Insight into the mechanism of the asymmetric addition of alkyl groups to aldehydes catalyzed by titanium-BINOLate species

The asymmetric addition of alkyl groups to aldehydes catalyzed by BINOLate-titanium complexes has become the testing grounds to evaluate the potential of new BINOL-based ligands. We have investigated the mechanism of this reaction and report our findings here. Model systems for the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)(3)](2), based on mono-oxygen-alkylated BINOL ligands have been examined. Comparison of the reactivity and enantioselectivity of the mono-alkyl BINOL derivatives with those of BINOL indicate that the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)(3)](2), is not active in the asymmetric addition reaction. Several BINOLate-titanium complexes have been synthesized and characterized by X-ray crystallography. These include the dinuclear (BINOLate)Ti(O-i-Pr)(2).Ti(O-i-Pr)(4), which contains a bridging naphtholate and isopropoxy group, trinuclear (BINOLate)Ti(O-i-Pr)(2).[Ti(O-i-Pr)(4)](2), and trimeric [(BINOL)Ti(O-i-Pr)(2)](3). The solid-state and solution structures reported here indicate that (BINOLate)Ti(O-i-Pr)(2) prefers to bind to titanium tetraisopropoxide rather than to itself, explaining why no nonlinear effects are observed in the catalytic reaction. Additionally, experimental evidence suggests that the BINOLate-titanium species responsible for the catalytic and stoichiometric asymmetric addition reactions are different, indicating that the proposed intermediate, (BINOLate)Ti(R)(aldehyde)(O-i-Pr), is not involved in either of these processes. Reactions were examined using different sources of the alkyl group [ZnMe(2) or MeTi(O-i-Pr)(3)]. Under similar conditions, it was found that the product ee's were the same, independent of whether ZnMe(2) or Me-Ti(O-i-Pr)(3) was used as the source of the alkyl groups. This indicates that the role of the dialkylzinc is not to add the alkyl group to the carbonyl but rather to transfer the alkyl group to titanium. On the basis of these results, we hypothesize that the intermediate in the asymmetric addition involves (BINOLate)Ti(O-i-Pr)(2)(aldehyde).MeTi(O-i-Pr)(3).     

Metal alkoxides as versatile precursors for group 4 phosphonates: synthesis and X-ray structure of a novel organosoluble zirconium phosphonate

Reactions of Ph2P(O)(OH) and t-BuP(O)(OSiMe3)(OH) with Ti(O-i-Pr)4 in equimolar ratios gave titanium phosphonates of the type [(O-i-Pr)3Ti(mu-O)2PR1R2]2 (1, R1 = R2 = Ph; 2, R1 = t-Bu, R2 = OSiMe3) as colorless crystalline solids in moderate yields. Reactions of Ph2P(O)(OH) and the isopropoxides of zirconium and hafnium resulted in products of the composition [(O-i-Pr)3M(mu-O-i-Pr)2(mu-OPOPh2)M(O-i-Pr)2]Ph2P(O)(OH) (M = Zr (3), Hf (4)) in high yields. The compounds were characterized by 1H, 31P, and 29Si NMR, infrared (IR), and mass spectroscopic (MS) techniques. The molecular structures of 2 and 3 were confirmed by X-ray crystallography.     

Asymmetric synthesis of allyl- and alpha-allenylamines from chiral imines and alkynes via (eta(2)-imine)Ti(O-i-Pr)2 complexes

[reaction: see text] The reaction of a divalent titanium reagent Ti(O-i-Pr)(4)/2i-PrMgX with optically active arylaldimines derived from arylaldehydes and O-methylphenylglycinol provided, in a highly diastereoselective manner, chiral (eta(2)-imine)Ti(O-i-Pr)(2) complexes, which in turn reacted with 1-alkynes or propargyl compounds to give optically active allyl- and alpha-allenylamines, respectively.     

Preparation of titanated alkoxyallenes from 3-alkoxy-2-propyn-1-yl carbonates and (eta(2)-Propene)Ti(O-i-Pr)(2) as an efficient ester homoaldol equivalent

3-Alkoxy-2-propyn-1-yl carbonates (2) react with a divalent titanium reagent (eta(2)-propene)Ti(O-i-Pr)(2) to afford titanated alkoxyallenes 1 which, in turn, react with aldehydes regiospecifically to provide the corresponding gamma-addition products in good to excellent yields, thus affording a convenient method for synthesizing gamma-hydroxy esters 3 and/or gamma-butyrolactones 4.     

