Radical trifluoromethylation of Ti ate enolate: possible intervention of transformation of Ti(IV) to Ti(III) for radical termination

The radical trifluoromethylation of ketone Ti ate enolates gave α-CF₃ ketones in good yields. The use of excess amount of LDA and Ti(OⁱPr)₄ in the preparation of Ti ate enolates is the key to the efficient radical trifluoromethylation. Theoretical studies on the spin density of the Ti(IV) ate ketyl radical intermediate suggest the involvement of transformation from Ti(IV) ate ketyl radical intermediates to Ti(III) species in a radical termination step.     

A practical, solvent free, one-pot synthesis of C2-symmetrical secondary amines

A novel one-pot reductive amination of ketones using the combination Ti(OⁱPr)₄/H₂/Pd-C is reported. This practical procedure does not require any solvent, and affords C₂-symmetrical secondary amines in high yields and excellent diastereoselectivities.     

Titanium-mediated cross-coupling reactions of imines with ketones or aldehydes: an efficient route for the synthesis of 1,2-amino alcohols

The cross-coupling reactions of imines with ketones using Ti(OⁱPr)₄/c-C₅H₉MgCl reagent lead to 1,2-amino alcohols after hydrolysis. The coupling reactions with aldehydes could also afford 1,2-amino alcohols, however, in some cases, aziridines were obtained as major products in a stereoselective manner.     

Rapid ring‐opening polymerization of 1,4‐dioxan‐2‐one initiated by titanium alkoxides

Ring‐opening polymerization of 1,4‐dioxan‐2‐one in bulk was initiated by three titanium alkoxides, titanium dichlorodiisopropoxide (TiCl₂(OiPr)₂), titanium chlorotriisopropoxide (TiCl(OiPr)₃), and titanium tetraisopropoxide (Ti(OiPr)₄). The results indicate that the polymerization rate increased with number of OiPr groups in the initiator. High conversion of monomer (90%) and high molecular weight (11.9 × 10⁴ g/mol) of resulting polymer can be achieved in only 5 min at 60 °C with Ti(OiPr)₄ as an initiator. Analysis on nuclear magnetic resonance (NMR) spectra suggests the initiating sites for TiCl₂(OiPr)₂, TiCl(OiPr)₃, and Ti(OiPr)₄ to be 1.9, 2.6, and 3.8, respectively. Coordination‐insertion mechanism for the polymerization via cleavage of the acyl–oxygen bonds of the monomer was proved by NMR investigation. Kinetic studies indicate that polymerization initiated by Ti(OiPr)₄ followed a first‐order kinetics, with an apparent activation energy of 33.7 kJ/mol. It is noteworthy that this value is significantly lower than earlier reported values with other catalysts, namely La(OiPr)₃ (50.5 kJ/mol) and Sn(Oct)₂ (71.8 kJ/mol), which makes it an attractive catalyst for reactive extrusion polymerization. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis of some new chiral bifunctional o-hydroxyarylphosphonodiamides and their application as ligands in Ti(IV) complex catalyzed asymmetric silylcyanation of aromatic aldehydes

Some new chiral bifunctional o-hydroxyarylphosphonodiamides were synthesized starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine and the absolute configuration of the phosphorus atom was determined by X-ray diffraction analysis. Excellent enantioselectivity (up to 98% ee) was achieved in asymmetric silylcyanation of aromatic aldehydes using a chiral titanium complex formed in situ from Ti(OⁱPr)₄ and o-hydroxyarylphosphonodiamide as the catalyst.     

Diastereoselective reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane with prochiral ketones using the Ti(OiPr)4/NaBH4 system

A simple and convenient one-pot method for the reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane by prochiral ketones using a Ti(OⁱPr)₄/NaBH₄ system to obtain the corresponding alkyl amine derivatives in 76–95% yields with good diastereoselectivity (dr = up to 23:1:1) is reported.     

