Optically selective synthesis

The classification rests on the recognition of the four broad categories (A) resolution of optically stable racemates, (B) optically selective inversion of configuration in optically labile racemates, (C) optically selective synthesis of new centers of dissymmetry, and (D) optically selective inactivation of existing centers of dissymmetry. 

The identity in sign and similarity in optical rotations of sultones (+)-52A,B, obtained from (—)-49A and (+)-49B, indicate that the absolute configuration of the y-carbon in both sultones as well as in both sultines is the same. In conclusion, the authors suggested113,114 that of the four possibilities shown below, y-sultines 48A-51A and 48B-51B may be assigned the (R)c-(Sf and (R)c-(Rf absolute configurations, respectively. Although initiated by mechanistic interest, this study has also resulted in a new method for selective synthesis of... 

The addition of crotyl-9-BBN to the chiral imino ester 2 provides a syrc-selective synthesis of optically active amino esters.1... 

Scheme 4.15 A highly flnt/-selective synthesis of haloallenes and prediction of stereochemistry of haloallenes by optical rotations with revised parameters.

This reaction can furthermore be applied on chiral aminals, affording a straightforward route to optically pure frawi-2,5-pyrrolidines or chiral alkyl-substituted 1,3-oxazoUdines. This method was used for the en an tio selective synthesis of substituted piperidines . 

Several additional Diels-Alder cycloaddition strategies have been applied to the total synthesis of the steroid skeleton. For example, the first enanlio-selective synthesis of (+)-conisone was accomplished by the intramolecular [4 + 21 cycloaddition of an otefinic o quinodimethane that contained an optically active stereodirecting group as the key chemical step. 

Selective synthesis of a target stereoisomer is one of the most important and significant processes. Hence, achievement of stereoselective synthesis by photocatalytic reaction is also strongly desired. There are three possibilities for the stereoselective syntheses by semiconductor photocatalytic reaction in the step of (1) oxidation by a positive hole, (2) included chemical reaclion(s), e.g., condensation into a Schiff base, and/or (3) reduction by an excited electron. An example of (1) is the photocatalytic L-PCA synthesis from Lys the optical purity depends on the position of the amino group which the positive hole attacks. To the... 

Hisano developed a solid phase copolymer incorporating the M-oxide functionality that was able to catalyse the reaction, furnishing good yields of thiols [117]. The method has been used recently for the enantio-selective synthesis of thiols catalysed by optically active pyridine M-oxides (Scheme 47) [118]. 

Synthesis of Optically Active p-Hydroxy Esters. Chiral amino alcohols such as quinine have been used in the enantio-selective synthesis of (3-hydroxy esters via an indium-induced Re-formatsky reaction (eq 14). Although the enantioselectivities are not particularly high, aromatic aldehydes have produced the best results to date. The absolute stereochemistry of the products has not yet been assigned. 

Since the Diels-Alder reaction is both experimentally and theoretically well characterized, we now have a thorough understanding of this important transfonnation. This allowed one to influence rates and selectivities of this cycloaddition. An illustrative example is the selective synthesis of a key prostaglandine precursor (Scheme 2) in which all stereochemical information derives from the starting materials. Although the general mechanism of Diels-Alder reactions is well understood, it is still uncertain if these reactions occur in biosynthesis. An instructive example is represented by the total synthesis of optically active plagiospirohdes 1 and 2 (Scheme 3) -. These syntheses were considered to be biomimetic and are indications that Diels-Alder reactions may also occur in vivo. 

The Kabachnik Fields reaction, which involves the hydrophosphonylation of phos phites with imines generated in situ from carbonyl compounds and amines, is an attractive method for the preparation of a amino phosphonates. Optically active a amino phosphonic acids and their phosphonate esters are an attractive class of compounds due to their potent biological activities as nonproteinogenic analogues of a amino acids. Therefore, considerable attention has been given to their enantio selective synthesis by hydrophosphonylation of preformed imines, using either metal based catalysts or organocatalysis [107]. 

An exciting prospect in synthetic organic electrochemistry is the selective synthesis of specific optical isomers by taking advantage of the asymmetry afforded by certain types of surface sites achieved with chemically modified electrode surfaces on substrates such as carbon. 

The essential feature for a selective synthesis of one optical isomer of a chiral substance is an asymmetric site that will bind a prochiral olefin preferentially in one conformation. The recognition of the preferred conformation can be accomplished... 

It has been shown by Ojima in the synthesis of depsipeptides (see the last five lines in Table 6) that optical selectivities are much higher in the hydrosilylation reactions, where asymmetric induction by the chiral catalyst predominates over that of the chiral center already present in the N- (a- ketoacyO-a- aminoester substrates. 

Many optically-active organic molecules are present in plants and animals, and they can often be isolated and obtained in a pure form. In recent years, considerable success has been achieved in the selective synthesis of individual isomers. However, laboratory preparations of compounds that can exhibit optical activity normally yield 50-50 (racemic) mixtures of the two optical isomers and hence produce an optically-inactive material (Section 3.4). Therefore, the basic step in the laboratory preparation of an optically-active coordination compound is separation from its optical isomer. For example, racemic [Co(en)3] is readily prepared by the air oxidation of a cobalt(II) salt... 

These processes resulted in racemic mixtures. However, the resolution of this mixture is believed to have occurred by spontaneous crystallization. This process most likely occurred by chance. Minerals such as natural dissymmetric quartz crystals and metal ions may have played a crucial role of optical selection by selective chelation of only one stereoisomer. After all, stereoselective polymerization of olefins by metal surfaces (Ziegler-Natta catalysts) is a well-documented industrial process for the synthesis of isotactic polymers. We also know the importance of metal ion binding in many biochemical transformations. It is essential for the maintenance of the native structure of nucleic acids and numerous proteins and enzymes. Other physical forces through radioactive elements, 7-radiation, or from cosmic rays, may have also been involved in optical selection. For instance, recent experiments with strontium-90 indicate that D-tyrosine is destroyed more rapidly than the naturally occurring L-isomer. It is tempting to incorporate such factors into the origin of dissymmetry in life process (46). 

Absolute asymmetric synthesis. Optically selective formation of dissymmetric molecules by the interaction erf symmetrical molecules or groups under the influence of an unssunmetrieal physical agency e.g., circularly polarized light). 

Asymmetric synthesis (eliminative). Optically selective formation of new centers of stable dissymmetry under the intramolecular directing influence of an optically active grouping, the latter being subsequently eliminated from the product. 

It seems not unlikely that a similar catalytic role is played by an alkaloid in the asymmetric synthesis of d-phenyl-n-butyric acid recorded by Lipkin and Stewart (76), by a reduction of the hydrocinchonine salt of /9-methylcinnamic acid, and also in the optically selective bromination of cinchotine cinnamate and glucosamine cinnamate noted by Erlenmeyer (38). A more complicated example recorded by Stewart and Lipkin (136) may perhaps be an extension of the same principle here, j8-methylcin-namic acid was selectively reduced by glucose in the presence of Raney nickel. 

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