Phenylenebis(ethynyl)-tethered bis-BINOL ligands for enantioselective catalyst based on dimeric TiIV aggregate

Bis-BINOLs 7a-c in which two BINOL units are tethered by phenylenebis(ethynyl) groups react with titanium tetraisopropoxide (2 equiv) to form intramolecular dimeric titanium(IV) aggregates 2a-c. Of these, 2a,b with an o-phenylenebis(ethynyl) tether are stable in the presence of excess titanium tetraisopropoxide. Complex 2a exhibits a relatively high enantioselectivity in asymmetric addition of diethylzinc to an aldehyde. [structure: see text]     

Achiral tetrahydrosalen ligands for the synthesis of C(2)-symmetric titanium complexes: a structure and diastereoselectivity study

Achiral tetrahydrosalen ligands have been employed in the synthesis of chiral C(2)-symmetric titanium complexes. When combined with tetrahydrosalen ligands 2a and 2b, titanium tetraisopropoxide liberated 2 equiv of isopropyl alcohol and generated the (tetrahydrosalen)Ti(O-i-Pr)(2) complexes 3a and 3b. These complexes were shown to be C(2)-symmetric by (1)H and (13)C[(1)H] NMR spectrometry and X-ray crystallography. X-ray structures of 3a and 3b indicate that the bonding of the tetrahydrosalen ligand to titanium is different than the bonding of salen ligands to titanium. Whereas salen ligands usually bind to titanium in a planar arrangement, the tetrahydrosalen is bonded with the phenoxide oxygens mutually trans. When bound in this fashion, the nitrogens of the tetrahydrosalen ligand and the titanium become stereogenic centers. The use of titanium complexes of high enantiopurity in the generation of tetrahydrosalen titanium adducts resulted in a maximum diastereoselectivity of 2:1. The diastereoselectivity obtained using chiral titanium alkoxide complexes was greater than the diastereoselectivity observed when a tetrahydrosalen ligand derived from (S,S)-trans-diaminocyclohexane was employed.     

Snapshots of titanium BINOLate complexes with diverse solid state structures

[structure: see text]. Many important asymmetric reactions are catalyzed by (BINOLate)Ti species with unknown structures. Reported here are three structures of BINOLate titanium complexes that show an interesting aggregation of (BINOLate)Ti(OiPr)2 with itself and with titanium tetraisopropoxide. These complexes are potential intermediates in the asymmetric addition of alkyl groups to aldehydes.     

Catalytic asymmetric allylation of ketones and a tandem asymmetric allylation/diastereoselective epoxidation of cyclic enones

A simple procedure is reported for the catalytic asymmetric allylation of ketones, utilizing titanium tetraisopropoxide, BINOL, 2-propanol additive, and tetraallylstannane as allylating agent. A variety of ketone substrates, including acetophenone derivatives and alpha,beta-unsaturated cyclic enones, reacted to form tertiary homoallylic alcohols in good yields (67-99%) and with high levels of enantioselectivity (generally >80%). A novel one-pot enantioselective allylation/diastereoselective epoxidation has also been introduced. Thus, upon completion of the allyl addition to conjugated cyclic enones, 1 equiv of tert-butyl hydroperoxide is added and the directed epoxidation of the allylic double bond ensues to afford the epoxy alcohol with high diastereoselectivity.     

A concise and straightforward approach to total synthesis of (+)-Strictifolione and formal synthesis of Cryptofolione via a unified strategy

We describe a concise and straightforward approach to the total syntheses of (+)-Strictifolione and Cryptofolione in the longest linear sequences of four steps and six steps from 3-phenyl propanal and trans-cinnamaldehyde, respectively. The route utilized a titanium tetraisopropoxide/(R)-[1,1'-binaphthalene]-2,2'-diol catalyzed Mukaiyama aldol reaction, indium(0)-promoted Barbier reaction, and olefin cross-metathesis as the key reactions.     

Diisopropyloxy(η-cyclopentene)titanium for the diastereoselective synthesis of various 1,2-disubstituted cyclopentanes

The reaction of 3 equiv of cyclopentylmagnesium chloride with 2 equiv of titanium(IV) isopropoxide at low temperature (−70 to −50 °C) leads to the formation of 1 equiv of diisopropyloxy(η²-cyclopentene)titanium containing low amounts of the starting Grignard reagent. The sequential addition of two electrophiles onto this titanium complex involved as an intermediate in Kulinkovich-type reactions delivers various 1,2-disubstituted cyclopentane rings with generally high diastereoselectivity. Mechanistic considerations and possible extensions of this method are discussed.     

