4-Indolylbutanals from rhodium-catalyzed hydroformylation of allylindoles as precursors of benzofused indolizines

New 4-indolylbutanals have been prepared via a rhodium-catalyzed hydroformylation of differently substituted N-allylindoles. The aldehydes bearing an electron-donating group on the indole nucleus 3-position can evolve into benzofused indolizines via a one pot intramolecular cyclodehydration.     

Novel C1-symmetric dibenzophosphole ligands: application in hydroformylation reactions

A new family of non-symmetrical disubstituted dibenzophospholes possessing different steric and electronic effects have been synthesized and characterized. Their preliminary evaluation in rhodium-catalyzed hydroformylation reactions is presented.     

Synthesis, complexation behavior and application of a new diphosphite ligand in rhodium-catalyzed hydroformylation

Oxidative coupling of 3-(3-tert-butyl-4-hydroxyphenyl)propionic acid methyl ester (2) gave dimethyl 3,3′-(5,5′-di-tert-butyl-6,6′-dihydroxybiphenyl-3,3′-diyl)-dipropionate (1c), which upon phosphorylation/transesterification with a phosphochloridite derived from (R)-binaphthol, formed the new unsymmetrical binaphthol-bridged diphosphite 4. A rhodium catalyst based on 4 as ligand gave predominantly iso-selectivity in the hydroformylation of selected styrenes but opposite regioselectivity with 2,6-disubstituted derivatives. New chelate metal complexes (acac)RhL, PdCl₂L and PtCl₂L have been synthesized by reacting 4 with (acac)Rh(CO)₂, PdCl₂(MeCN)₂ and PtCl₂(COD), respectively. The structure of obtained compounds is determined based on ¹H, ¹³C, ³¹P and ¹⁹⁵Pt NMR spectroscopy and mass spectrometry data.     

Domino reaction sequences in the rhodium-catalyzed hydroformylation of 3-acetyl-1-allylpyrrole: a short route to 5,6,7,8-tetrahydroindolizines

When 3-acetyl-1-allylpyrrole (1) was subjected under hydroformylation conditions, with Rh₄(CO)₁₂ as catalyst precursor, to 30 atm CO/H₂ (1:1) total pressure and 140 °C, an equimolar mixture of the isomeric 5,6,7,8-tetrahydroindolizines 4′ and 5′ was obtained as the almost exclusive product. In both cases a domino hydroformylation/cyclization on the α pyrrole positions by the aldehyde 3 carbonyl group occurs which involves different intermediates: while 4′ is generated via the dihydroindolizine 4, 5′ forms via direct reduction of 8-hydroxytetrahydroindolizine 5, a structure that has never been observed before from 1-allylpyrroles under oxo conditions.     

N-phosphanylamidine ligands and their catalytic activity in the hydroformylation of 1-octene and styrene

Pyridine-based N-phosphanylamidine ligands i-Pr₂N-C(pyr)N-PR₂ (R = Ph (3), i-Pr (4)) were synthesized and fully characterized by NMR spectroscopy and X-ray crystallography. Mononuclear rhodium complexes 7 and 8 were obtained in one step from the [RhCl(COD)]₂ dimer and the monodentate ligands 1 and 2. Their single-crystal X-ray diffraction studies revealed the structural adaptive behavior of the monodentate N-phosphanylamidine ligands 1 and 2 upon k¹-P coordination mode in rhodium(I) complexes with the imino nitrogen atom of the amidine function which behaves as a “universal joint”. Compounds 1-4 were evaluated as ligands in the 1-octene and styrene hydroformylation reactions. The results obtained are encouraging and represent the first report on the use of N-phosphanylamidine ligands of the type R″₂N-C(R′)N-PR₂ in catalytic reactions.     

