Chokol

An intramolecular palladium-catalyzed cycloisomerization of enyne 170 was used to access the antifungal agent, chokol C (Scheme 43).102 The choice of ligand and catalyst was essential to the efficiency of the Alder-ene reaction. Enone 171 was obtained as a single olefinic isomer resulting from migration of only Ha during the cycloisomerization reaction. 

Scheme 4.46. Conjugate additions of 1,1-borazircono alkenes en route to chokol A and G precursors.

Stereospecific syntheses of temarotene (a retinoid) [130] and of chokols A and G (fun-gitoxic sesquiterpenes) [131—133] have been developed using 1,1-boriozirconocene complexes 45. 

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],... 

Sesquiterpenes Phleum pratense Epichloe typhina chokol A-G 67... 

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. 

Koshino H, Togiya S, Terada S, Yoshihara T, Sakamura S, Shimanuki T, Sato T, Tajimi A. New fungiotoxic sesquiterpenoides, chokols A-G, from stromata of Epichloe typhina and the absolute configuration of chokol E. Agric Biol Chem 53 789-796, 1989a. 

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. 

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