Synthesis of salan (salalen) ligands derived from binaphthol for titanium-catalyzed asymmetric epoxidation of olefins with aqueous H2O2

A series of chiral salan (salalen) ligands, easily prepared from the aldehyde derived from chiral binaphthol, are effective ligands for the titanium-catalyzed asymmetric epoxidation of olefins with aqueous H₂O₂ as the oxidant. One of the titanium–salan complexes was determined by X-ray crystallography.     

Asymmetric catalysis of metal complexes with non-planar ONNO ligands: salen, salalen and salan

Chiral metal (M)-salen complexes are one of the most versatile asymmetric catalysts and the catalysis of trans-M(salen) complexes has been well cultivated. On the other hand, non-planar cis-beta M(salen) complexes were recently found to show unique asymmetric catalysis that cannot be attained by trans-M(salen) complexes. Moreover, related non-planar M(salalen) and M(salan) complexes were also found to exert unprecedented asymmetric catalysis. This Feature Article summarizes the seminal studies on asymmetric catalysis of non-planar M(ONNO) complexes, full utilization of which will provide marked improvement in asymmetric synthesis.     

Iron(II) complexes with tetradentate bis(aminophenolate) ligands: synthesis and characterization, solution behavior, and reactivity with O(2)

Tetradentate bis(aminophenolate) ligands H(2)salan(X) and H(2)bapen(X) (where X refers to the para-phenolate substituent = H, Me, F, Cl) react with [Fe{N(SiMe(3))(2)}(2)] to form iron(II) complexes, which in the presence of suitable donor ligands L (L = pyridine or THF) can be isolated as the complexes [Fe(salan(X))(L)(2)] and [Fe(bapen(X))(L)(2)]. In the absence of donor ligands, either mononuclear complexes, for example, [Fe(salan(tBu,tBu))], or dinuclear complexes of the type [Fe(salan(X))](2) are obtained. The dynamic coordination behavior in solution of the complexes [Fe(salan(F))(L)(2)] and [Fe(bapen(F))(L)(2)] has been investigated by VT (1)H and (19)F NMR spectroscopy, which has revealed equilibria between isomers with different ligand coordination topologies cis-α, cis-β and trans. Exposure of the iron(II) salan(X) complexes to O(2) results in the formation of oxo-bridged iron(III) complexes of the type [{Fe(salan(X))}(2)(μ-O)] or [{Fe(salan(X))(L)}(2)(μ-O)]. The lack of catalytic activity of the iron(II) salan and bapen complexes in the oxidation of cyclohexane with H(2)O(2) as the oxidant is attributed to the rapid formation of stable and catalytically inactive oxo-bridged iron(III) complexes.     

Copper(II)‐Catalyzed Nitroaldol (Henry) Reactions: Recent Developments

Self‐assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2‐symmetric N,N′‐substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Brønsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives.     

Enantioselective fluorescent recognition of mandelic acid by unsymmetrical salalen and salan sensors

As sensors with multiple chiral centers, salalen 1 and salan 2 composed of trans-cyclohexane-1,2-diamine (trans-DACH) and 1,1'-bi-2-naphthol (BINOL) units were designed and synthesized. Fluorescent recognition studies of resulting sensors towards mandelic acid (MA) reveal that salan 2a containing (R)-BINOL and (R,R)-DACH exhibits highly sensitive and enantioselective response towards MA. The relationship between the chirality combination and the enantioselectivity is discussed. Based on the studies of concentration and solvent effect on the recognition process of 2a, it was found that the sensitivity and enantioselectivity could be enhanced via changing the concentration of sensors or altering the polarity of solvents. To explain why higher enantioselectivity can be achieved in moderate polar solvent other than in nonpolar or polar solvent, a solvent-guest competition mechanism, which may shed a light on the enhancement of the enantioselectivity of chiral recognition and noncovalent asymmetric catalysis, has been proposed and validated.     

Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by Salan–Aluminum Catalysts

Alkyl aluminum complexes of chiral salan ligands assembled around the 2,2′‐bipyrrolidine core form as single diastereomers that have identical configurations of the N donors. Active catalysts for the polymerization of lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange between enantiomorphous aluminum species had a dramatic effect on the tacticity of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac‐LA): The enantiomerically pure catalyst of the nonsubstituted salan ligand led to isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The enantiomerically pure catalyst of the chloro‐substituted salan ligand led to PLA with a slight tendency toward heterotacticity, whereas the racemic catalyst led to PLA of almost perfect heterotacticity following an insertion/auto‐inhibition/exchange mechanism.     

Redox-active tetrahydrosalen (salan) complexes of titanium

A diarylamino-substituted N-methyl tetrahydrosalen (salan) ligand, (An2N)LH(2), is prepared in four steps and overall 53% yield from 5-bromosalicylaldehyde, with the key step a palladium-catalysed Hartwig-Buchwald amination of the tert-butyldimethylsilyl-protected 5-bromo-N-methylsalan ligand. Reaction of (An2N)LH(2) or its bromo analogue with Ti(O(i)Pr)(4) or TiF(4) results in metalation of the ligand. The isopropoxide groups are readily exchanged with α- or β-hydroxyacids to form chelated complexes. X-ray crystallography and NMR spectroscopy indicate that the salan ligands are quite flexible, with (An2N)LTiF(2), for example, showing four stereoisomers in its (19)F NMR spectrum. The major stereoisomer of (salan)Ti(X)(Y) depends principally on the trans influence of the X and Y groups. Complexes of (An2N)L show two reversible, closely spaced redox couples at approximately + 0.1 V vs. ferrocene/ferrocenium, and a second set of two closely spaced redox couples at ~ + 0.8 V vs. Fc/Fc(+).     

Titanium Salan/Salalen Complexes: The Twofaced Janus of Asymmetric Oxidation Catalysis

Optically pure chiral epoxides and sulfoxides are ubiquitous building blocks in fine organic synthesis, employed in the pharmaceutical, agrochemical, and cosmetic industries. On the road to chiral epoxides and sulfoxides, efficient and stereoselective transition metal‐based catalysts are the most promising guides. Among transition metals, we favor titanium for its cheapness and availability, nontoxicity, and well‐known ability to catalyze a variety of stereoselective transformations, including oxidations with environmentally benign H₂O₂. In this personal account, we summarize the state‐of‐the‐art of rational design of chiral titanium(IV) salan and salalen catalysts, and investigations of their catalytic reactivities and stereoselectivities in the epoxidations of olefins and oxidations of thioethers, unraveling the peculiarities and mechanisms of their catalytic action.     

Unexpected influence of stereochemistry on the cytotoxicity of highly efficient Ti(IV) salan complexes: new mechanistic insights

The effect of stereochemistry on the cytotoxicity of highly active and hydrolytically stable N-methylated Ti(IV) salan complexes is reported. Four bis(isopropoxo) complexes incorporating N-methylated salan ligands with different aromatic substitution patterns have been prepared in racemic and optically active forms for the first time by ligand-to-metal chiral induction from trans-diaminocyclohexyl-based chiral ligands. The configuration of the metal center that derives from that of the ligand has an enormous influence on cytotoxicity, with the racemic mixture mostly being more active than the single enantiomers that are of either similar or different activity. This implies that the active species is a salan-bound heterochiral polynuclear compound, interacting with a chiral target. Four additional complexes of achiral salan and chiral labile sec-butoxo ligands, analyzed as racemic and as homochiral, revealed no influence of stereochemistry, supporting early dissociation of the labile ligands to give the polynuclear products.     

Salalen aluminium complexes and their exploitation for the ring opening polymerisation of rac-lactide

In this paper we report the first use of Al(III) salalen complexes for the ring opening polymerisation of rac-lactide. Polylactides with narrow polydispersities (PDIs range from 1.04-1.65) and moderate degrees of stereoselectivity were formed. Eight salalen Al(III) complexes have been prepared and fully characterised by solution-state NMR spectroscopy and, where appropriate, single crystal X-ray diffraction. With ligand 3H(2) either a monomeric or dimeric Al(III) species was formed, the dimeric species was favoured at low concentrations. The complexes were tested for the ring opening polymerisation of rac-lactide in toluene at 80 or 100 °C. Interestingly, various tacticities of polymer were formed, which were dependent upon the nature of the group bound to the amine nitrogen centre.     

