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Enantioselective conjugate addition (ECA) reactions between organometallic reagents and cyclohexadienone 165 are being investigated. Previous studies have shown that ECAs, of organometallic reagents to á,â-unsaturated cyclohexadienones, are useful in many natural product syntheses. The substrates used in earlier studies were simple 2,5-cyclohexadienones, with a proton at the C-3 position, resulting in the synthesis of a trisubstituted C-3 atom. ECAs that afford all-carbon quaternary stereogenic centers are a much more challenging problem and few examples have been reported. Some natural products contain a ã-hydroxy group, however, no ECA substrates have incorporated this motif. ECAs have been accomplished with substrates having a g-ether substituent. The cyclohexadienone 165 system presents three challenging problems to overcome for an ECA reaction: the tertiary methyl substituents at the 3 and 5 positions, facial selectivity and enantioselectivity. An ECA to 165 using an organoaluminum reagent and an external chiral ligand 26 was successful in producing a product that showed the reaction was moderately stereoselective. A diastereoselective conjugate addition reaction (DCA) to 165 using a chiral auxiliary 68 was also successful in producing a product that showed the reaction was moderately enantioenriched. Lastly, a variable temperature NMR study was performed to establish the presence of dynamic motions of the C=N bond present in sulfinyl imines 229 and 230. As a result, the sulfinyl imines 229 and 230 were found to be interconverting at -78°C.

In order to extend the scope of asymmetric conjugate alkenylation catalyzed by 3,3′-disubstituted binaphthols, two classes of compounds were examined. Asymmetric 1,4-addition of alkenylboronates onto N-acylimines was investigated. Chiral allylic amides were obtained in good yields and high enantioselectivities. This represents one of the very few methods for synthesizing chiral allylic amides without the use of transition metal catalysts. Chiral binaphthol-catalyzed conjugate addition of alkenylboronates to -silyl--unsaturated ketones afforded highly enantioenriched chiral -silylcarbonyls. Asymmetric addition onto -silyl-enones is still a largely unexplored area, with only a handful of transition metal-catalyzed reactions reported. The first asymmetric reaction using these silicon-containing enones without using transition metal were described.

In order to extend the scope of asymmetric conjugate alkenylation catalyzed by 3,3′-disubstituted binaphthols, two classes of compounds were examined. Asymmetric 1,4-addition of alkenylboronates onto N-acylimines was investigated. Chiral allylic amides were obtained in good yields and high enantioselectivities. This represents one of the very few methods for synthesizing chiral allylic amides without the use of transition metal catalysts. Chiral binaphthol-catalyzed conjugate addition of alkenylboronates to -silyl--unsaturated ketones afforded highly enantioenriched chiral -silylcarbonyls. Asymmetric addition onto -silyl-enones is still a largely unexplored area, with only a handful of transition metal-catalyzed reactions reported. The first asymmetric reaction using these silicon-containing enones without using transition metal were described.

Enantioselective conjugate addition (ECA) reactions between organometallic reagents and cyclohexadienone 165 are being investigated. Previous studies have shown that ECAs, of organometallic reagents to á,â-unsaturated cyclohexadienones, are useful in many natural product syntheses. The substrates used in earlier studies were simple 2,5-cyclohexadienones, with a proton at the C-3 position, resulting in the synthesis of a trisubstituted C-3 atom. ECAs that afford all-carbon quaternary stereogenic centers are a much more challenging problem and few examples have been reported. Some natural products contain a ã-hydroxy group, however, no ECA substrates have incorporated this motif. ECAs have been accomplished with substrates having a g-ether substituent. The cyclohexadienone 165 system presents three challenging problems to overcome for an ECA reaction: the tertiary methyl substituents at the 3 and 5 positions, facial selectivity and enantioselectivity. An ECA to 165 using an organoaluminum reagent and an external chiral ligand 26 was successful in producing a product that showed the reaction was moderately stereoselective. A diastereoselective conjugate addition reaction (DCA) to 165 using a chiral auxiliary 68 was also successful in producing a product that showed the reaction was moderately enantioenriched. Lastly, a variable temperature NMR study was performed to establish the presence of dynamic motions of the C=N bond present in sulfinyl imines 229 and 230. As a result, the sulfinyl imines 229 and 230 were found to be interconverting at -78°C.

