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The first diastereoselective synthesis of trisubstituted cubanes was achieved using a chiral auxiliary. To establish chirality within the cubane skeleton, at least three substituents must be introduced at the appropriate positions. Ready conversion of cubane carboxylic acid to a chiral amide followed by sequential ortho -selective deprotonations and electrophilic trapping afforded the corresponding 1,2,3-trisubstituted cubanes with high diastereoselectivity. This route opens new possibilities for the preparation of enantio-enriched cubanes.

The organocatalytic enantio- and diastereoselective cycloetherification of 1,3-cyclohexanedione-bearing enones involving the in situ generation of chiral cyanohydrins was developed. This transformation offers the first catalytic asymmetric approach to oxadecalin derivatives containing contiguous tetrasubstituted chiral carbons at the bridge heads of the fused ring systems. Depending on substituents, both cis - and trans -decalin-type scaffolds were synthesized with good to excellent stereoselectivities, and a range of functional groups accumulated on the chiral quaternary carbon moieties of the trans -oxadecalin derivatives.

In the hexahedral hydrocarbon cubane, replacing hydrogen with other atoms at three positions within any one of the internal tetrahedrons can conceptually lead to the formation of a unique class of chiral molecules. In pursuit of this endeavor, we prepared 1,3-dibromo-4-deuteriocubane- N , N -diisopropylcarboxamide, which upon treatment with zincates affords 1,3,5-trisubstituted cubanes via simultaneous two-position substitution reactions. The proposed chiral attributes of this stereogeometric class were confirmed by enantiomeric resolution of a p -bromobenzyl derivative using chiral HPLC.

Cationic cobalt porphyrin-catalyzed allylation of aldehydes with allyltrimethylsilanes is developed. The formation of the aldehyde-cobalt porphyrin complex, the key intermediate for the addition of allylsilanes, is confirmed by theoretical studies and synchrotron-based X-ray absorption fine-structure measurements. Facile dissociation of the product by allylation from the cobalt complex regenerates the active complex with the aldehyde. The readily obtainable [Co(TPP)]SbF 6 complex serves as an efficient catalyst for this allylation.

An efficient iron porphyrin Lewis acid-catalyzed cycloaddition of aziridines with aldehydes has been developed to provide oxazolidines with high regio- and diastereoselectivity. The cycloaddition proceeds in toluene with 1 mol % of the iron catalyst at 25 °C. A theoretical study and synchrotron-based X-ray absorption fine structure measurements provided fundamental insights into the aziridine-iron porphyrin complex, which is the key intermediate for the generation of the 1,3-dipole synthon.

An organocatalytic method for the asymmetric synthesis of syn-1,3-dioxanes as protected 1,3-diols via dynamic kinetic resolution of in situ generated chiral cyanohydrins has been developed. This method involves a reversible cyanohydrin formation/hemiacetalization/intramolecular oxy-Michael addition reaction cascade, affording a chiral syn-1,3-diol structure with simultaneous construction of two stereogenic centers. The use of trifluoromethyl ketones is crucial for the efficient three-component cascade reaction, and a chiral bifunctional organocatalyst imparts high enantio- and diastereoselectivities in the formation of the chiral syn-1,3-diol motifs.

The organocatalytic enantio- and diastereoselective cycloetherification of in situ generated cyanohydrins through the concomitant construction of three chiral carbon centers is reported. This protocol facilitates the concise synthesis of optically active tetrahydropyran derivatives, which are ubiquitous scaffolds found in various bioactive compounds, through the simultaneous construction of multiple bonds and stereogenic centers, including tetrasubstituted chiral carbons. The resulting products also contain multiple synthetically important functional groups, which expand their possible usefulness as chiral building blocks.

The iodine-metal exchange reaction on cubane was examined using various lithium organozincates. Among these, the dianionic zincate, n-Bu 4 ZnLi 2 , gave optimum results. The resulting cubyl metal species could be converted into various cubane derivatives via addition reactions with electrophiles, such as an organohalide or aldehyde. The potential functional group tolerance of organozincates lends this protocol to the synthesis of polyfunctionalized cubane derivatives.

