Chiral salen complexes

Figure 6.14. Chiral salen complexes used in the asymmetric epoxidation of alkenes.[7]...

Recently, asymmetric NHK reactions have been investigated. Among them, catalytic versions of this reaction have been successful a Cr-chiral salen complex 127,226-228 a Cr-chiral sulfonylamide complex 128,229 a Cr-tridentate ligand 129 complex,230,231 and a Cr-chiral oxazoline ligand 130 complex232 were found to be effective to achieve good to high enantioselectivity (Scheme 57). 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

In the realm of hydrolytic reactions, Jacobsen has applied his work with chiral salen complexes to advantage for the kinetic resolution of racemic epoxides. For example, the cobalt salen catalyst 59 gave the chiral bromohydrin 61 in excellent ee (>99%) and good yield (74%) from the racemic bromo-epoxide 60. The higher than 50% yield, unusual for a kinetic resolution, is attributed to a bromide-induced dynamic equilibrium with the dibromo alcohol 62, which allows for conversion of unused substrate into the active enantiomer <99JA6086>. Even the recalcitrant 2,2-disubstituted epoxides e.g., 64) succumbed to smooth kinetic resolution upon treatment with... 

The purely siliceous MCM-41 and Ti-containing MCM-41 were synthesized by the solvent evaporation method. The chiral salens were immobilized step by step on the siliceous MCM-41 by the new grafting method using 3-aminopropyltrimethoxysilane and 2,6-diformyl-4-tert-butylphenol. The enantioselective diols could be synthesized directly from olefins using the hybrid catalysts of chiral salen complexes and Ti-MCM-41. 

Recently. Frunza et al.[15] have investigated the embedding of enantioselective homogeneous chiral Mn(III) cationic salen complexes into the pore of mesoporous MCM-41 materials. Very few asymmetric catalytic reactions have been examined using chiral salen complexes immobilized on MCM-41. 

For this study, the chiral salen complexes were synthesized and immobilized onto the MCM-41 by a new multi-grafting method according to the procedure as shown in Scheme 1. In addition, homogeneous symmetrical and unsymmetrical chiral salen complexes of similar structure to the immobilized ones were synthesized to compare the enantioselectivity in the reactions. 

Ti-MCM-41 could be synthesized within 4 hours with a high crystallinity by the evaporation method and the pore size could be controlled by addition of TMB in this work. The TEM image of Ti-MCM-41 which was obtained in the presence of TMB indicates the regular and expanding pore arrangements. The purely siliceous MCM-41 sample was also synthesized and used to immobilize the chiral salen complexes as in Scheme 1, which was synthesized without addition of Ti source by the same method as adopted for Ti-MCM-41 using a C22TMAC1 surfactant in methanol solvent without addition of TMB. 

The power of this methodology lies in the ability to prepare unnatural amino acid derivatives by asymmetric alkylation of prochiral enolates. Several asymmetric alkylations of the alanine derivative 7, catalysed by the C2-symmetrical quaternary ammonium salt 6d, have been reported these reactions yield unnatural amino acids such as 8 in high enantiomeric excess (Scheme 2) [7]. The chiral salen complex 9 has also been shown to be an effective catalyst for the preparation of a,a-dialkyl a-amino acids [8, 9]. For example, benzylation of the Schiff base 10 gave the a-methyl phenylalanine derivative 11 in 92% ee (Scheme 3) [8]. Similar reactions have been catalysed by the TADDOL 12, and also give a,a-dialkyl a-amino acids in good enantiomeric excess [10]. 

One of the most significant discoveries in asymmetric catalysis in the last 15 years was the importance of chiral metal salen catalysts. Chiral salen complexes exhibit high enantioselectivities in several mechanistically distinct reactions. As a result, they have been classified as privileged structures . ... 

Baleizao C, Garcia H. Chiral salen complexes an overview to recoverable and reuseable homogeneous and heterogeneous catalysts. Chem. Rev. 2006 106 3987-4043. 

The only known metal catalyst for the asymmetric catalytic Strecker reaction is the aluminum salen catalyst 465 (Sch. 65) recently reported by Sigman and Jacobsen [97]. They prepared 11 different chiral salen complexes from different transition and main group metals and screened these complexes for the addition of trimethylsilyl cyanide to imine 460 at room temperature. The aluminum catalyst 465 was optimum in terms both of asymmetric induction and rate. This constitutes the first aluminum salen complex successfully developed for an asymmetric catalytic reaction. 

This process (hetero Diels-Alder reaction leading to a dihydropyran system) may be also conducted in an asymmetric version application of chiral transition-metal catalysts based on BINOL, BDMAP, bisoxazolines, etc. provides adducts in very high optical purity (ee up to 99%) [1,6], In a series of papers Jurczak reported recently a highly enantioselective cycloaddition of 1-methoxy-1,3-butadiene and butyl glyoxylate catalyzed with chiral salen complexes [21],... 

