Substrates achiral

The main strategy for catalytic enantioselective cycloaddition reactions of carbonyl compounds is the use of a chiral Lewis acid catalyst. This approach is probably the most efficient and economic way to effect an enantioselective reaction, because it allows the direct formation of chiral compounds from achiral substrates under mild conditions and requires a sub-stoichiometric amount of chiral material. 

Enantioselective synthesis (Chapter 19 Focus On) A reaction method that yields only a single enantiomer of a chiral product starting from an achiral substrate. 

Steric Approach Chelate Control Achiral Substrate Chiral Substrate... 

Diastereoselective addition has been carried out with achiral reagents and chiral substrates, similar to the reduction shown on page. 1201, but because the attacking atom in this case is carbon, not hydrogen, it is also possible to get diastereoselective addition with an achiral substrate and an optically active reagent. Use of suitable reactants creates, in the most general case, two new chiral centers, so the product can exist as two pairs of enantiomers ... 

This chapter deals with recent developments in this area, in particular DKR by enzyme-metal combinations. Each successful DKR is exempfified with several substrates and novel metal catalyst. Asymmetric transformations of achiral substrates via DKR of racemic intermediates also are described. 

Although second-generation methods have proved useful, the requirement for two extra steps, namely, the attachment and the removal of the chiral auxiliary, is a cumbersome feature. This is avoided in the third-generation method in which an achiral substrate is directly converted to the chiral product using a chiral reagent (Fig. 1-30, 3). In contrast to the first- and second-generation methods, the stereocontrol is now achieved intermolecularly. 

Consider Sharpless epoxidation with an achiral substrate. With certain ligands, the epoxidation can take place at any one of the four stereotopic faces of the substrate, affording X1, X2, X3, and X4. In Scheme 4-28, X1 reacts fast when A or B is OH, and the reaction is performed in an asymmetric way. When... 

Many attempts have been made during the past 30 years to imitate enzymes. Studies in the preparation of artificial enzymes (6) and model enzymes abound. While it is undoubtedly true that most enzymes can achieve the transformation of an achiral substrate to a chiral one more rapidly and with higher specificity than can be achieved using nonenzymic catalysts, the many limitations to which enzymic catalysis is subject should be properly evaluated. These are as follows ... 

Chiral Auxiliary A chiral auxiliary is an intermediate formed by the attachment of a pure enantiomer to an achiral substrate. The attachment, called a chiral auxiliary, restricts the approach of reactants to react in specihc ways to produce the chiral molecule. The antibacterial drug aztreonam is synthesized using the chiral auxiliary method. 

The bis(oxazoline) S, 5)-(115) has been used as an external chiral ligand to induce asymmetric diastereoselective lithiation by r-BuLi during [2,3]-Wittig rearrangement of achiral substrates, (fj-crotyl propargylic ethers.It is believed that the enantios-electivity is determined predominantly at the lithiation step. 

A descriptor for an enzyme active site that permits binding of a family of related compounds (e.g., mimics of the reaction intermediate) that can be derived from the initial binding and conformational changes in the substrate. This concept arose from the observation that a number of monoterpene cyclases were incapable of discriminating between enantiomers of the reaction intermediate, even though the enzyme catalyzes the synthesis of an enantiomerically pure product from an achiral substrate. An example is trichodiene synthase which catalyzes the cyclization of farnesyl diphosphate to trichodiene. 

D. Deprotonation of Achiral Substrates with a Chiral Base and... 

As illustrated in Section 2.3, enantioface differentiation occurs in addition reactions to hetero double bonds (C = X, with X = O, NR, etc.) and olefinic double bonds in achiral substrates. Thus, the enantioface differentiation can only arise from the reagent, either stoichiometrically (eq. I)18 or catalytically, e.g., from an enzymatic partner (eq. 2)19. 

Chiral Organometallic Reagents with Achiral Substrates... 

DIASTEREOSELECTIVE ADDITIONS OF CHIRAL CARBON NUCLEOPHILES TO ACHIRAL SUBSTRATES... 

This reaction sequence transforms an achiral substrate, meso compound 4, into the chiral substance 5. 

