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We report three different transformations in the reaction of the hydroxyamide-functionalized azolium chloride 1 with Ag2O. These transformations were controlled by the N-substituent at the azolium ring of 1. Treatment of 1c (R = Me, alkyl) with Ag2O afforded the corresponding monodentate NHC-Ag (NHC represents N-heterocyclic carbene) complex, 6c, in 95% yield. In contrast, the reaction of 1b (R = Ph, aryl) with Ag2O yielded the corresponding 2-hydroxyoxazolidine-substituted azolium hydroxide, 7b, in 90% yield. In this transformation, perhaps the cyclization of the hydroxyamide moiety of 1b to 2-hydroxyoxazolidine occurred under the influence of the hydroxide counter anion. Several aryl-substituted azolium chlorides, 1d-f, were also converted into the corresponding cyclization products, 7d-f. However, the reaction of 1h (R = 2,4,6-Me3C6H2, aryl) with Ag2O afforded the corresponding NHC-Ag complex, 6h, in 93% yield, whereas the reaction of 1i (R = 4-MeOC6H4, aryl) with Ag2O provided a mixture of 6i and 7i in 56% and 32% yields, respectively. Moreover, the reaction of azolium chloride, 1j (R = 2,6-iPr2C6H3, aryl), which has a more sterically hindered substituent at the ortho-position of the aryl side-arm, was investigated. Treatment of 1j with Ag2O gave unexpected urea derivative, 8j, in 99% yield.

Enantioselective reduction of ketones with (EtO) 2 MeSiH catalyzed by an in-situ generated N -heterocyclic carbene (NHC) Ir complex at room temperature has been developed. A series of benzimidazolium salts were synthesized and screened in the asymmetric hydrosilylation reaction. As a result, propiophenone was efficiently reduced by the combined catalytic system of [IrCl(cod)] 2 and NHC–Ag complex derived from N -(1-naphthalenylmethyl)-substituted benzimidazolium salt L12 , affording the corresponding alcohol in 92% yield and with 92% ee. Moreover, the evaluation of an Ir catalyst precursor showed that cationic [Ir(cod) 2 ]BF 4 complex could be used. Furthermore, the introduction of a chiral hydroxyamide side arm into the benzimidazolium salt was critical for the successful design of the NHC ligand.

C 2 -symmetric ester-amide functionalized azolium salt was synthesized from readily available α-amino ester such as L -serine methyl ester. The combination of a Cu salt and the chiral azolium salt promoted the asymmetric conjugate addition reaction of enones with dialkylzincs. Thus, treatment of acyclic enone such as chalcone with Et 2 Zn afforded the corresponding 1,4-adduct with up to 85% ee. An excellent ee value of 93% was obtained when 3-nonen-2-one was reacted with Et 2 Zn. The present catalytic system was found to be useful for the 1,4-addition reaction of cyclic enone. For example, the reaction of 2-cyclohepten-1-one with Et 2 Zn produced ( R )-3-ethylcycloheptanone with 80% ee.

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ­ligand was designed and synthesized from readily accessible l -leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et2Zn to 2-cyclohexen-1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee.

Bis(NHC) ligand precursors, L1, based on trans-1,2-diaminocyclohexane were designed and synthesized. To introduce chirality at the hydroxyamide side arm on the NHC of L1, a chiral &beta, amino alcohol, such as enantiopure leucinol, was used. Cu-catalyzed asymmetric conjugate addition reactions of cyclic and acyclic enones with Et2Zn were selected to evaluate the performance of L1 as a chiral ligand. For the reaction of cyclic enone, a combination of [bis(trimethylsilyl)acetylene]-(hexafluoroacetylacetonato)copper(I) (Cu(hfacac)(btmsa)) with a (&plusmn, )-trans-1,2-cyclohexanediamine-based bis(NHC) ligand precursor, (rac, S,S)-L1, which was prepared from (S)-leucinol, was the most effective. Thus, treating 2-cyclohexen-1-one (3) with Et2Zn in the presence of catalytic amounts of Cu(hfacac)(btmsa) and (rac, S,S)-L1 afforded (R)-3-ethylcyclohexanone ((R)-4) with 97% ee. Similarly, use of (rac, R,R)-L1, which was prepared from (R)-leucinol, produced (S)-4 with 97% ee. Conversely, for the asymmetric 1,4-addition reaction of the acyclic enone, optically pure (&minus, )-trans-1,2-cyclohexanediamine-based bis(NHC) ligand precursor, (R,R, S,S)-L1, worked efficiently. For example, 3-nonen-2-one (5) was reacted with Et2Zn using the CuOAc/(R,R, S,S)-L1 catalytic system to afford (R)-4-ethylnonan-2-one ((R)-6) with 90% ee. Furthermore, initially changing the counterion of the Cu precatalyst between an OAc and a ClO4 ligand on the metal reversed the facial selectivity of the approach of the substrates. Thus, the conjugate addition reaction of 5 with Et2Zn using the Cu(ClO4)2/(R,R, S,S)-L1 catalytic system, afforded (S)-6 with 75% ee.

