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Self-assembled multilayer iron(0) nanoparticles (NPs, 6-10 nm), namely, sulfur-modified Au-supported Fe(0) [SAFe(0)], were developed for ligand-free one-pot carbon-carbon/carbon-nitrogen bond-forming reactions. SAFe(0) was successfully prepared using a well-established metal-nanoparticle catalyst preparative protocol by simultaneous in situ metal NP and nanospace organization (PSSO) with 1,4-bis(trimethylsilyl)-1,4-dihydropyrazine (Si-DHP) as a strong reducing agent. SAFe(0) was easy to handle in air and could be recycled with a low iron-leaching rate in reaction cycles.

By using Co(acac)2/Xantphos with AlMe3, the C(sp3)–H bonds of allylarene derivatives were cleaved for reaction with various ketones, affording the homoallylic alcohols in moderate to good yields. The branch/linear selectivity depended on the steric and electronic factors of the ketone electrophiles. The intermediate in this reaction is thought to be a low-valent allylcobalt(I) species, which exhibits high nucleophilicity toward ketones.

Arylative carboxylation of allenes proceeded in an intramolecular manner to afford the corresponding β,γ-unsaturated carboxylic acids in high yields using PdCl2/PAr3 (Ar = C6H4-p-CF3) and ZnEt2 under 1 atm of CO2. The intermediate of the cyclization/carboxylation sequence is thought to be a nucleophilic η1-allylethylpalladium, which reacts with CO2 at the γ-position of palladium. The products obtained could be efficiently converted into 3-substituted indole-2-carboxylate derivatives. One-pot synthesis of strychnocarpine, a β-carboline alkaloid, from the carboxylated product was also demonstrated.

Rhodium(I)-catalyzed enantioselective hydroacylation of 4-allenals was found to proceed smoothly, giving six-membered ketones in good yields (up to 84% yield) with high enantiomeric excess (up to 96% ee) even from racemic allenes as substrates. Mechanistic studies revealed that racemization of the allene moiety in the substrate would occur via a dynamic kinetic resolution (DKR) process during the hydroacylation.

By using a new catalytic system (PdCl2[P( n-Bu)3]2 in combination with ZnEt2), various 3-indolylmethanol derivatives were successfully carboxylated with CO2 (1 atm) via dearomatization of the indole nucleus, affording 3-methyleneindoline-2-carboxylates. In contrast, carboxylation of 2-indolylmethanol derivatives afforded unexpected doubly carboxylated products, which are useful synthetic precursors for biologically active compounds.

By using a palladium catalyst with ZnEt2, activated vinylcyclopropanes were successfully converted into the corresponding β,γ-unsaturated carboxylic acids in high yields under a CO2 atmosphere (1 atm). The intermediate in this reaction is thought to be a nucleophilic η(1)-allylethylpalladium species, which would be produced from π-allylpalladium and ZnEt2 (umpolung reactivity).

By using a strained four-membered ring disilane (3,4-benzo-1,1,2,2-tetraethyldisilacyclobutene) and CsF, a wide range of aryl, alkenyl, alkynyl, benzyl, allyl, and alkyl halides was successfully carboxylated under an ambient CO2 atmosphere (CO2 balloon) at room temperature within 2 h. In this carboxylation, a highly reactive silyl anion, which is generated from the disilane and CsF, is a key to facilitating the formation of a carbanion equivalent. The resulting anionic species can be trapped with CO2 to produce carboxylic acids with high efficiency.

By using Co(acac)

A catalytic enantioselective silylation of N-tert-butylsulfonylimines using a Cu-secondary diamine complex was demonstrated. The resulting optically active α-amino silanes could be carboxylated under a CO2 atmosphere (1 atm) to afford the corresponding α-amino acids in a stereoretentive manner. This two-step sequence provides a new synthetic protocol for optically active α-amino acids from gaseous CO2 and imines in the presence of a catalytic amount of a chiral source.

In the presence of three readily available chemicals, Mn powder, BF3·OEt2, and LiCl, N-acyl-N,O-acetals were successfully converted into the corresponding α-amino acids (arylglycine derivatives) under 1 atm of a CO2 atmosphere in high yields. The LiCl additive is necessary in order to increase the solubility and the nucleophilicity of an organomanganese intermediate. The products thus obtained were transformed into free α-amino acids in two steps.

In the presence of CsF, a wide range of α-substituted α-siloxy silanes were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A variety of α-substituents including aryl, alkenyl, and alkyl groups were tolerated to afford α-hydroxy acids in moderate-to-high yields. One-pot synthesis from aldehydes using PhMe2SiLi and CO2 was also possible, providing α-hydroxy acids without the isolation of an α-hydroxy silane.

One of the most challenging transformations in current organic chemistry is the catalytic carboxylation of a C(sp(3))-H bond using CO(2) gas, an inexpensive and ubiquitous C1 source. A sequential protocol for C(sp(3))-H carboxylation by employing a nitrogen-directed, metal-assisted, C-H activation/catalytic silylation reaction in conjunction with fluoride-mediated carboxylation with CO(2) was established. The carboxylation proceeded only at the benzylic C(sp(3))-Si bond, not at the aromatic C(sp(2))-Si, which is advantageous for further manipulations of the products.

A ruthenium-catalyzed hydrovinylation-type cross-coupling of ynamides and ethylene proceeds via ruthenacyclopentene to give 2-aminobuta-1,3-diene derivatives in a highly regioselective manner. It was also demonstrated that 2-aminobuta-1,3-diene derivatives reacted with various dienophiles or singlet oxygen to give a cyclic enamide derivative.

