Chokol synthesis

The stereoselective synthesis of rac-chokols A (61) and G (62) from the same precursor gem-boriozirconocene 59 involves a conjugate addition to 2-methylcyclopentenone to give the common intermediate 60. The latter is then transformed through a series of reactions to provide the chokols in overall yields of 16% and 17%, respectively (Scheme 7.19) [131],... 

The stereoselectivity of these processes has proved useful in the synthesis of natural products. For example, a key step in an elegant synthesis of ( )-chokol-A was achieved by heating the Grignard reagent whose synthesis is described on p. 36 at 130° for 6 h [35] ... 

This type of stereocontrol is featured in a synthesis of the fungitoxin ( )-chokol-A (156) (Scheme 32). Alcohol (147) (easily prepared from l-hexen-5-one in two steps) efficiently gave the allyl chloride (148) (CCI4/PBU3). The metallation/cyclization/oxidation step (148) - (l49) -> (150) (151) (de-... 

Mash has recently employed a methylcerium reagent in the synthesis of (-)-chokol The reagent reacts with the readily enolizable cyclopentanone derivative (4) to give (-)-chokol A in 80% yield, as shown in Scheme S. 

This method was used in a synthesis of (—)-modhephene (78% ee) which incorporates a [3.3.3]propellane skeleton65. Enantioselective syntheses of (7 )-muscone (>95% ee)66, (+ )-/ -eudesmol (75% ee)67, and (—)-chokol A (80 % ee)68 also make use of this asymmetric cyclo-propanation, employing chiral dioxolanes as inductors. 

In a stereoselective synthesis of (-)-chokol A 130, Suzuki and Kametani [30] introduced the side chain by Claisen-Johnson rearrangement with a modest stereoselectivity. However the stereogenic center in / -position to the ester group in compound 132 is suppressed later in the synthesis (Scheme 6.18). 

This cyclization has been used in an efficient synthesis of chokol A 11.219, an anti-fungal compound (Scheme 11.74). The acetal 11.216, in which the tartrate moiety functions as an economical chiral auxiliary, cyclized using palladium acetate to give an 8.5 1 mixture of stereoisomers. Aeidic hydrolysis removed the acetal to give a ketone 11.217, which could be taken through to the natural product 11.219 by selective reduction of the electron-poor alkene, stereoselective addition of a methyl group, allylic oxidation and desilylation. 

---