I. Enantioselective Rhodium-Catalysed Arylation of Electron-Deficient Alkenylarenes β-substituted alkenyl-para-nitroarenes, an unexplored substrate class for catalytic asymmetric addition reactions, undergo highly enantioselective rhodium-catalysed arylations with arylboronic acids in the presence of a dibenzylamide-containing chiral diene ligand. One example of the asymmetric arylation of an alkenyl-p-cyano-m-( trifluoromethyl)benzene is also reported. The scope of this process is broad with variation in the β-position of the alkene, additional substituents on the electrondeficient arene, and sterically and electronically unique arylboronic acids all tolerated. The synthetic utility of the developed methodology is demonstrated by smoothly converting one arylated product into its corresponding indole via the Bartoli reaction. II. Enantioselective Copper-Catalysed Reductive Coupling of Alkenylazaarenes with Ketones Catalytic enantioselective methods for the preparation of chiral azarene-containing compounds are of high value. By combining the utility of copper hydride catalysis with the ability of C=N-containing azaarenes to activate adjacent alkenes toward nucleophilic additions, the enantioselective reductive coupling of alkenylazaarenes with ketones has been developed. The process is tolerant of a wide variety of azaarenes and ketones, and provides aromatic heterocycles bearing tertiary-alcoholcontaining sidechains with high levels of diastereo- and enantioselection.

[Rh(CO]2Cl]2 has been shown to catalyze sequential, mechanistically- distinct transformations in one pot. Tandem allylic alkylation/cycloisomerization sequences have been developed to access valuable, complex structures from relatively simple substrates. A methodology for the enantioselective conjugate addition of 2-heteroaryl nucleophiles to a variety of Michael acceptors has been developed. This method was used successfully in an ongoing approach to the synthesis of cortistatin A. 10 linear steps have been completed towards the synthesis of cortistatin A, including a highly regioselective propargylation to install a quaternary carbon and a diastereoselective intramolecular Diels-Alder reaction. / text

The research presented herein is concerned with the exploration of rhodium-catalysed addition reactions with organoboranes encompassing the 1,4-addition enolate protonation to benzyl acrylate esters, and the synthesis of chiral organoboranes for use in the synthesis of natural products Hermitamides A and B. Chapter 1 introduces the area of rhodium-catalysed conjugate addition as a tool for asymmetric synthesis. An extensive discussion of this methodology is included and recent advances in the area will be highlighted. In addition to this some recently published alternatives to organoboranes are outlined and their use in rhodium-catalysed chemistry documented. Chapter 2 discusses the tandem process of rhodium-catalysed conjugate addition enolate protonation, a recently observed asymmetric development. By using a novel route to benzyl acrylic esters the synthesis of α,α′-dibenzyl esters is achieved in excellent yields and selectivity. This study highlights the fact that when dealing with 1,1-disubstituted activated alkenes it is more difficult to produce enantioselective results as the chirality is determined in the protonation step and not during insertion. Some insights into the mechanism are proposed based on the outcomes observed. Chapter 3 describes the total synthesis of Lyngbic Acid and related structures Hermitamides A and B. Synthesis of these natural products are achieved by synthesis of an enantiopure organoborane species and its subsequent coupling via rhodium catalysis. Some interesting insights into the addition of alkenyl organoborane species to unsubstituted 1,1-activated alkenes are detailed. Chapter 4 describes the synthesis and characterisation for the compounds discussed in the previous chapters.

Conjugate addition reactions are one of the most widely used carbon-carbon bond forming reactions in organic synthesis. This reaction can form a chiral center and can be used for the synthesis of structurally complex compounds. Until now it has been necessary to use a chiral heavy metal catalyst in order to carry out asymmetric addition of aromatic groups to α,b-unsaturated enones via conjugate addition. Recently we have been successful in achieving the same task using an arylboronate as well as a catalytic amount of a chiral substituted binaphthol (BINOL). Using this reaction method great yields and enantioselectivities were achieved when diethyl phenylboronate was added to various enones and when various diethyl arylboronates were added to chalcone. This reaction is exciting because it eliminates the chance of having trace amounts of heavy metals in the final product, which is advantageous in such areas as the pharmaceutical industry.

Conjugate addition reactions are one of the most widely used carbon-carbon bond forming reactions in organic synthesis. This reaction can form a chiral center and can be used for the synthesis of structurally complex compounds. Until now it has been necessary to use a chiral heavy metal catalyst in order to carry out asymmetric addition of aromatic groups to α,b-unsaturated enones via conjugate addition. Recently we have been successful in achieving the same task using an arylboronate as well as a catalytic amount of a chiral substituted binaphthol (BINOL). Using this reaction method great yields and enantioselectivities were achieved when diethyl phenylboronate was added to various enones and when various diethyl arylboronates were added to chalcone. This reaction is exciting because it eliminates the chance of having trace amounts of heavy metals in the final product, which is advantageous in such areas as the pharmaceutical industry.