Iridium(III)-Catalyzed Asymmetric Site-Selective Carbene C-H Insertion during Late-Stage Transformation.

C-H functionalization has recently received considerable attention because C-H functionalization during the late-stage transformation is a strong and useful tool for the modification of the bioactive compounds and the creation of new active molecules. Although a carbene transfer reaction can directly convert a C-H bond to the desired C-C bond in a stereoselective manner, its application in late-stage material transformation is limited. Here, we observed that the iridium-salen complex exhibited efficient catalysis in asymmetric carbene C-H insertion reactions.

Iron-catalysed asymmetric tandem spiro-cyclization using dioxygen in air as the hydrogen acceptor.

A tandem combination of ortho-quinone methide (o-QM) formation/Michael addition/asymmetric dearomatization, which is catalysed by an iron-salan complex in air with high enantioselectivity, provides an efficient method for spirocyclic (2H)-dihydrobenzofuran synthesis from 2-naphthols and phenols. The key to the success of the tandem synthesis is the development of aerobic oxidative o-QM formation.

Ruthenium-catalyzed oxidative kinetic resolution of unactivated and activated secondary alcohols with air as the hydrogen acceptor at room temperature.

Enantiopure alcohols are versatile building blocks for asymmetric synthesis and the kinetic resolution (KR) of racemic alcohols is a reliable method for preparing them. Although many KR methods have been developed, oxidative kinetic resolution (OKR), in which dioxygen is used as the hydrogen acceptor, is the most atom-efficient. Dioxygen is ubiquitous in air, which is abundant and safe to handle.

Asymmetric nitrene transfer reactions: sulfimidation, aziridination and C-H amination using azide compounds as nitrene precursors.

Nitrogen functional groups are found in many biologically active compounds and their stereochemistry has a profound effect on biological activity. Nitrene transfer reactions such as aziridination, C-H bond amination, and sulfimidation are useful methods for introducing nitrogen functional groups, and the enantiocontrol of the reactions has been extensively investigated. Although high enantioselectivity has been achieved, most of the reactions use (N-arylsulfonylimino)phenyliodinane, which co-produces iodobenzene, as a nitrene precursor and have a low atom economy.

Iron-catalyzed dioxygen-driven C-C bond formation: oxidative dearomatization of 2-naphthols with construction of a chiral quaternary stereocenter.

Iron(salan) complex 1 was found to catalyze the oxidative dearomatization of 1-substituted 2-naphthols with the formation of an all-carbon quaternary stereocenter in air in the presence of nitroalkanes, to afford the corresponding cyclic enones with high enantioselectivity of 88-96% ee.

Ru(CO)-salen-catalyzed synthesis of enantiopure aziridinyl ketones and formal asymmetric synthesis of (+)-PD 128907.

Aziridination of vinyl ketones using SESN(3) in the presence Ru(CO)-salen complex 1 provides the enantiopure aziridinyl ketones that can serve as useful chiral building blocks. A formal asymmetric synthesis of (+)-PD 128907 was achieved in an eight-step sequence via aziridination.

Asymmetric olefin aziridination using a newly designed Ru(CO)(salen) complex as the catalyst.

Highly enantioselective and good to high-yielding aziridination of conjugated and non-conjugated terminal olefins and cyclic olefins was achieved using a newly designed Ru(CO)(salen) complex as the catalyst in the presence of SESN(3) under mild conditions.

What factors influence the catalytic activity of iron-salan complexes for aerobic oxidative coupling of 2-naphthols?

A few Fe-salan dimer complexes serve as catalysts for aerobic oxidative coupling (AOC) of 2-naphthols, but some others do not. X-Ray and cyclic voltammetry studies of various Fe-salan complexes revealed that the absence or the presence of double hydrogen bonding in Fe-salan dimers, the oxidation potential of monomeric Fe-salan species and the location of the resulting radical cation are critical factors for the catalytic activity of iron-salan complexes for the AOC.

Enantioselective intramolecular benzylic C-H bond amination: efficient synthesis of optically active benzosultams.

'Salen' along: the iridium(III)-salen complex 1 efficiently catalyzes the title reaction of 2-ethylbenzenesulfonyl azides to give five-membered sultams with high enantioselectivity. Other 2-alkyl-substitued substrates lead to five- and six-membered sultams with high enantioselectivity; the regioselectivity depends upon the substrate and the catalyst used. EDG=electron-donating group.

Aerobic oxidative kinetic resolution of secondary alcohols with naphthoxide-bound iron(salan) complex.

The first general method for iron-catalyzed aerobic oxidative kinetic resolution of secondary alcohols was achieved with good to high enantiomeric differentiation (k(rel) = 7-50). Although iron(salan) complex 1 does not catalyze alcohol oxidation, the naphthoxide-bound iron(salan) complex does.

Efficient iron-mediated approach to pyrano[3,2-a]carbazole alkaloids--first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine, first asymmetric synthesis and assignment of the absolute configuration of (-)-trans-dihydroxygirinimbine.

Iron-mediated oxidative cyclisation provides an efficient approach to pyrano[3,2-a]carbazole alkaloids. Thus, improved routes to girinimbine and murrayacine as well as the first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine are reported. Asymmetric epoxidation of girinimbine led to (-)-trans-dihydroxygirinimbine and the assignment of its absolute configuration.

Catalytic asymmetric oxidation of cyclic dithioacetals: highly diastereo- and enantioselective synthesis of the S-oxides by a chiral aluminum(salalen) complex.