Novel one-pot synthesis of 3-amino-1-alkenylphophonates by addition of imines to alkynylphosphonate titanium(II) complexes

[reaction: see text] A new method of synthesis of 3-amino-1-alkenylphosphonates is described. It involves the addition of imines to the alkynylphosphonate titanium(II) complexes 2, which are prepared in situ from 1-alkynylphosphonates and Ti(O-i-Pr)(4)/2 equiv of i-PrMgCl. Compounds 4a-i were obtained regio- and stereoselectivily in high yields.     

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.     

Efficient and practical method for synthesizing optically active indan-2-ols by the Ti(O-i-Pr)(4)/2 i-PrMgCl-mediated metalative Reppe reaction

An efficient and practical synthesis of optically active indan-2-ols 1 has been developed starting from readily accessible optically active 4-siloxy-1,6-alkadiynes 2 and ethynyl p-tolyl sulfone, where the metalative Reppe reaction mediated by an economical divalent titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, is a key step.     

Non-Cp titanium alkoxide-based homolytic ring-opening of epoxides by an intramolecular hydrogen abstraction in β-titanoxy radical intermediates

A low-valent titanium species derived in situ from Ti(O-i-Pr)(4), Me(3)SiCl and Mg powder in tetrahydrofuran reacted with epoxides to selectively provide less hindered alcohols via a homolytic ring-opening of epoxides, in which the intermediate β-titanoxy radical intramolecularly abstracted a hydrogen atom from an alkoxy moiety in the titanium complexes.     

(RO)(2)Ta[tris(2-oxy-3,5-dimethylbenzyl)amine]: structure and lactide polymerization activities

The novel atrane-like six-coordinate (RO)(2)TaL complexes [where R = Me or Et and L = tris(2-oxy-3,5-dimethylbenzyl)amine] containing three six-membered rings have been synthesized and characterized. The R = Me complex is the first group 5 representative of this class of compounds structurally characterized by X-ray means. Somewhat surprisingly, these compounds failed to function as single-site initiators for the polymerization of l-LA to isotactic PLA and rac-LA to atactic PLA, whereas Ta(OEt)(5) and two titanium analogues ROTiL (where R = 2,6-di-i-PrC(6)H(3) and i-Pr) as well as Ti(O-i-Pr)(4) were effective catalysts for both polymerizations.     

Application of n-Bu4NHF2 as a fluorinating agent for the preparation of fluoroanions: synthesis and crystal structure of the anions [t-BuPO3AlF2]2(2-), [PhPO3AlF2]2(2-), and [(O-i-Pr)3Ti(mu-F)2(mu-O-i-Pr)Ti(O-i-Pr)3]-

The first phosphonate anions of aluminum-containing fluorine and an anionic bridged fluoroalkoxy derivative of titanium have been realized using n-Bu4NHF2 as a fluorinating agent in organometallic synthesis. Reactions of [RPO3AlMe]4 [R = Ph (1), t-Bu] with n-Bu4NHF2 yield organic-soluble compounds of the type [n-Bu4N]2[RPO3AlF2]2 [R = Ph (2), t-Bu (3)], whereas the reaction of Ti(O-i-Pr)4 with n-Bu4NHF2 results in the formation of [n-Bu4N][O-i-Pr)3Ti(mu-F)2(mu-O-i-Pr)Ti(O-i-Pr)3] (4). These compounds have been obtained in high yields and have been adequately characterized through spectroscopic techniques and X-ray diffraction studies.     

pH-dependent isolations and spectroscopic, structural, and thermal studies of titanium citrate complexes