A series of new N-heterocyclic carbene (NHC)–Ru(II) complexes functionalized with additional hemilabile donor groups, such as a hydroxy-amide group, were successfully synthesized and structurally characterized. Preliminary studies indicated that the complexes acted as precatalysts with moderate activity in the asymmetric transfer hydrogenation at room temperature without temperature control. The investigation of the effect of varying the η 6 -arene ligands showed that these ligands appeared to significantly alter the activity of the complexes as precatalysts. Furthermore, it was revealed that the hydroxy functional group on the NHC ligand side-arm not only induced the stereoselectivity of the reaction but also enhanced the reaction rate.

The versatility of the anionic tethered NHC ligand system for the Pd-catalyzed allylic asymmetric alkylation (AAA) reaction was investigated. A well defined anionic amidate/NHC–Pd(II) complex catalyzed the AAA reaction of 1,3-diphenylprop-3-en-1-yl acetate (5) with NaCH(CO2Me)2. Similarly, the AAA reaction occurred by employing an NHC–Pd(II) complex that was generated in situ. Screening of a wide variety of NHC ligand precursors revealed that the combination of [Pd(allyl)Cl]2 and the azolium salt 9, containing a 3-pentyl group at N(3) position in the NHC ring, efficiently promoted the AAA reaction to afford the corresponding alkylated product 7 with 67% ee. Furthermore, it was found that the Pd/NHC ratio was an important factor; the AAA reaction with a Pd/NHC ratio of 1:1 took place smoothly, whereas utilization of a Pd/NHC ratio of 1:2 resulted in low conversion of the substrates probably by the formation of the catalytically inert bis(NHC)–Pd(II) complex. In fact, an independent experiment showed that the bis(NHC)–Pd(II) complex was formed by treating [Pd(allyl)Cl]2 with two equivalents of NHC–Ag complex. Further investigations on the catalytic AAA reaction revealed significant improvements in both the product yield (99%) and the enantioselectivity (81% ee) when cyclopentyl methyl ether was used as a solvent. A plausible reaction intermediate was discussed.

A series of highly tunable, functionalized azolium compounds have been synthesized from chiral α-amino acid derivatives such as β-amino alcohols or α-amino esters. The combination of a Cu salt and a chiral azolium efficiently facilitated the asymmetric conjugate addition (ACA) reactions of acyclic enones with dialkylzinc under ambient conditions without temperature control. Of the (hydroxy amide)-functionalized azolium ligand precursors, which were derived from β-amino alcohols, an azolium salt containing a tert-butyl group as the stereodirecting group was found to be the best choice of ligand. Ligand screening revealed that the use of an azolium salt containing a sterically bulky alkyl substituent such as N-CHRR′ on the azolium ring led to a marked increase in the enantioselectivity of the ACA reaction. Thus, a new efficient (hydroxy amide)-functionalized azolium ligand precursor such as 26, which was prepared from 1-(diphenylmethyl)benzimidazole and (S)-tert-leucinol, has been developed. The treatment of benzalacetone (30) with Et2Zn in the presence of catalytic amounts of [Cu(OTf)]2(C6H6) and 26 at room temperature gave the corresponding 1,4-adduct 31 with excellent enantioselectivity (92 % ee). On the other hand, the enantioselectivity of the ACA reactions of acyclic enones with dialkylzinc was successfully reversed by the use of (ester amide)-functionalized azolium salts, which were obtained from α-amino esters. Several functionalized azolium ligand precursors from readily available serine esters have been designed and synthesized. Finally, it was found that 30 could react with Et2Zn under the influence of a bis(hexafluoroacetylacetonato)copper(II) salt and C2-symmetric azolium salt 36 to afford ent-31 in almost quantitative yield with 89 % ee. A plausible reaction mechanism for the switching of the stereoselectivity in the ACA reaction by these two functionalized azolium compounds is described.

