Demethyl calamenene

In 2009, Nicolaou and co-workers reported an organocatalytic total synthesis of demethyl calamenene (168), a potent cytotoxic agent, which is a beautiful application of SOMO-activated catalysis (Scheme 17.29) [68]. The key step involved an asymmetric intramolecular Friedel-Crafts reaction of aldehyde 166 to achieve the bicyclic aldehyde 167 using imidazolidinone 122 as a SOMO-activated catalyst (56% yield, 90% ee). 

Scheme 82 SOMO-activated Friedel-Crafts-type a-arylation in the synthesis of demethyl calamenene (359)...

In 2009, Nicolaou et al. reported the asymmetric total synthesis of the antitumour natural product demethyl calamenene based on an enantioselective organocatalytic intramolecular Friedel-Crafts type a-arylation of aldehydes bearing electron-donating groups on their aromatic nucleus. This reaction, catalysed by chiral /err-butyl-3-methyl-5-benzyl-4-imidazolidinone, afforded the corresponding polycyclic products in good to high yields and with excellent enantioselectivities for a broad variety of aldehydes, as shown in Scheme 10.4. 

Enantioselective intramolecular F-C-type a-arylation of simple aldehydes, based on the concept of organo-SOMO catalysis, paved the way to the synthesis of two natural products via very sophisticated and well-designed strategies (Section 35.2.1). In 2009, Nicolaou and coworkers published the synthesis of the antitumor natural product demethyl calamenene [50] and, independently, in the same year the group of MacMillan developed an elegant route to (—)-tashiromine (Scheme 35.29) [5b]. 

The reduction of simple trisubstituted olefins derived from 25d has found use in the enantioselective total synthesis of pseudopteroxazole 31c, demethyl methoxy-calamenene 32c, and both enantiomers of mutisianthol 33c (Scheme 4) [41,46,47]. 

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