Permanganate Oxidation of Myrtenal to Form Potentially Useful Chiral Auxiliaries
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Chiral auxiliaries are molecular segments useful in asymmetric synthesis. Terpenes, such as pinene are broadly used for this purpose. Myrtenal, a pinene derivative, has not been widely used for this purpose, even though it is readily available in good enantiomeric purity. A new oxidative transformation of myrtenal has been discovered that offers potentially useful new pinene-derived chiral auxiliaries. Permanganate oxidation of (IR)-myrtenal, 1, gives three products (3, 5, and 7). The structure of these products was proved, including the confirmation of structure 7 by x-ray crystallography. This reaction was optimized for yield and distribution of products. The optimal conditions for the reaction are 5 equiv. NaHZP04 and 3 equiv. NaMn04 in a water/methanol solvent system, using minimal amount of acid and bisulfite in the reaction work-up. Furthermore, the yield improved when the temperature was kept about 10°C. The optimized overall yield was 96%. The optical purity of 3 was determined to be >97% ee by enantioselective chromatography. This reaction also was carried out with the other enantiomer of myrtenal, 2, synthesized (25%, >99%ee) by the catalytic SeOz/t- BuOOH oxidation of (+)-a.-pinene. The thermal decarboxylation of7 resulted in 9 (73%), the thermodynamically more favorable diastereomer of 3. Dione, 5, may be obtained as a major product (71%) by the catalytic tetra-n-propylammonium perruthenate (TPAP)/ Nmethylmorpholine- N-oxide (NMO) oxidation of a mixture of 3 and 9 prepared by permanganate oxidation and thermal decarboxylation of the crude reaction mixture.