Titanium(IV) citrate complexes (NH(4))(2)[Ti(H(2)cit)(3)].3H(2)O (1), (NH(4))(5)[Fe(H(2)O)(6)][Ti(H(2)cit)(3)(Hcit)(3)Ti].3H(2)O (2), Ba(2)[Ti(H(2)cit)(Hcit)(2)].8H(2)O (3), and Ba(3)(NH(4))(7)[Ti(cit)(3)H(3)(cit)(3)Ti].15H(2)O (4) (H(4)cit = citric acid) were isolated in pure form from the solutions of titanium(IV) citrate with various countercations. The isolated complexes were characterized by elemental analyses, IR spectra, and (1)H NMR and (13)C NMR spectra. The formation of titanium(IV) citrate complexes depends mainly on the pH of the solutions, that is, pH 1.0-2.8 for the formation of ammonium titanium(IV) citrate 1, pH 2.5-3.5 for ammonium iron titanium(IV) citrate 2, pH 2.8-4.0 for dibarium titanium(IV) citrate 3, and pH 5.0-6.0 for ammonium barium titanium(IV) citrate 4. X-ray structural analyses revealed that complexes 2-4 featured three different protonated forms of bidentate citrate anions that chelate to the titanium(IV) atom through their negatively charged alpha-alkoxyl and alpha-carboxyl oxygen atoms. This is consistent with the large downfield shifts of the (13)C NMR spectra for the carbon atoms bearing the alpha-alkoxyl and alpha-carboxyl groups. The typical coordination modes of the barium atoms in complexes 3 and 4 are six-coordinated, with three alpha-alkoxyl groups and three beta-carboxyl groups of citrate ions. The strong hydrogen bonding between the beta-carboxylic acid and the beta-carboxyl groups [2.634(8) A for complex 2, 2.464(7) A for complex 3, and 2.467(7) A for complex 4] may be the key factor for the stabilization of the citrate complexes. The decomposition of complex 3 results in the formation of a pure dibarium titanate phase and 4 for the mixed phases of dibarium titanate and barium titanate at 1000 degrees C.     

Ti(O-i-Pr)4/Me3SiCl/Mg-mediated reductive cleavage of sulfonamides and sulfonates to amines and alcohols

A low-valent titanium generated in situ from Ti(O-i-Pr)(4), Me(3)SiCl, and Mg powder in THF reacted with aryl- and alkyl-sulfonamides of aryl and alkyl amines in a reductive N-S/S-O/S-C bond cleaving pathway to provide the corresponding amines and hydrocarbons (and thiols) derived from the sulfonyl moiety. The reagent could also cleave sulfonates to the corresponding alcohols.     

Cyclopropyl alkynes as mechanistic probes to distinguish between vinyl radical and ionic intermediates

[reaction: see text] The reactions of (trans-2-phenylcyclopropyl)ethyne, 1a, (trans,trans-2-methoxy-3-phenylcyclopropyl)ethyne, 1b, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1c, with either aqueous sulfuric acid or tris(trimethylsilyl)silane (or tributyltin hydride) and AIBN have been investigated. Protonation and addition of the silyl (or stannyl) radical occurred at the terminal position of the alkyne giving an alpha-cyclopropyl-substituted vinyl cation or radical, respectively. Under both reaction conditions, 1a yielded products derived from ring opening toward the phenyl substituent. Alkynes 1b and 1c, however, gave different products depending on whether radical or cationic conditions were used. When radical conditions were employed, products derived from regioselective ring opening toward the phenyl substituent were obtained. In contrast, when cationic conditions were employed, products derived from selective ring opening toward the methoxy substituent were isolated. The corresponding alpha-cyclopropyl-substituted vinyllithium derivatives were also synthesized and were found to be stable toward rearrangement. An estimate of the rate constants for ring opening of the alpha-cyclopropylvinyl cations was also made: values of 10(10)-10(12) s(-1) were found for the vinyl cations derived from protonation of the terminal carbon of alkynes 1a-c. Based on these results, cyclopropyl alkynes 1a-c can be classified as hypersensitive mechanistic probes for the detection of vinyl radical or cationic intermediates generated adjacent to the cyclopropyl ring and, in the case of 1b and 1c, the distinction between a radical or cationic intermediate is possible.     

Intramolecular Nucleophilic Acyl Substitution Reaction of 3,4-Alkadienyl Carbonates Mediated by Ti(O-i-Pr)(4)/2 i-PrMgCl Reagent. Efficient Synthesis of Optically Active beta,gamma-Unsaturated Esters with an alpha-Substituent

Treatment of 3,4-alkadienyl carbonates 2a-i with a low-valent titanium reagent diisopropoxy(eta(2)-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)(4) with 2 i-PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford vinyltitanium compounds 3 which, in turn, reacted with H(3)O(+), D(2)O, or iodine to give alpha-substituted beta,gamma-unsaturated esters 4 in good to excellent yields. The olefin moiety of the hydrolysis product 4 has (Z)-geometry mainly except for 4h. Starting from chiral 2f or 2g, the reaction proceeded stereospecifically to give optically active alpha-substituted beta,gamma-unsaturated ester 4f or 4g having (Z)-olefin geometry exclusively.     