A new chiral N -heterocyclic carbene (NHC) ligand derived from a natural α-aminoester has been designed and synthesized. The coupling of N -methylbenzimidazole with an α-chloroacetamide derivative, which was prepared from chloroacetyl chloride and ( S )-serine methyl ester, gave the corresponding ester/amide-functionalized azolium compound 20 . The reaction of 2-cyclohexen-1-one ( 17 ) with Et 2 Zn in the presence of catalytic amounts of Cu(OTf) 2 and 20 produced ( R )-3-ethylcyclohexanone ( 18 ) as a major product. In contrast, the enantioselective conjugate addition (ECA) reaction catalyzed by Cu(OTf) 2 under the influence of a hydroxy-amide-functionalized azolium compound 15 , which was derived from ( S )- tert -leucinol, produced ( S )- 18 in preference to ( R )- 18 . A series of azolium salts were synthesized from ( S )-serine esters, and the reaction conditions for the ECA reaction were optimized to produce ( R )- 18 with 69% ee. The best results were obtained in the case of the reaction of 4,4-dimethyl-2-cyclohexen-1-one ( 34 ) with Et 2 Zn catalyzed by Cu(OTf) 2 in combination with azolium compounds. When the reaction of 34 with Et 2 Zn was carried out in the presence of catalytic amounts of Cu(OTf) 2 and 20 , ( S )-3-ethyl-4,4-dimethylcyclohexanone ( 35 ) was obtained with 97% ee, whereas the ECA reaction under the influence of hydroxy-amide-functionalized azolium 15 afforded ( R )- 35 with >99% ee. In this manner, the reversal of enantioselectivity was achieved by controlling the structure of chiral ligands.

Amide-functionalized N-heterocyclic carbene (NHC) precursors such as azolium compounds have been designed and synthesized. Reaction of PdCl 2 (CH 3 CN) 2 with the NHC–Ag complex derived from the azolium salt gave [(NHC)PdCl 2 ] 2 or (NHC) 2 PdCl 2 , whereas PdCl 2 (PPh 3 ) 2 reacted with the Ag complex to afford a mixed carbene/phosphine complex such as (NHC)(PPh 3 )PdCl 2 together with a cationic [(NHC)(PPh 3 ) 2 PdCl] + Cl − whose structure was characterized by X-ray crystallographic studies. Thus, the library of NHC–Pd complexes with a tethered amide group has been successfully expanded.

A new chiral N-heterocyclic carbene (NHC) ligand was designed. Thus, an efficient synthetic route to C 2 -symmetric bis(hydroxyamide)-functionalized benzimidazolium salts from chiral β-amino alcohols was developed. The combination of Cu(OTf) 2 and the chiral azolium compound efficiently promoted the conjugate addition reaction of cyclic enone with dialkylzinc to give the corresponding adduct in good yield. Among a series of chiral NHC proligands, the functionalized benzimidazolium chloride possessing a tert -butyl group as a stereodirecting group was found to be the best choice of ligand. Under optimized reaction conditions, an excellent enantioselectivity (96% ee) was realized by allowing 2-cyclohepten-1-one to react with Bu 2 Zn at room temperature.

While developing novel catalysts for carbon-carbon or carbon-heteroatom coupling (N, O, or F), we were able to introduce tridentate NHC-amidate-alkoxide palladium(II) complexes. In aqueous solution, these NHC-Pd(II) complexes showed high ability for C-H activation of various hydrocarbons (cyclohexane, cyclopentane, dimethyl ether, THF, acetone, and toluene) under mild conditions.

ω-Hydroxy ketones and diketones, which are important starting materials for the synthesis of cycloalkanones and heterocyclic compounds, were prepared by the one-step reaction of methyl ketones with...

Carboxylation of benzenes with CO was successfully achieved by a combined catalytic system of Pd(OAc)2 with H5PMo10V2O40·nH2O (HPMo10V2) under the influence of O2 to form the corresponding benzoic acids in relatively high selectivity and moderate yields. The regioselectivity in the carboxylation of alkylbenzenes with CO was dominated by the steric factor rather than the electronic effect of substituents. However, the carboxylation of benzoic acid proceeded with high ortho-selectivity to give phthalic acid in preference to terephthalic acid, which shows coordination of Pd species to the carboxyl group of benzoic acid.

Concomitant introduction of COOH and OH groups to biphenyl was achieved by allowing biphenyl to react with CO and O2 using the Pd/molybdovanadophosphoric acid catalytic system. For instance, biphenyl reacted under a mixed gas of CO (0.5 atm) and O2 (0.5 atm) in the presence of catalytic amounts of Pd(OAc)2 and H5PMo10V2O40·26H2O in acetic acid to give the corresponding hydroxybiphenylcarboxylic acids. The reaction was found to proceed through the formation of biphenylcarboxylic acid followed by hydroxylation of the resulting carboxylic acid.

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ­ligand was designed and synthesized from readily accessible l -leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et2Zn to 2-cyclohexen-1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee.

