Thesis (Ph. D.)--University of Michigan, 1935. / Cover title. By Paul F. Bartunek and E.F. Barker. "Reprinted from the Physical review, vol. 48, no. 6, September 15, 1935."

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

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

Environmental concerns have birthed an awareness of how we conduct ourselves as citizens of this planet. To reduce environmental impact, we have learned that we must be responsible stewards in all ranges of life: from buying locally grown food to how scientific research and industrial processes are executed. In the realm of chemical research, "green chemistry" has initiated the development of new, sustainable methods that make use of atom economy, step economy, and utilize renewable materials to minimize waste and production of toxic by-products. The formation of carbon-carbon bonds lies at the very heart of organic synthesis, and traditional methods for forming such bonds generally require the use of at least one stoichiometrically preformed organometallic reagent. This corresponds to at least one equivalent of metallic waste byproduct. The in situ formation of alkyl metal nucleophiles for carbonyl additions via hydrogenation of [pi]-unsaturates represents an alternative to use of preformed organometallic reagents. Comprising nearly 90% of the atoms in the universe, hydrogen is vastly abundant and very cheap. The Krische group seeks to contribute new technologies which make use of catalytic hydrogenation and transfer hydrogenation in the reductive coupling of basic chemical feedstocks. / text

This thesis investigates the stabilization of divalent germanium using substituted diethanol amine ligands. Germylenes of type RN(CH2CH2OH)2Ge were obtained from N-heterocyclic germylenes and N-alkyl diethanol amines in yields of up to 94%. Single crystal X-ray diffraction confims the presence of a transannular Ge-N dative bond in all cases. In addition, intermolecular dimers containing Ge2O2 rings are formed for R = Me and Et. Reaction of the four germylenes L with nickel carbonyl yielded the respective germylene complexes L2Ni(CO)2 and LNi(CO)3. The germylenes and their complexes were investigated with DFT methods. Only four methods, SVWN, BB1K, MPWB1K and M062x gave acceptable Ge-N distances. Dimerization energies of the germylenes were examined with the thermochemically accurate M062x method. At the M062x/Def2-TZVP level, the dimerization energies of the germylenes are very small (ΔG° ≈ 0 kcal/mol). The experimentally observed dimerization or lack thereof may accordingly be determined by packing effects in the solid state or solvation energies in solution.

This thesis describes the application of (arene)Cr(CO)3 methodology to the Stereoselective and enantioselective synthesis of substituted arenes. Chapter one reviews the main methods of preparation and decomplexation of (arene)Cr(CO)₃ complexes and the electronic and steric influences of the Cr(CO)₃ unit on the arene. Chapter two demonstrates that the benzylic oxygen directing effect in complexation reactions operates via a direct oxygen bond to the incoming metal unit. Attachment of bulky ft-acceptor groups, such as t-butyldimethylsilyl, to the benzylic oxygen overrides this directing effect. Chapter three describes the regioselective Cl functionalisation of the cryptopine skeleton. Complexation of dihydrocrytopine gives only a single product, the relative configuration of the product being determined using an X-ray crystal structure analysis. Subsequent alkylation of the O-methyl derivative gives Cl alkylated products. Chapter four describes the regioselective ortho functionalisation of ephedrine and pseudoephedrine derivatives. Treatment of (1S,2R)-(N,O-dimethylpseudoephedrine) Cr(CO)₃ with n-butyllithium leads to exclusive removal of the pro-(R) ortho proton. The observed stereoselectivity arises via</em deprotonation from cyclic bidentate five-membered chelates. Chapter five describes the regioselective C4 and C5 functionalisation of (hydrocotarnine)Cr(CO)₃. Complexation of 1-methylhydrocotarnine occurs to give exclusively the exo-1-methyl derivative. Further functionalisation to give the 1,5- and 4,5-dimethyl products is also described. Chapter six describes the synthesis of ortho substituted (benzaldehyde)Cr(CO)₃ complexes. Chiral material is available via preferential kinetic hydrolysis of, or classical separation of, the L-valinol derived imines. Chapter seven describes the Stereoselective addition of nucleophiles to (o-anisaldehyde) Cr(CO)₃ and (o-trialkylsilylbenzaldehyde)Cr(CO)3. With (o-anisaldehyde)- Cr(CO)₃ the additions are completely stereoselective giving the (RR,SS) diastereoisomer. With (o-trialkylsilylbenzaldehyde)Cr(CO)₃ the ratio of products is influenced by the nature of Lewis acidic species present. Chapter eight describes the Stereoselective benzylic elaboration of (o-methoxybenzyl methyl ether)Cr(CO)₃ achieved via selective removal of the exo benzylic proton from transition states with the methoxy groups anti to each other.

