Stereoselective incorporation of halogen atom(s) into organic molecules is a highly valuable process because chiral fluorinated compounds are recognized as fascinating building blocks of drug candidates and chiral chlorinated—, brominated—, iodinated compounds are useful synthetic intermediates for a range of optically active molecules. In this paper, we describe several synthetic methods for the construction of halogenated chiral carbon centers utilizing chiral Lewis acid catalysts or organocatalysts. For example, we succeeded in the enantioselective synthesis of α-chloro-α-fluoro carbonyl compounds, asymmetric chlorination of active methine compounds and their derivatization via SN2 substitution, and asymmetric Diels-Alder reaction of α-fluoroenones. Some methods for the asymmetric construction of trifluoromethylated chiral carbon centers are also described.
Catalytic consecutive reactions could provide not only short-step syntheses without work-up at each step and isolation of many intermediates but clean and atom economical processes. Therefore, toward straightforward and powerful procedures for the construction of heterocycles, we undertake the research on the catalytic consecutive reactions of alkyne compounds, which are versatile molecules. In this paper, our recent findings on synthetic methods of heterocyclic compounds by means of catalytic consecutive reactions are described. That is, (1) syntheses of highly substituted indoles and pyrroles via Au-catalyzed Claisen rearrangement reactions of propargylamines, (2) syntheses of oxazoles and furans concomitantly with incorporation of allyl groups or oxygen functional groups via Pd-catalyzed cyclization-allylation sequences or metal-free oxidative cyclization reactions of propargylamides, and (3) syntheses of dihydroquinolines and iminoquinolinones via hetero-enyne metatheses of phenylalkynes and aldehydes.
This review consists mainly of stoichiometric reaction and catalytic reaction using niobium complexes. As an example of stoichiometric reaction, synthesis of 1H-indenes from the reaction of aliphatic ketones and aryl-substituted alkynes in the presence of stoichiometric amount of NbCl3(DME) has been documented. Alternatively, development of catalytic reaction of using low-valent Nb is intriguing. Our research group reported that low-valent Nb catalyzed intermolecular [2+2+2] cycloaddition reaction of alkynes with alkenes leading to tri- or tetra-substituted 1,3-cyclohexadienes in chemo- and regioselectivity. In addition, low-valent Nb catalyzed cycloaddition reaction of tert-butylacetylene with aryl-substituted nitriles to tri-substituted pyridines has been reported.
Inorganic metal oxides-supported metal nanoparticle catalysts are designed for green molecular transformation system. The supported metal nanoparticle catalysts such as hydrotalcite-supported gold and silver nanoparticles show unique and excellent catalytic activities for versatile organic reactions such as aerobic oxidations, oxidative carbonylations, and chemoselective reductions of epoxides to alkenes and nitrostyrenes to aminostyrenes using alcohols and CO/H2O as reducing reagents. These high catalytic performances are derived from the cooperative effect between metal nanoparticles and supports. Furthermore, as a new strategy for increasing the metal-support interaction, core-shell nanoparticles consisting of active metal nanoparticles in the core with metal oxide supports in the shell are designed to maximize their metal nanoparticle-support interface areas. These core-shell nanocomposite catalysts exhibit excellent chemoselective hydrogenation of nitrostyrenes to aminostyrenes, unsaturated aldehydes to allyl alcohols, and alkynes to alkenes. Moreover, these solid catalysts developed are easily recovered from the reaction mixture by simple filtration and reusable with retaining their high catalytic activities.
Unique cyclooligopyrroles with figure of 8 conformation were prepared from useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Octaphyrin-(220.127.116.11.18.104.22.168) 1 with 32π-cycloconjugation exists in a P,P- and a M,M-helical form, which are rapidly interchanged by the stretching-compressing mechanism. Cyclooctapyrrole 1 was successfully applied to a chirality sensor for determining absolute configuration of chiral carboxylic acids taking advantage of the unique chiroptical property. Calixphyrin 2 having interrupted π-conjugation also undergoes rapid conformational change in solution, but its dinuclear CuII complex 2Cu2 was resolved into enantiomers by HPLC on chiral phase. Metal insertion into 2 in the presence of (R)-(+)-1-(phenyl)ethylamine caused helix sense bias to the P,P-helicity. Cyclotetrapyrroletetrapyridine 3 composed of eight heterocycles also takes helical conformation and provides dual monoanionic tridentate coordination environment. Its dinuclear CoII complexes 3Co2L2 with an amino acid anion (L−) at each metal site could be isolated to show full helix sense bias in the case of Thr, Phe, Tyr, and Trp. An open chain oligopyrrole was also studied to generate helix sense bias. Dinuclear PdII complex 4Pd2 of hexapyrrole-α,ω-dialdehyde was reacted with (R)-(−)-1-cyclohexylethylamine to give the corresponding α,ω-diimines with 85% diastereoselectivity in favor of the P helical conformation, the chiroptical property of which could be tuned by redox.
Poly(alkyl propiolate)s (PAP), e.g., Poly(n-heptyl propiolate) (PnHepP) and Poly((s)-2-octyl propiolate) (Ps2OctP) having an achiral or a chiral ester side chain were stereoregularly prepared with a Rh complex catalyst, [Rh(nbd)Cl]2 (nbd=norbornadiene), at 40 °C in methanol, respectively. The temperature dependence 1H and 13C NMR spectra of PAPs and their spectral simulations indicated that the restricted rotation around the ester O-C bond takes place through the so-called 3-site jump conformation. The spectra also exhibited that the helical conjugated main-chain of Ps2OctP was largely oscillating between the sequences of contracted helix and stretched helix in the time scale of the NMRs, although the degree of the oscilation of PnHepP was fairly small compared to that of Ps2OctP. The UV-vis and IR spectra of them supported that PAPs have at least two helical conformations, i.e., contracted and stretched helices. Therefore, these spectra supported the oscillation of the helix along the main-chain axis. The proposed model calculated by MMFF94 also indicated the accordion-like helix oscillation of contracted and stretched helices (HELIOS) of PAPs which was synchronized with restricted 3-site jump rotation around the ester O-C bond in the side-chain.
Investigating the function of native biomolecules is an important but challenging task due to the highly complex nature of biological systems. To understand complex biological systems in terms of simple biomolecular interactions, organic chemists have developed many bioorthogonal reactions over the past few years. These bioorthogonal reactions have been applied for the efficient construction of functionalized biomolecules. In this mini review, the development and the applications of such bioorthogonal reactions are described.
Taiwaniaquinoids are unique diterpenoids having rearranged structures and biological activities. In this review, recent total syntheses on this class of natural products utilizing originally or newly proposed biomimetic transformation as a key step are described.
Using two transition metals to simultaneously catalyze a reaction can offer distinct opportunities for reactivity and selectivity when compared to using single-metal catalyst systems. Recently, dual-catalyzed transformations, which are not accessible by single-metal catalyst, have been developed by combining palladium/gold co-catalysis. In this review, unique reactivity and mechanisms realized by palladium/gold co-catalysis are discussed.