The oxidation of trimethylbenzenes was examined with air or O 2 using N , N ′, N ″-trihydroxyisocyanuric acid (THICA) as a key catalyst. Thus, 1,2,3-, 1,2,4-, and 1,3,5-trimethylbenzenes under air (20 atm) in the presence of THICA (5 mol %), Co(OAc) 2 (0.5 mol %), Mn(OAc) 2 , and ZrO(OAc) 2 at 150 °C were oxidized to the corresponding benzenetricarboxylic acids in good yields (81–97%). In the aerobic oxidation of 1,2,4-trimethylbenzene by the THICA/Co(II)/Mn(II) system, remarkable acceleration was observed by adding a very small amount of ZrO(OAc) 2 to the reaction system to form 1,2,4-benzenetricarboxylic acid in excellent yield (97%). In contrast, no considerable addition effect was observed in the oxidation of 1,3,5-trimethylbenzene. This aerobic oxidation by the present catalytic system provides an economical and environmentally benign direct method to benzenetricarboxylic acids, which are very important polymer materials.

The addition of water and alcohols to non-activated terminal alkynes was found to be promoted by an iridium complex combined with Lewis acid and phosphite. Thus, terminal alkynes reacted with water or alcohols to give ketones or ketals, respectively, in good to excellent yields. α,ω-Diyne like 1,7-octadiyne was converted into 1-(2-methyl-cyclopent-1-enyl)ethanone through the intramoleculer aldol condensation of the resulting 2,7-octanedione induced by Lewis acid.

The cross-dimerization of an electron-rich terminal alkyne with an electron-deficient internal alkyne was promoted by an iridium complex to produce a 1 : 1 adduct in high regio- and stereoselectivities. This reaction was extended to various combinations of terminal alkynes with internal alkynes such as alkynyl esters and alkynyl aldehydes. The selectivity of the reaction was found to markedly depend on the ligands used. When dppe was used as a ligand, the 1 : 2 cross-cyclotrimerization reaction took place to form substituted benzene derivatives. A plausible reaction path was suggested based on a labeling experiment. This reaction provides a method for the production of complicated enynes which are difficult to be prepared by conventional methods.

We have found that the [{IrCl(cod)} 2 ] complex catalyzes several reactions involving three-component couplings, hydrogen migration, vinyl ethers synthesis, and α-alkylation of ketones with alcohols, etc. Thus, the reaction of aldehydes, amines, and alkynes under the influence of a catalytic amount of [{IrCl(cod)} 2 ] complex led to three-component coupling products through a new type of C-H bond activation adjacent to the nitrogen atom of imines. Aziridines were also synthesized by three-component couplings of aldehydes, amines, and ethyl diazoacetate in the presence of a catalytic amount of [(IrCl(cod)} 2 ]. An innovation in the synthesis of vinyl ethers, which are very useful monomer materials in polymer syntheses but have been difficult to synthesize so far, was made by a simple exchange reaction of alcohols with vinyl acetates through a catalytic process using [{IrCl(cod)} 2 ]. A unique α-alkylation of ketones with alcohols was successfully achieved under the influence of [{IrCl(cod)} 2 ] and KOH without any solvents, leading to saturated ketones that elongated the carbon chain. Allyl homoallyl and diallyl ethers were converted by [(Ircl(cod)} 2 ] into y, δ-unsaturated aldehydes via a Claisen rearrangement of in situ-generated allyl vinyl ethers. These reactions provide a novel synthetic tool for important chemicals like vinyl ethers and ketones, which are practically synthesized in the chemical industry.

Nitrotoluenes are efficiently oxidized with air to the corresponding nitrobenzoic acids by the use of N -acetoxyphthalimide (NAPI) as a key catalyst. Thus, p - and m -nitrotoluenes under 10 atm of air in the presence of NAPI combined with Co(OAc) 2 (0.5 mol%) and Mn(OAc) 2 (0.05 mol%) at 130°C afforded p - and m -nitrobenzoic acids in 81 and 92% yields, respectively. o -Nitrotoluene was oxidized to o -nitrobenzoic acid in 51% yield by the aid of NO 2 .

Selective Wacker-type oxidation of long-chain terminal alkenes to methylketones was successfully achieved by using Pd(OAc) 2 /molybdovanadophosphate (NPMoV)/O 2 system. The selectivity of the reaction increased by slow addition of the alkenes to the catalytic solution. The oxidation of α,ω-dienes was also examined, and the selectivity of the oxidation was found to depend on the chain length of the dienes used.

