2-Cycloalken-1-one-(-)-erythro-hydrobenzoin ketals undergo efficient and diastereoselective cyclopropanation when treated with an excess of Simmons-Smith reagent. The resulting crystalline products yield enantiomerically pure cyclopropyl compounds upon recrystallization. For example, 2-cyclohexen-1-one-(-)-erythro-hydrobenzoin ketal gave, in 90% yield, a 19:1 mixture of diastereomeric cyclopropanes as established by 62.9 MHz ¹³C NMR spectroscopy. Upon one recrystallization, diastereomerically pure cyclopropane was obtained in 78% recovery. Hydrolysis gave (+)-norcaranone of greater than 99% ee. Three other examples are presented which demonstrate the advantages of hydrobenzoin ketals over previously used homochiral ketals, as well as several techniques for the synthesis of chiral hydrobenzoin.

Thesis (Ph. D.)--University of Pennsylvania, 1895.

Chapter 1: An assessment of the mechanism of the benzoin condensation. The reaction under non-hydroxylic conditions. The generally accepted mechanism for the well known benzion condensation is unviable for the following reasons: 1) No experimental evidence for formation of carbanion from oxyanion. 2) No experimental reports on pKa of ‘C-H” in intermediate oxyanion. 3) From previous reports, these types of carbanion are stable only at -78° C. 4) Carbanions possessing nucleofuges generally form carbenes. It was observed that the O- protected benzaldehyde cyanohydrin (1) and O-MOM protected ethyl mandelate (2) are possibly less acidic than benzyl cyanide (3). Attempts to affect hydrogen-deuterium exchange in the O-methyl ether of benzaldehyde cyanohydrin (1) did not yield clear-cut results; neither could the analogous carbanion from O-MOM protected ethyl mandelate be formed, under analogous conditions. O-Protected benzaldehyde cyanohydrin and O-MOM protected ethyl mandelate (2) did not condense with electrophiles like benzaldehyde (4); however benzyl cyanide (3) was condensed with benzaldehyde to form the stilbene cyanide (5) under similar conditions to the benzoin condensation. Scheme 1: Reactions under benzoin conditions. All these evidences indicate that carbanions derived from 1 and 2 are not formed under the conditions of the benzoin reaction. An alternative mechanism via intramolecular participation in the cyanohydrin oxyanion leads initially to an imino-oxirane intermediate; electrophilic capture of this in the key step finally leads to benzoin (Scheme 2). This is an attractive possibility that avoids many of the problems of the earlier mechanism, and is also not incompatible with most of the available experimental evidence. Further experimental and theoretical work is indicated before an acceptable mechanism for the benzoin condensation finally emerges. Scheme 2: A possible alternative mechanism of benzoin condensation Scheme 2: A possible alternative mechanism of benzoin condensation From the studies on mechanism of benzoin condensation, it seems possible to form imino-oxirane from oxyanion of benzaldehyde cyanohydrin instead of carbanion by participation of cyanide ion. To prove the cyanide ion participation in mechanism of benzoin condensation and to avoid ambiguities from O-H peak, the reaction was performed in 1,4 dioxane solvent with benzaldehyde (4) and cyanide with the phase transfer catalyst 18-crown-6, instead of EtOH and H2O as solvent. After mixing the IR spectra for the crude product, indicated the formation of benzoin (8), which was confirmed upon work up. This led to the developing of a novel method for the benzion under anhydrous conditions. Scheme 3: Formation of benzoin under anhydrous conditions Chapter 2: Stereochemical stability of benzion. Generally α-hydroxy ketones undergo tautomerism to the enediol form, which are stabilized by intramolecular hydrogen bonding. Because of this, they undergo racemisation. Benzoin is also a α-hydroxy ketone, but it can be resolved into its enantiomeric forms. It indicates enediol form of benzion is unstable possibly due to steric interference. It was observed from the crystal structure of the carbonate analog of ene-diol form of benzoin that there is steric interference between the two phenyl rings. These were twisted out of the plane of the carbonate moiety by 19.92° and -47.32°. (The crystal structure of 4,5-diphenyl-1,3-dioxol-2-one (9) was reported first time.) This structure also indicated the existence of atropisomerism in the crystalline lattice. Chapter 3: Polymerisation of benzaldehyde. α-Hydroxy esters can be viewed as surrogates of cyanohydrins. To prove the cyanohydrin anion intermediate in classical benzoin condensation mechanism is very difficult. An interesting alternative is to employ α-hydroxy esters instead. It was observed that methyl 2-phenylglyoxylate and methyl 2-(methoxymethyl)-2-phenylglyoxylate (2) failed to react with benzaldehyde in aqueous methanol with sodium carbonate as base. IR spectra indicated that the carbonyl peak of benzaldehyde has disappeared, but NMR spectra showed a mixture of methyl 2-(methoxymethyl)-2-phenylglyoxylate (2) and benzaldehyde (4). This seems to indicate the polymerization of benzaldehyde (10) (Scheme 4). However, the product was not stable enough to be isolated and purified. Scheme 4: Reaction between benzaldehyde and MOM-protected methyl mandalate (For structural formula pl see the abstract file.)