The rigid, chiral salen complexes of Mn(III) shown below catalyze the asymmetric epox-idation of alkenes when treated with commercial bleach (NaOCl). This synthesis of enan-tio-enriched epoxides is particularly powerful since the method is applicable to unfunctionalized olefins. In general, (Z)-l,2-disubstituted alkenes afford higher enantioselectiv-ities than do the ( )-isomers or trisubstituted alkenes. The reaction mechanism is com-plex and proceeds via the formation of a Mn(III,IV) dinuclear species. ... 

The polymer-supported chiral salen complex 146 was also prepared by the condensahon reachon between (lS,2S)-l,2-cyclohexanediamine 144 and... 

Chiral Co(III)-salen complexes can also serve as efficient catalysts for HKR of terminal epoxides. Polymer-supported chiral salen complexes 156 were prepared from chiral Co complex 154 and ethylene glycol dimethacrylate 155, as shown in Scheme 3.45. The chemical reduction of 156, followed by treatment with acetic acid under aerobic conditions, produced the catalytically active polymer 157, which was used in the HKR of propylene oxide [87]. Some other examples of polymeric salen-Co complexes have also been reported for the same reaction [88, 89]. 

Substituted alkenes as well as terminal olefins and styrene derivatives are epoxidized in high yield and enantiomeric excess under homogeneous reaction conditions. Very recently, the first chiral salen complexes which are selectively soluble in perfluorinated solvents have been synthesized and their application in asymmetric synthesis has been investigated [39,40]. 

Katsuki chiral salen complex for the epoxidation of prochiral alkcncs. The state of the art can be summarized as follows. 

In addition, chiral salen complexes of Mn [59] and Cu [60] have been found to catalyze similar reactions with moderate enantioselectivities. In contrast to the salen complexes used in Mn-mediated epoxidation reaction, which use tetradentate complexes, the best results were obtained with bidentate ligands. Mechanistic work has implicated a metal-bound nitrene species in the reaction [61]. 

Scheme 3. Enantioselective opening of meso epoxides catalysed by chiral Salen complexes.

The importance to use optically pure isomers as pharmaceuticals, food additives, agrochemicals, (etc) is becoming more and more evident. The classical resolution still accounts for a large part of chiral production, however the asymmetric synthesis and the use of chiral separation system one becoming increasingly popular. The enantioseletive hydrolytic resolution of racemic epoxides was performed in the ZSM-5/MCM-41 membrane system containing chiral salen complexes. The chiral salen complexes immobilized on the membrane showed a very high enantioselectivity in the hydrolysis of epichlorohydrine, epoxybutane, styrene oxide and 1,2-epoxyhexane. 

Fallis lA, Murphy DM, Willock DJ et al (2004) Direct observation of enantiomer discrimination of epoxides by chiral salen complexes using ENDOR. J Am Chem Soc 126 15660-15661... 

Katsuki et al. reported the Claisen rearrangement of aryl cinnamyl ether 39 for the preparation of a chiral salen complex [39]. They noted that the addition of an equimolar amount of CaCOj is effective to minimize the para rearrangement. 

Titanium-catalyzed oxidations with 35% aqueous H2O2 using Schiff-base (salen) titanium 0x0 complexes as catalysts showed very high activity [28]. The oxidation of methyl phenyl sulfide required only 0.1mol% of catalyst. The use of chiral salen complexes gave low enantioselectivity (<20% ee). 

The attempts to achieve enantioselective synthesis of cycloadduct compounds by using a chiral Lewis acid associated with achiral cobaltoxime resulted in moderate Another approach is to replace the dimethylglyoxime ligand set by salen ligands. Cobalt(ii) salen complexes synthesized in achiral form showed good results in Diels-Alder reactivity. In the chiral salen complex, the corresponding optically active dienylcobalt complexes 189 have been obtained by the reaction of optically active cobalt(ll) salen complexes 188 with allenic compounds (Equation (28)). 

Enantioselective addition of various nucleophiles to carbonyl compounds has received significant attention in modem asymmetric synthesis. This objective has been accomplished with the aid of chiral organoaluminum complexes. Kee et al. examined organoaluminum-chiral salen complex 55 catalyzed addition of dialkylphosphites 56 to aldehydes, known as Pudovik reaction, to give a-hydroxyphosphonates 57 (Scheme 39) [70, 71]. 

The general term Salen-type is used in literature to describe the class of [O, N, N, O] tetradentate bis-Schiff base ligands. Some of the salen ligands 167,168 and 169 and their metal complexes are illustrated in Fig. 9.9. Commercial synthesis of chiral Salen complex 171, from chiral diamine salt 172 and salicylaldehyde derivative 173 is presented in Scheme 9.45 [83]. 

Komatsu synthesized the chiral salen complex 185 and demonstrated that aziridinations of various styrene derivatives proceeded enantioselectively in the presence of pyridine N-oxide (Equation 31) [145], Thus, treatment of... 

Jacobsen has developed a number of methods that employ chiral salen complexes as catalysts for enantioselective conjugate addition processes [166,167]. Notable among these is the addition of azide to substituted N-ben-zoyl imides as acceptors (Equation 44) [166]. The addition of HNj to imide 224 gave azide 226 in high yield (97 %) and optical purity (97 % ee). The subsequent reduction of the azide adducts to the corresponding amines provides convenient access to optically active j8-amino acids. 

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