Gelsemine (1) has been recognized as the major alkaloid component of Gelsemium sempervirens since 1870. It has attracted numerous synthetic efforts since the 1960s due to its unique rigid, hexacyclic cage structure. The first completely stereocontrolled total synthesis of gelsemine (1) via 21-oxogelsemine (3) is described herein. This synthesis features a stereospecific condensation between cyclopropyl carboxaldehyde (240) and 4-iodo-oxindole (259), facile construction of the tetracyclic intermediate (262) through a novel application of divinylcyclopropane-cycloheptadiene rearrangement, and an unprecedented silver-mediated cyclization between carbamoyl chloride and ene-carbamate.(UNFORMATTED TABLE OR EQUATION FOLLOWS)$$\vbox{\vskip108pt}$$(TABLE/EQUATION ENDS)

A key improvement to the original saframycin B synthesis involves efficient sequential piperazinedione condensations to yield a basic saframycin skeleton from which all congeners might be made. Approaches toward the total synthesis of saframycin A result in formation of two advanced intermediates. The first, a pentacyclic diphenol nitrile with at least four out of five stereocenters established, is synthesized via a multistep scheme which involves a Pictet-Spengler type phenolic cyclization. The second advanced intermediate is produced via a route which involves cleavage of an imidazolidine ring with concomitant introduction of cyanide. An isomer of saframycin A is synthesized using this approach.

Synthetic studies on ecteinascidin 743 (b), an antitumor antibiotic, are described. The key reactions include: (1) an acylimmium ion-mediated stereoselective construction of the optically pure diazobicyclo (3.3.1) nonane nucleus 6, (2) a stereocontrolled Pictet-Spengler cyclization for the formation of tetrahydroisoquinoline 2, and (3) the attempted benzylic oxidation of the pentacyclic phenol 22.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)

Azoalkanes usually decompose to yield nitrogen and neutral radicals. However, in recent years their oxidative decomposition by stable cation radical salts has been studied. In this instance, cation derived products are typically observed. This work concentrated on the reactivity of an unsymmetrical azoalkane with cation radical salts. The azoalkane studied was a hybrid of an azoalkane that decomposed completely in the presence of cation radical salts and one that did not decompose at all. The reactivity of the hybrid was found to lie between the two aforementioned azoalkanes. In addition, radical derived products were observed, one of which apparently arose by coupling with the cation radical. Coupling of neutral radicals and cation radicals is a rare occurrence as both species are typically transient.

The lipase from Pseudomonas sp. K-10 catalyzes enantioselective hydrolyses of methyl sulfinylacetates. These are used in the asymmetric SPAC (Sulfoxide Piperidine And Carbonyl) transformation, a multistep reaction of a sulfinylacetate, an $\alpha$-methylene aldehyde and piperidine, to produce a $\gamma$-hydroxy-$\alpha$,$\beta$-unsaturated ester. Superior asymmetric induction is obtained using methyl sulfinylacetates which incorporate aromatic electron-withdrawing groups. Diastereomerically and optically pure sulfinylacetates incorporating chiral auxiliaries in the ester functionality are also synthesized. Double diastereoselection occurs when these are used in the SPAC reaction, with the chirality of the sulfoxide always assuming the dominant stereochemical role. The lipase from Pseudomonas sp. K-10 is also used to resolve $\gamma$-hydroxy-$\alpha$,$\beta$-unsaturated esters via irreversible acylations in hexane. The substrates which incorporate a relatively small or large side chain are resolved efficiently, but with opposite selectivity, while those of intermediate size are acylated with poor induction. When used in tandem with the asymmetric SPAC reaction, $\gamma$-hydroxy-$\alpha$,$\beta$-unsaturated esters are obtained in good yield and high optical purity. One such chiron is used in the synthesis of (3S,4S)-4-amino-S-cyclohexyl-3-hydroxypentanoic acid, an analogue of the unusual amino acid statine. Monoacylations of pentitol-derived diols catalyzed by lipase from Candida cylindracea are described, wherein the symmetry of the product is reduced with respect to the staring material; chirons containing three asymmetric centers are generated by these biocatalytic desymmetrization processes. Some of these monoacylations are accomplished with high stereoselectivity, depending on the structure of the diol. Changing the protecting groups on the diols has little effect on the stereoselectivity. An extensive review of the syntheses of the stereoisomers and analogues of castanospermine is given. Methodology based on an asymmetric allylation reaction is then described which allows access to eight previously unreported stereoisomers. Three of these are synthesized; 1,6,8-triepicastanospermine via desymmetrization of an adonitol-derived meso diol, and 1,7,8-triepicastanospermine and 1,6,7,8-tetraepicastanospermine from L-arabinose and D-xylose respectively. (1S,2R,7R,7aR)-1,2,7-Trihydroxypyrrolizidine, the ring-contracted analogue of swainsonine, was also synthesized from D-isoascorbic acid as a model study.

