Racemization metal complexes

Among the J ,J -DBFOX/Ph-transition(II) metal complex catalysts examined in nitrone cydoadditions, the anhydrous J ,J -DBFOX/Ph complex catalyst prepared from Ni(C104)2 or Fe(C104)2 provided equally excellent results. For example, in the presence of 10 mol% of the anhydrous nickel(II) complex catalyst R,R-DBFOX/Ph-Ni(C104)2, which was prepared in-situ from J ,J -DBFOX/Ph ligand, NiBr2, and 2 equimolar amounts of AgC104 in dichloromethane, the reaction of 3-crotonoyl-2-oxazolidinone with N-benzylidenemethylamine N-oxide at room temperature produced the 3,4-trans-isoxazolidine (63% yield) in near perfect endo selectivity (endo/exo=99 l) and enantioselectivity in favor for the 3S,4J ,5S enantiomer (>99% ee for the endo isomer. Scheme 7.21). The copper(II) perchlorate complex showed no catalytic activity, however, whereas the ytterbium(III) triflate complex led to the formation of racemic cycloadducts. 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

Figure 4.5 Simplified mechanism of the racemization of sec-alcohols catalyzed by transition metal complexes.

The racemization mechanism of sec-alcohols has been widely studied [16,17]. Metal complexes of the main groups of the periodic table react through a direct transfer of hydrogen (concerted process), such as aluminum complexes in Meerwein-Ponn-dorf-Verley-Oppenauer reaction. However, racemization catalyzed by transition metal complexes occurs via hydrogen transfer processes through metal hydrides or metal dihydrides intermediates (Figure 4.5) [18]. 

In general the metal complexes are charged. It is thus possible to convert the racemic mixture of such a complex into a pair of diastereoisomeric species with different physico-chemical properties, in particular solubihty, by association with an enantiomerically pure chiral coimterion [19]. Examples of frequently used such ions are shown in Fig. 3. Then the separation can be achieved by ... 

Molecules having only a sulfoxide function and no other acidic or basic site have been resolved through the intermediacy of metal complex formation. In 1934 Backer and Keuning resolved the cobalt complex of sulfoxide 5 using d-camphorsulfonic acid. More recently Cope and Caress applied the same technique to the resolution of ethyl p-tolyl sulfoxide (6). Sulfoxide 6 and optically active 1-phenylethylamine were used to form diastereomeric complexes i.e., (-1-)- and ( —)-trans-dichloro(ethyl p-tolyl sulfoxide) (1-phenylethylamine) platinum(II). Both enantiomers of 6 were obtained in optically pure form. Diastereomeric platinum complexes formed from racemic methyl phenyl (and three para-substituted phenyl) sulfoxides and d-N, N-dimethyl phenylglycine have been separated chromatographically on an analytical column L A nonaromatic example, cyclohexyl methyl sulfoxide, did not resolve. 

The cyclooctapyrroles shown in Figure 55 appear predestined to form binuclear metal complexes since the loop-shaped conformation of these macrocycles exhibits two structurally identical, helical N4 cavities. Enantiomers of such complexes, which are presumably generally very stable towards racemization owing to the rigidity of the molecule imposed by the incorporation of the metal, are of interest as possible models for binuclear metalloenzymes and as potential catalysts in asymmetric synthesis. The first two ligands as well as their recently obtained palladium complexes601 were... 

The subject of asymmetric synthesis generally (214, 215) gained new momentum with the potential use of transition metal complexes as catalysts. The use of a complex with chiral ligands to catalyze a synthesis asymmetrically from a prochiral substrate is advantageous in that resolution of a normally obtained racemate product may be avoided, for example,... 

A closer similarity exists between the C2-symmetric octahedral isospecific model sites, which have been proposed for the heterogeneous polymerization catalysts,13 15 and some slightly distorted octahedral metal complexes, including bidentate or tetradentate ligands, which have recently been described as active in isospecific olefin polymerization in the presence of MAO.128-130 In fact, all these catalytic systems can be described in terms of racemic mixtures of active species with A or A chiralities. 