The oxidative coupling reaction of benzene to biphenyl was examined by the use of a Pd(OAc)2/molybdovanadophosphoric acid/O2 system under mild conditions. Pd(OAc)2 combined with two different types of molybdovanadophosphoric acids exhibited the highest catalytic activity for the biphenyl synthesis. The best turn-over number (TON) of Pd(OAc)2 and the yield of biphenyl reached 109 and 14.3% based on the benzene used, respectively. The rate-determining step of the coupling was found to be the reoxidation step of the reduced molybdovanadophosphoric acid by molecular oxygen.

The reaction of various ethers with alkenes bearing an electron-withdrawing substituent in the presence of N -hydroxyphthalimide combined with Co(OAc) 2 under dioxygen produced the corresponding adducts in which oxygen is incorporated to alkenes in good yields. Oxcetane, furan and pyrane smoothly added to ethyl fumarate even at room temperature to give coupling products in high yields. An acyclic ether like dibutyl ether also added to fumarate under mild conditions to give a hydroxylated adduct in satisfactory selectivity.

A series of new N-heterocyclic carbene (NHC)–Ru(II) complexes functionalized with additional hemilabile donor groups, such as a hydroxy-amide group, were successfully synthesized and structurally characterized. Preliminary studies indicated that the complexes acted as precatalysts with moderate activity in the asymmetric transfer hydrogenation at room temperature without temperature control. The investigation of the effect of varying the η 6 -arene ligands showed that these ligands appeared to significantly alter the activity of the complexes as precatalysts. Furthermore, it was revealed that the hydroxy functional group on the NHC ligand side-arm not only induced the stereoselectivity of the reaction but also enhanced the reaction rate.

Meerwein–Ponndorf–Verley-type reductive acetylation of carbonyl compounds to acetates was successfully carried out in the presence of isopropenyl acetate under the influence of a catalytic amount of Ln(O i Pr) 3 at room temperature. Various carbonyl compounds were converted into the corresponding acetates in fair to good yields.

Wacker-type oxidation of cyclopentene to cyclopentanone under dioxygen atmosphere was successfully achieved by the use of Pd(OAc) 2 and molybdovanadophosphate supported on activated carbon, [Pd(OAc) 2 –NPMoV/C], catalyst. Thus, the reaction of cyclopentene under O 2 (1 atm) in aqueous acetonitrile acidified by CH 3 SO 3 H in the presence of [Pd(OAc) 2 –NPMoV/C] at 50°C produced cyclopentanone in 85% yield along with a small amount of cyclopentenone (1%).

Dehomologation of aldehydes has been first successfully achieved via oxidative cleavage of silyl enol ethers, derived from aldehydes and trimethylchlorosilane, using aqueous hydrogen peroxide in the presence of a catalytic amount of peroxotungstophophate (PCWP) under phase-transfer conditions. For instance, the oxidation of 1-[(trimethylsilyl)oxy]-1-octene resulting from octanal and Me3SiCl with 35% H2O2 catalyzed by PCWP in dichloromethane at room temperature afforded the one-carbon shorter aldehyde, heptanal, in 79% yield. A variety of silyl enol ethers were also converted into one-carbon shorter aldehydes in good yields. The oxidation under homogeneous conditions using tert-butyl alcohol gave hydrolysis products such as 2-oxooctanol and octanal. It is of interest that [1-(trimethylsilyl)oxy]-1,10-undecadiene involving an enol moiety and a terminal double bond afforded exclusively 9-decenal, in which the enol moiety was selectively oxidized. A plausible reaction path for the oxidative cleavage of silyl ...

Aerobic oxidation of primary alcohols to aldehydes was efficiently performed using a Ru(PPh 3 ) 3 Cl 2 /hydroquinone system under atmospheric oxygen at 60 °C. A primary alcohol even in the presence of a secondary one was selectively oxidized to the corresponding aldehyde in high yield.

Highly selective aerobic oxidation of isobutane to t-butyl alcohol was successfully achieved by the use of a radical catalyst, N-hydroxyphthalimide (NHPI) in the presence of Co(II) salt under relatively mild conditions. The oxidation of isobutane by NHPI combined with Co(acac)2 under a pressure of air (10 atm) in benzonitrile at 100 °C gave t-butyl alcohol in high yield (84%) along with acetone (13%). The reaction is thought to proceed via hydrogen abstraction from isobutane by the phthalimidooxyl radical (PINO), which seems to be a key active species. The formation of acetone can be explained by a partial β-scission of the t-butoxy radical, generated from the redox decomposition of t-butyl hydroperoxide by cobalt ion. Alkyl-substituted butanes and pentanes were difficult to be oxidized selectively under these conditions because of easy degradation to smaller fragments of the resulting alkoxyl radical intermediates.