Aluminum(salalen) complex 1 [salalen = half-reduced salen, salen = N,N'-ethylenebis(salicylideneiminato)] was found to be a highly efficient catalyst for asymmetric oxidation of cyclic dithioacetals in the presence of 30% hydrogen peroxide as an oxidant. In the reaction of a series of 2-substituted 1,3-dithianes bearing alkyl, alkenyl, alkynyl, and aryl groups as the substituent, the trans-monoxides were obtained in high yields with 19:1 → >20:1 dr (diastereomeric ratio) and 98-99% ee (enamtiomeric excess). The reaction of nonsubstituted 1,3-dithiane also proceeded in a highly enantioselective manner to give the monoxide with a small formation of the trans-1,3-dioxide, an overoxidation product.

Enantioenriched synthesis of cyclopropenes with a quaternary stereocenter, versatile building blocks.

Ir(salen) complexes were found to catalyze enantioselective cyclopropenation efficiently. Cyclopropenation can be carried out using either a donor/acceptor- or an acceptor/acceptor-substituted diazo compound such as α-aryl-α-diazoacetates, α-phenyl-α-diazophosphonate, 2,2,2-trifluoro-1-phenyl-1-diazoethane, and α-cyano-α-diazoacetamide as carbenoid precursors. The reactions provide highly enantioenriched cyclopropenes (84-98% ee) with a functionalized quaternary carbon as versatile building blocks.

Enantioenriched synthesis of C1-symmetric BINOLs: iron-catalyzed cross-coupling of 2-naphthols and some mechanistic insight.

Highly enantioselective aerobic oxidative cross-coupling of 2-naphthols with broad substrate scope was achieved using an iron(salan) complex as the catalyst. Enantiomeric excesses of the products ranged from 87 to 95%. The scope of the cross-coupling reaction was found to be different from that of the homocoupling reaction under the same reaction conditions.

Photopromoted Ru-catalyzed asymmetric aerobic sulfide oxidation and epoxidation using water as a proton transfer mediator.

Ru(NO)-salen complexes were found to catalyze asymmetric aerobic oxygen atom transfer reactions such as sulfide oxidation and epoxidation in the presence of water under visible light irradiation at room temperature. Oxidation of sulfides including alkyl aryl sulfides and 2-substituted 1,3-dithianes using complex 2 as the catalyst proceeded with moderate to high enantioselectivity of up to 98% ee, and epoxidation of conjugated olefins using complex 3 as the catalyst proceeded with good to high enantioselectivity of 76-92% ee. Unlike biological oxygen atom transfer reactions that need a proton and electron transfer system, this aerobic oxygen atom transfer reaction requires neither such a system nor a sacrificial reductant.

Room-temperature synthesis of enantioenriched non-protected cyanohydrins using vanadium(salalen) catalyst.

Room-temperature synthesis of enantioenriched non-protected cyanohydrins using acetone cyanohydrin as the cyanide source was achieved by V(salalen) catalyst. Aliphatic aldehydes underwent the cyanation with 89-95% ee in the presence of only 0.2-0.

Oxidation catalysis of Nb(salan) complexes: asymmetric epoxidation of allylic alcohols using aqueous hydrogen peroxide as an oxidant.

Several optically active Nb(salan) complexes were synthesized, and their oxidation catalysis was examined. A dimeric mu-oxo Nb(salan) complex that was prepared from Nb(OiPr)(5) and a salan ligand was found to catalyze the asymmetric epoxidation of allylic alcohols using a urea-hydrogen peroxide adduct as an oxidant with good enantioselectivity. However, subsequent studies of the time course of this epoxidation and of the relationship between the ee of the ligand and the ee of the product indicated that the mu-oxo dimer dissociates into a monomeric species prior to epoxidation.

Iridium(III)-catalyzed enantioselective Si-H bond insertion and formation of an enantioenriched silicon center.

Iridium(III)-salen complexes were found to efficiently catalyze enantioselective carbene Si-H bond insertion. Highly enantioselective Si-H insertion with alpha-alkyl-alpha-diazoacetates (>or=97% ee) was achieved for the first time by using the iridium complex 4 {(aR,S), Ar = 4-TBDPSC(6)H(4)} bearing a concave-shaped salen ligand as the catalyst. Formation of a chiral silicon center was also achieved for the first time by the Si-H insertion into prochiral silanes: the reactions between prochiral silanes and tert-butyl alpha-diazopropionate in the presence of complex 5 {(aR,S), Ar = Ph} proceeded with high stereoselectivity (84-99% de, 94-->99% ee).

Iridium(III) catalyzed diastereo- and enantioselective C-H bond functionalization.

Iridium(III)-salen complexes were found to efficiently catalyze the enantioselective C-H carbene insertion. The insertion reaction at the alpha-position of tetrahydrofuran or at the methylene of 1,4-cyclohexadiene proceeded with high enantio- (up to 99%) and diastereoselectivity (up to >20:1 dr; in the former reaction) by using an appropriate combination of complex (1, 2, or 3) and alpha-diazoacetate (alpha-aryl-alpha-diazoacetates or alpha-diazopropionate) as the carbene source.

Iron-catalyzed asymmetric aerobic oxidation: oxidative coupling of 2-naphthols.

Fe(salan) complexes were found to be efficient catalysts for the asymmetric aerobic oxidative coupling of 2-naphthol derivatives. This reaction can be carried out in air at 60 degrees C with high enantioselectivity up to 97% ee. This is the first report for asymmetric aerobic oxidation using molecular oxygen in air in the absence of additives.