Diastereoselective alkylation of chiral

Figure 3.8 Diastereoselective alkylation of chiral fumaric acid derivatives.

Diastereoselective Alkylation of Chiral Ester and Amide Enolates Generation of Enantiomerically Pure Carboxylic Acids with Chiral Centers in the a-Position... 

Side Note 13.4 presents the diastereoselective alkylation of a very special ester enolate in which one can easily understand what the stereocontrol observed is based upon. However, only very specific carboxylic acid derivatives are made accessible by those alkylations. Much more broadly applicable diastereoselective alkylations of chiral ester or amide enolates will be introduced in Figures 13.42 and 13.43. Figure 13.42 shows alkylations of a propionic acid ester—derived from an enantiomerically pure chiral alcohol—via the and Z -enolate. 

The substrates are available by diastereoselective alkylation of chiral p-hydroxy acids followed by conversion to the aldehyde and Wittig olefination. The overall process provides a diastereoselective synthesis of compounds with three consecutive asymmetric centers. Tetrahydropyridines.5 Danishefsky has used an intramolecular version of the Giese... 

Diastereoselective Alkylation of Chiral Keto- and Formylaminals. Diamine (1) forms a chiral ketoaminal by condensation with phenylglyoxal monohydrate. Diastereoselective addition of a Grignard reagent to the ketoaminal and subsequent hydrolysis affords optically active t-a-hydroxyaldehydes with >94% ee (eq 2). Various... 

The method has been applied to the diastereoselective synthesis of naturally occurring compounds such as frontalin (84-100% ee) and(—)-malyngolide (95% ee). On the other hand, diastereoselective alkylation of chiral formylaminal with Grignard reagents and the subsequent hydrolysis afford optically active S-a-hydroxyaldehydes with moderate stereoselectivity (60% ee). ... 

On the other hand, the diastereoselective reduction of the chiral hydrazone derived from V-aminoephedrine and acetophenone and subsequent hydrogenolysis affords (5)-a-phenylethylamine with 30% ee. Optically active a-phenylethylamine with high ee is obtained from the diastereoselective alkylation of chiral hydrazones derived from (/ )- or (S)-l-amino-2-(methoxymethyl)pyrrolidine. ... 

Diastereoselective Alkylation of Chiral Amides Derived from Ephedrine. Chiral amides derived from ephedrine are converted to the corresponding dianion. The subsequent diastereoselective alkylation with alkyl iodides affords chiral a-substituted amides with >90% de. Acid hydrolysis affords optically active a-substituted acids with 78% ee as a result of racemization in the cleavage step (eq 2). 

Scheme 70 Chiral Auxiliaries Used in the Derivatization of Glycine Equivalents and Diastereoselective Alkylation of Chiral A -Alkylidene Amino Acid Derivatives ...

Other methods of preparation and diastereoselective alkylation of chiral butyrolactones (44) are summarized in the recent review of asymmetric synthesis of lignans (16). 

In this segment aryl alanines have proven very effective in many cases. The meanwhile classical way to prepare aryl alanines is the diastereoselective alkylation of chiral glycine derivatives e.g. by the methods of Schollkopf [3], Evans [4], Oppolzer [5], Seebach [6] and others. (Fig.4)... 

The first three sections of this chapter describe diastereoselective alkylations of chiral enolates including heteroatom-substituted enolates [15, 20]. Section 3.4 deals with the class of enolate alkylations that have typically been included under the rubric of chiral-auxiliary-controlled processes. As suggested by the term, the auxiliary is only transiently utilized and, following alkylation, is subsequently excised. The facile use of chiral auxiliaries in asymmetric enolate alkylations has played and continues to play a pivotal role in the stereoselective formation of new C-C bonds. After a brief survey of the relatively few developments in catalytic enantioselective enolate alkylations (Section 3.5) [21, 22], selected examples of enolate a-hydroxylations (Section 3.6) [23-25] and a-halogenations (Section 3.7) [26, 27] are covered. The corresponding a-aminations of enolates are discussed in Chapter 10, describing stereoselective formation of a-amino acids. 

There are numerous examples of diastereoselective alkylations of chiral enolates, in which the extant asymmetry of the substrate exerts suitable stereochemical control in the alkylation step [15, 20]. Several useful guiding principles have been determined to aid in predicting the stereochemical outcome. The examples discussed in the following sections have been selected to showcase the power of enolate alkylations for the stereoselective formation of new C-C bonds, as well as to highlight selected historical aspects in the development of the field. 

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