Dactylol synthesis

The power of this tropylium ion cycloaddition strategy for the synthesis of complex molecules can be seen in synthesis of dactylol 231 by Feldman and coworkers (Scheme 52)111. Irradiation of 229 (prepared from 4-methyltropone in two steps) afforded... 

Furstner succeeded in the synthesis of dactylol using ring-closing metathesis of 9d. Crimmins synthesized enantioselectively diene 9e, and RCM of 9e gave eight-membered ring compound lOe, which is an intermediate for the synthesis of laurencin [Eq. (6.12)] ... 

The intramolecular photocycloaddition of the alkenyltropone (55) is reported to yield (56) which is then used as the starting material for a synthesis of the natural product dactylol, (57)... 

DIASTEREOSELECTIVE INTRAMOLECULAR 4+3 CYCLOADDITION AND AN ENANTIOSELECTIVE TOTAL SYNTHESIS OF (+)-DACTYLOL... 

A number of nonbiogenetic total syntheses of dactylol in both racemic and optically pure forms have appeared in literature. The first example is the work reported in 1986 by Gadwood and eo-workers. (Scheme 3). This synthesis began with the eonversion of enone 5 into cyclobutanone 6. The cyclooctanoid framework was constructed using an oxy-Cope... 

The first non-racemic synthesis of dactylol was demonstrated by Molander and Eastwood using a 5+3 annulation strategy (Scheme 5). In... 

The lack of diastereoselectivity in the intramolecular 4+3 cycloaddition reactions of cyclopentenyl oxyallylic cations with tethered butadienes has prohibited the application of this methodology to the synthesis of natural produets. Therefore, the development of stereocontrol in cycloadditions of this type is of great significance. Our study in this area was conducted in the context of the synthesis of (+)-dactylol. 

There are several important applications of the Mo-carbene complex (1) in the synthesis of natural products, illustrating the power of the ring-closing olefin metathesis. Thus, elegant syntheses of coronafacic acid, dactylol, and fluvirucin have been reported. 

In cases where metathesis with the catalyst 84 is unsuccessful or very sluggish, then the Schrock catalyst 85 or catalysts such as 86 are often effective. This is particularly the case for the formation of tri- or tetrasuhstituted alkenes, which are normally too hindered to he formed using the catalyst 84. For example, ringclosing metathesis of the diene 91 is unsuccessful with the Grubbs catalyst 84, but the cyclohexene 92 can be formed in excellent yield with the catalyst 86 (2.113). An efficient synthesis of the medium-ring terpene dactylol 94 was accomplished with the Schrock catalyst 85 (2.114). Attempted metathesis of 93 with the catalyst 84 failed to give any of the medium-ring trisubshtuted alkene product. 

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