Stereochemistry enantiomerically pure starting materials

The olefin metathesis reaction was also a key feature of the synthesis of epothilone A completed by a group at the Technical University in Braunschweig, Germany (Scheme 13.61). This synthesis employs a series of stereoselective additions to create the correct substituent stereochemistry. Two enantiomerically pure starting materials... 

When we first introduced the concept of enantiomers and chirality in Chapter 16, we stressed that any imbalance in enantiomers always derives ultimately from nature. A laboratory synthesis, unless it involves an enantiomerically pure starting material or reagent, will always give a mixture of enantiomers. Here is just such a synthesis of the Japanese beetle pheromone you have just met. You can see the Z-selective Lindlar reduction in use—only one geometrical isomer of the double bond is formed— but, of course, the product is necessarily racemic and therefore useless as beetle bait, because in the original addition of the lithiated alkyne to the aldehyde there can be no control over stereochemistry. If all the starting materials and reagents are achiral, the product must be... 

In summary, these compounds represent a novel series of chiral grass herbicides that provide yet another example where chirality is very important for herbicidal activity. Additionally, the use of the sugar D-glucose as a chiral and enantiomerically pure starting material also offers the advantage of having the correct stereochemistry established inherently in the molecule. 

Predominant stereochemistry of 90% inversion (retention) indicates a reaction path involving 90% inversion (retention) and 10% retention (inversion), giving a product that is 80% enantiomerically pure from an enantiomerically pure starting material. 

A third method for enantioselective synthesis involves the use of a stoichiometric amount of a chiral auxiliary. This is an enantiomerically pure material that can control the stereochemistry of one or more reaction steps in such a way as to give product having the desired configuration. Once the chiral auxiliary has achieved its purpose, it can be eliminated from the molecule. As in syntheses involving resolution or enantiomerically pure starting materials, subsequent steps must be controlled to give the correct configuration of newly created chiral centers. 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

A noteworthy synthetic application for the reaction of J with a,g-unsaturated phosphoryl compounds is represented by the addition involving hitherto unknown (-)-(Sp)-methylphenylvinylphosphine oxide J 2. The resulting tertiary phosphine oxides 13 with saturated carbon chains and known stereochemistry at phosphorus constitute attractive starting materials for the preparation of optically pure phosphines. The organophosphorus substrate 12 was obtained by decarbomenthoxylation of the enantiomeric ester... 

The discovery synthesis starts with enantiomerically pure (L)-alanine. Unfortunately, the enantiomeric purity is lost during die synthetic manipulations. We reasoned that, if the stereochemistry at the tertiary carbon could be somehow efficiently preserved, then cheap alanine derivatives could be very practical starting materials. This approach led to two distinct highly efficient processes, which will form the subject of the next sections. 

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