Cross-coupling reaction of organic halides with main group organometallic reagents has now become one of the most practical and reliable methods for constructing C-C bonds in organic synthesis. During the last three decades numbers of such reactions using organic halides bearing C (sp2) -X bond have been developed by the aid of transition-metal catalysts, especially Pd and Ni. On the other hand, the use of alkyl halides in transition-metal catalyzed cross-coupling reaction had not well been developed until quite recently. This is probably due to the low reactivities of alkyl halides toward oxidative addition and also to undesirable facile β-elimination from alkylmetal intermediates. Since several years ago, however, some significant methodological evolutions to overcome these difficulties have been achieved by tuning up the ligands and/or constructing novel catalytic systems based on new mechanisms. This review article summarizes recent progress in transition metal-catalyzed cross-coupling reaction of alkyl halides with organometallic reagents.
The batrachotoxins are a unique class of steroidal alkaloids isolated in minute quantities from the skins of poison arrow frogs (genus Phyllobates) as well as from the skins and feathers of New Guinea birds (genus Pitohui and Iflita) and exhibit various unique structural features, including a steroid-based pentacyclic core skeleton, an intramolecular 3-hemiketal, and a seven-membered oxazapane ring. These compounds are extremely potent neurotoxins (batrachotoxin (2), LD50 in mice 2 μg/kg) that act as selective and irreversible Na+-channel activators. In this paper, we review historical background of isolations and structure determinations of batrachotoxins and our studies on the total synthesis of (-) -batrachotoxinin A (1). Strategic bond-forming events include the stereospecific epoxidation of the double bond (9→10), a new Garst-Spencer protocol to construct 3, 4-disubstituted furan (14b→17b), the stereoselective intramolecular furan Diels-Alder reaction to assemble the steroidal skeleton (20d→22d), a novel intramolecular oxy-Michael reaction to close the oxazapane ring (31→33), an organocerium addition to form the α-enone (39b→40), and the simultaneous reduction and optical resolution of the racemic ketone to provide both enantiomers of a molecule (rac-41→43, 44).
Encapsulation complexes are molecular hosts that completely surround their guests. The hosts are self-assembled reversibly through weak intermolecular forces such as hydrogen bonds. To understand the thermodynamic and kinetic behavior of encapsulation, we have been using nuclear magnetic resonance methods for study of these systems in solution. Through our investigations with various types of hydrogen-bonded capsules, we have found that these assemblies exist on timescales of milliseconds to hours, long enough for many types of interactions and even reactions to take place within them. Furthermore, extensive study of the encapsulation and guest exchange processes revealed a guest exchange mechanism involving partial disruption of the hydrogen-bonded seam by conformational changes, rather than complete dissociation of the capsule. Through the thermodynamic and kinetic studies of supramolecular capsules, we have learned how molecules behave through weak interaction, which may give us some hint of how biological systems organize themselves.
The N21, N22-etheno-bridged porphyrin was used as a bidentate nitrogen ligand applicable to organometallic chemistry. X-ray crystallography of Rh and Pd complexes of the bidentate porphyrin ligand indicated that a N-M-N plane is canted by 53 63° from the mean porphyrin plane. The metal complexes of this bidentate porphyrin are stable not only against the elimination of the N21, N22- bridge, but also against the ligand substitution by strongly coordinating ligands such as ethylenediamine and isocyanide. Some organopalladium porphyrins were synthesized and their properties were investigated. Apparent ligand rotation in the (π-allyl) Pd porphyrin occurred by way of the dissociation of a Pd-N bond and the activation free energy was much larger than those measured for the corresponding phenanthroline Pd complexes. Insertion of CO, isocyanide, and alkenes into the Pd-C bond of (methyl) Pd porphyrins proceeded in good yields. The stereochemical features of these organopalladium porphyrins were determined by NMR with the aid of the porphyrin ring current effect. Stereochemical and electronic interaction of the organo ligand with the bidentate porphyrin ligand were observed.
Our recent study on the oligodeoxyribonucleotide (ODN) containing 5-substituted pyrimidine nucleosides is described. 5-Substituted 2 '-deoxyuridine derivatives and 5-substituted arabinofuranosyluracil derivatives were synthesized from 2, 2 '-anhydro-5-methoxycarbonylmethyluridine, which was synthesized from arabinoaminooxazoline and dimethyl α-bromomethylfumarate. Modified ODNs bearing these nucleoside analogs were prepared chemically by pre-synthetic modification method or post-synthetic modification method. Effect of 5-substituent groups on DNA/DNA or DNA/RNA duplexes was investigated by measuring the melting behaviors. Some of these modified ODNs are expected as antisense ODNs since these could induce RNase H activity and impart stability against nuclease. Also, 5-substituted 2 '-deoxyuridine analog triphosphates served as substrates of thermophilic family B DNA polymerases in a primer extension reaction or PCR, to give the modified ODNs. 5-Methoxycarbonylmethy1-2'-deoxyuridine residues incorporated into DNA by PCR could be used to post-synthetic derivatization. This finding is useful for in vitro selection of the functionalized DNA.
Esterification, sulfonylation, amide formation, and silylations are well recognized as frequently used reactions for organic syntheses. Recent syntheses of fine chemicals and complex natural products, however, require further rationalization of these reactions. We describe herein our recent studies in this area including related representative known methods. (i) Recent progresses of catalytic esterifications are surveyed and we introduce two efficient ammonium triflate catalysts (DPAT and PFPAT) for esterification between 1 : 1 mixture of carboxylic acids and alcohols. (ii) Conventional condensation reagents for esterifications, thioesterifications, and amide formation, are listed and we introduce efficient methods using Me2NSO2Cl/ Me2NR and p-TsCl/N-methylimidazole. (iii) As a promising method for the replacement of conventional pyridine-method, we introduce efficient pyridine-free improved methods, which utilize sterically uncrowded tertiary amines such as Me3N·HCl/Et3N and Me2N (CH2) nNMe2 as a key protocol. (iv) We introduce highly powerful, neutral, and catalytic methods for silylations of alcohols (giving enol ethers) and ketones (giving enol silyl ethers) using hydrosilanes, disilanes, and silazanes.