Synthesis of new o-alkyl substituted arylalkylphosphanes: study of their molecular structure and influence on rhodium-catalyzed propene and 1-hexene hydroformylation

A set of new phosphane ligands designed to increase the branched-to-normal ratio of the hydroformylation reaction were prepared in the same way as the previously reported ortho-alkyl substituted arylphosphanes, which have shown increased i/n ratios in the hydroformylation of propene and 1-hexene. In order to determine the relationship between the catalytic behavior and stereoelectronic properties of the ligands, various functional alkyl groups (methyl, isopropyl, cyclohexyl) were placed on the phosphorus atom directly and in the ortho position of the phenyl ring connected to phosphorus. In the hydroformylation reaction of propene and 1-hexene a higher i/n ratio resulted with nearly all the ligands compared with that of triphenylphosphane. Additionally as the ortho-alkyl-substituent became larger, it had a favorable effect on the i-selectivity. Characterization of the ligands was carried out by NMR spectroscopy (mainly ¹H, ³¹P{¹H}, ¹³C{¹H}, HSQC/HETCOR and COSY-90). Properties of the ligands were also studied by quantum mechanical calculations and by synthesizing three Rh(acac)(CO)(PR₃) derivatives. The o-alkyl-substituent was orientated outside the ligands’ cone angle in the X-ray crystal structures of (2-cyclohexylphenyl)dicyclohexylphosphane and (2,5-dimethylphenyl)bis(4-pyridyl)phosphane, and Rh(acac)(CO)(PR₃) complex of (2-methylphenyl)dicyclohexylphosphane.     

Platinum complexes of 2-diphenylphosphinobenzaldehyde-derived P-alkene ligands and their application in the hydroformylation of styrene

Neutral complexes of the formula PtCl₂L₂ (where L = diethyl 2-diphenylphosphino-benzylidene-malonate (1), diisopropyl 2-diphenylphosphino-benzylidene-malonate (2), di-tert-butyl 2-diphenylphosphino-benzylidene-malonate (3), methyl E-2-(2′-diphenylphosphinophenyl)-acrylate (4), tert-butyl E-2-(2′-diphenylphosphinophenyl)acrylate (5)) were prepared. These complexes proved to be excellent precursors to active catalysts for the hydroformylation of styrene. The platinum-containing catalytic systems prepared from malonate-based ligands 1 and 2 provided the highest activity. Chemoselectivities of up to 87% were obtained, while the two aldehyde regioisomers were formed in almost equimolar ratio. The in situ studies by using lower ligand to Pt ratios resulted in slight decrease in both regio- and chemoselectivities.³¹P NMR studies on the PtCl₂L₂ complexes revealed that the formation of trans isomers is highly preferred in the case of benzylidene malonate-type ligands with two ester functionalities (1-3) probably due to steric hindrance. A mixture of cis/trans geometrical isomers (on the Pt) with a predominance of the trans isomer was formed when acrylate-type ligands with one ester functionality (4 and 5) were used.     

A quantum chemical study on the mechanism of chiral N-oxides-catalyzed Strecker reaction

The mechanism for the Strecker reaction of silyl cyanide (H₃SiCN) and benzaldehyde N-methylimine (PhCHNCH₃) catalyzed by chiral 3,3′-dimethyl-2,2′-bipyridine N,N′-dioxide was investigated using the density functional theory (DFT) at the B3LYP/6-31G* level. The calculations revealed that the non-catalyzed reaction proceeded in a concerted way via a five-membered ring transition state, while the catalytic one occurred stepwisely via a hexacoordinate hypervalent silicate intermediate. It was predicted that both non-catalyzed and catalytic Strecker reactions involved two competitive reaction pathways, that is, addition followed by isomerization or isomerization followed by addition. The calculations indicated that two reaction pathways were comparable for both non-catalyzed and catalytic Strecker reactions. In the catalytic reaction, the strong electron donor (N-O) of chiral N-oxide played an important role in enhancing the reactivity and nucleophilicity of H₃SiCN by coordinating O atom to the Si atom of H₃SiCN. Chiral N-oxide could be used as a good catalyst for the reaction, which was in agreement with the experimental observations.     