Optically active poly(hydroxyurethane)s derived from cyclic carbonate and L-lysine derivatives

The polyaddition of L -lysine hydrochloride and bifunctional five-membered cyclic carbonate 1 was carried out in DMAc in the presence of 1 equiv of DBU or 2 equiv of sodium hydride for 24 h to afford optically active polyurethane 2 bearing hydroxy and carboxyl group. The polyaddition of L -lysinol and 1 was also carried out in NMP to afford higher molecular weight of optically active polyurethane 3 bearing hydroxy group in quantitative yield. These polyurethanes reacted with cupric acetate, sodium tetrahydroborate, and titanium tetraisopropoxide to afford the corresponding crosslinked gels immediately. © 1996 John Wiley & Sons, Inc.     

First catalytic enantioselective synthesis of the cocaine abuse therapeutic agent (S)-(+)-1-(4-{2-[bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol

(S)-(+)-1-(4-{2-[Bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol, which is a promising candidate as a cocaine abuse therapeutic agent, is prepared in several steps. The key asymmetric step is the catalytic enantioselective addition of dimethylzinc to either 2-chloro or 2-bromoacetophenone catalyzed by the use of different chiral isoborneolsulfonamide ligands in the presence of titanium tetraisopropoxide. The synthesis of a new isoborneolsulfonamide ligand bearing a trifluromethyl substituent and its use in this addition is also presented.     

Copper(I)-catalyzed reaction of acylzirconocene chloride: cross-coupling and conjugate addition

For the purpose of exploring a new reaction of acylzirconocene chloride as an acyl anion donor, Cu(I)-catalyzed cross-coupling and conjugate addition reactions of acylzirconocene chloride were studied. The coupling reaction with allylic or propargylic halides efficiently proceeded to yield β,γ-unsaturated ketone or allenyl ketone derivatives, respectively. The conjugated addition reaction to ,β-enones was carried out in the presence of 2 equiv. of BF₃·OEt₂ giving 1,4-diketone compounds.     

trans-1-Sulfonylamino-2-isoborneolsulfonylaminocyclohexane derivatives: excellent chiral ligands for the catalytic enantioselective addition of organozinc reagents to ketones

The catalytic enantioselective addition of different organozinc reagents (such as alkyl and aryl derivatives or in situ generated aryl, allyl alkenyl, and alkynyl derivatives obtained through different transmetallation processes) to simple ketones has been accomplished by using titanium tetraisopropoxide and chiral ligands derived from substituted trans-1-sulfonylamino-2-isoborneolsulfonylaminocyclohexane, producing the corresponding tertiary alcohols with enantiomeric excesses (ee) up to >99 %. A simple and efficient procedure for the synthesis of the chiral ligands used in these reactions is described.     

Polymerization Behaviour of Organically Modified Titanium Alkoxides in Solution

Modified titanium alkoxides with polymerizable organic ligands allow the synthesis of copolymers consisting of hybrid organic/inorganic networks. In this work titanium based-precursors were characterized in relation to the polymerization behaviour of the organic matrix. Alkoxide sols were prepared by reaction of methacrylic acid, itaconic acid anhydride, isoeugenol, p-vinylbezoic acid, p-vinylphenylacetic acid, and acetoxyacetomethacrylate with titanium tetraisopropoxide and titanium tetraethoxide. Polymerization reactions were carried out in solution using UV-irradiation and a redox-system of dibenzoylperoxide/N, N-dimethyl-p-toluidine as radical initiators. Especially for chemical activation some complexes showed high reactivity similar to silica-based methacrylates. The systems investigated are capable of acting as adhesive promoters between metal and polymer in dental applications.     

Syntheses of Chiral Phosphazenes with Stereogenic Centers: NMR Behavior in the Presence of a Chiral Solvating Agent

The condensation reactions of tetrachloro mono ( 1 and 2 ) and bisferrocenyl spirocyclotriphosphazenes ( 3 – 5 ) with morpholine in tetrahydrofuran gave the partly morpholino‐substituted ferrocenylphosphazenes. When the reactions were carried out with equal amounts of 1 – 5 and morpholine, the mono‐substituted ferrocenylphosphazenes ( 1a, 3a–5a ) formed as the major product. While the reactions were made with 1 equiv of 1–5 and 2 equiv of morpholine, the corresponding geminal–phosphazenes ( 1b–5b ) were isolated. In addition, the condensation reactions of 1 equiv of 1–5 and 3 equiv of morpholine resulted in the formation of di‐( 1b–5b ), tri‐( 2c–5c ), and tetra‐substituted phosphazenes. The tri‐substituted compounds were isolated as major products. Some new phosphazenes have stereogenic P center(s). The stereogenic properties of 1a and 2c were investigated using ³¹P nuclear magnetic resonance (NMR) spectroscopy in the presence of the chiral solvating agent; (S)‐(+)‐2,2,2‐trifluoro‐1‐(9′‐anthryl)ethanol. The structures of all the phosphazenes were characterized by one‐dimensional ¹H, ¹³C, and ³¹P NMR, and two‐dimensional heteronuclear single quantum coherence spectral data. The salient spectral properties of the phosphazenes were presented.     