Optically active allylic, propargylic, and aliphatic alcohols (33 examples) were obtained by kinetic resolution using transesterification catalyzed by an enzyme from Pseudomonas sp. (Amano Enzyme Co., AK). In every case for which the absolute configuration of the resolved alcohol was determined, the R-enantiomer of the substrate was esterified. In comparison with other methods for resolving chiral allylic alcohols, this methodology is applicable in some cases where other methods do not work well. Kinetic resolutions of two substrates (allenol 18 and dienol 13) by Sharpless asymmetric epoxidations were performed for comparison with the methodology presented in this paper. This method is also widely applicable and extremely convenient for the resolution of alkynols and allenic alcohols. The combined data collected in this work gave an indication of what structural features of the substrates could be correlated with high enantioselectivites in the resolution of chiral secondary alcohols. Molecular modeling and energy minimization programs were used to refine our observation that the lipase catalyzed the esterification of the R-enantiomer of a substrate and a space filling model of the lipase active-site was produced from these results. This model is useful for rationalizing the results of other published resolutions of chiral secondary alcohols by transesterification catalyzed by lipase from Pseudomonas sp. Furthermore, the results account for the apparent reversal of enantioselectivity previously observed in resolutions of $\gamma$-hydroxy-$\alpha,\beta$-unsaturated esters. Enzyme-mediated acylations were also used to resolve $\alpha$-methylene-$\beta$-hydroxy ester and ketones, a useful class of compounds for which no effective asymmetric synthesis has been reported. This methodology was complementary to, and much more convenient than, kinetic resolution by chiral transition-metal complex catalyzed hydrogenation. An asymmetric synthesis of a chiral phosphine by enzyme-mediated enantiogroup selective acylation of a phosphine diol is also reported. This is the first reported use of enzymes to prepare optically active phosphines chiral at phosphorous. The synthesis and partial resolution of other chiral phosphines is also reported.

2,2$\sp\prime$-Bismethylenebicyclopropane rearranges to 6-methylenespiro (2.4) hept-4-ene and 3,6-bismethylenecyclohexene in solution at 195$\sp\circ$C. The formation of six dimers is also observed. 2,2$\sp\prime$-Bismethylenebicyclopropane equilibrates between meso and dl diastereomers. 6-Methylenespiro (2.4) hept-4-ene undergoes a facile surface catalyzed rearrangement to 5-methylspiro (2.4) hepta-4,6-diene. The surface rearrangement occurred both in solution and during preparative gas chromatography. The equilibrium of 2,2$\sp\prime$-bismethylenebicyclopropane favors the meso diastereomer. The activation parameters for the equilbrium process were found to be: k$\sb{\rm forward}$= 10$\sp{\rm 14.1}$ exp($\sp{-}$38,500cal/RT) and k$\sb{\rm reverse}$ = 10$\sp{15.1}$ exp($\sp{-}$36,700cal/RT); where the forward reaction is defined as the dl racemate isomerizing to the meso diastereomer. The exact structural identity of the six dimers was not achieved due to experimental difficulty. Flash Vacuum Pyrolysis of 2,2$\sp\prime$-bismethylenebicyclopropane also resulted in the formation of 3,6-$\sp\prime$-bismethylenecyclohexene and 6-methylenespiro (2.4) hept-4-ene. No bimolecular reactions were observed. The major product in the gas phase is 3,6-bismethylenecyclohexene. Both concerted or diradical mechanisms could describe the rearrangements of 2,2$\sp\prime$-bismethylenebicyclopropane. Either type of mechanism could explain the interconversion of meso and dl 2,2$\sp\prime$-bismethylenebicyclopropane and the formation of 1-methylene-2-(cyclopropylidenemethyl)cyclopropane. 3,6-Bismethylenecyclohexene must result from either a concerted rearrangement of the trimethylenemethane diradical from 2,2$\sp\prime$-bismethylenebicyclopropane or directly from a concerted rearrangement of 2,2$\sp\prime$-bismethylenebicyclopropane. Overall, a diradical mechanism is implicated due to the observation of dimerization between 2,2$\sp\prime$-bismethylenebicyclopropane and 3,6-bismethylenecyclohexene. No concerted mechanism could explain this result. The formation of 6-methylenespiro (2.4) hept-4-ene is thought to occur through the intermediacy of 1-methylene-2-(cyclopropylidenemethyl)cyclopropane. 1-Methylene-2-(cyclopropylidenemethyl)cyclopropane is not observed, as it rapidly undergoes a vinylmethylenecyclopropane rearrangement to 6-methylenespiro (2.4) hept-4-ene. Dimerization could result through the combination of monomers with the diradical formed from 2,2$\sp\prime$-bismethylenebicyclopropane. Other mechanistic possibilities include (4+2) cycloadditions between 5-methylspiro (2.4) hepta-4,6-diene and 3,6-bismethylenecyclohexane or 5-methylenespiro (2.4) hepta-4,6-diene with itself. (Abstract shortened by UMI.)