Radical addition of 1,3-dimethyladamantane to diethyl acetylenedicarboxylate was catalyzed by NHPI combined with Co species under O 2 to give different adducts, ethyl 2-(3,5-dimethyladamantyl)-2-oxoethanoate and a normal adduct whose ratio was found to depend on the O 2 concentration of the reaction system.

Aldol type condensation of imines has first been achieved via a catalytic process using samarium diiodide (Sml 2 ) at room temperature to form α,β-unsaturated imines in good yields. The condensation was markedly facilitated by the presence of formates or aldehydes which promote the elimination of amines from aldol adducts. It was found that the 1:2 reaction of amines with aldehydes under the influence of Sml 2 also led to α,β-unsaturated imines in satisfactory yields.

Adamantanes were successfully converted into the corresponding mono- and dihydroxy adamantanes with molecular oxygen in the presence of N-hydroxyphthalimide (NHPI) combined with cobalt salts under mild conditions. For example, exposure of adamantane under oxygen atmosphere in the presence of NHPI (10 mol%) and Co(acac)2 (0.5 mol%) in acetic acid at 75 °C for 6 h afforded adamantan-1-ol (43 %) and adamantane-1,3-diol (40 %) along with adamantan-2-one (8 %) in 93 % conversion. Similarly, 1,3-dimethyladamantane produced 3,5-dimethyladamantan-1-ol (47 %) and 5,7-dimethyladamantane-1,3-diol (37 %).

A facile method for the synthesis of organophosphonates from alkenes and dialkyl phosphites was developed by the use of Mn(II) under air. Thus, the reaction of 1-octene with diethyl phosphite in the presence of Mn(OAc)2 (5 mol %) under air at 90 degrees C led to diethyl octylphosphonate (78%) and diethyl (2-hexyl)decylphosphonate (6%). Internal alkenes such as cis-2-octene gave a regioisomeric mixture of the corresponding hydrophosphorylation products in 84% yields.

A novel strategy for production of mono- and dicarboxylic acids by the addition of carboxyalkyl radicals to alkenes and dienes, respectively, was successfully developed through a catalytic process with use of Mn(II)/Co(II)/O2 system. Thus, a variety of carboxylic acids were prepared by the reaction of alkenes and dienes with acid anhydrides in the presence of a very small amount of Mn(OAc)2 (0.5 mol %) and Co(OAc)2 (0.1 mol %) under dilute dioxygen.

A series of hydroxy-amide functionalized azolium salts have been designed and synthesized for Cu-catalyzed asymmetric conjugate addition reaction. The (CH(2))(2)-bridged hydroxy-amide functionalized azolium ligand precursors 2, in addition to the previously reported CH(2)-bridged azolium salts 1, have been prepared from readily available enantiopure β-amino alcohols. The combination of a Cu species with 1 or 2 efficiently promoted the 1,4-addition reaction of cyclic enones with dialkylzincs. For example, the reaction of 2-cyclohepten-1-one (17) with Bu(2)Zn in the presence of catalytic amounts of Cu(OTf)(2) and 1 gave (S)-3-butylcycloheptanone (20) in 99% yield and 96% ee. On the other hand, when the reaction was carried out under the influence of Cu(OTf)(2) combined with 2, (R)-20 in preference to (S)-20 was obtained in 98% yield and 80% ee. In this manner, the enantioselecvity was switched by controlling the structure of chiral ligand. Additionally, the reversal of enantioselectivity was also achieved by changing the Cu precatalyst from Cu(OTf)(2) to Cu(acac)(2) with the same ligand. The combination of Cu(acac)(2) with CH(2)-bridged azolium salt 1 in the reaction of 17 with Bu(2)Zn led to formation of (R)-20 as a major product in 55% yield and 80% ee. This result was in contrast to the Cu(OTf)(2)/1 catalytic system, where the 1,4-adduct with opposite configuration was obtained. Moreover, use of the Cu(acac)(2)/2 catalytic system produced (S)-20, while (R)-20 was formed by the Cu(OTf)(2)/2 catalytic system. Thus, it was found that either varying the linker of the chiral ligands or changing the counterion of Cu species between a OTf and acac ligand initially on the metal led to dual enantioselective control in the 1,4-addition reaction.

The addition of dialkylzinc to cyclic enones can give the (R)- and/or (S)-enantiomers using the same chiral ligand AZO but different Cu salts.