Metathesis polymerization of norbornene and terminal acetylenes catalyzed by bis(acetonitrile) complexes of molybdenum and tungsten

The ring-opening metathesis polymerization (ROMP) of norbornene catalyzed by bis(acetonitrile) molybdenum and tungsten complexes, [M(η³-C₃H₅)Cl(CO)₂(NCMe)₂] (1-Mo: M = Mo, 1-W: M = W), which have two labile acetonitrile ligands, has been investigated. These complexes catalyzed the ROMP of norbornene as a single-component initiator. The highly cis-selective polymerization proceeded in a THF solution (95% for 1-Mo and 96% for 1-W), whereas polymerization in CH₂Cl₂ or toluene resulted in lower cis selectivity. The polymerization of terminal acetylenes using these complexes was also examined. The tungsten complex 1-W showed a high catalytic activity for the polymerization of terminal acetylenes, such as phenyl- and tert-butylacetylene. A highly active catalytic system for the ROMP of norbornene was achieved by the activation of the tungsten complex, 1-W, with one equivalent of phenylacetylene, giving poly(norbornene) with a high molecular weight (M_n = 391 × 10⁴) and a high cis selectivity (cis  89%).     

Unusual product distribution in ethylene oligomerization promoted by in situ ansa-chloroneodymocene–dialkylmagnesium systems

Ethylene polymerization using in situ combinations between a chloroneodymocene precursor and a dialkylmagnesium reagent has been investigated to prepare tailor-made oligomers. Combinations of [Cp^*₂NdCl₂Li(OEt₂)₂] (1) with 40 equiv. of n-butylethylmagnesium (BEM) or di(n-hexyl)magnesium (DHM) gave oligoethylenes with M_n up to 2500 and narrow molecular weight distributions (M_w/M_n<1.10) in moderate activity (A_{1 h}=79 kg/(mol of Nd h atm) at 80 °C, 1 atm). Under these conditions, ethylene polymerization proceeded in a controlled fashion, with a linear growth of M_n vs monomer conversion, ascribed to an effective chain transfer between the Nd and Mg centers. Combinations of [rac-{Me₂Si(η⁵-2-SiMe₃-4-t-Bu-C₅H₂)₂}Nd(μ-Cl)₂Li(THF)₂] (2) with either BEM or DHM (20–40 equiv.) showed decreased activity, suggesting possibly a different rate-determining-step for ethylene polymerization than for that of higher -olefins. The oligoethylenes obtained from combinations based on 2 have narrow molecular weight distributions (M_w/M_n<1.2) but higher contents of vinyl terminations. Monitoring of the reactions showed also a non-linear growth of M_n vs monomer conversion, especially marked when DHM was used as co-reagent. The 2/DHM combination behaves as a “self-correcting” catalyst system that deviates from the calculated M_n values for a controlled-living polymerization in the early stage of the reaction and re-approach them progressively in the second stage.     

Chiral bis-pi-allylpalladium complex catalyzed asymmetric allylation of imines: enhancement of the enantioselectivity and chemical yield in the presence of water

The chiral pi-allylpalladium complex 2a, prepared from exoethylidenenorpinane 7, catalyzed the allylation of diverse imines with allyltributylstannane in the presence of 1 equiv of water in good to high enantioselectivities. The catalyst prepared from a 1:1 mixture of (E)- and (Z)-7 was found to be consisting of two stereoisomers 2a and 2b in 1.3:1 ratio. On separation, 2a catalyzed the allylation of imines in much higher enantioselectivities than 2b, giving the same major enantiomer and thereby justifying the need to separate 2a free of 2b. We have achieved the highest separation ratio of >400:1 for 2a:2b by repeated recrystallizations. Isomerization of 2b to 2a during recovery of 2a from the filtrates was observed as more of 2a was recovered each time during recrystallization. Although dry THF was the best solvent, we tried various additives and found that addition of one equivalent of water gave the best results with respect to shorter reaction time, higher yields and enantioselectivities. Thus, we have developed a more general, reproducible, robust and a non-Lewis acid catalyzed procedure for catalytic asymmetric allylation of imines under essentially neutral conditions.     