Instantaneous room-temperature and highly enantioselective ArTi(O-i-Pr)3 additions to aldehydes

Direct asymmetric additions of ArTi(O-i-Pr)(3) to aldehydes catalyzed by a titanium catalyst of (R)-H(8)-BINOL are reported. The reactions proceed instantaneously at room temperature, affording alcohols in ≥90% ee. Importantly, the ArTi(O-i-Pr)(3) reagent differentiates the ligand effectiveness in an order of H(8)-BINOL > BINOL > TADDOL > diol 3 > disulfonamide 2.     

Tetravalent titanium, zirconium, and cerium oxo and peroxo complexes containing an imidodiphosphinate ligand

Dinuclear Ti(IV), Zr(IV), and Ce(IV) oxo and peroxo complexes containing the imidodiphosphinate ligand [N(i-Pr(2)PO)(2)](-) have been synthesized and structurally characterized. Treatment of Ti(O-i-Pr)(2)Cl(2) with KN(i-Pr(2)PO)(2) afforded the Ti(IV) di-μ-oxo complex [Ti{N(i-Pr(2)PO)(2)}(2)](2)(μ-O)(2) (1) that reacted with 35% H(2)O(2) to give the peroxo complex Ti[N(i-Pr(2)PO)(2)](2)(η(2)-O(2)) (2). Treatment of HN(i-Pr(2)PO)(2) with Zr(O-t-Bu)(4) and Ce(2)(O-i-Pr)(8)(i-PrOH)(2) afforded the di-μ-peroxo-bridged dimers [M{N(i-Pr(2)PO)(2)}(2)](2)(μ-O(2))(2) [M = Zr (3), Ce (4)]. 4 was also obtained from the reaction of Ce[N(i-Pr(2)PO)(2)](3) with 35% H(2)O(2). Treatment of (Et(4)N)(2)[CeCl(6)] with 3 equiv of KN(i-Pr(2)PO)(2) afforded Ce[N(i-Pr(2)PO)(2)](3)Cl (5). Reaction of (Et(4)N)(2)[CeCl(6)] with 2 equiv of KN(i-Pr(2)PO)(2) in acetonitrile, followed by treatment with Ag(2)O, afforded the μ-oxo-bridged complex [Ce{N(i-Pr(2)PO)(2)}Cl](2)[μ-N(i-Pr(2)PO)(2)](2)(μ-O) (6). 6 undergoes ligand redistribution in CH(2)Cl(2) in air to give 5. The solid-state structures of [K(2){N(i-Pr(2)PO)(2)}(2)(H(2)O)(8)](n) and complexes 1-6 have been determined.     

Terminal titanium-ligand multiple bonds. Cleavages of C=O and C=S double bonds with Ti imido complexes

Treatment of (t-)BuN=TiCl(2)Py(3) with 2 equiv lithium ketiminate compound, Li[OCMeCHCMeN(Ar)] (where Ar = 2,6-diisopropylphenyl), in toluene at room temperature gave (t-)BuN=Ti[OCMeCHCMeN(Ar)](2) (1) in high yield. The reaction of 1 with phenyl isocyanate at room-temperature resulted in imido ligand exchange producing PhN=Ti[OCMeCHCMeN(Ar)](2) (2). Compound 1 decomposed at 90 degrees C to form a terminal titanium oxo compound O=Ti[OCMeCHCMeN(Ar)](2) (3) and (t-)BuNHCMeCHCMeNAr (4). Also, the compound 3 could be obtained by reacting 1 with CO(2) under mild condition. Similarly, while 1 reacts with an excess of carbon disulfide, a novel terminal titanium sulfido compound S=Ti[OCMeCHCMeN(Ar)](2) (5) was formed via a C=S bond breaking reaction. A novel titanium isocyanate compound Ti[OCMeCHCMeN(Ar)](2)(NCO)(OEt) (6) was formed on heating 1 with 1 equiv of urethane, H(2)NCOOEt. Compounds 1-6 have been characterized by (1)H and (13)C NMR spectroscopies. The molecular structures of 1, 3, 5, and 6 were determined by single-crystal X-ray diffraction. A theoretical calculation predicted that the cleavage of the C-S double bonds for carbon disulfide with the Ti=N bond of compound 1 was estimated at ca. 21.8 kcal.mol(-1) exothermic.     