Reversal of enantioselectivity in a Cu-catalyzed asymmetric conjugate addition reaction of dialkylzinc to cyclic enone with use of the same chiral ligand was successfully achieved. The reaction of 2-cyclohexen-1-one (30) with Et(2)Zn catalyzed by Cu(OTf)(2) in the presence of an azolium salt derived from a chiral beta-amino alcohol gave (S)-3-ethylcyclohexanone (31) in good enantioselectivity. Among a series of chiral azolium compounds examined, the benzimidazolium salt (10) having both a tert-butyl group at the stereogenic center and a benzyl substituent at the azolium ring was found to be the best choice of ligand in the Cu(OTf)(2)-catalyzed reaction. Good enantioselectivity was observed when the reaction was conducted by employing a benzimidazolium derivative rather than an imidazolium derivative. The influence of the substituent at the azolium ring on the stereoselectivity of the reaction was also examined. In addition, from the results of the reaction catalyzed by Cu(OTf)(2) combined with an azolium compound derived from (S)-leucine methyl ester, it was found that the hydroxy side chain in the chiral ligand is probably crucial for the enantiocontrol of the conjugate addition reaction. On the other hand, it was discovered from a screening test of copper species that the reversal of enantioselectivity was realized by allowing 30 to react with Et(2)Zn in the presence of Cu(acac)(2) combined with the same ligand precursor to afford (R)-31 as a major product. The influence of the stereodirecting group at the chiral ligand on the stereoselectivity in the Cu(acac)(2)-catalyzed reaction differed completely from that observed in the Cu(OTf)(2)-catalyzed reaction. Reaction with a cyclic enone consisting of a seven-membered ring such as 2-cyclohepten-1-one (40) resulted in increasing the enantioselectivity of the reaction. Thus, treatment of 40 with Et(2)Zn catalyzed by Cu(OTf)(2) combined with a benzimidazolium salt produced the corresponding (S)-conjugate adduct in a 92:8 enantiomer ratio (er), while the Cu(acac)(2)-catalyzed reaction with the same ligand afforded (R)-product in a 9:91 er.

Aerobic oxidation of various alcohols has been accomplished by using a new catalytic system, N-hydroxyphthalimide (NHPI) combined with Co(acac)3. The oxidation of alcohols by NHPI was found to be markedly enhanced by adding a slight amount of Co(acac)3 (0.05 equiv. to NHPI). Thus, secondary alcohols and vic-diols which are difficult to be oxidized by NHPI alone were smoothly oxidized with molecular oxygen (1 atm) to the corresponding carbonyl compounds under relatively mild conditions (65 ∼ 75 °C).

A novel class of catalysts for alkane oxidation with molecular oxygen was examined. N-Hydroxyphthalimide (NHPI) combined with Co(acac)n (n = 2 or 3) was found to be an efficient catalytic system for the aerobic oxidation of cycloalkanes and alkylbenzenes under mild conditions. Cycloalkanes were successfully oxidized with molecular oxygen in the presence of a catalytic amount of NHPI and Co(acac)2 in acetic acid at 100 °C to give the corresponding cycloalkanones and dicarboxylic acids. Alkylbenzenes were also oxidized with dioxygen using this catalytic system. For example, toluene was converted into benzoic acid in excellent yield under these conditions. Ethyl- and butylbenzenes were selectively oxidized at their α-positions to form the corresponding ketones, acetophenone, and 1-phenyl-1-butanone, respectively, in good yields. A key intermediate in this oxidation is believed to be the phthalimide N-oxyl radical generated from NHPI and molecular oxygen using a Co(II) species. The isotope effect (kH/kD) in t...

The oxidation of vinyl and silyl enol ethers with aqueous hydrogen peroxide was first achieved by the use of peroxotungstophosphate (PCWP) as the catalyst. For example, the oxidation of 1-ethoxy-1-octene with a stoichiometric amount of 35% H2O2 in the presence of PCWP (0.5 mol %) in a mixed solvent of methanol and dichloromethane at room temperature gave 1-ethoxy-1-methoxy-2-hydroxyoctane, a synthetic equivalent of 2-hydroxyoctanal, in 70% yield. The oxidation of acyclic silyl enol ethers such as 1-[(trimethylsilyl)oxy]-1-octene under these conditions gave 1-hydroxy-2-octanone in 72% yield, while the same oxidation in dichloromethane alone resulted in cleavage of the enol double bond to form heptanal in 71% yield. Cyclic silyl enol ethers were converted into the corresponding α-hydroxy ketones in 48−71% yields under similar reaction conditions.