This investigation applied the techniques of polarography and controlled potential electrolytic reduction to the study of a series of unsymmetrical benzils. Eleven unsymmetrical benzils were synthesized and studied in 50% ethanol-water (by volume) solvent systems buffered at pH 1, 5, and 13. The results showed that, with unsymmetrical benzils substituted with electron-withdrawing or electrondonating groups, the carbonyl closest to the ring with the least electron-donating power was the preferred reaction site. However, the dicarbonyl system was nevertheless reduced as a unit, and Hammett sigma values of disubstituted symmetrical benzils were approximately additive. This was ascertained by comparing the ease of reduction of eight unsymmetrical benzils to the ease of reduction of the corresponding disubstituted symmetrical benzils. It was proposed that the electrons were added to the oxygen of one carbonyl, and that the second carbonyl was involved in the reduction chiefly through complete polarization of the dicarbonyl system at the electrode. In general, the reduction of unsymmetrical benzils appeared to follow the same path previously reported for symmetrical benzils.

The plant used in this study was the woodland shrub, Spicebush, Lindera benzoin (L.) Blume. Spicebush, is characteristically found on a poorly drained soil, within Beech-Maple or Mixed Mesophytic forests. It commonly occurs as pure stands in small patches within the shrub layer of mesophytic forests.The objective of this study was to characterize the soil type upon which Spicebush crows and to relate the soil-plant relationship in tears of establishment, growth, and development of the Spicebush. The variables used in accomplishing this objective were based on the physical and chemical regimes of Spicebush subcommunities. Ginn Woods, a climax beech-maple forest in Delaware County, Indiana, was used as a study area. Spicebush subcommunities within the woods were rapped and three representative sites were selected. The factors examined in the study were soil profile, soil moisture and temperature, soil and tissue levels of nitrate, phosphorus and the trace element metals Cr, Cu, Zn, Mn, Fe, Pb, Ni, and Cd. Analysis of the soil horizons was performed by soil core and visual characterization at the representative sites. Soil moisture blocks and temperature probes were buried at 5 centimeter and 20 centimeter depths at the sites for determination of soil temperature and available soil moisture. Data was collected at the sites every other day. Nitrate and phosphorus levels for plant tissue and soil were analyzed by the Kjeldahl Method and Spectrophotcznetric Method, respectively. An Atomic Absorption Spectrophotanetric Unit was used to determine amounts of ppm. of the metallic salts in samples of soil and leaf tissue.Ball State UniversityMuncie, IN 47306

Benzoin is an important a-hydroxy ketone which can be used as chiral intermediate for the synthesis of several drugs. In this study, it was aimed to synthesize this compound by high stereoslectivity and yield by the use of fungal bioconversions. For this purpose, whole cells of four different Fusarium spp. (F. anguoides, F. roseum, F. solanii, F.bulbigenum) were used for reduction of readily available achiral compound benzil. The reaction conditions were optimized as glucose peptone broth consisting of 30g/L glucose and 10 g/L peptone, inoculum size as 20 mg/L and substrate concentration as 200 mg/L. A complete set of derivatives substituted with electron donating and electron withdrawing groups of the benzils were also reduced to the corresponding benzoin derivatives with the same optimized condition with up to 98% ee.