N-Acetyl-N,N-dipyrid-2-yl (cyclooctadiene) rhodium (I) and iridium (I) complexes: Synthesis, X-ray structures, their use in hydroformylation and carbonyl hydrosilylation reactions and in the polymerization of diazocompounds

The synthesis of novel N-acetyl-N,N-dipyrid-2-yl complexes of Rh^I and Ir^I, i.e. [RhCl(CH₃CONPy₂)(COD)] (1) and [IrCl(CH₃CONPy₂)(COD)] (2), respectively, is described. Upon prolonged treatment in CH₂Cl₂ at room temperature, complex 1 is transformed into a cationic Rh-complex, i.e. [Rh(CH₃CONPy₂)(COD)⁺RhCl₂(COD)⁻] (1a). Compound 1a crystallizes in the monoclinic space group P2₁/c, complex 2 crystallizes in the triclinic space group . Compound 1 was investigated for its catalytic activity in the hydroformylation of cyclooctene as well as of 1-octene. In addition, 1 was used in various carbonyl hydrosilylation reactions of both aldehydes and ketones. There, turn-over numbers up to 50 000 and yields in the range of 85-100% were observed. Finally, compound 1 was successfully used for the polymerization of N₂CHCOOEt yielding highly stereoregular poly(ethoxycarbonylcarbene) with M_w = 67 000 g/mol and a polydispersity index (PDI) of 2.59.     

Platinum complexes of malonate-derived monodentate phosphines and their application in the highly chemo- and regioselective hydroformylation of styrene

Neutral complexes of the formula PtCl₂L₂ (where L = diethyl 2-diphenylphosphino-malonate (1), diethyl 2-methyl-2-diphenylphosphinomalonate (2), dibenzyl 2-diphenylphosphinomalonate (3), 1,3-dihydroxy-2-methyl-2-diphenylphosphinopropane (4)) were prepared. These proved to be precursors to active catalysts for the hydroformylation of styrene. The platinum-containing catalytic systems prepared from ligand 4 provided the highest activity, while the platinum compounds prepared from other ligands all showed similar levels of reactivity to each other. The matching of high chemo- and regioselectivities were observed in most cases. Surprisingly, the complexes were practically inactive in imidazolium-type ionic liquids. ³¹P NMR studies on the PtCl₂L₂ complexes revealed that the stereoselectivity of the cis/trans geometrical isomers is strongly dependent on the structure of the ligand.     

A further breakthrough in biphasic, rhodium-catalyzed hydroformylation: the use of Per(2,6-di-O-methyl)-β-cyclodextrin as inverse phase transfer catalyst

Solvent free biphasic hydroformylalion of various water-insoluble terminal olefins can be achieved in high yields and sclcctivitics by using a water-soluble rhodium/triphenylphosphine trisulfonate catalyst and per(2,6-di-o-mclhyl)-β-cyclodcxtrin as inverse phase transfer catalyst. The catalytic activities were up to ten times higher than those observed without pcr(2,6-di-o-methyl)-β-cyclodextrin.     

An easy and versatile approach to the synthesis of chiral pheromone lactones via 4,4-dimethyl-2-oxazoline derivatives

As part of our ongoing investigation on the versatility of 4,4-dimethyl-2-oxazoline derivatives, we present a straightforward synthesis of chiral lactone pheromones from readily available starting materials. As an application, we describe the diastereoselective synthesis of cis and trans-2-methyl-5-hexanolide (1), a pheromone component of the carpenter bee Xylocopa hirutissima, and a formal synthesis of (4R,5Z)-5-tetradecen-4-olide (2), the sex pheromone of the Japanese beetle Popillia japonica.     

Stereoselective synthesis of 3-substituted tetrahydroisoquinolines from phthalan and chiral N-sulfinylimines

The reaction of the dianionic intermediate [resulting from the reductive opening of phthalan (1) with lithium] with chiral N-tert-butylsulfinyl aldimines 3 in the presence of ZnMe₂ gives, after hydrolysis, N-tert-butylsulfinyl amino alcohols 4 with high diastereoselectivity. Successive treatment of compounds 4 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide yields 3-substituted tetrahydroisoquinolines 6.     

