nucleophile concentrations, and minimizing crosslinking activity at 100oC without impacting negatively on cure rates at 160oC. The scorch problems generated by primary amines extend to BIIR cure formulations employing conventional sulfur and ZnO curatives. In contrast, imine analogues are shown to provide low temperature scorch stability without impacting negatively on high temperature cure rates and extents. / Thesis (Master, Chemical Engineering) -- Queen's University, 2010-02-01 15:18:16.004

Nitrogen-containing molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for the formation of these motifs is of great importance. Hydroamination, that is the addition of an N-H bond across an unsaturated carbon-carbon bond of an alkene or alkyne, stands out as a potential approach to obtain such molecules. To date, most research in this area relies on transition-metal catalysis to enable such reactivity. In efforts directed towards metal-free alternatives, we have developed a simple, metal-free hydroamination of alkenes using hydrazides. Further investigation into the corresponding reactivity of alkynes with hydrazides has provided access to novel azomethine imine products. In Chapter 2, expansion of the substrate scope with respect to the intramolecular hydroamination of alkenes using hydrazides, as well as studies directed towards elucidation of the mechanism of this reaction will be presented. The intramolecular hydroamination of alkynes using hydrazides and methods to access and isolate the azomethine imine products formed will be discussed in Chapter 3.

Universiẗat-Gesamthochsch., Diss.--Paderborn, 1996.

In this project cyclisation chemistry using palladium and radical methodologies has been developed. The aim was to compare palladium and radical mediated cyclisations. Initially small molecules containing amine and amide functional groups were synthesised to screen the methodology. Later the design of these molecules was changed to be based on the imidoyl functional group. A series of N-benzyl protected aliphatic amine and amides were synthesised in the hope (with the aim of cyclisation) that they could be cyclised using both palladium and radical conditions. When these examples failed, which was attributed to the strain of the cyclic molecules, alternative precursors were sought. Initially, the N-protecting group was changed to a tosyl-group. However, when this had no positive effect, the size of the precursor molecules were examined. Two alternative amine precursors were designed which would remove the strain element in the cyclised molecules. The lengthy synthesis of these two molecules was not favourable for the development of methodology. Although it appeared that the cyclisations were now occurring it did not prove favourable to carry on down this path. The final part of this research project utilises imines and imidoyl selenides as radical and palladium cyclisation precursors respectively. A series of aromatic imines and imidoyl selenides were synthesised. The irnines were synthesised from amino-biphenyl and a range of p-substituted benza1dehydes. The corresponding imidoyl selenides were synthesised from amino-biphenyl and a range of p-substituted benzoyl chlorides to give the amides which in tum were converted to the target molecules via the imidoyl chlorides. The successful cyclisations using both methodologies resulted in a series of phenanthridines. This success of these cyclisations led to further precursors being developed which included bisphenanthridine, alkyne, alkyl and heteroaromatic precursors. However, most of the cyclisations of these molecules proved problematic and require further development of methodology.

Nitrogen-containing molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for the formation of these motifs is of great importance. Hydroamination, that is the addition of an N-H bond across an unsaturated carbon-carbon bond of an alkene or alkyne, stands out as a potential approach to obtain such molecules. To date, most research in this area relies on transition-metal catalysis to enable such reactivity. In efforts directed towards metal-free alternatives, we have developed a simple, metal-free hydroamination of alkenes using hydrazides. Further investigation into the corresponding reactivity of alkynes with hydrazides has provided access to novel azomethine imine products. In Chapter 2, expansion of the substrate scope with respect to the intramolecular hydroamination of alkenes using hydrazides, as well as studies directed towards elucidation of the mechanism of this reaction will be presented. The intramolecular hydroamination of alkynes using hydrazides and methods to access and isolate the azomethine imine products formed will be discussed in Chapter 3.

This thesis shed lights on metal-nitrogen organometallic fragments supported on silica surface for catalytic applications. It Focuses on group IV and V metal transition as a well-defined single-site catalysts, specifically titanium, hafnium, and tantalum to utilize them in the development of selective heterogeneous catalysis for imine metathesis, hydroamination and hydroaminoalkylation of olefins and alkynes. Developing new metal-nitrogen containing fragments by using easily available and abundant precursors which is silica SiO2 and metal amides complexes. Here, we describe metal fragments starting with hafnium-nitrogen fragment. All the catalysts were prepared by reacting homoleptic metal amido of group IV and V with partially dehydroxylated silica. In most cases the resulting surface amido is monopodal and leads to well defined single site catalysts precursors. In particular with Hf we have isolated hafniaaziridine 2.1 [(≡Si-O-)Hf(η2-MeNCH2)(η1-NMe2)(η1-HNMe2)], imido, and amido fragments 2.3 [(≡Si-O-)Hf(=NMe)(η1-NMe2)], and two intermediates the five-membered ring 2.2 [≡Si-O-Hf(HNMe2)(η2-NMeCH2CH(C6H13)CH2)(NMe2)] and 2.4 [(≡Si-O-)Hf(=NCH2Ar) (η1-NMe2)]. For tantalum 3.1 [(≡Si-O-)Ta=NtBu)(η1-NMeEt)2]; we have isolated two intermediates after treating 3.1 catalyst with aniline substrate lead to isolating 3.3 [(≡Si-O-)Ta(η1σ-NEtMe)2(η1σ-NHtBu)(NHC6H10)], and upon treating with 1-octyne lead to isolating 3.2 [(≡Si-O-)Ta(η1σ-NEtMe)2(η2-NtBuC=CC7H13)]. For titanium-nitrogen fragments, we isolated on silica SiO2-200 4.1 [(≡Si-O2-)Ti(NMe2)2 (η1-HNMe2)] and on SiO2-700 the titaniaaziridine 4.2a [≡Si-O-Ti(NMe2)3] 4.2b, [(≡Si-O-)Ti(η2-MeNCH2)(η1-NMe2)(η1-HNMe2)], the imido, and amido fragments 4.4 [(≡Si-O-)Ti(=NMe)(η1-NMe2)], and the five-membered ring intermediate 4.3 [≡Si-O-Ti(HNMe2)(η2-NMeCH2CH(C6H13)CH2)(NMe2)]. Research in this area has led to isolating several intermediates containing nitrogen fragments, this is the strength of surface organometallic chemistry which allows a deeper understanding of catalytic phenomena which could not be approached either in homogeneous catalysis or in classical heterogeneous catalysis. A molecular level characterization of the surface nitrogen containing fragments have been characterized by SOMC tools such as FTIR and EXAFS spectroscopy, elemental analysis, solid-state single and multiple quantum NMR, advanced DNP-SENS and DFT. A catalytic cycle was proposed based not only on the isolation of intermediates but also based on DFT calculations.