Highly selective aerobic oxidation of isobutane to t-butyl alcohol was successfully achieved by the use of a radical catalyst, N-hydroxyphthalimide (NHPI) in the presence of Co(II) salt under relatively mild conditions. The oxidation of isobutane by NHPI combined with Co(acac)2 under a pressure of air (10 atm) in benzonitrile at 100 °C gave t-butyl alcohol in high yield (84%) along with acetone (13%). The reaction is thought to proceed via hydrogen abstraction from isobutane by the phthalimidooxyl radical (PINO), which seems to be a key active species. The formation of acetone can be explained by a partial β-scission of the t-butoxy radical, generated from the redox decomposition of t-butyl hydroperoxide by cobalt ion. Alkyl-substituted butanes and pentanes were difficult to be oxidized selectively under these conditions because of easy degradation to smaller fragments of the resulting alkoxyl radical intermediates.

Aliphatic aldehydes underwent trimerization in the presence of a catalytic amount of Cp ∗ 2 Sm(thf) 2 under ambient conditions to form 1,3-diol monoesters in good yields. For example, the reaction of acetoaldehyde catalyzed by Cp ∗ 2 Sm(thf) 2 gave 4-acetoxy-2-butanol ( 2a ) and 3-acetoxy-1-butanol ( 3a ) in 86% yield.

Carbonylation of terminal alkynes was performed using a new triple catalytic system, Pd(II)/chlorohydroquinone/NPMoV, under carbon monoxide and oxygen. For instance, phenylacetylene was converted into methyl phenylpropiolate (85%) in methanol and phenylmaleic anhydride (62%) in dioxane. The reaction did not take place in the absence of oxygen.

An approach for partial oxygenation through a carbocation as an intermediate was successfully developed by using nitric oxide under the influence of N-hydroxyphthalimide. Thus, a variety of benzylic ethers were converted into the corresponding partially oxidized compounds, which are difficult to prepare by conventional methods, in high yields. For example, the reaction of phthalane with NO in the presence of a catalytic amount of NHPI at 60 degrees C gave phthalaldehyde in 80% yield. The reaction was found to proceed through the formation of a hemiacetal, such as 1-hydroxyphthalane. In addition, 1,3-di-tert-butoxymethyl benzene afforded 1,3-benzenedicarbaldehyde in good yield. On the other hand, isochroman was converted into 1,1'-oxodiisochromane under these reaction conditions. The reaction of ethers with NO in the presence of a NHPI catalyst is thought to proceed via the formation of a carbocation as an intermediate. A possible reaction path was suggested.

A variety of vic-diols were first successfully cleaved to the corresponding aldehydes with dioxygen catalyzed by Ru(PPh3)3Cl2 on active carbon in fair to good yields. For example, treatment of 1,2-octandiol and 1,2-cyclooctanediol with dioxygen in the presence of Ru(PPh3)3Cl2/C in PhCF3 at 60 °C for 15 h produced heptanal and 1,8-octanedial in 77% and 76% yields, respectively.

Exposure of a mixture of adamantane and biacetyl under O2 in the presence of Co(OAc)2 (0.1 mol%) in AcOH led to 1-acetyladamantane (47%) and 1,3-diacetyladamantane (20%) as major products along with small amounts of adamantan-1-ol (4%) and adamantan-2-one (3%).

Dehomologation of aldehydes has been first successfully achieved via oxidative cleavage of silyl enol ethers, derived from aldehydes and trimethylchlorosilane, using aqueous hydrogen peroxide in the presence of a catalytic amount of peroxotungstophophate (PCWP) under phase-transfer conditions. For instance, the oxidation of 1-[(trimethylsilyl)oxy]-1-octene resulting from octanal and Me3SiCl with 35% H2O2 catalyzed by PCWP in dichloromethane at room temperature afforded the one-carbon shorter aldehyde, heptanal, in 79% yield. A variety of silyl enol ethers were also converted into one-carbon shorter aldehydes in good yields. The oxidation under homogeneous conditions using tert-butyl alcohol gave hydrolysis products such as 2-oxooctanol and octanal. It is of interest that [1-(trimethylsilyl)oxy]-1,10-undecadiene involving an enol moiety and a terminal double bond afforded exclusively 9-decenal, in which the enol moiety was selectively oxidized. A plausible reaction path for the oxidative cleavage of silyl ...

Three-component coupling reactions of aliphatic aldehydes, aliphatic amines and ethyl diazoacetate to the corresponding aziridine derivatives has been achieved by the use of [Ir(cod)Cl]2 as a catalyst under mild conditions; for instance, the reaction of n-butyraldehyde, tert-butylamine and ethyl diazoacetate in the presence of a catalytic amount of [Ir(cod)Cl]2 in THF at −10 °C gave 1-tert-butyl-2-ethoxycarbonyl-3-propylaziridine in 85% yield in high stereoselectivity (cis : trans = 96∶4).