Synthesis of monofluorinated indolizines and their derivatives by the 1,3-dipolar reaction of N-ylides with fluorinated vinyl tosylates

Monofluorinated indolizines 4, benzo[d]indolizines 7 and 4H-pyrrolo[1,2-a]benzimidazoles 8 were synthesized in moderate yields by 1,3-dipolar reaction between fluorinated vinyl tosylates 2a and N-ylides of pyridinium, isoquinolinium and benzimidazolinium, generated in situ from their halides salts. When the same N-ylides were allowed to react with 2,3,3-trifluoro-1-propenyl tosylate 2b, the unexpected product formylated indolizines and their derivatives 9 were obtained. The reaction mechanism is also proposed.     

A novel chiral mesoporous binaphthyl-silicas: Preparation, characterization, and application in HPLC

Mesoporous organosilicas with both R-(+)-1,1'-binaphthyl-2,2'-diamine and ethane moieties bridging in the framework were synthesized. This mesoporous material was prepared via the one-step co-condensation of N,N'-bis-[(triethoxysilyl)propyl]-(R)-bis-(ureido)-binaphthyl (Si-DABN) with 1,2-bis(triethoxysilyl)ethane (BTSE) using octadecyltrimethylammonium chloride (C(18) TMACl) as a structural directing agent with the aid of a co-solvent (ethanol) in basic medium. The morphology of these bifunctionalized mesoporous organosilicas is sensitive to the Si-DABN mole fraction and the base concentration. And the mesostructure becomes less ordered as the mole fraction of Si-DABN in the initial mixture increases from 10 to 40%. Elemental analysis and Fourier transform infrared (FT-IR) spectrometer indicate that the binaphthyl diamine was successfully introduced to the mesoporous organosilicas. Acidic conditions are more suitable than basic ones for the hydrolysis and condensation of (R)-2,2'-dicyanomethoxy-6,6'-di[(2-triethoxysilyl)ethenyl]-1,1'-binaphthyl, a chiral silane precursors with a short silane side chain on the binaphthyl group. A column packed with these bifunctionalized mesoporous organosilica spheres exhibits greater selectivity for R/S-1,1'-bi-2,2'-naphthol than one packed with commercial SiO(2) grafted with N,N'-bis-[(triethoxysilyl)propyl]-(R)-bis-(ureido)-binaphthyl. Binaphthol and bromosubstituted binaphthol were fully resolved, but two ether derivatives were only partially enantioseparated and the other three ester derivatives were no fully resolved on the column via co-condensation method.     

Tetraphenol-based diphosphite ligands: synthesis, characterization, and application in the rhodium-catalyzed hydroformylation of octenes

A new class of diphosphites is described, based on a tetraphenol backbone. Ligands TP1-TP5 were synthesized and fully characterized and their application in the hydroformylation of octenes was investigated. Ligand TP3, bearing a 1-naphthoxy substituent on the phosphorus, shows the highest regioselectivity toward the linear aldehyde.     

quiral: a computer program for the synthesis of chiral molecules from sugars

The quiral computer program analyzes the 3D structure of a target organic molecule to find which sugar(s) can be used as a starting material for its synthesis. The program also proposes schemes for the preparation of rare or unavailable sugars whose chiral centers fit with those of the target molecule. Castanospermine, an anti-HIV natural compound is chosen as an example to illustrate what the quiral program achieves.     

Ti-mediated intramolecular cyclopropanation of N-alkenyl thioamides: scope and mechanistic study

Although thioamides generally undergo a reductive alkylation process when they are treated with a Grignard reagent in the presence of Ti(OiPr)₄, substrates fitted with a but-3-enyl substitution at the nitrogen atom are shown to be converted into bicyclic aminocyclopropanes. These reactions are compared with the similar cyclisations of the corresponding carboxylic amide substrates. A mechanistic study is provided. Coincidently, new reagent systems are identified for the mediation of the same transformation.     

Tandem enantioselective conjugate addition-Mannich reactions: efficient multicomponent assembly of dialkylzincs, cyclic enones and chiral N-sulfinimines

A convenient access to enantiopure β-amino ketones through a multicomponent reaction of dialkyl zinc reagents, cyclic enones and chiral N-tert-butanesulfinimines is disclosed. Four diastereoisomers can be selectively obtained by the appropriate choice of the chiral ligand (L or ent-L) and the chiral N-sulfinimine (R_S or S_S). The protocol is particularly efficient when enolisable N-sulfinimines are used.