Chiral olefination reactions

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

In addition to providing a novel approach to the preparation of chiral compounds, this type of chemistry may allow one to inquire into the subtle stereochemical details of some crystal-state reactions. For example, what are the approach geometry and the preferred side of attack in the addition of bromine to a chiral olefin (259) What can be learned of the geometry of the labile electronically excited species involved in (2 + 2) photocycloaddition reactions (260) ... 

Thus, in the example of the chiral olefin 3, there is simple diastereoselectivity of (m4a + m4b)/(m4c + m4d) and induced diastereoselectivities of m4a/m4b and m4c/m4d. It is not strictly necessary, but conversely there is no harm, in applying the term simple diastcrcosclcc-tivity to the first case, i.e., to a diastereoselective reaction of achiral reactants. In this volume the presentation of a given reaction type always begins with simple diastereoselectivity of achiral reactants. 

A quite unique approach is also the complexation of chiral olefins by a ligand exchange type reaction with the chiral platinum(lV) complex (Table 1, entry 57). It is an equilibrium... 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

Depending upon the choice of substrates, the hydrosilylation of alkenes can also be highly stereoselective. Two examples are given below. The reaction with methylmaleic anhydride proceeded regiospecifically to the less substituted side, but also diastereose-lectively to afford the thermodynamically less stable cis isomer. The stereoselectivity decreased by increasing the reaction temperature, indicating the difference in enthalpy of activation for syn vs anti attack (equation 32). On the other hand, a complete stereocontrol has been achieved in the reaction with the a-chiral olefins (equation 33, R = Me)56. The observed stereoselectivity was rationalized in terms of steric and Felkin-Anh... 

The TB ( + )-l adduct of methyltrioxorhenium [(+ )-Re03CH3], characterized by its crystal structural and spectroscopic data, was reported by Herrmann et al. The catalytic properties of this complex were tested in the epoxidation of olefins and the oxidation of sulfides. However, no enantioselective reactions of the pro-chiral olefins and sulfides were observed (97JOM(538)203). 

Enantiomerically pure olefin metathesis catalysts can be used to promote reactions whereby simple achiral substrates are transformed into more complex chiral molecules. Much like their achiral counterparts, chiral olefin metathesis catalysts can be used in three distinct fashions. Chiral metathesis reactions have been reviewed.51-53... 

Asymmetric Wittig-Homer reaction chiral olefinations. 2 Reaction of the chiral ketone 1 with the ylide from (- )-8-phenylmenthyl phosphonoacetate (2) at -30 to -60° gives the (E)-olefin in a 90 10 ratio. The geometry of the alkene is determined mainly by the chiral auxiliary. Use of ent-2 results in 3 with the E/Z... 

Fig. 3.25. Thought experiment I Products from the addition of a racemic chiral dialkylborane to a racemic chiral olefin. Rectangular boxes previously discussed reference reactions for the effect of substrate control (top box reaction from Figure 3.20) or reagent control of stereoselectivity [leftmost box reaction from Figure 3.24 (rewritten for racemic instead of enantiomerically pure reagent)]. Solid reaction arrows, reagent control of stereoselectivity dashed reaction arrows, substrate control of stereoselectivity red reaction arrows (kinetically favored reactions), reactions proceeding with substrate control (solid lines) or reagent control (dashed lines) of stereoselectivity black reaction arrows (kinetically disfavored reactions), reactions proceeding opposite to substrate control (solid lines) or reagent control (dashed lines) of stereoselectivity.

If, as in the reaction example in Figure 3.26, during the addition to enantiomerically pure chiral olefins, substrate and reagent control of diastereoselectivity act in opposite directions, we have a so-called mismatched pair. For obvious reasons it reacts with relatively little diastereoselectivity and also relatively slowly. Side reactions and, as a consequence, reduced yields are not unusual in this type of reaction. 

Fig. 3.28. Thought experiment IV Reaction of 0.5 equiv of an enantiomerically pure chiral dialkylborane with a racemic chiral olefin to effect a kinetic resolution of the latter.

Ketones are rarely used as electrophiles in the enantioselective aldolization while they find application to enantioselective olefination reactions such as the Horner-Wadsworth-Emmons or the Peterson reaction. For instance, the deprotonation of an achiral phos-phonoacetate by a set of chiral 2-aminoalkoxides led to the corresponding enolate that... 

Several reactions were carried out with chiral olefines. For example, only one stereoisomer ii was isolated from the Patemo-Btichi reaction of D-glucal triacetate 10 with acetone (Scheme 3) [9]. 

F. E. Kiihn, J. Zhao, W. A. Herrmann, Chiral monomeric organorhenium(Vll) and organomo-lybdenum(VI) compounds as catalysts for chiral olefin epoxidation reactions. Tetrahedron Asvmm. 16 (2005) 3469. 

Considerable work was done to induce chirality via chiral auxiliaries. Reactions with aromatic a-ketoesters like phenylglyoxylates 21 and electron-rich al-kenes like dioxoles 22 and furan 23 were particularly efficient (Scheme 6). Yields up to 99% and diastereoselectivities higher than 96% have been observed when 8-phenylmenthol 21a or 2-t-butylcyclohexanol 21b were used as chiral auxiliaries [14-18]. It should be noted that only the exoisomers 24 and 25 were obtained from the reaction of dioxoles 22. Furthermore, the reaction with furan 23 was regioselective. 24 were suitable intermediates in the synthesis of rare carbohydrate derivatives like branched chain sugars [16]. Other heterocyclic compounds like oxazole 28 [19] and imidazole 29 [20] derivatives as well as acyclic alkenes 30, 31, and 32 [14,15,21,22] were used as olefinic partners. Numerous cyclohexane derived alcohols [18,21-24] and carbohydrate derivatives [25] were used as chiral... 

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