Stereodifferentiating reactions

Izumi, Y. Tai, A. 1977, Stereodifferentiating Reactions The Nature of Asymmetric Reactions, Kodansha Ltd. Tokyo, Japan, Academic Press New York London... 

Y. Izumi and A. Tai, "Stereodifferentiating Reactions", Kodansha Ltd., Tokyo-Academic Ress, New York, 1977. 

Izumi, Y., Tai, A. Stereodifferentiating Reactions, New York Academic Press 1977... 

D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in Asymmetric Synthesis -Stereodifferentiating Reactions, Part B (J. D. Morrison, Ed.), Vol. 3, 1, AP, New York, 1984. 

In 1997 Katsuki found a considerably better system (Scheme 97) [230]. This time E-cinnamyl phenyl sulfide 285 was converted under Co catalysis using a salen ligand to generate anti-396 and syn-396 (85 15) with much improved diastereoselectivity and 65% ee, in favor of the (2R,3S)-anti diastereomer (presumably via TS-i s, Scheme 95, see also [231]). When t-Bu in the diazo compound was replaced by (-)-menthyl, the anti isomer was generated with 74% ee and 93% ds in a matched double stereodifferentiating reaction. 

Synthesis of Cyclopropanes. Chiral imide enolates which contain y-halide substituents undergo intramolecular displacement to form cyclopropanes. Halogenation of y,5-unsamrated acyl imides occurs at the y-position in 85% yield with modest stereoinduction. The (Z) sodium enolates of these compounds then cyclize through an intramolecular double stereodifferentiating reaction (eq 61). 

For practical reasons, the stereochemical results of acyclic and cyclic compounds are treated separately. In both cases, the reaction can be enantio- or diastereodifferentiating. In the first case, the stereochemical differentiation is controlled by the reagent and in the second case the stereochemical outcome is either determined by the chiral substrate or by both the chiral substrate and the chiral reagent (double stereodifferentiating reactions)81-83. 

A compilation of different catalytic stereoselective processes seems unnecessary for the purpose of a classification of the stereoselective syntheses. However, a few examples of some less frequently encountered catalytic kinetic resolutions and chiral catalyst mediated multiple stereodifferentiating reactions will be presented in Fig. 8. 

The Carroll rearrangement is often used as one of many key steps in the preparation of natural products due to its reliability as a stereodifferentiating reaction. Snider and Beal recently showed this in their formal synthesis of isocomene (41) (Scheme 8.17) [19]. Ketone 36 was reduced to alcohol 37 and treated with diketene to form the yS-keto ester 38. The [3,3]-sigmatropic Carroll rearrangement was performed using Wilson s procedure (2eq. of LDA, -78 to 65 °C) [6] to give the desired ketone 39 in 72% yield. This step was key in setting up the desired hindered carbon-carbon bond needed in the final product. An intramolecular cycloaddition and a few additional steps provided ketone 40, which is a late intermediate in Wenkert s isocomene (41) synthesis [20]. 

SCHEME 7.2 Olefin polymerization reaction schemes (a) conventional Cossee-Arhnan reaction sequence (b) counteranion displaced reaction sequence (c) stereodifferentiation reaction sequence. P and P represent polymer chains of length n and n + 1, respectively. 

Let us now consider in more detail the nature of this difference in activation energy. The transition states leading to the/ and Sproducts are diastereomeric, and therefore non-equivalent, and of different energies. In most of the stereodifferentiating reactions described in this book the key step involves preferential addition from the/ e or 5/ face to a trigonal carbon, which is usually unsaturated. 

In fact this hardly qualifies as a stereodifferentiating reaction, since the diastereofacial selectivity on the prochiral ketone is quite low and unpredictable. Nonetheless the method is useful, especially with aryl ketones which allow clean separation of the diastereomers, giving e.e.s in the range 85-95%. For aldehydes and dialkyl ketones the results are poorer. 

Despite that, these undesired results from the dianion aldol reactions can be used to understand some principles of the double stereodifFerentiating reactions. The C3 protected series, such as Schinzer-type aldol reactions described before required the (S)-configuration at C3 to establish the (R)-configuration at C6 and the (S)-configuration at C7 with a similar a-chiral (S)-aldehyde. The matching chirality in the protected series corresponds to the mismatched case in the unprotected series of these double stereodifFerentiating aldol reactions. This disparity could be a result of different transition states. 

Evans, D.A. (1984) Asymmetric Synthesis, Stereodifferentiating Reactions, Part B,... 

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