Double stereo-differentiation

A chiral vanadium complex, bis(3-(heptafluorobutyryl)camphorato)oxovana-dium(IV), can catalyze the cycloaddition reaction of, mainly, benzaldehyde with dienes of the Danishefsky type with moderate to good enantioselectivity [21]. A thorough investigation was performed with benzaldehyde and different activated dienes, and reactions involving double stereo differentiation using a chiral aldehyde. 

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

Asymmetric induction is reported in the addition of enolates of methyl ketones to aldehydes.55 Double stereo-differentiation—in which simultaneous 1,3-control can be obtained hi the aldehyde moiety—is shown to be achievable with proper selection of the aldol type. 

The above examples have presented a better induction effect when the chiral auxiliary was located at the enone molecule. Double auxiliary induction has been examined by Scharf and coworkers99. Systematic study on the photoaddition of chiral enones 203 to chiral ketene acetals 204 provides examples of matched (45% de) and mismatched (9% de) double stereo differentiation (Scheme 44). 

Double stereo-differentiation was also tested using catalyst 96 and chiral a-ami-... 

The first enantioselective synthesis of mikanecic acid, ( + )-162, a terpene dicarboxyhc add was achieved by Basavaiah et via a double stereo-differentiating asymmetric Diels Alder reaction involving the same molecule as chiral diene and chiral dienophile generated in situ. Treatment of MBH adduct with MsQ/NEts afforded the chiral dienes 161, through a Diels-Alder reaction of the in situ generated chiral l,3-butadiene-2-carboxylate 160. Hydrolysis of the diesters then afforded the desired mikanecic acid 162 (25-74% ee) in good... 

In recent years, even chemists have become concerned about terminology to be used for asymmetric syntheses and asymmetric reaction processes . Since catalysis by enzymes represents the ultimate in an asymmetric reaction, it is appropriate to consider briefly a new proposal. Izumi and Tai have proposed that the time has come to abandon the use of stereoselective and stereospecific [62], They point to two components in the transformation of a substrate to a product. The first resides in chemical structures (e.g., a double bond) rather than in a particular steric structure and the reaction is governed by the nature of the reagent or catalyst (whether the process proceeds with retention or inversion whether an addition is syn or anti). In the second component, the reagent or catalyst interacts topologically with the three-dimensional structure of the substrate. This is described as stereodifferentiation and results from the stereo-differentiating ability of the catalyst or reagent. 

It seems likely that biochemists will continue to use a more pragmatic and less comprehensive approach. In biochemical processes, two important features are the structures of substrate and product. The overall steric structure of the substrate (and not just the possession of some structural feature such as a double bond) is important in terms of binding to an enzyme or receptor. Since many enzymatic reactions are readily reversible, overall product structure is important for the same reason. Furthermore, since many enzymes make more than one type of stereodifferentiation, the use of the stereo-differentiating terminology of Izumi and Tai would be somewhat cumbersome. The overall steric structure of molecules (as opposed to isolated structural features) is also important in the area of drug-receptor interactions. 

Reactions of titanated hydrazones with aldehydes occur cleanly at —20 °C (Equation 69). It is not clear whether the observed erythro-selectivity (Table 8) depends upon the geometry of the double bond, since attempts to prepare Z configurated analogs were not rewarding115). The lithiated precursors themselves are unsuitable for selective additions. Titanation not only increases stereo-differentiation, but also chemoselectivity 115). The assumption of a pericyclic transition state means that chair orientations 213 and 214 must be considered, the latter being of higher energy. However, boat transition states also explain the results U5). 

Ito, K., Harada, T., and Tai, A. (1980) The stereo-differentiating (asymmetric) hydrogenation of the C=0 double bond with a modified nickel catalyst, XXXV. A facile method for the preparation of optically pure -diols. Bull. Chem. Soc. Jpn. 53, 3367 - 3368. 

Zhu and Panek s total synthesis [148] is described in Scheme 89. After conversion of aldehyde 609 to di-benzyl acetal, treatment with chiral crotylsilane 610 afforded l,2-5y -611 with high stereo- and enantioselectivity. The oxidative cleavage of the double bond and subsequent aldol reaction with silyl ketene acetal 612 provided 613, which was converted into a,P-unsaturated ester 614 via Wittig olelination. The C8 methyl group was stereoselectively introduced by treatment with dimethylcuprate in the presence of TMSCl. DIB AH treatment differentially reduced the C3 and CIO esters to alcohol and aldehyde, respectively. Protection of the alcohol as silyl ether followed by the Wittig reaction afforded 615. In a manner similar to Danishefsky s synthesis [142d], an inteimolecular Suzuki... 

Probably, the dramatic distinction in stereo-selectivity between cometathesis products obtained from Z-cyclodecene and from cycloolefins C5-C9 (Table 3), is connected with the fact that Z-cyclodecene gives the cyclic transition state having eleven atoms in the cycle (10 C-atoms + 1 Mo-atom). Meanwhile, it is known that the thermodynamic stability of E-isomers in the range of unsaturated cycles of different size dramatically increases beginning from cycloundecene [33]. So, Z-cycloolefins C5, and C7-C9 in cometathesis reaction with a-olefins allow predominantly Z-isomer new double bonds to be obtained (in l,A-dienes). This radically differentiates them from cycloolefins with number of C-atoms of 10 and more, as well as from open-chain olefins. 

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