Thesis (Ph. D.)--Institute of Paper Chemistry, 1965. / Includes bibliographical references (p. 88-89).

This study presents synthetic studies on camptothecin, a potent antitumor agent in order to improve its stability and solubility without reducing its activity. The study consists of the modification of camptothecin at 20-OH position a new strategy for the targeted and controlled release of the drug and modification at C-7 position to overcome the stability and solubility problems of the free drug. In the first part of the study, the 20-OH functional group of camptothecin was replaced with an unsymmetrical benzoin derivative that is able to release the drug under photolysis at 350 nm. The new prodrugs synthesized possessed higher stability than the camptothecin itself. The in vitro irradiation of the prodrugs at 350 nm was satisfactory without any decomposition of the active substance. The second part of the study comprises the studies on the modification of the 7th position of camptothecin, which is the most suitable position for the modification. In this part of the study, 7-amino and silyl substituted camptothecins were synthesized.Combination of camptothecin with some other drugs such as cisplatin was also investigated in this study. The synthetic efforts showed that the reactions are very promising and the combination studies can be studied as a major subject in the future.

This thesis describes our physical organic and mechanistic investigations into N Heterocyclic Carbene (NHC) mediated organocatalytic transformations, through a collaboration with the research group of Dr AnnMarie O'Donoghue and PhD student Richard Massey at Durham University. Initial research focused upon the determination of kinetic acidities and associated pKₐ values for a range of triazolium salts using C(3) H/D exchange, monitored by ¹H NMR spectroscopy. Estimates for pKₐ values in the range 16.6 17.4 were obtained, which are some ~2 and ~3 5 pK units lower than analogous imidazolium and thiazolium species respectively, with modest N substituent (0.3 pK units) effects observed. At lower pD values, an altered pD dependence indicates a dicationic triazolium species is formed (through N(1) protonation) with an estimated pKₐᴺ¹ of -0.2-0.5 and C(3) H pKₐ values at least 2 units lower than their monocationic analogues. This methodology was subsequently extended to mesoionic NHCs, where pKa values of 23.0 27.1 for a range of triazolium and 30.2 31.0 for a range of imidazolium salts were estimated. A detailed study of the NHC catalysed intramolecular Stetter reaction was also undertaken using ¹H NMR spectroscopy. A range of 3 (hydroxybenzyl)azolium salts (adducts), formed from the addition of NHC to aldehyde were isolated, enabling the generation of reaction profiles and the determination of rate constants. The reaction proceeds via rapid and reversible adduct generation, followed by rate limiting Breslow intermediate formation, with electron withdrawing N aryl substituents increasing the rate of product formation. Consistent with rate limiting deprotonation, deuterium exchange studies of O methylated adduct analogues found electron withdrawing N-aryl units gave faster exchange. Examination of the equilibrium constants for adduct formation revealed that both in the case of NHCs bearing 2,6 disubstituted N aryl units and aldehydes bearing a 2 ether substituent, the equilibrium position is significantly shifted towards adduct. Finally, studies at sub-stoichiometric NHC concentrations, monitored by HPLC, imply the reaction is first order with respect to NHC precursor, but zero order in aldehyde, again indicative of rate limiting deprotonation.

This thesis presents a new developed method for first intermolecular aldehyde/ketone cross benzoin coupling. Protected &amp / #945 / -keto tertiary alcohols are synthesized starting from easily available acyl phosphonates and ketones via Brook rearrangement in the presence of catalytic amount of cyanide ion. The scopes and the limitations of the methods for the synthesis of tertiary alcohols with &amp / #945 / -keto group are discovered.