Formation of racemic

Fig. 4. Chiroselective inclusion formation of racemic l-phenylethylammonium salt ((R/S)-14) using optically active crown compound ((i, 5)-13) [53955-48-9]. The diastereomeric inclusion complex (R)-(14) is more stable than (3, 3)-(13)-(3)-(14) (top views, dotted lines represent hydrogen...

This intermediate serves to explain the formation of racemic product, since it is achiral. The cation has a plane of symmetry passing through C-4, C-5, C-6, and the midpoint of... 

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. 

The steroid ring structure is complex and contains many chiral carbons (for example at positions 5, 8, 9,10,13,14 and 17) thus many optical isomers are possible. (The actual number of optical isomers is given by 2" where n = the number of chiral carbons). From your knowledge of biochemistry you should have realised that only one of these optical isomers is likely to be biologically active. Synthesis of such a complex chemical structure to produce a single isomeric form is extremely difficult, especially when it is realised that many chemical reactions lead to the formation of racemic mixtures. Thus, for complete chemical synthesis, we must anticipate that... 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

Heating optically active (5)-3-bromo-3-methylhexane with aqueous acetone results in the formation of racemic 3-methyl-3-hexanol. 

When the reaction is conducted in the presence of added fumarate, the yield of pyrrolidine (130) increases at the expense of the aziridine. Jacobsen suggests that the aziridines and pyrrolidines arise from a common intermediate, azo-methine ylide (132), Scheme 6, which may also be partly responsible for the poor levels of asymmetric induction in this reaction. Electrocyclic ring closure of the azo-methine while still within the coordination sphere of the metal (131) may provide aziridine with some induction, while decomplexation (132) will lead to the formation of racemic aziridine and pyrrolidine. 

Thus, chiral discrimination may be observed that differentiates the force-area curves of the enantiomers of some surfactants from their racemic modifications. Apparent phase changes in the monolayer can be related to parallel behavior in the crystalline state through X-ray diffraction and differential scanning calorimetry. Formation of racemic compounds and quasi-racemates can be observed in some cases. 

Hydroboration occurred from the less hindered top face of rac-29 and resulted in the formation of alcohol rac-30. After a three-step sequence which included oxidation with tetrapropylammonium perruthenate (TPAP), methyl lithium addition and repeated oxidation with TPAP, ketone rac-31 was isolated. Finally, epimerization of the stereogenic center at C-7 to the correct configuration and methylenation with the Lombardo reagent led to the formation of racemic kelsoene (rac-1). 

Sharpless Asymmetric Epoxidation This is a method of converting allylic alcohols to chiral epoxy alcohols with very high enantioselectivity (i.e., with preference for one enantiomer rather than formation of racemic mixture). It involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetra isopropoxide [Ti(0—/Pr)4] and a specific stereoisomer of tartaric ester. For example,... 

Shaking of rac-3,4-dihydro-6-methyl-2-(l-oxopropyl)-2/f-pyran with baker s yeast resulted in initial formation of racemic 6-hydroxy-2,7-nonanedione and then by kinetic resolution/ diastereoselective reduction in the production of (67 ,7S)-6,7-dihydroxy-2-nonanone (2) where both relative and absolute configuration had to be determined (see p 470)134. 

Stepwise solvolysis of chiral substrates through a planar achiral carbocation reaction intermediate normally results in the formation of racemic products. However, the solvolysis of chiral tertiary derivatives 6-Y proceeds with either... 

The direct formation of racemic a-tocopherol from trimethylhydroquinone and isophytol occurs at low temperature in the presence of boron trifluoride or aluminum chloride (71JOC2910). It is important that the solvent should not be able to complex with the Lewis acid rather, it is the phenol-catalyst complex which is alkylated. 

It is not difficult to visualize how sugars such as ribose may be formed. Methanal is known to be converted by bases through a series of aldol-type additions to a mixture of sugarlike molecules called formose. Formation of racemic ribose along with its stereoisomers could occur as follows ... 

A crude mixture of enzymes isolated from Rhodococcus sp. is used for selective hydrolysis of aromatic and aliphatic nitriles and dinitriles (117). Nitrilase accepts a wide range of substrates (Table 8). Even though many of them have low solubility in water, such as (88), the yields are in the range of 90%. Carboxylic esters are not susceptible to the hydrolysis by the enzyme so that only the cyano group of (89) is hydrolyzed. This mode of selectivity is opposite to that observed upon the chemical hydrolysis at alkaline pH, esters are more labile than nitriles. Dinitriles (90,91) can be hydrolyzed regioselectively resulting in cyanoacids in 71—91% yield. Hydrolysis of (92) proceeds via the formation of racemic amide which is then hydrolyzed to the acid in 95% ee (118). Prochiral 3-substituted glutaronitriles (93) are hydrolyzed by Phodococcus butanica in up to 71% yield with excellent selectivity (119). 

The typical technologies used for the preparation of amines have also been used for the synthesis of optically pure (R)- or (S)-l-aminoindane. For example, resolution approaches include the diastereoisomeric salt formation of racemic A-bcnzyl- l -aminoindane with (,S )-mandclic acid41 or (R,R) tartaric acid,42 which resulted in, after hydrogenation, (R)-l-aminoindane with >99% ee. Also, resolutions that use enzymatic acylation concepts have been described.43 44 The maximum theoretic yield of 50% is a clear limitation of these methods. Asymmetric synthetic approaches to chiral 1-aminoindanes have been described, including enantioselective hydrosilylation of l-indanoxime45 46 and hydroboration of indene 47 However, ee values were low to moderate. 