Trans ruthenium(II) complexes with NH-bridged tetradentate symmetric and asymmetric polypyridyl ligands

NH-Bridged tetradentate ligands were synthesized to achieve stable trans Ru(II) bis(polypyridyl) complexes. The polypyridyl part of the ligand was either symmetric, as in N,N-bis(1,10-phenanthroline-2-yl)amine (phen-NH-phen), or asymmetric, as in N-(1,10-phenanthroline-2-yl)-N-(6-yl-dipyridyl[2,3-a:2',3'-c]phenazine)amine (dppz-NH-phen). Protonation of phen-NH-phen with trifluoroacetic acid and the subsequent reaction with RuCl3 yield trans-[Ru(phen-NH-phen)Cl2]. The chloro ligands in this compound can easily be replaced by stronger ligands, such as CH3CN and DMSO. In this way, complexes trans-[Ru(phen-NH-phen)(CH3CN)(DMSO)](PF6)2 (1), trans-[Ru(phen-NH-phen)(DMSO)2](PF6)2 (2), and trans-[Ru(phen-NH-phen)(CH3CN)2](PF6)2 (3) were obtained. X-ray structures were determined for 1 and 3. Following a procedure similar to that used with phen-NH-phen, the complex trans-[Ru(dppz-NH-phen)(CH3CN)2](PF6)2 (4) was obtained. To our knowledge, this is the first reported trans ruthenium(II) bis(polypyridyl) complex with two different polypyridyl ligands in the equatorial plane.     

Iron-mediated preparation of vinylcyclopropanecarboxylates: scope,mechanism, and applications

The addition of stabilized carbon nucleophiles to tricarbonyl(1-methoxycarbonylpentadienyl)iron(1+) cation (1a) proceeds via attack at C2 on the face of the ligand opposite the Fe(CO)(3) group to generate tricarbonyl(pentenediyl)iron complexes 2. Oxidation of complexes 2 affords vinylcyclopropanecarboxylates in good yield. In general, the relative stereochemistry about the cyclopropane ring reflects reductive elimination with retention of configuration. In cases where the C2 substituent is bulky (i.e., 2b) the major cyclopropane product 9b represents ring closure with inversion at C3. A mechanism involving pi-sigma-pi rearrangement of the initially oxidized (pentenediyl)iron species is proposed to account for these results. Experiments which probe the stereochemistry of deuterium labeling in the vinyl group of the vinylcyclopropanecarboxylate products were carried out, and these results are consistent with the proposed mechanism. This methodology for the preparation of vinylcyclopropanecarboxylates was applied to the synthesis of 2-(2'-carboxycyclopropyl)glycines (+)-22 and (-)-23 and the cyclopropane triester (-)-26.     

Heterobimetallic Bi(III)-Ti(IV) coordination complexes: synthesis and solid-state structures of BiTi4(sal)6(mu-OiPr)3(OiPr)4, and the cyclic isomers Bi4Ti4(sal)10(mu-OiPr)4(OiPr)4 and Bi8Ti8(sal)20(mu-OiPr)8(OiPr)8

The reaction of a 1:2 mixture of bismuth(III) salicylate with titanium(IV) isopropoxide in refluxing toluene has been investigated and found to proceed with ligand exchange to produce the new heterobimetallic complexes BiTi(4)(sal)(6)(mu-O(i)Pr)(3)(O(i)Pr)(4) (1), Bi(4)Ti(4)(sal)(10)(mu-O(i)Pr)(4)(O(i)Pr)(4) (2), and Bi(8)Ti(8)(sal)(20)(mu-O(i)Pr)(8)(O(i)Pr)(8) (3). Complex 1 is the major product, while 2 and 3 were identified as minor products from the reaction. Compound 1 is produced pure and in high yield by employing stoichiometric amounts of reagents; its crystal structure consists of a [Ti(4)(sal)(6)(O(i)Pr)(7)](3)(-) ion capped by a Bi(3+) ion. Complexes 2 and 3 exhibit cyclic ring structures of bismuth and titanium atoms showing crystallographically imposed inversion symmetry. Both structures occlude large quantities of lattice solvent. The compositional and structural parameters from the single crystal studies indicate that complexes 2 and 3 may represent sequential steps in a ligand exchange process between the two metal species, while the reactivity patterns that were observed provide clues about the solution state structure of bismuth(III) salicylate itself. The 2D COSY (1)H NMR spectrum of 1 indicates retention of the asymmetric structure in solution as evidenced by the presence of 14 diastereotopic isopropoxide methyl resonances.