Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.     

Reductions by titanium(II) as catalyzed by titanium(IV)

The cobalt(III) complexes, [(NH3)5CoBr]2+ and [(NH3)5CoI]2+ are reduced by Ti(II) solutions containing Ti(IV), generating nearly linear (zero-order) profiles that become curved only during the last few percent of reaction. Other Co(III)-Ti(II) systems exhibit the usual exponential traces with rates proportional to [Co(III)]. Observed kinetics of the biphasic catalyzed Ti(II)-Co(III)Br and Ti(II)-Co(III)I reactions support the reaction sequence: [Ti(II)(H20)n]2+ + [Ti(IV)F5]- (k1)<==>(k -1) [Ti(II)(H2O)(n-1)]2+ + [(H2O)Ti(IV)F5]-, [Ti(II)(H2O)(n-1)]2+ + Co(III) (k2)--> Ti(III) + Co(II) with rates determined mainly by the slow Ti(IV)-Ti(II) ligand exchange (k1 = 9 x 10(-3) M(-1) s(-1) at 22 degrees C). Computer simulations of the catalyzed Ti(II)-Co(III) reaction in perchlorate-triflate media yield relative rates for reduction by the proposed active [Ti(II)(H2O)(n-1)]2+ intermediate; k(Br)/k(I) = 8.     

Dearomatization of naphthalene: novel stereoselective cyclization reactions promoted by Osmium(II)

A series of Michael acceptors has been combined with the Os(II) eta(2)-naphthalene complex (1) to form stable 1H-naphthalenium species. Under acidic conditions, these complexes undergo ring closure at C2 to form the phenanthrenone core. In contrast, the corresponding 1-methylnaphthalene complex (15) upon addition of MVK at C8 undergoes ring closure at C5 to form a bridged tricyclic complex (18). Michael addition of MVK to the naphthalene complex (1) followed by deprotonation, an inter-ring linkage isomerization, and ring closure forms a 9-methylphenalene complex (21). In all cases, the organic cyclization products may be decomplexed by heating with silver triflate and isolated in moderate yield.     

Polymerization of substituted olefins initiated by organometallic compounds of titanium (IV)

Polymerization tests were carried out in homogeneous systems on various substituted olefins CH₂=CRZ (R = H or CH₃; Z = CN, COOR, C₆H₅ or OCOR) with compounds of titanium (IV) Ti X_4?x Y_x (X and/or Y = Cl, OR, NR₂, C₅H₅, OCH₂ CF₃, CH₃, C₆H₅ …) or with the bimetallic complex CH₃Ti(OR)₃, Al(CH₃)₃. The activity of the initiator varies with the co-ordination environment of the titanium and to a considerable extent with the functional groups linked to the olefin.     

The formation of organotitanium-(II) and -(IV) compounds from titanium trichloride

Interaction between titanium trichloride and trimethylsilyllithium (RLi) in hydrocarbon media provides TiR₂ and TiR₄.     

Asymmetric cyclization of 2-alkenylphenols. A comparative study on the use of palladium(II) and titanium(IV) complexes

The oxidative cyclization of 2-(3-pentenyl)phenol catalyzed by [(η³-pinene)PdOAc]₂ gives optically active (+)-2-vinylchroman (25% e.e.), while (−)-2-(1-hydroxyethyl)chroman (56% e.e.) is formed as a single diastereomer upon treatment with t-BuOOH in the presence of Ti(OⁱPr)₄ and -(+)-diethyl tartrate. 2-(2-Butenyl)phenol also undergoes the Ti-promoted asymmetric cyclization to give (2S,1′R)-(−)-2-(1-hydroxyethyl)-2,3-dihydrobenzofuran (29% e.e.).     

One-pot tandem complexity-generating reaction based on Ugi four component condensation and intramolecular cyclization

A novel complexity-generating reaction is described, which can be used in a high-throughput parallel solution-phase combinatorial format. The synthetic pathway features the Ugi four component reaction followed by intramolecular cyclization via C-C bond formation. Starting from readily available initial reactants, the described approach leads to generation of novel 3-oxoisoindoline-1-carboxamides with four points of diversity around the core scaffold. The scope and limitations of the involved chemistry and some chemical transformations of the synthesized compounds are discussed.     

Convenient indole synthesis from 2-iodoanilines and terminal alkynes by the sequential Sonogashira reaction and the cyclization reaction promoted by tetrabutylammonium fluoride (TBAF)

The sequential Sonogashira reaction and the cyclization reaction of various 2-iodoanilines and terminal alkynes in the presence of a palladium catalyst and tetrabutylammonium fluoride (TBAF) gave the corresponding 2-substituted indoles in good yields.     