Enantioselective alkynylation of aromatic and heteroaromatic aldehydes catalyzed by resin-supported oxazolidine-titanium complexes

Highly enantioselective asymmetric addition of terminal alkynes to various aromatic and heteroaromatic aldehydes catalyzed by the readily available, low-cost, and reusable resin-supported oxazolidine 4 together with Ti(OⁱPr)₄ provides the chiral propargylic alcohols with good to excellent yields (up to 98%) and enantioselectivities (up to 95%). The immobilized catalyst can be recovered and used for five cycles.     

3,3′-Functionalized octahydro-BINOL: a facile synthesis and its high enantioselectivity in the alkyne addition to aldehydes

A facile synthesis of an enantiomerically pure 3,3′-bismorpholinylmethyl H₈-BINOL ligand has been developed. This compound in combination with Et₂Zn and Ti(OⁱPr)₄ is found to catalyze the highly enantioselective reaction of phenylacetylene with aromatic aldehydes. The enantioselectivity of this catalytic process for the reactions of ortho-substituted benzaldehydes is significantly higher than that based on H₈-BINOL.     

Catalytic Enantioselective Addition of Alkylzirconium Reagents to Aliphatic Aldehydes

A catalytic methodology for the enantioselective addition of alkylzirconium reagents to aliphatic aldehydes is reported here. The versatile and readily accessible chiral Ph-BINMOL ligand, in the presence of Ti(OⁱPr)₄ and a zinc salt, facilitates the reaction, which proceeds under mild conditions and is compatible with functionalized nucleophiles. The alkylzirconium reagents are conveniently generated in situ by hydrozirconation of alkenes with the Schwartz reagent. This work is a continuation of our previous work on aromatic aldehydes.     

Reversal of enantioselectivity by adding Ti(OiPr)4: novel sulfamide-amine alcohol ligands for the catalytic asymmetric addition of diethylzinc to aldehydes

Novel sulfamide-amine alcohol ligands (6) derived from (−)-ephedrine (4a) and (+)-pseudoephedrine (4b) with multiple stereogenic centers were applied to the catalytic asymmetric addition of diethylzinc to aldehydes, providing (S)-products in high yields and good enantioselectivities. These sulfamide-amine alcohols together with Ti(OⁱPr)₄ were shown to obtain the (R)-products in significant enantiomeric excesses (e.e.) and high yields. In addition, sulfamide-amine alcohols were superior to the original chiral sources 4a and 4b, which afforded no enantioselectivity in the Ti(OⁱPr)₄-mediated reaction.     

Coordination of mono- and diamines to titanium and zirconium alkoxides

The structural chemistry of crystalline adducts M₂(OR)₈(amine)₂ (M = Ti: OR = OⁱPr, amine = NH₂CH₂Ph, NH₂Bu; M = Ti: OR = OEt, amine = piperidine; M = Zr: OR = OⁱPr, amine = NH₂CH₂Ph, NH₂C₆H₁₁) is discussed. The adducts were obtained by reaction of Ti(OEt)₄ or M(OⁱPr)₄ with primary or secondary amines. The monoamine adducts are centrosymmetric dimers in which the amines are coordinated axially to the M₂μ-OR)₂ ring and hydrogen-bonded to neighboring alkoxo ligands. The adducts are sufficiently stable if the hydrogen bond is strong. ¹⁵N NMR studies revealed that the amines are also coordinated in solution. Coordination polymers were obtained when diamines with two terminal NH₂ groups are reacted with Ti(OⁱPr)₄. The general structure is the same as that of Ti₂(OⁱPr)₈(RNH₂)₂. However, the diamines bridge the Ti₂(OⁱPr)₈ units. When Zr(OⁱPr)₄ was reacted with NH₂CH₂CH₂NHMe, the adduct Zr₂(OⁱPr)₈[NH₂CH₂CH₂NHMe]₂ was obtained where only the NH₂ group is coordinated.     

Enantioselective phenylacetylene addition to aldehydes induced by Cinchona alkaloids

Enantioselective addition of phenylacetylene to various aldehydes was studied in the presence of inexpensive and commercially available Cinchona alkaloids. A maximum of 85% ee was obtained using cinchonidine in the presence of Ti(OⁱPr)₄.     