The aza-Diels-Alder reaction of nonactivated dienes and imines was realized through the action of the ion-paired Lewis acid catalyst [FeCl 2 ] + [FeCl 4 ] - generated by the in situ disproportionation of FeCl 3 . The uniquely high reactivity of [FeCl 2 ] + [FeCl 4 ] - was attributed to both the highly Lewis acidic FeCl 2 + and thermodynamically stable FeCl 4 - acting as an ion-paired catalyst. Synchrotron-based X-ray absorption fine structure measurements provided fundamental insights into the disproportionation and structure of the resulting ion-paired iron complex. A theoretical study was performed to analyze the catalytic reaction and better understand the "ion-pairing effect" which transforms simple FeCl 3 into a high turnover frequency Lewis acid catalyst in the aza-Diels-Alder reaction of nonactivated dienes and imines.

Three-component coupling between an alkyne, iodoarene, and bis(iodozincio)methane yields allylic zinc with a tetrasubstituted alkene moiety in the presence of a nickel catalyst. The reaction proceeds via aryl nickelation of the alkyne and subsequent cross-coupling with bis(iodozincio)methane. Meanwhile, the same combination in the presence of a palladium and cobalt catalyst gives tetrasubstituted alkenylzinc. The reaction proceeds via a palladium-catalyzed cross-coupling of iodoarene with bis(iodozincio)methane followed by a cobalt-catalyzed benzylzincation of alkyne.

A new efficient synthetic route to unsymmetrically substituted dihydropyridine scaffolds via dehydrative [4 + 2] cycloaddition of N-tosylated α,β-unsaturated imines with aldehydes has been developed. This transformation is enabled by (i) the remarkable catalytic ability of the cationic Ru(IV) porphyrin complex to activate both the imino and carbonyl groups and (ii) the hydrophobic nature of the porphyrin ligand, which helps realize robust Lewis acidity in the dehydrative cycloaddition.

Formaldehyde was utilized as an oxygen-centered nucleophile in an asymmetric oxy-Michael addition to γ-hydroxy-α,β-unsaturated carbonyl compounds using bifunctional organocatalysts through hemiacetal intermediates. The cyclic acetal product could be further transformed into β-hydroxycarbonyl compounds, useful synthetic intermediates leading to various important target molecules. As such, this method is an example of a novel formal asymmetric hydration of α,β-unsaturated carbonyl compounds.

A new synthetic method for thiochromones was developed by using nickel-catalyzed decarbonylative cycloaddition of readily available thioisatins with alkynes. This reaction proceeded under very mild conditions and has quite high functional group compatibility.

Lewis acid catalyzed cycloaddition of cyclohexenone and butadiene affords trans-fused octalone with high regio- and diastereoselectivity. The use of the ruthenium porphyrin complex as the Lewis acid catalyst is key to the reaction. The cycloaddition proceeds in toluene with 1 mol % of the ruthenium catalyst at 25 °C.

We present a novel methodology for the asymmetric synthesis of β-mercaptolactones via isomerization of ω-hydroxy-α,β-unsaturated thioesters by means of a bifunctional aminothiourea catalyst. The catalyst interacts with the substrate through the cooperative action of both a covalent bond at the amino group and noncovalent bonding at the thiourea group. The potential for an enantiodivergent synthesis could also be demonstrated by carrying out the reaction in a different solvent system.

A novel method for the asymmetric synthesis of 2-substituted indolines, employing bifunctional amino(thio)urea catalysts, was developed. The reaction proceeded via an intramolecular aza-Michael addition mediated by activation through hydrogen bonding. The catalytic process was shown to be highly versatile and applicable to a wide range of substrates due to the flexible catalytic mechanism utilizing a noncovalent interaction.

Treatment of phenyl isocyanate with bis(iodozincio)methane gave a zinciomethylenated product, which acts as an amide-enoate equivalent. It did not react with an aldehyde efficiently, but gave the corresponding adduct in good yield in the presence of an aminoalcohol. Use of a catalytic amount of chiral aminoalcohol led the process to the catalytic asymmetric Aldol-type reaction.

Nickel-catalyzed intermolecular [3 + 2] cycloaddition of vinylcyclopropanes to imines has been developed. This transformation generates substituted pyrrolidines in high yields, with good regio- and diastereo- selectivity under mild reaction conditions. A variety of imines can be used in this reaction. An asymmetric variant of the reaction has also been demonstrated.

Substituted quinolones were efficiently synthesized via the nickel-catalyzed cycloaddition of o-cyanophenylbenzamide derivatives with alkynes. The reaction involves elimination of a nitrile group by cleavage of the two independent aryl-cyano and aryl-carbonyl C-C bonds of the amides.