Photocatalytic reaction of neat alcohols by metal-loaded titanium(IV) oxide particles

The photocatalytic reaction (excitation wavelength, greater than 300 nm) of neat alcohols (ethanol or 2-propanol) by metal-loaded titanium(IV) oxide (TiO₂) was conducted under argon at room temperature. The dehydrogenation products hydrogen (H₂) and acetaldehyde (or acetone in the case of 2-propanol) were found in the absence of additives. The corresponding acetals, ethers, and alkanes were obtained by the addition of concentrated hydrochloric acid (HCl). The measurement of the product yields during the post-irradiation dark reaction in the presence of photocatalyst (TiO₂) loaded with platinum(IV) oxide (PtO₂) revealed that the production of ether and ethane and the regeneration of ethanol proceed by the hydrogenation of acetal over loaded metal, presumably via a hemiacetal intermediate. X-ray diffraction (XRD) analyses showed that the loaded PtO₂ is reduced to platinum metal during the course of the photocatalytic reaction. For the production of ether from HCl-acidified ethanol, Pd-loaded catalysts, especially prepared by precipitation—reduction, exhibit the highest activity of several metal-loaded TiO₂ catalysts. From XRD and X-ray photoelectron spectroscopy studies of Pd-loaded TiO₂ particles, it was shown that the smaller the size of the Pd particles, the higher the selectivity for ether production from the acidified ethanol suspension. The application of this photocatalytic O-alkylation to the synthesis of cyclic ethers was demonstrated.     

Reductions of oxo species by aquatitanium(II) as catalyzed by titanium(IV)

Titanium(II) solutions, prepared by dissolving titanium wire in triflic acid + HF, contain equimolar quantities of Ti(IV). These preparations react readily with oxidizing species such as VO(2)(+), substituted benzoquinones, and the biguanide complex of Mn(IV). Reactions with excess Ti(II) yield Ti(III). Reductions of 1,4-benzoquinones and the Mn(IV) complex are catalyzed by added Ti(IV) but stoichiometry is unaffected. Rate laws for the Ti(IV)-catalyzed reactions are consistent with formation of a Ti(II)-Ti(IV) complex (K(formation) 4 x 10(2) M(-1)), which, in some cases, also partakes in contributing deprotonated and halogen-catalyzed paths.     

NNNO-Heteroscorpionate nickel (II) and cobalt (II) complexes for ethylene oligomerization: the unprecedented formation of odd carbon number olefins

The unprecedented observation of odd carbon number olefins is reported during nickel- catalyzed ethylene oligomerization. Two complexes based on Co (II) and Ni (II) with novel tetradentate heteroscorpionate ligand have been synthesized and fully characterized. These complexes showed the ability to oligomerize ethylene upon activation with various organoaluminum compounds (Et₂AlCl, Et₃Al₂Cl₃, EtAlCl₂, MMAO). Ni (II) based catalytic systems were sufficiently more active (up to 1900 kg·mol (Ni)⁻¹·h⁻¹·atm⁻¹) than Co (II) analogs and have been found to be strongly dependent on the activator composition. The use of PPh₃ as an additive to catalytic systems resulted in the increase of activity up to 4,150 kg·mol (Ni)⁻¹·h⁻¹·atm⁻¹ and in the alteration of selectivity. All Ni (II) based systems activated with EtAlCl₂ produce up to 5 mol. % of odd carbon number olefins; two probable mechanisms for their formation are suggested – metathesis and β-alkyl elimination.     

Titanium(IV) chloride and quaternary ammonium salt promoted Baylis-Hillman reaction.

The Baylis-Hillman reaction of aldehydes with alpha,beta-unsaturated ketones can be drastically affected by the reaction temperature and Lewis bases. When the reaction was carried out at -78 degrees C using catalytic amounts of quaternary ammonium salts (R4N+X-, X = Cl, Br, I) as Lewis bases, in the presence of titanium(IV) chloride, the chlorinated aldol adduct 1 was obtained as the major product. Quaternary ammonium bromides and iodides (R4N+X-, X = Br, I) have higher catalytic activity than corresponding chlorides (R4N+Cl-). Quaternary ammonium fluorides (R4N+F-) do not have activity at all. The amounts of Lewis acid and quaternary ammonium salts used affect the reaction rate and product. A plausible reaction mechanism is proposed. If the reaction was carried out at room temperature (about 20 degrees C) in the presence of titanium(IV) chloride and quaternary ammonium salts (R4N+X-, X = Cl, Br, I), the elimination product 3, derived from 1, was formed as the major product.     