This thesis describes the synthesis of novel lead(IV) tetracarboxylates and the development of their use in carbon-carbon bond formation processes, with a particular emphasis on the construction of chiral, quaternary centres. Organolead(IV) tricarboxylates have been widely used in the functionalisation of a range of β-dicarbonyl compounds, and the available evidence suggests that these reactions occur by a ligand coupling mechanism. For this reason, by using chiral lead(IV) compounds, it may be possible to achieve a transfer of asymmetry in the bond formation reaction. A variety of achiral and chiral dicarboxylic acid ligands were synthesised, either by reaction of phthalic or camphoric anhydride with a range of diols, or by elaboration of the camphoric acid skeleton directly. A range of novel lead(IV) compounds were constructed using these ligands, both as bis-complexes and as mixed ligand complexes. The complexes were characterised by a combination of IR and NMR techniques, including ²⁰⁷Pb NMR spectroscopy, and elemental analysis. The reactivity of some of the complexes was demonstrated via reaction with allyltributyltm. The lead(IV) complexes were used in the α-phenylation of a range of β-dicarbonyl substrates. Yields ranged from poor to excellent, but in all cases the enantiomeric excesses of the reactions were found to be no greater than 12%. Studies of these complexes by ²⁰⁷Pb NMR spectroscopy revealed that each complex was present as more than one species in solution, which is thought to be the reason for the poor overall transfer of chirality in the phenylation reactions. The arylation procedure uses catalytic mercury(II) acetate, which can in turn introduce further potential ligands to the exchanging system. It was found that alternative catalysts, such as mercury(II) chloride, could be used successfully in the α-phenylation reaction.

This thesis investigates the use of arene chromium complexes as phenyl cation synthons in the synthesis of homochiral N-phenylamino esters, and the dianion formation of a series of complexed aryl ethers. Chapter 1 reviews the properties of arene chromium tricarbonyl complexes and discusses in detail the ability of some of these complexes to undergo nucleophilic aromatic substitution. Chapter 2 outlines the biological importance of homochiral N-phenylamino esters. The N-phenylation of a series of amino alcohols are first investigated both by direct reaction of haloarene complexes with amino alcohols and also via a Smiles rearrangement of an aryl ether derivative. In addition, methodology is developed for the synthesis of a series of homochiral N-phenyl-α-amino esters and N-phenyl-β-amino esters. The synthetic strategy is then applied to the synthesis of some N-phenyl-β-lactams, in particular (+)SCH 48461. Chapter 3 reviews the directed metallation of complexed and uncomplexed arene compounds and discusses the mechanism involved. The generation of dianions in a series of complexed aryl ethers is investigated. Regioselective deprotonation is observed using different alkyllithium bases and the degree of dianion formation is confirmed by electrophilic quench of the dianionic intermediates with CD₃OD and TMSC1.

No description available.

Some physicochemical properties of several series of transition metal chalcocarbonyls such as ((eta)('6)-C(,6)H(,6))Cr(CO)(,2)(CX) and Cr(CO)(,5)(CX) (X = O, S, Se) have been investigated. In particular, the infrared, ('13)C and ('17)O nuclear magnetic resonance and ultraviolet spectra have been examined. The results show that the order of (sigma)-donor and (pi)-acceptor capabilities of the ligands is CO CS. The M((pi)) (--->) CX((pi)*) ultraviolet charge-transfer bands are shown to correlate with the respective (mu)'(,MCX) and ('13)C NMR data. Also, the ('13)C NMR chemical shifts and GQVFF force constants are found to be highly correlated. The ('17)O NMR spectra of the metal chalcocarbonyl complexes display chemical shifts in the opposite direction to the corresponding ('13)C ones. No correlation is found between the ('17)O shieldings and the other spectroscopic data. Reaction of Cr(CO)(,5)(CX) (X = S, Se) with halide ions (Y('-)) afforded mixtures of {Cr(CO)(,5)Y}('-) and trans-{Cr(CO)(,4)(CX)Y}('-) while Cr(CO)(,5)(CS) reacted with cyclohexylamine to give Cr(CO)(,5)(CNC(,6)H(,11)). The similarities and differences in the physicochemical behaviour of the metal chalcocarbonyls compared to related systems are discussed in the light of the different bonding patterns.