Organic Catalysis And Homogeneous Gold Catalysis Strategy In The Synthesis Of New Potential Fragrant Substances

Synthetic fragrance chemistry is an important part of synthetic organic chemistry. The discovery of new patentable fragrance ingredients and new fragrance production processes is the core competitiveness of fragrance industry. In this dissertation, the design and development of novel organic reactions are described aiming at accessing new green, woody and floral fragrance molecules. Based on the odor evaluation results, the relationship between structure and odor of the new molecules has also been investigated.Nowadays, organocatalysis and homogeneous gold catalysis are two of the most exciting research topics in chemistry. The corresponding methodologies have been successfully applied to complex natural product and drug synthesis. The elaboration of organocatalysis and Au catalysts to develop new reactivity patterns benefits greatly from a fundamental understanding of the mechanisms involved, and integrates theoretical models and preparative findings in the development of a new methodology. Such improvement has attracted great attention from industry. In this dissertation, we intended to study these two types of synthetic methods for the synthesis and screening of new fragrances and to explore the possibility of the application of organocatalysis and gold catalysis in the production of fragrance ingredients. This thesis focuses on novel organocatalytic multi-component reactions as well as gold-catalyzed homo-Rautenstrauch rearrangements. The main contents are as follows:1. In Chapter 1, after introducing the background of fragrance chemistry, organocatalysis, multi-component reactions (MCRs) and homogeneous gold catalysis, we selected elegant examples of total synthesis of natural products utilizing organocatalytic domino processes and homogeneous gold catalytic strateges.2. Organocatalytic multicomponent domino processes are appealing because they combine advantages of both sustainable organocatalysis and economical multi-component reactions. Today, organocatalytic MCRs represent ideal strategies for the preparation of complex structures from unstable and inseparable reaction intermediates and are particularly attractive for both natural product and diversity-oriented syntheses (DOS). In Chapter 2, the subsequent optimization study of the reaction conditions is described which lead to the development of a novel organocatalytic a-methylation/Diels-Alder (D-A) cycloaddition reaction. In this one-pot transformation,2-formyl-1,3-butadienes 43 were prepared in situ from a,p-unsaturated aldehydes 47 and formalin and were subsequently trapped with a variety of 1,3-butadienes to access vinyl-cyclohexene carboxaldehydes 41 and 42 in highly regioselective fashion. The outcome of the reaction depended on the electronic properties of the dienes. endo-D-A adducts of 1-vinylcyclohexene carbaldehydes 41 were predominantly formed by reaction with acyclic electron-rich dienes 44a-b, while the initially formed exo-configured cycloadducts with cyclopentadiene underwent subsequent Cope rearrangements leading to the formation of tetrahydro-3H-indene-5-carbaldehyde 42. Furthermore, the method was extended to a one-pot four-component hydrolysis/methylenation/Diels-Alder reaction of dihydrofurans and dihydropyrans to yield spirocyclic-lactols 72. Again, endo-DA adducts were formed by reaction with acyclic electron-rich dienes, while exo-DA adducts were obtained by reaction with cyclopentadiene. In these reactions, the instable intermediate hydroxyethyl and hydroxypropyl acroleins behaved as dienophiles undergoing cycloaddition reactions with dienes in good yields and selectivities. After simple chemical modification, the spiro-lactols were transformed into elegant woody and ambery odorants 165 and 168.3. In Chapter 3, we have elaborated a new Au-catalyzed homo-Rautenstrauch rearrangement of 1-cyclopropylpropargylic esters to cyclohexenones 109 and cyclopentenyl ketones 117 under mild conditions. The gold catalyzed rearrangement was highly efficient, rapid and mild. In addition, enantiomerically enriched cyclohexenones (R)-118 and cyclopentenyl ketones (R)-119 were prepared by the gold-catalyzed cycloisomerization of optically active propargyl acetates. Although the rearrangements are cationic in nature, the high degree of chirality transfer in these reactions suggests that gold-stabilized nonclassical carbocations with a certain configurational stability are involved. The absolute configurations of the products were determined by comparison of the measured ROA with the calculated spectra. New compounds have been characterized by IR, NMR, GC-MS and HRMS analysis. Homogeneous gold catalysis has witnessed rapid growth in recent years and became an important tool in organic synthesis. However, although there are many beautiful gold-catalyzed organic reactions reported, their underlying mechanisms are far from being completely understood, in contrast for instance to the mechanisms of palladium-catalyzed reactions. Following Furstner's canonical proposal that gold species have non-classical carbocation character, we were able to interpretate our result of the chirality transfer via the formation of intermediate resonance structures. We then reviewed controversial history of "non-classical carbocation" issue from four decades ago. Combined with the latest controversy of "gold carbenes" and "gold-stabilized carbocations," the reaction mechanism was discussed based on the chirality transfer results. In the attempt to synthesis of carvone, isolation of compounds 149 and 150 provided the "non-classical carbonium ion" scenario.4. Molecular structure-odor correlations have puzzled fragrance chemists for many years. Although many theories have been proposed relating to the primary events in olfaction and to relationships between molecular structure and odor, the prediction of odor remains a statistical exercise. So far, not yet a reliable theory or some kind of bio-molecular model can predict the molecular structure of the aroma characteristics. In Chapter 4, a number of new molecules have been synthesized in olfactory pure form by distillation. The odor assessment was carried out by professional perfumers. Evaluation results show that many of the compounds synthesized have very interesting green, herbal, and woody scents.