An efficient protocol for the aza-Diels-Alder reaction of electron-deficient 1,3-dienes with unactivated imines in the presence of a cationic cobalt(III) porphyrin complex was developed. The transformation proceeded smoothly to afford the desired piperidine scaffold within 2 h at ambient temperature. Highly chemoselective cycloaddition of imines with dienes in the presence of a variety of carbonyl compounds was also demonstrated.

Cycloisomerization of 1,6-enynes to five- or six-membered ring systems is successfully carried out in the presence of a cationic manganese(III) catalyst. The use of a structurally rigid tetradentate porphyrin as the equatorial ligand and a weakly coordinating axial ligand is the key to bringing out the catalytic reactivity of manganese for the reaction. The axial ligand of the catalyst has a marked effect on the product and selectively aids the formation of five- or six-membered cyclic products.

A novel asymmetric formal [3 + 2] cycloaddition reaction for the synthesis of 1,3-dioxolanes using cinchona-alkaloid-thiourea-based bifunctional organocatalysts is reported. The reaction proceeds via the formation of hemiacetal intermediates between γ-hydroxy-α,β-unsaturated ketones and aldehydes.

The dehydrogenative cycloaddition of dieneynes, which possess a diene in the form of a styrene moiety and a dienophile in the form of an alkyne moiety, produces naphthalene derivatives when heated. It was found that a key requirement of this process is the presence of a silyl group attached to the alkyne moiety, which forces a dehydrogenation reaction to occur., (© 2011 American Chemical Society)

A 1,10-phenanthroline-ligated cationic silver complex allows the intramolecular chloroamination of allenes with N-chlorosuccinimide using 2,6-lutidine as a base. This process proceeds under mild conditions and can tolerate a variety of functional groups. The chloroamination products are useful synthetic intermediates and can be easily transformed into functionalized 3-pyrroline and pyrrole derivatives.

A nickel-catalyzed [4+1] cycloaddition of enones with methylenecyclopropanes leading to dihydrofurans was developed. The reaction outcome is attributed to the transformation of methlenecyclopropane, which is incorporated into a five-membered ring as a one-carbon fragment., (© 2011 American Chemical Society)

Nickel-catalyzed cycloadditions have been developed where thiophthalic anhydrides react with alkynes to afford substituted sulfur-containing heterocyclic compounds. Selective formations of thioisocoumarins, benzothiophenes, and thiochromones were accomplished with three different reaction conditions., (© 2011 American Chemical Society)

The decarbonylative cycloadditions of phthalic anhydrides with allenes were performed by using nickel catalyst. The asymmetric variant of the cycloaddition was also achieved by using chiral phosphine ligands to provide δ-lactones enantioselectively.

A nickel-catalyzed cycloaddition has been developed where readily available anthranilic acid derivatives react with alkynes to afford substituted indoles. The reaction involves oxidative addition of Ni(0) to an ester moiety, which allows intermolecular addition to alkynes via decarbonylation and 1,3-acyl migration.

Treatment of 1,6-dialkylhexa-1,5-diene-3,4-diones with bis(iodozincio)methane gave zinc alkoxides of cis-5,6-dialkylcyclohepta-3,7-diene-1,3-diol in good yields at room temperature. The reaction proceeded with high stereospecificity. Bis(iodozincio)methane converted the diketone into the cis-divinylcyclopropane-1,2-diol stereoselectively; this diol transformed into the corresponding cycloheptane derivative stereospecifically via Cope rearrangement.

Imidazole derivatives substituted by a normal alkyl group are shown to be efficient as a ligand for the copper(Ι)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. An alkyl chain on the imidazole ligands shows an efficient steric effect and benefits the reaction. Such functionalities of an alkyl chain allow a rapid CuAAC reaction of even a bulky alkyne, which has been difficult to perform under conventional conditions.

The decarbonylative cycloadditions of phthalimides with 1,3-dienes were performed by using nickel catalyst. The reactions afford 3-vinyldihydroisoquinolones regioselectively with respect to both 1,3-dienes and phthalimides.

A Tosylation of primary alcohol with tosyl chloride was performed effectively with an N-hexadecylimidazole catalyst in water containing K(2)CO(3). aggregation of the catalyst carrying a hydrophobic methylene chain worked as a substitute for organic solvent.