Pd(0)‐catalyzed polycondensation of methyl propargyl carbonate and bisphenols under stoichiometrically imbalanced conditions

We found that a novel Pd(0)‐catalyzed polycondensation of methyl propargyl carbonate ( 1 ) and bisphenol analogs 4 such as 4,4′‐dihydroxydiphenyl ether (4b ) proceeded successfully and gave polyethers 5 having exomethylene groups. The polycondensation was affected by the kind of bisphenol analogs used. The molar ratio of 1 and 4 also affected the polymerization behavior. Polyethers 5 with higher molecular weights were obtained by polymerization with 0.5 equiv of 4 toward 1 . The use of 1 equiv of 4 gave poor results. When 4,4′‐dihydroxybenzophenone ( 4d ) was employed as a nucleophile, benzenesulfonamide ( 13 ) was needed as an additive for obtaining the corresponding polyether with higher molecular weight. The Pd(0)‐catalyzed condensation of 1 and p‐hydroxyacetophenone was conducted as a model reaction. The desired compound and three by‐products were produced. Two of the by‐products were formed by reaction of 1 and methanol liberated from 1 . The other one appeared to be formed via hydrogenolysis. The formation of the by‐products suggested that some terminal reactions took place in the polycondensation of 1 and 4 . © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2250–2261, 2008     

The Synthesis of Lead-Free Ferroelectric Bi<Subscript>1/2</Subscript>Na<Subscript>1/2</Subscript>TiO<Subscript>3</Subscript> Thin Film by Solution-Sol–Gel Method

Bi_1/2Na_1/2TiO₃ (described as BNT) is considered as a promising lead-free ferroelectric material. In this study, BNT sol was synthesized by mixing bismuth oxide and sodium carbonate dissolved in nitric acid and titanium tetraisopropoxide in ethylene glycol, which was called a solution-sol–gel method and very cost-effective synthesis method, while very high-cost metal alkoxides are used as precursors in conventional sol–gel method. FT-IR and Raman analyses indicated that the chemical modification of titanium tetraisopropoxide by glycolic acid or oxalic acid occurred and the synthesis of stable BNT sol was possible. In the results of high temperature X-ray analysis and DTA/TG analyses, the crystallization of BNT was thought to occur at between 500 and 700C following the evaporation of solvent and organics and poly-condensation processes. The main crystal phase of the film was identified as rhombohedral crystal phase of Bi_1/2Na_1/2TiO₃ by XRD and Raman spectroscopy analyses, although a small amount of Bi₄Ti₃O₁₂ existed as a second phase.     

Synthesis of a Novel Chiral Ionic Liquid and Its Application in Enantioselective Aldol Reactions

A novel chiral ionic liquid, compound 1 , based on camphorsulfonic acid, was prepared. A catalytic amount of 1 readily promotes L ‐proline‐catalyzed aldol reactions, with good chemoselectivity, both in H₂O and in organic solvents. Further, the aldol reaction of cyclohexanone with 4‐nitrobenzaldehyde afforded 2‐[hydroxy(4‐nitrophenyl)methyl]cyclohexanone ( 6 ) in 98% yield with high enantioselectivity (94% ee) when large amounts of 1 (5 equiv.) were used as promoter.     

Asymmetric aldol additions: use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones.

Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidinone, oxazolidinethione, and thiazolidinethione propionates proceed with high diastereoselectivity for the Evans or non-Evans syn product depending on the nature and amount of the base used. With 1 equiv of titanium tetrachloride and 2 equiv of (-)-sparteine as the base or 1 equiv of (-)-sparteine and 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to > 99:1 were obtained for the Evans syn aldol products using N-propionyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adducts are available with the oxazolidinethione and thiazolidinethiones by altering the Lewis acid/amine base ratios. The change in facial selectivity in the aldol additions is proposed to be a result of switching of mechanistic pathways between chelated and nonchelated transition states. The auxiliaries can be reductively removed or cleaved by nucleophilic acyl substitution. Iterative aldol sequences with high diastereoselectivity can also be accomplished.     

A novel trinuclear titanium(IV) complex with a C3 axis along Ti1–Ti2–Ti3 containing 3-[(1H-1,2,4-triazol-1-yl)methyl]-BINOLate ligands: synthesis,structure, and reactivity

A new modified BINOL, (S)-3-[(1H-1,2,4-triazol-1-yl)methyl]-1,1′-binaphthol, was prepared. In the presence of titanium tetraisopropoxide, this ligand showed moderate catalytic properties for the asymmetric addition of diethylzinc to aldehydes. By treating rac-3-[(1H-1,2,4-triazol-1-yl)methyl]-1,1′-binaphthol with excess titanium tetraisopropoxide, a novel trinuclear titanium(IV) complex was obtained. A C₃ axis along Ti1–Ti2–Ti3 is present in the molecule.