A nickel-catalyzed intramolecular cyclization of alkynylalkanone in the presence of Et(3)SiH using an NHC ligand produced various carbo- and heterocycles in a stereoselective manner. The reaction would proceed via formation of oxanickelacycle followed by sigma-bond metathesis with silane to give a bi- or tricyclic compound.

The reaction pathway of Cp*RuCl(cod)-catalyzed cyclization of allenynes was dramatically changed depending on the type of solvent employed. That is, while a cyclodimerization of allenyne proceeded to give a pentacyclic compound in toluene, a bicyclo[4.2.0]octa-1(8),5-diene derivative was exclusively produced by [2 + 2] cycloaddition of allenyne in methanol. It was also demonstrated that the [2 + 2] cycloaddition was catalyzed by a cationic ruthenium complex generated from Cp*RuCl(cod) and methanol in situ.

Nickel(0)-catalyzed asymmetric three-component coupling of 1,3-dienes, aldehydes, and silanes has been realized utilizing a chiral N-heterocyclic carbene as a ligand. On the basis of the screening of various NHC precursors, an imidazolium salt having 1-(2,4,6-trimethylphenyl)propyl groups on the nitrogen was designed and synthesized. In this reaction, various coupling products were produced in good yields with high regio-, diastereo- (anti selective in the case of the internal 1,3-diene), and enantioselectivities (up to 97% ee).

Reactions of pyridynes with cyclic urea and 1-methyl-2-oxazolidone were demonstrated. 3,4-Pyridyne and 2,3-pyridyne were reacted with N,N-dimethylimidazolidone, N,N-dimethylpropylene urea, and 1-methyl-2-oxazolidone to give the corresponding pyridodiazepines, pyridodiazocines, and pyridooxazepines, respectively.

In the presence of 1.1 equiv of PhMe(2)Si-Bpin, 5 equiv of CsF, and 20 mol % of TsOH·H(2)O, precursors of N-Boc-imines can be converted into the corresponding α-aryl or α-alkenyl glycine derivatives under gaseous CO(2) in moderate-to-high yields with a single operation. α-Isobutenyl glycine thus obtained can be further derivatized into various types of α-amino acids including N-Boc-leucine, serine, and glycine derivatives in short steps.

The total syntheses of (−)-herbindoles A, B, and C as naturally occurring forms were accomplished for the first time through transition-metal-catalyzed intramolecular [2 + 2 + 2] cyclization between ynamide and diynes. This strategy provided a highly efficient synthetic route to all three herbindoles from an identical indoline derivative as a common intermediate.

In the presence of TMSSnBu(3) and CsF, stannylation of N-Boc- and N-Cbz-α-amido sulfones proceeded very well to afford the corresponding α-amido stannanes in moderate-to-high yields. This reaction tolerated α-aryl-, alkenyl-, and alkyl-substituted α-amido sulfones as well as substrates containing either an ester or cyano moiety, which might be reactive with lithium or magnesium stannides employed in conventional stannylation.

[reaction: see text] A novel procedure for synthesizing eight-membered ring compounds was developed using ruthenium-catalyzed enyne metathesis. When a CH2Cl2 solution of enyne connected with catechol, o-amino phenol, or o-phenylenediamine was stirred in the presence of benzylidene ruthenium carbene complex (10 mol %) at room temperature overnight, an eight-membered ring compound was obtained in high yield. In a similar manner, monocyclic 1,4-diaza- or 1-oxa-4-azacyclooctene derivative was obtained in high yield.

A new method for preparation of functionalized enamides by a nickel-catalyzed multicomponent coupling of ynamides, aldehydes, and silane has been developed. The coupling reaction proceeded in the presence of a nickel-IMes catalyst to give the corresponding gamma-silyloxyenamide derivative, which has an allylic alcohol moiety in the molecule, in a highly stereoselective manner.

Synthetic methods of highly stereocontrolled E- and Z-allylsilanes were developed. When a toluene solution of diene having a silicon moiety and aldehyde was refluxed in the presence of silane using a catalytic amount of Ni(cod)(2) bearing PPh(3), E-allylsilane was obtained in high yield. On the other hand, when the reaction was carried out in THF upon heating in the presence of Ni(cod)(2), imidazolium salt, Cs(2)CO(3), and PPh(3), Z-allylsilane was formed as a sole product.

[formula: see text] ROM-RCM (ring-opening and ring-closing metatheses) of cycloalkene-yne was demonstrated using a second-generation ruthenium complex. When cycloalkene bearing the alkyne moiety at the C-1 position was reacted with a ruthenium-carbene complex under an atmosphere of ethylene, ROM-RCM proceeded smoothly to give bicyclic compound and/or dimeric compound in good yields.

[see reaction]. A novel procedure for the synthesis of an indole skeleton was developed. Treatment of a cyclohexenol derivative having a silyloxymethyl group at the 2-position with N-tosyl-o-bromoaniline in the presence of Pd2dba3*CHCl3 and (S)-BINAPO gave compound 6a with 84% ee in 75% yield. Compound 6a was converted into 11, which was treated with Pd(OAc)2 and Me(2)PPh in the presence of Ag2CO3 to give indoline derivative 12. From 12, we succeeded in the total syntheses of (-)-dehydrotubifoline and (-)-tubifoline.