Pulegone oxidation

The Favorski rearrangement normally goes with inversion at the terminus, as in 86 (semi-ezo-S) rather than 87 (semi-17). Reusch and Mattison (1967) have verified this for the pulegone oxides of which only one of the optically active forms is given in (181). It is of interest that the cyclopropanone intermediate opens abnormally, that is with retention. These authors note that their conditions are similar to those for electrophilic substitution with retention, namely frontside proton transfer from a polar aggregate (Cram, 1965). 

Further reactions on these compounds lead to other oxidised products in which the lack of stereochemical control in the epoxidation is unimportant, so, for example isophorone oxide rearranges with various catalysts to the cyclopentanone 182 (80% yield) while both isomers of pulegone oxide 179 gives the cycloheptadione29 183 (78% yield). Exhaustive methylation of the extended enolate produced by reduction of 181 gives 184 in good yield.28... 

Finally, with the aim of discovering novel chiral oxomolybdenum catalysts able to perform enantioselective alkene epoxidations, Kuhn et al. have reported the exploration of the catalytic behaviour of a series of dioxomolybdenum(VI) complexes with chiral cw-8-phenylthiomenthol ligands derived from ( + )-pulegone. Therefore, the epoxidation of c -p-methylstyrene using t-butyl-hydroperoxide as the oxidant and performed in the presence of ( + )-(2i ,5i )-2-[1-methyl-l-(phenylthio)ethyl]-5-methylcyclohexanone oxime as the ligand, did not produce, however, a significant optical induction in these conditions. 

S )-3-nydroxy-2-mcthylpropanoic acid, 13-A, can be obtained in enantiomeri-cally pure form from isobutyric acid by a microbiological oxidation. The aldehyde 13-B is available from a natural product, pulegone, also in enantiomerically pure form. Devise a synthesis of enantiomerically pure 13-C, a compound of interest as a starting material for the synthesis of a-tocopherol (vitamin E). 

FIGURE 4.49 Mechanism for the oxidative rearrangement of (R)-pulegone to (7 )-menthofuran. 

The antimicrobial activity of piperitone oxide rich Mentha rotundifolia M. suaveolens) oil was investigated by Oumzil et al., who found it less significant than that of pulegone or piperitone rich oils. The biosynthesis of the two levorotatory diastereomers from (15,25)(+)-piperitenone oxide... 

Hydroxy-2-mcthylpropanoic acid, E, can be obtained enantiomerically pure from isobutyric acid by a microbiological oxidation. The aldehyde F is available from a natural product, pulegone, also in enantiomerically pure form. 

Manganese(lll) acetate oxidation of (+)-p-menth-l-ene yields the two lactones (165 X=0, Y = CH2) and (165 X = CH2, Y = O) as major products together with anticipated acetates similar oxidation of (+)-pulegone yields the C-2 acetates in low yield and oxidation of isomenthone in the presence of isopropenyl acetate results in acetonylation at C-2 and C-4. Further examples of the rearrangement of epoxides with KOBu -aprotic solvents (pyridine is favoured) have been reported (c/. Vol. 6, p. 44), e.g. (166) to (167), although with the corresponding 1,2-epoxy-... 

In both these cases where an Insect cytochrome P-A50 system has been shown to be responsible for the oxidation of a-plnene and pulegone, the enzyme had to be Induced to higher activity to effectively catalyse the reaction. This leads to the question of whether Insect P-A50-dependent oxidations are sufficiently active In natural situations to produce a significant amount of the metabolites. Due to the Importance of cytochrome P-A50 oxidations In pesticide metabolism, there are, fortunately, several studies which show that the Insect oxidase system Is easily and rapidly Induced In response to a large variety of non-nutrient chemicals In the food. 

Reaction with aji-unsaturated ketones and lactonesThe reactivity of a,/ -enones to singlet oxygen depends on the conformation. Systems that exist in s-trans-conformations (e.g., A4-3-ketosteroids) react slowly if at all. However, s-cis-enones react readily. For example, (R)-( + )-pulegone (1) reacts to give the products 2-4. The same products are obtained by oxidation with triphenyl phosphite ozonide (3, 324 325). 

An asymmetric synthesis of mevalolactone in over 87% e.e. employs a 1,3-oxathiane as the chiral auxiliary (81TL2859). The reagent (818), easily prepared from (+)-pulegone (81TL2855), was metallated with u-butyllithium and the anion reacted with acetaldehyde. Oxidation of the diastereomeric mixture of alcohols to the ketone (819) and reaction of... 

R,S)-Citronellal can be purchased from BASF, and (R)-citronellal from Dragoco, Fluka, or Takasgo Perfumery Co., Ltd., Japan. (R)-Citronellal can also be synthesized from pulegone with ee >99%.5 (S)-Citronellal may be obtained by oxidation of (S)-citronellol,6 which is accessible by different routes with ee 95%.7 The optical purity of citronellal can be determined by GLC after conversion to the acetal of (-)-(2R,4R)-pentanediol.8 For the reactions described, (R,S)-citronellal from BASF, (R)-citronellal from Dragoco, and (S)-citronellol from Fluka were used. (R,S)-Citronellal... 

In their enantioselective total synthesis of (+)-triptocallol (3-79), a naturally occurring terpenoid, Yang and coworkers made use of a concise Mn(OAc)rmediated and chiral auxiliary-assisted oxidative free-radical cyclization [39]. Reaction of 3-77, bearing a (R)-pulegone-based chiral auxiliary, with Mn(OAc)3 and Yb(OTf)3 yielded tricyclic 3-78 in a twofold ring closure in 60% yield and a diastereomeric ratio of 9.2 1 (Scheme 3.20). A further two steps led to (-i-)-triptocallol (3-79). For the interpretation of the stereochemical outcome, the authors proposed the hypothetical transition state TS-3-80, in which chelation of the (3-keto ester moiety with Yb(OTf)3 locks the two carbonyl groups in a syn orientation. The attack of the Mn -oxidation-generated radical onto the proximate double bond is then restricted to the more accessible (si)-face, as the (re)-face is effectively shielded by the 8-naphthyl moiety. 

Silverstein and coworkers have used the peroxy add oxidation of exo-all lidene cycloalkanones as a route to keto acids (Scheme 23). Oxidation of pulegone (72) and hydrolysis of the derived enol lactone led to the keto acid 3). 

---