According to this mechanism (Scheme 7.19), the process is amenable to asymmetric modifications. Among a variety of silicon reagents that were examined, only tetrachlorosilane proved to be suitable for the asymmetric process, while the application of other chlorosilanes resulted in the formation of racemates. A... 

Fig.24 Overview of the synthesis and resolution of solution stable, chiral tetrahedron 6 [119]. a Formation of racemic, homochiral (AAAA)-6 and (AAAA)-6 b Chiral resolution and separation upon addition of s-nic ions (38) by formation of diastereomeric ion-pair (AAAA)-6-38 c Ion-exchange of chiral auxiliary 38 by achiral counterions such as NMe4+ and NEt4+ maintains the chirality of the resolved tetrahedra (AA AA)-6...

The formation of racemic mixtures of homochiral oligopeptides is not confined to racemates undergoing spontaneous segregation into enantiomor-phous domains it can also be extended to racemic 2-D crystallites, provided the reaction pathway takes place preferentially between homochiral molecules related by translation symmetry, as in the case of the thioethylester of N -slearoyl-lysinc (Cis-TE-Lys) [193]. It has been experimentally proven by GIXD that racemic Cis-TE-Lys self-assemble into racemic 2-D crystallites, Fig. 15. Moreover, MALDI-TOF MS analyses of oligopeptide samples obtained from the polycondensation of deuterium enantiolabeled monomers have revealed a clear trend toward enhanced formation of di- to hexa-peptides with homochiral sequences, in agreement with a reaction pathway between homochiral monomer molecules related by translation symmetry [193,195]. 

Indeed, MALDI-TOF MS analyses of the oligopeptide products demonstrated the preferential formation of racemic mixtures of oligopeptides with homochiral sequences, Fig. 20, generated from deuterium enantiolabeled racemic monomer [206]. The degree of stereospecificity observed in this reaction increased as the homochiral oligopeptide length increased, as shown in Fig. 21. 

Unfunctionalised and chlorohybrid materials were used in the model reaction in order to determine the activity of the uncovered mineral surface in the formation of racemic 1-phenyl-propan-l-ol. Results are shown in Figure 3. ... 

Acridine 94 and (R)-( — )-2-phenylpropionic acid (R)-95 formed the chiral 3 2 cocrystal 94 (/ )-95. Irradiation of these cocrystals gave enantiomeric products 96 and 98 as well as the diastereomeric product 97 through photodecarboxylative condensation, with all positive [a]j> values (Scheme 22) [94]. Similarly, the opposite handed cocrystal afforded 96-98 with negative [a] d values. In contrast, photolysis of a 1 1 solution of 94 and (/ )-95 in acetonitrile resulted injhe formation of racemic 96 and biacridane 99. 

By analogy, it seemed plausible that alcohol racemizations catalyzed by the same type of ruthenium complexes involve essentially the same mechanism (Fig. 9.11), in which the active catalyst is first generated by elimination of HC1 by the added base. This 16e complex subsequently abstracts two hydrogens from the alcohol substrate to afford an 18e complex and a molecule of ketone. Reversal of these steps leads to the formation of racemic substrate. 

The reactions of alkyl cuprates with allylic acetates are always stereospecifi-cally anti 5.114 —> 5.115, although the formation of racemic product shows that regiocontrol has been lost. These reactions are not mechanistically Sn2 reactions, since they involve in the first step coordination of the copper on the lower surface, followed by the formation of a re-allyl system at the same time as the acetate leaves. The delivery of the methyl group to the same surface, and equally to both ends of the allylic system, is a reductive elimination. It seems likely that the decisive step determining the stereoselectivity is that coordination of the copper anti to the nucleofugal group is needed before it will leave. 

To create stereochemical diversity within MCRs there is need for stereoselective (or -specific) reactions. Since many MCRs involve flat intermediates, like imines and a,p-unsaturated ketones, they result in the formation of racemic products. Moreover, often mixtures of diastereomers are obtained if more than one stereo-genic centre is formed. However, there are several examples known of asymmetric induction, by the use of chiral building blocks (diastereoselective reactions). For example, it has been successfully applied to the Strecker, Mannich, Biginelli, Petasis, Passerini, Ugi, and many other MCRs, which has been excellently reviewed by Yus and coworkers [33]. Enantioselective MCRs, which generally proved to be much harder, have been performed with organometaUic chiral catalysts and orga-nocatalysts [33, 34]. 

However, not everyone was convinced by the existence of the non-classical carbocation. H. C. Brown 1977 pointed out that the norbornyl compounds are compared with cyclopentyl rather than with cyclohexyl analogues, 2.21 (eclipsing strain), and in such a comparison the endo-isomev is abnormally slow, the exo-isomer being only 14 times faster than cyclopentyl analogues. He also pointed out that the formation of racemic product is due to two rapidly equilibrating classical carbocation species (Scheme 2.17). The interconversion of enantiomeric classical carbocation species must be very rapid on the reaction timescale. 

The application of the same principle to the formation of o-alanine is possible but lacks applicability due to its slowness. In this case, in the presence of ammonia, pyruvate is in equilibrium with its imine. This is reduced at the cathode under formation of racemic alanine. The L-alanine of the racemic mixture is reoxidized by L-alanine dehydrogenase under anodic regeneration of the necessary cofactor NAD to give pyruvate and ammonia, while the o-alanine is not accepted by the enzyme and accumulates in the reaction mixture. The drawback of this reaction is the kinetic control by imine formation, which is very slow, so that a complete inversion of a lOmAf solution of L-alanine would require 140 h [105]. 

Example Crystallization of Mixtures of Optical Isomers Formation of Racemic Compounds. 

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