Highly cytotoxic vanadium(V) complexes of salan ligands; insights on the role of hydrolysis

Vanadium(V) oxo complexes with tetradentate diamine bis(phenolato) "salan" ligands of the type LVO(OiPr) (L is salan) with different steric and electronic substitutions at the ortho and para positions to the binding phenolato moiety were synthesized and their hydrolytic stability and cytotoxicity were analyzed. With one exception bearing large steric groups, all complexes examined displayed marked cytotoxic activity, comparable to, and often higher than, that of cisplatin. While the hydrolytic stability changed significantly depending on the substituent at the ortho position relative the O-donor with little effect of para substitutions, the cytotoxic activity largely was not affected, and high cytotoxicity was recorded also for relatively unstable complexes. Additional measurements revealed that the cytotoxicity is largely maintained following pre-incubation of up to 18 hours of the complexes in the biological medium prior to cell addition, suggesting that hydrolysis products might serve as the active species. In addition, appreciable cytotoxic activity was measured for an isolated hydrolysis product that was analyzed crystallographically to exhibit a dimeric structure with bridging oxo ligand where both metal centers are bound to the salan ligand, supporting the aforementioned conclusions.     

Encapsulation of chiral Fe(salan) in nanocages with different microenvironments for asymmetric sulfide oxidation

The solid catalysts for asymmetric oxidation of sulfides were prepared by encapsulating a chiral iron salan complex [Fe(salan)] in the nanocages of mesoporous silicas. The microenvironment of nanocages was finely tuned using silylation reagents with different kinds of organic groups, such as propyl (C3), 1-butyl-3-propyl-4,5-dihydroimidazolium bromide (ILBr), N-propyl-N,N,N-tri-n-butylammonium chloride (TBNCl) and N-propyl-N,N,N-tri-n-butylammonium bromide (TBNBr), and investigated by water and benzene adsorption. Fe(salan) encapsulated in the amphiphilic nanocage shows much higher enantioselectivity and activity than that in hydrophobic or hydrophilic nanocage for the asymmetric oxidation of thioanisole using H(2)O(2) as oxidant. The TOF of Fe(salan) encapsulated in the nanocage modified with TBNBr can reach as high as 220 h(-1), even higher than homogeneous Fe(salan) with a TOF of 112 h(-1). The enhanced catalytic activity is mainly due to the fast diffusion of H(2)O(2) and sulfide in the amphiphilic nanocage. The above results suggest that the microenvironment modification of the nanocage is an efficient method to synthesize highly efficient solid catalysts for asymmetric catalysis.     

Titanium–salan‐catalyzed asymmetric sulfoxidations with H2O2: design of more versatile catalysts

Titanium–salan complexes with 3,3’‐diphenyl substituents in the salicylidene rings of the salan ligand are efficient sulfoxidation catalysts, capable of catalyzing the asymmetric oxidation of bulky aryl benzyl sulfides with H₂O₂ with good to high enantioselectivities. In this paper, substituent effects on titanium‐salan‐catalyzed enantioselective oxidation of sulfides to sulfoxides have been systematically investigated. Titanium–salan catalysts with halogen substituents at the 5,5’‐positions (3,3’‐H₂dihydrogen substituted) have been found to catalyze the oxidation of both bulky aryl benzyl sulfides and small alkyl phenyl sulfides with good to high enantioselectivities. Kinetic data witness a direct attack of the sulfide to the electrophilic active oxygen species; a consistent reaction mechanism is proposed. Copyright © 2013 John Wiley & Sons, Ltd.     