Less satisfactory results have been frequently encountered in the related asymmetric cycloaddition of a vinyl epoxide to an isocyanate as in Scheme 8E.30 [160]. The modest enantioselectivities of this process are indicative of the competitive intramolecular nucleophilic addition with enantioface exchange. When the oxazolidinone was generated from an achiral substrate, somewhat higher enantioselectiviites were obtained presumably due to superposition of the enantioselection obtained in the ionization step. 

Scheme 2 Polymer imprinted with the structure (6) were able to convert the achiral substrate (7) in the chiral substrate (8)...

The first reported attempt of using MIPs to control the stereochemical course of a reaction dates back to 1980, when the two research groups of Neckers and Shea published, simultaneously, examples of bulk polymers able to control the formation of the product by using a chiral template. Shea et al. reported that bulk polymers imprinted with stereochemically pure ( )-/ra/w-l,2,cyclobutane-dicarboxyilic acid (6) were able to keep a molecular memory of the asymmetry of the template [8]. In fact, this was transferred to an achiral substrate, such as fumaric acid (7), inducing a diastereoselective methylation, which led to trans-1,2,cyclopropane-dicarboxyilic... 

A number of stereospecific non-enzyme catalysts have been developed that convert achiral substrates into chiral products. These catalysts are usually either complex organic (Figure 10.8(a)) or organometallic compounds (Figure 10.8(b)). The organometallic catalysts are usually optically active complexes whose structures usually contain one or more chiral ligands. An exception is the Sharpless-Katsuki epoxidation, which uses a mixture of an achiral titanium complex and an enantiomer of diethyl tartrate (Figure 10.8(c)). 

Using a chiral auxiliary. The achiral substrate is combined with a pure enantiomer known as a chiral auxiliary to form a chiral intermediate. Treatment of this intermediate with a suitable reagent produces the new asymmetric centre. The chiral auxiliary causes, by steric or other means (see section 10.2.2), the reaction to favour the production of one of the possible stereoisomers in preference to the others. Completion of the reaction is followed by removal of the chiral auxiliary, which may be recovered and recycled, thereby cutting down development costs (Figure 10.10). An advantage of this approach is that where the reaction used to produce the new asymmetric centre has a poor stereoselectivity the two products of the reaction will be diastereoisomers, as they contain two different asymmetric centres. These diastereoisomers may be separated by crystallization or chromatography (see section 10.2.1) and the unwanted isomer discarded. 

Using achiral substrates and reagents. A wide variety of achiral substrates and reagents can give rise to asymmetric centres. For example, electrophilic addition of hydrogen chloride to butene gives rise to a racemic mixture of... 

As already implied by the above scheme, it is essential that chiral amplification and symmetry breaking comprising the generic autocatalytic steps A + R -> 2R and A+S 2S, require some sort of cross-inhibition between the two enantiomers, for instance expressed by R + S —> P. Here A denotes an achiral substrate and P an unspecified product. In the absence of crossinhibition, the ee will at best stay at its initial value but amplification remains impossible [66]. 

Abstract Theoretical models and rate equations relevant to the Soai reaction are reviewed. It is found that in production of chiral molecules from an achiral substrate autocatalytic processes can induce either enantiomeric excess (ee) amplification or chiral symmetry breaking. The former means that the final ee value is larger than the initial value but is dependent upon it, whereas the latter means the selection of a unique value of the final ee, independent of the initial value. The ee amplification takes place in an irreversible reaction such that all the substrate molecules are converted to chiral products and the reaction comes to a halt. Chiral symmetry breaking is possible when recycling processes are incorporated. Reactions become reversible and the system relaxes slowly to a unique final state. The difference between the two behaviors is apparent in the flow diagram in the phase space of chiral molecule concentrations. The ee amplification takes place when the flow terminates on a line of fixed points (or a fixed line), whereas symmetry breaking corresponds to the dissolution of the fixed line accompanied by the appearance of fixed points. The relevance of the Soai reaction to the homochirality in life is also discussed. 

We consider a production of chiral enantiomers R and S from an achiral substrate A in a closed system. Actually, in the Soai reaction, chiral molecules are produced by the reaction of two achiral reactants A and B as A + R or A + B -> S. But in a closed system a substrate of smaller amount controls... 

The spontaneous production of chiral molecules R or S from an achiral substrate A is described by reactions ... 

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