Polymerization of substituted olefins initiated by organometallic compounds of titanium (IV)—II. Evidence for a predominant radical process with methyltitanium derivatives

Polymerizations of methyl methacrylate (MMA), vinyl acetate, acrylonitrile or styrene (St) initiated by methyl derivatives of Ti(IV) are consistent with a radical process. This conclusion is supported by tacticities of the resulting polymers which are close to those for conventional radical samples and show that propagation obeys a Bernoullian statistics. The major evidence is provided by statistical MMA-St copolymerization which clearly exhibits radical reactivity ratios.     

One-pot sequential Ti-/Cu-catalysis for tandem amidation/Ullmann-type cyclization: synthesis of model benzodiazepine(di)ones promoted by microwave irradiation

The application of sequential Ti-/Cu-catalysis in the model one-pot synthesis of benzodiazepine(di)ones promoted by microwave irradiation demonstrates the expediency of dual catalysis in coupling-cyclization methods useful for diversity-oriented synthesis.     

1,2-Acyl transfer reaction for the construction of multiple carbonyl-functionalized architecture by Sm(II)-induced tandem formation and breaking of cyclopropanol

[reaction: see text] An efficient 1,2-acyl group migration reaction based on contiguous formation and breaking tactics of 1-oxycyclopropane-2-carboxylate as an intermediate is developed. Thus, the reduction of 2-cyclohexenones, bearing gem-acyl/alkoxycarbonyl groups at the C4 position, with Sm(II) reagent leads to 2-acyl-4-oxycyclohexanecarboxylates via cyclization followed by retro-aldol cleavage of the resulting donor/acceptor cyclopropane. Mechanistic insights and the scope of the reaction are described.     

Complex formation and precipitation reaction of titanium(IV) from (Na,H)Cl aqueous solution containing phosphate

An equilibrium study has been made of complex formation and precipitation of titanium (IV) in 2.0 mol dm⁻³ (Na, H)Cl aqueous solution at 25°C, in the presence of 1.3–5.4 times (in molar ratio) as much phosphate, using measurements of the free hydrogen ion, saturated titanium (IV), and phosphate concentrations. Under these condition, titanium (IV) mono-orthophosphate complex TiO(HPO₄) alone was found in the solution; its stability constant and solubility product were determined. A scheme of complex formation and precipitation equilibria is presented.     

Pd(II)-catalyzed enantioselective oxidative tandem cyclization reactions. Synthesis of indolines through C-N and C-C bond formation

We have developed an efficient Pd(II)-catalyzed enantioselective oxidative tandem cyclization strategy using molecular oxygen as a green oxidant for the double 5-exo-trig cyclizations of N-(2-allylaryl) amides to afford a variety of indolines in good yields without the formation of undesired monocyclization products. By employing Pd(TFA)2/(-)-sparteine as the chiral catalyst, we obtained tandem cyclization products with high enantioselectivity (up to 91% ee).     

Spectroscopic and equilibrium studies of adduct formation between sulfoxides and bis(2,4-pentanedionato)oxovanadium(IV)

The adducts formed between VO(acac)₂ and a number of alkyl and aryl sulfoxides in dichloromethane were investigated by means of visible and IR spectroscopy. The sulfoxides all interact with the vanadium of the VO(acac)₂ via their oxygen atoms to form weak adducts with formation constants (2.4 < K_f < 6.4) which show a linear correlation with the pKa values found for these sulfoxides in aqueous H₂SO₄.     

Polycarbosilane‐supported titanium(IV) catalyst for Knoevenagel condensation reaction

Polycarbosilane (PCS) was synthesized by the polycondensation of trichloromethylsilane and trimethoxyvinylsilane in the presence of sodium metal. PCS has a highly crosslinked structure, high ceramic yield and high surface area. Titanium metal ion was attached to the polycarbosilane and its catalytic activity was investigated. The Knoevenagel condensation reaction catalysed by titanium‐incorporated polycarbosilane is reported. The titanium‐incorporated PCS catalysed the reaction well and with a diverse set of substrates the reaction proceeded with good yield. PCS‐supported transition metal catalysts have been prepared for the first time and used successfully in the Knoevenagel condensation reaction. Copyright © 2012 John Wiley & Sons, Ltd.