Enantiodivergent transformation

The above described total synthesis features the first enantiodivergent approach to (+)- and (—)-scopadulcic acid A. The central transformations are the stereoselective carbonyl group reduction with (S)-Alpine Borane , the use of enolization stereoselection to dictate which enantiomer is produced, and the palladium-catalyzed bis-Heck cyclization which occurs with complete stereo- and regiocontrol to establish the scopadulan scaffold. 

The latter reaction was further described by Koizumi et al. [86b] with slightly different results (lower facial selectivity for the exo-approach), in connection with the enantiodivergent synthesis of fused bycyclo [2,2,1] heptane lactones 91 (see Scheme 47). The key step of this transformation was the regioselective DIBAL reduction of only one of the two ester groups in the adducts, followed by... 

Apparently, the reaction proceeds in an enantiodivergent manner, i.e., the re-gioisomeric lactones 8a and 8b emanate from opposite enantiomeric ketones and show different ee values. Transformations of this kind are rare, and the most significant examples of these have been summarized by Kagan [27]. 

The first natural product in this family to be synthesized with this methodology was (+)-erogorgiaene (201) [142], and provided an excellent proof of concept for the more complex structures to follow (Scheme 50). Importantly, this synthesis began with racemic dihydronaphthalene precursor 205, and included a powerful enantiodivergent carbenoid transformation. In this key step, one enantiomer of the substrate was poised to react with the rhodium carbenoid to form the desired C-H... 

Chiral monoesters, obtained either from a prochiral diol or diester, may be converted by a suitable series of chemoselective transformation to either enantiomer of a given target compound (enantiodivergent synthesis) (Scheme 11.1-13)110 40l... 

Whilst the whole-cell approach has proved invaluable, the associated problems of overmetabolism and side reactions can be encountered. Another way to counter the problems of high cost in using isolated BVMOs is to use an NADH dependent enzyme, as NADH retails at approximately one tenth of the cost of NADPH. The Type 2 DKCMOs from Pseudomonas putida ATCC 17453 (= NCIMB 10007) are NADH dependent, and Grogan et al. were successftd in applying a complement of these enzymes, termed MOl, to the transformation of bicyclo[3.2.0]hept-2-en-6-one, to yield another enantiodivergent mix of lactones enantiomeric to those obtained... 

In the alkaloid domain, several hydroxylated alkaloids were chosen to demonstrate that arene cw-dihydrodiols can serve as synthons in heterocyclic synthesis. The first venture into this area was the enantiodivergent synthesis of pyrolizidine triols from erythruronolactone 30, as shown in Figure 8 (30-32). The same principles of enantiodivergent design of the pinitols were applied here to yield the two enantiomeric azido dienes 40 and 41, which were then transformed to the alkaloids by previously documented azide-diene cycloaddition followed by vinylaziridine- yrroline rearrangement (33). 

A wide diversity of products may be generated from the transformation of a racemic mixture under the action of an enantiopure reagent. An interesting situation is the preferential formation of two products, one deriving exclusively from the (R)-substrate and the other one deriving from the (S)-substrate (Scheme 2.4a). This is an enantiodivergent reaction - Pjj, Sg -> Pg. The actual situation is... 

As the complementary aldehyde 306 can be prepared in the same way from aldehyde 303 the whole transformation constitutes an enantiodivergent sequence. 

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