Total Synthesis of Eight-Membered Lactones

Total Synthesis of Eight-Membered Lactones 211 5.2.2.9 Cossy Synthesis of the Lactone Moiety (2005)... 

The secondary marine metabolite (+)-acetoxycrenulide has unprecedented structural features which prompted L.A. Paquette et al. to embark on its total synthesis. The eight-membered carbocycle of the target was constructed via a Claisen rearrangement. The bicyclic p,y-unsaturated lactone was subjected to Simmons-Smith conditions, that delivered the cyclopropyl ring exclusively from the p-face of the molecule as a result of the predominant ground-state conformation. 

An example of a surprisingly facile and stereoselective formation of an eight-membered lactone from an acyclic precursor diene ester was observed during the total synthesis of the antitumor agent octalactin A (148) (Scheme 27) [81]. The dense substitution pattern in cyclization substrate 146 presumably imposes... 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

The esterification was used in the preparation of an eight-membered lactone in the total synthesis of a new natural product, cephalosporolide D (Eq. 16) [21c]. 

Martin first reported the total synthesis of solandelactone E (4e) by construction of the eight-membered lactone ring (Scheme 5.25) [73]. By the complete asymmetric... 

Aggarwal performed the stereoselective total synthesis of solandelactones E and F by a stereocontrolled allylboration reaction of the eight-membered lactone 83, which was prepared by cyclization of 81 (Scheme 5.28) [76]. Treatment of the seco-acid 81 under Yamaguchi conditions according to the protocol previously established by Martin et al. [73] and Pietruszka [75] for a similar reaction resulted in the formation of the target lactone 82 in good yield. 

On the contrary, Mohapatra and Yellol [77] attempted Ru-catalyzed RCM for the preparation of the eight-membered ring and accomplished the formal total synthesis of solandelactones (Scheme 5.30). Cychzation of 86 was conducted using an Ru catalyst [78] to give the desired eight-membered lactone 85 bearing the cis double bond in 71% yield. 

---