Structural characterization of dinuclear Ti(IV) complexes of rigid tetradentate dianionic diamine bis(phenolato) ligands; effect of steric bulk on coordination features

A small difference in diamine bis(phenolato) ligands, namely an additional single methylene unit, directs formation of dinuclear Ti(IV) complexes rather than mononuclear ones as characterized by X-ray crystallography. Varying steric bulk of the ligand affects the coordination number in the dinuclear complexes and the ligand to metal ratio. A ligand with reduced steric bulk leads to a L₂Ti₂(OiPr)₄ type complex featuring two octahedral metal centers bridged only by the two phenolato ligands, whereas a bulky ligand leads to a Ti₂(μ-L¹)(μ-OiPr)₂(OiPr)₄ type complex with a single chelating ligand, two bridging isopropoxo ligands, and two terminal isopropoxo groups on each of the two metal centers, which are of trigonal bi-pyramidal geometry.     

1,1′-Binaphthyl ligands with bulky 3,3′-tertiaryalkyl substituents for the asymmetric alkyne addition to aromatic aldehydes

The BINOL ligand (R)-2 that contains bulky 3,3′-tertiaryalkyl groups shows improved catalytic properties over the previously reported 3,3′-substituted BINOL ligands in the asymmetric alkyne addition to aromatic aldehydes. It catalyzes the phenylacetylene addition to aromatic aldehydes with high enantioselectivity (86-94% ee) and good yields without using Ti(OⁱPr)₄ and a Lewis base additive. The catalytic properties of several analogs of (R)-2 in the asymmetric alkyne addition to aldehydes have also been studied.     

Synthesis of Chiral Sulfamide–Amine Alcohol Ligands for Enantioselective Alkylation of Aldehydes

A series of chiral sulfamide–amine alcohols (SAA) (1–6) has been easily synthesized from commercially available chiral amino alcohols. In the absence of Ti(O ⁱ Pr)₄, ligand 4 catalyzed the asymmetric addition of diethylzinc to aromatic aldehydes with moderate to good yields and enantioselectivities.     

First enantioselective synthesis of manoalide: application of aldehyde–dioxinone enantioselective condensation

Manoalide, an analgesic and anti-inflammatory sesterterpene, has been stereoselectively synthesized for the first time. The C-4 stereogenic centre has been introduced in an early step by enantioselective aldol condensation using a Ti(OiPr)₄/(R)-(+)-binol complex.     

Reversible double insertion of aryl isocyanates into the Ti-O bond of titanium(IV) isopropoxide

The insertion of phenyl isocyanate into titanium isopropoxide leads to the formation of a dimeric complex [Ti(OⁱPr)₂(μ-OⁱPr){C₆H₅N(OⁱPr)CO}]₂ (1) which has been structurally characterized. Reaction of titanium isopropoxide with two and more than 2 equiv. of phenyl isocyanate is complicated by competitive, reversible insertion between the titanium carbamate and titanium isopropoxide. The ligand formed by insertion of phenyl isocyanate into the titanium carbamate has been structurally characterized in its protonated form C₆H₅N{C(OⁱPr)O}C(O)N(H)C₆H₅ (3aH). Insertion into the carbamate is kinetically favored whereas insertion into isopropoxide gives the thermodynamically favored product.     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by Ti(IV) complexes of C2-symmetrical chiral BINOL derivatives

Enantioselective addition of diethylzinc to a series of aromatic aldehydes is developed using new chiral C₂-symmetric ligand (S)-2,2′-(1,1′-binaphthyl-2,2′-diylbis(oxy))bis(methylene)bis(4-nitrophenol) (S)-2b. The catalytic system employing 10 mol % of (S)-2b and 120 mol % of Ti(OiPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes with electron-donating and electron-withdrawing substituents, giving up to 89% ee and up to 95% yield of the corresponding secondary alcohol under mild conditions.     

A Lewis acid-promoted reduction of acylsilanes to α-hydroxysilanes by diethylzinc

We report here the first example of the reduction of acylsilanes to α-hydroxysilanes, in which diethylzinc was used as a highly reactive agent in the presence of Ti(OiPr)₄ or other Lewis acids. The reduction typically proceeds to give synthetically useful α-hydroxysilanes in good yields.