Methods using enantiomerically pure building blocks

4 Methods using enantiomerically pure building blocks 

We conclude this section with two examples of the synthesis of chiral products by starting from an appropriate chiral building block. This has been named the chiron approach by Hanessian, and is described in great detail in his book.t l The distinctive feature of this type of reaction is that no new stereogenic units are formed and all the stereogenic units of the product are directly derived from the starting material. For this reason these cannot be considered as asymmetric synthesis but methods of this type are of some practical importance in areas where suitable chiral starting materials are readily available. 

The first application involves an amino acid as chiral starting material in the synthesis of wnnatural amino acids, those never imagined by nature.t l 5-Serine (15) is converted into its N-protected analogue 

The second example in this section is taken from some work performed by chemists at Squibb, The target molecule is aztreonam, 

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Enantiomerically pure amines are extremely important building blocks for biologically active molecules, and whilst numerous methods are available for their preparation, the catalytic enantioselective hydrogenation of a C=N bond potentially offers a cheap and industrially viable process. The multi-ton synthesis of (S)-metolachlor fully demonstrates this [108]. Although phospholane-based ligands have not proven to be the ligands of choice for this substrate class, several examples of their effective use have been reported. 

Kolbe electrolysis of trilfuoromethylated carboxylic acids has been shown to be a versatile method for providing useful building blocks having a CF3 group. Seebach and Renaud have prepared new types of trifluoromethylated chiral building blocks from enantiomerically pure 3-hydroxy-4,4,4-trifluorobutyric acid (Scheme 7.6) [76]. 

This method was used in the following example, in which an enantiomerically pure lactone, a useful synthetic building block, was made from naturally occurring glyceraldehyde. 

The aldol reaction is the preferred method for the stereoselective synthesis of 1,3-dioxygenated building blocks. In 1978, Enders et al. reported the first enantioselective aldol reaction in the difficult case of a-unsubstituted (3-ketols using SAMP and RAMP. Diastereo- and enantiomerically pure yyn-(3-ketols are available by aldol reaction of SAMP/RAMP... 

The synthetic utility of (5S)- and (5R)-menthyloxy-2(5H)-furanones has been extensively explored and is well documented. The ready availability of these enantiomerically pure butenolides via the singlet photooxygenation of furfuraF and their wide range of reactivity contribute to their popularity as chiral building blocks. The present procedure for the preparation of the title compound and the useful epimerization step are modifications of methods originally reported by Feringa and co-workers. ... 

One feasible method for the exploration of chiral open-framework compounds is the use of chiral chemical units as primary building blocks by coordinating with metal or other assembly methods to form 2-D layer or 3-D open-framework structures with optical activity. A notable example is the enantiomerically pure zinc phosphonate based on a mixed phosphonic acid-phosphine oxide chiral building block reported by Bujoli and coworkers in 2001.[91] The reaction procedures are shown as follows. 

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