Tetra-n-butylammonium fluoride supported on glass helices was used to generate cyclopropenes in the gas phase from $\beta$-halocyclopropylsilanes using the vacuum gas-solid reaction (VGSR) technique. The following cyclopropenes were the target molecules, most of which were prepared successfully and in very good (55-85%) yields. The appropriate precursors were prepared by addition of a halo- or dihalocarbene to an alkenyltrimethylsilane. 1H,5H-Dicycloprop(b,h) anthracene (53) and 1H,4H-dicyclopropa(b,g) phenanthrene (54) were synthesized in 38% and 84% yield, respectively, by dehydrohalogenation with potassium t-butoxide in tetrahydrofuran at $-$20$\sp\circ$C. A key step in the syntheses was the Diels-Alder reaction of two equivalents of 1-bromo-2-chlorocyclopropene with the reactive 1,2,4,5- and 1,2,3,4-tetramethylenecyclohexanes.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) The corresponding dihydro derivatives 64 and 71 were prepared in 31% and 77% yield, respectively. The interesting cyclopropa(b) naphthalene derivative 69 was isolated in 57% yield. The starting compound for 69 was the major product from the reaction of 1-bromo-2-chlorocyclopropene with 1,2,3,4-tetramethylenecyclohexane.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) X-ray structural determinations were performed on cyclopropenes 48 and 49 and on cycloproparenes 24 and 40, in collaboration with Dr. Roland Boese at der Universitat Essen in Essen, Germany. The photoelectron spectrum of 49 was also obtained in collaboration with Prof. Rolf Gleiter at der Universitat Heidelberg in Heidelberg, Germany. These studies showed 49 to exhibit unusual bonding features.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)

A synthetic route via the key intermediate DX-52-1 21 has resulted in the first total synthesis of the complex antitumor antibiotic quinocarcin 1. Salient features include an acyliminium ion-mediated stereoselective construction of a diazabicyclo (3.2.1) octane nucleus, a stereoselective Pictet-Spengler cyclization, and a silver assisted conversion of DX-52-1 to the title compound.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)

Model studies on rhodium catalyzed hydroborations of sterically unbiased alkenes with catecholborane provided evidence for the role of d$\pi$-p$\pi$ bonding in these transformations. Catalyzed hydroborations of 5-substituted-2-methylene adamantanes occurred predominantly from the face opposite the most electron withdrawing group, while uncatalyzed hydroborations gave the reversed selectivities. Deuterium labeling studies on rhodium catalyzed hydroborations of allylic silyl ethers revealed some new mechanistic features. Vinylboronate esters were produced in these transformations in addition to the expected alkylboronate esters. The formation of such dehydrogenative borylation products can be explained by alkene insertion into the rhodium-boron bond of a metal complex produced from oxidative addition of catecholborane to the catalyst. Oxidation of the catalyst can have a pronounced effect on the product distributions. Catalyzed hydroboration of phenylethene produced 1-phenylethanol with freshly prepared Wilkinson's catalyst, but 2-phenylethanol was the predominant product if the catalyst had been in contact with oxygen. Enantioselective hydroborations of prochiral alkenes in the presence of chiral phosphine ligands produced optically active alcohol products. The best results were obtained with DIOP or BDPP ligands. Asymmetric amplification was not observed in these reactions. Bis(cyclopentadienyl) (tetrahydroborato(1-)) titanium promotes the addition of borohydride to alkenes. In the reaction of phenylethene the predominant products were tetraalkylborates. 1-Decene and $\beta$-pinene gave organoboron products that are involved in a dynamic equilibrium with borohydride. A mechanism is proposed which explains the observed experimental characteristics of this reaction. (o-Aminophenyl)diphenylphosphine was prepared from aniline in two steps. Optically pure (S) N-(tert-butoxycarbonyl)-2-amino-3-diphenylphosphinoboranepropyl (p-nitrophenyl)carbonate was prepared from scL-serine.