Asymmetric cyanohydrin synthesis using an aluminium(salan) complex

The asymmetric addition of trimethylsilyl cyanide to aldehydes catalysed by chiral metal(salan) complexes has been investigated. Salan complexes of titanium and vanadium displayed only low catalytic activity, but a bimetallic aluminium(salan) complex gave high levels of catalytic activity and reasonable asymmetric induction when used with triphenylphosphine oxide as a cocatalyst. Mechanistic studies showed that the reactions were first order in catalyst and aldehyde concentrations, but zero order in trimethylsilyl cyanide and triphenylphosphine oxide concentrations. A Hammett analysis indicated that there was no significant change in the electron density at the aldehyde benzylic position during the rate determining step of the catalytic cycle. On the basis of the kinetic data, a catalytic cycle is proposed which accounts for the differences observed between [Al(salen)]₂O and [Al(salan)]₂O based catalysts.     

pi-Bonding in complexes of benzannulated biscarbenes, -germylenes, and -stannylenes: an experimental and theoretical study

Benzannulated bisstannylenes, exhibiting a CH(2)C(CH(3))(2)CH(2) linking unit and CH(2)tBu (1) or CH(2)CH(2)CH(2)NMe(2) (2) N-substituents, and their molybdenum tetacarbonyl complexes 3 and 4 have been prepared. The complexes 3 and 4 exhibit remarkably short Mo-E bond lengths compared to the related biscarbene and bisgermylene complexes. The experimentally determined bonding parameters of the molybdenum bisstannylene complexes are discussed based on DFT calculations.     

Phosphine-catalyzed nitroaldol reactions

Trialkyl phosphines and electron-rich triaryl phosphines are excellent catalysts for the nitroaldol (Henry) reaction. Aryl and alkyl aldehydes participate well in the reaction with nitromethane providing good yields of product. Care should be exercised in the use of phosphine-metal complexes as catalysts for the nitroaldol reaction, as the phosphine can alone function as the catalyst.     

Major impact of N-methylation on cytotoxicity and hydrolysis of salan Ti(IV) complexes: sterics and electronics are intertwined

A series of Ti(IV) complexes containing diamino bis(phenolato) "salan" type ligands with NH coordination were prepared, and their hydrolysis and cytotoxicity were analyzed and compared to the N-methylated analogues. Substituting methyl groups on the coordinative nitrogen donor of highly active and stable Ti(IV) salan complexes with H atoms has two main consequences: the hydrolysis rate increases and the cytotoxic activity diminishes. In addition, the small modification of a single replacement of Me with H leads to a different major hydrolysis product, where a dinuclear Ti(IV) complex with two bridging oxo ligands is obtained, as characterized by X-ray crystallography, rather than a trinuclear cluster. A partial hydrolysis product containing a single oxo bridge was also crystallographically analyzed. Investigation of a series of complexes with NH donors of different steric and electronic effects revealed that cytotoxicity may be restored by fine tuning these parameters even for complexes of low stability.     

The first asymmetric addition of organogallium to aldehydes catalyzed by chiral titanium catalysts

The addition of organogallium to aldehydes was realized with titanium tetrachloride as a Lewis acid catalyst. For the first time, the catalytic asymmetric addition of organogallium to aldehydes was investigated with chiral titanium complexes, which were formed from titanium tetrachloride and salan ligands, with mediocre to good chemical yields and enantioselectivities.     

Ligand effects on hydrogen atom transfer from hydrocarbons to three-coordinate iron imides

A new β-diketiminate ligand with 2,4,6-tri(phenyl)phenyl N-substituents provides protective bulk around the metal without exposing any weak C-H bonds. This ligand improves the stability of reactive iron(III) imido complexes with Fe═NAd and Fe═NMes functional groups (Ad = 1-adamantyl; Mes = mesityl). The new ligand gives iron(III) imido complexes that are significantly more reactive toward 1,4-cyclohexadiene than the previously reported 2,6-diisopropylphenyl diketiminate variants. Analysis of X-ray crystal structures implicates Fe═N-C bending, a longer Fe═N bond, and greater access to the metal as potential reasons for the increase in C-H bond activation rates.     

Utilization of organogallium and organoindium compounds as alkylation reagents in organic synthesis: the addition of trialkylgallium and trialkylindium to aldehydes catalyzed by Lewis acids

The utilization of organogallium and organoindium compounds as alkylation reagents to aldehydes was realized with titanium tetrachloride as the strong Lewis acid catalyst. Furthermore, the catalytic asymmetric addition of organogallium to aldehydes was investigated with chiral titanium complexes, which were formed from titanium tetrachloride and salan ligands, with mediocre to good chemical yields and enantioselectivities. Copyright © 2005 John Wiley & Sons, Ltd.