Trigonal ML3 metal complexes exist as optically active pairs. The complexes can show enantiomeric selective binding to DNA and in excited state quenching.<34) One of the optically active enantiomers of RuLj complexes binds more strongly to chiral DNA than does the other enantiomer. In luminescence quenching of racemic mixtures of rare earth complexes, resolved ML3 complexes stereoselectively quench one of the rare earth species over the other. 35-39 Such chiral recognition promises to be a useful fundamental and practical tool in spectroscopy and biochemistry. 

Cyclopropanations with diazomethane can proceed with surprisingly high diastereo-selectivities (Table 3.4) [643,662-664]. However, enantioselective cyclopropanations with diazomethane and enantiomerically pure, catalytically active transition metal complexes have so far furnished only low enantiomeric excesses [650,665] or racemic products [666]. These disappointing results are consistent with the results obtained in stoichiometric cyclopropanations with enantiomerically pure Cp(CO)(Ph3P)Fe=CH2 X , which also does not lead to high asymmetric induction (see Section 3.2.2.1). 

Fig. 2.15 Plot of AS (J K- mol ) vs AK (cm moK ) for racemization and geometrical isomerization of a variety of octahedral metal complexes. Only a few entries are selected from the 27 reactions tabulated in Ref. 180. The deviation of (four) Cr(IlI) complexes represented by Cr(phen) + (3) from the linear plot (best fit for 23 complexes) may indicate that these recemize by twist, and not dissociative, mechanisms. Racemization of Cr(C204)3 -(l), Co(Ph2dtc)3(2), Cr(phen)3 (3), Ni(phen)f+(4). Geometrical isomerization of trans-Cr(C204)2(H20)2 (5), trans-Co(en)2(H20) +(6), (3-Co(edda)en+(7).

The Schiff base can undergo a variety of reactions in addition to transamination, shown in Fig. 6.4 for example, racemization of the amino acid via the a-deprotonated intermediate. Many of these reactions are catalyzed by metal ions and each has its equivalent nonmetallic enzyme reaction, each enzyme containing pyridoxal phosphate as a coenzyme. Many ideas of the mechanism of the action of these enzymes are based on the behavior of the model metal complexes. 

The reasons for the increasing acceptance of enzymes as reagents rest on the advantages gained from utilizing them in organic synthesis Isolated or wholecell enzymes are efficient catalysts under mild conditions. Since enzymes are chiral materials, optically active molecules may be produced from prochiral or racemic substrates by catalytic asymmetric induction or kinetic resolution. Moreover, these biocatalysts may perform transformations, which are difficult to emulate by transition-metal catalysts, and they are environmentally more acceptable than metal complexes. 

Typically chiral metal complexes catalyzed asymmetric ring opening of achiral / racemic and chiral epoxides with various nucleophiles conveniently produce enantioenriched 1,2-... 

Enantiomerically pure 3-amino alcohols which are important intermediates for many bioactive compounds can be directly synthesized by the ARO reaction of readily accessible racemic and meso epoxides with appropriate amines. Indeed, some simple and multifunctional p-amino alcohols have been obtained using this strategy by the promotion of chiral BINOL [30-32,88,89], salen [35,52], bipyridine [33,40,90-94] and proline-A,JV-dioxide based metal complexes [95]. However, none of these systems demonstrated the recyclability of the precious chiral catalyst. 

Since the metal complexes can assume a number of closely related conformational structures and form racemic mixtures containing both right- and left-handed enantiomers in... 

All the above-discussed rare-earth metal complexes convert racemic p-BL to either syndiotactic or atactic polymers. Indeed, there is only one variant example... 

Bipyridyl (continued) as ligand, 12 135-1% catalysis, 12 157-159 electron-transfer reactions, 12 153-157 formation, dissociation, and racemization of complexes, 12 149-152 kinetic studies, 12 149-159 metal complexes with, in normal oxidation states, 12 175-189 nonmetal complexes with, 12 173-175 oxidation-reduction potentials, 12 144-147... 

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