Asymmetric induction using chiral transition

Asymmetric induction using a transition metal complex (67), use of a carbohydrate template (68), and use of the chiral lactone 49 (69) or ester 50 (70) have all given effective syntheses of stereospecifically labeled samples of glycine. A further synthesis by Santaniello etal. (71, 72) has used glutamate decarboxylase to prepare labeled samples of y-aminobutyric acid 51 (Scheme 16). On cyclization, protection, and oxidation, these gave the labeled enamides 55, which were degraded to the labeled samples of glycine 23 (71, 72). 

According to this correlation model, in which the principles of steric control of asymmetric induction at carbon (40) are applied, the stereoselectivity of oxidation should depend on the balance between one transition state [Scheme 1(a)] and a more hindered transition state [Scheme 1(6)] in which the groups and R at sulfur face the moderately and least hindered regions of the peroxy acid, respectively. Based on this model and on the known absolute configuration of (+)-percamphoric acid and (+)-l-phenylperpropionic acid, the correct chirality at sulfur (+)-/ and (-)-5 was predicted for alkyl aryl sulfoxides, provided asymmetric oxidation is performed in chloroform or carbon tetrachloride solution. Although the correlation model for asymmetric oxidation of sulfides to sulfoxides is oversimplified and has been questioned by Mislow (41), it may be used in a tentative way for predicting the chirality at sulfur in simple sulfoxides. 

The use of chiral leaving groups, e.g.. a camphorsulfonyl group, in substitution reactions with C-C bond formation was first reported in 19745. Since the leaving group is involved in the transition state of SN2 reactions, asymmetric induction is observed if a chiral leaving group is used. 

Principles. How shall we proceed toward catalytic asymmetric induction Scheme 5 illustrates a possible way to achieve enantioselective alkylation by using a small amount of chiral source. Under certain conditions, the presence of a protic chiral auxiliary HX can catalyze the addition of organometallic reagent, R2M, to a prochiral carbonyl substrate by way of RMX. To obtain sufficient chiral efficiency, the anionic ligand X must have a three-dimensional structure that allows differentiation between the diastereomeric transition states of the alkyl transfer step. In addition, unlike in stoichiometric reactions, the rate of... 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

Among the transition-metal catalysts that have been used, only those of Pd(II) are productive with diazomethane, which may be the result in cyclopropanation reactions [7,9,21] of a mechanism whereby the Pd-coordinated alkene undergoes electrophilic addition to diazomethane rather than by a metal carbene transformation in any case, asymmetric induction does not occur by using Pd(II) complexes of chiral bis-oxazolines [22],... 

Another impressive example of the transition metal-catalyzed Michael reaction was reported by Sawamura and Ito in 1992 (Scheme 6) [7]. a-Methylcyanoacetate was treated with enones using 1 mol% Rh-TRAP (12) complex, and the corresponding adduct 13 was formed in up to 93 % ee. For this reaction, the trans-coordination mode of the chiral diphosphine 12 was essential for high asymmetric induction. It was proposed that coordination of the nitrile group to Rh, then oxidative addition of the active methine C-H bond gave not the a-C-bound enolate, but the nitrile-coordinating enolate 14, which was considered to be a reactive intermediate. The unique structure of this enolate was supported by X-ray analysis of a similar achiral Ru-cyanoacetate complex [8]. 

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