Tricyclic ketal

As expected, other enol ethers work well in these procedures. For example, Jones and Selenski find that implementation of method F, which occurs by addition of MeMgBr to benzaldehyde 5 in the presence of dihydropyran (DHP) at 78 °C affords a 66% yield of the corresponding tricyclic ketal 59 with better than 50 1 endo diastereoselectivity (Fig. 4.31).27 On the contrary, Lindsey reports use of method H with the benzyl alcohol 35 and diethylketene acetal. The cycloaddition reaction occurs almost instantaneously upon deprotonation of the benzyl alcohol 35 by f-butyl-magnesium bromide in the presence of the ketene acetal and yields the corresponding benzopyran ortho ester 60 in a 67% yield.29... 

Hydrolysis of dioxetane 223, or of ketal 10, led to an inseparable mixture of expected product 225, as well as bicyclic isomer 226. The mixture was 1 2 (225 226), and underwent standard acylation reactions to give, for example, 179 on treatment with Ac20/pyridine/CH2Cl2. Carbonates such as 181 were available from 225 upon treatment with various chloroformates in pyridine/CH2Cl2. In other words, the alcohol 225 could be funneled away from the mixture by reaction with electrophiles, providing the desired tricyclic products. The bicyclic aldehyde 10 was isomerized to obtain tricyclic ketal 228 under dehydrating conditions in the presence of an alcohol. 

For example, ( )-hirsutene, a member of the triquinane class of natural products, has been prepared by tandem radical cyclization as shown in equation 132801. Also, in a key step in the synthesis of silphiperfolene, the tricyclic ketal precursor oxosilphiperfolene was generated by a tandem cyclization process (equation 133)805. The desired enantiomer was generated in a 5 2 excess over the unwanted one. 

In addition to siphonarin A [140], the fljian mollusk Siphonaria normalis has been reported to contain an unusual tricyclic ketal with a trioxaadamantane ring skeleton. The structure of muamvatin 2 [161] was determined by nmr spectroscopy (118). The possible roles of the polypropionate metabolites isolated from S honaria species could be associated with its trailfollowing habits along with defense against predators. 

Unsaturated macrolides such as (115) or (117) (Scheme 38) have been synthesized by Eschenmoser using a fragmentation reaction as a key step. The tricyclic ketal carboxylate (114) can be cleaved as an amidinium salt to give (115) in excellent yield simply on heating. Similarly, the macrolide (117) with ( , )-configuration is obtained from (116). This decarboxylative double fragmentation represents a nine-center Grob type. 

The tricyclic intermediate 58 was subsequently used to construct the pentacyclic nucleus of lycorine (1) by base-catalyzed Michael addition and aldol condensation. The key intermediate (58) was obtained from 3-pyrrolidone ethylene ketal with one equivalent of 4,5-methylenedioxyphtalic anhydride followed by LiAlH4 reduction,... 

In acid solution, the double bond of (203) is hydrogenated to the trans-fused sulfone (204). Presumably, this hydrogenation goes through a cis-fused intermediate that is rapidly epimerized to (204) under the acidic conditions of the reaction. Condensation of the sodium salt of 7,7-ethylenedioxy-3 Oxooctanoate (205) with (204) produces (206). Cmde (206) is cycUzed, hydrolyzed, and decarboxylated, producing the tricyclic compound (207). Hydrogenation of (207) followed by ketal hydrolysis and cydization affords (208) in an overall yield of 35% from hydtindandione (203). 

Kon and Isoe have also been examining routes from tricyclo[3.3.0.0 ]oc-tanes, but the latter were prepared by an alternative route from the diazoketone made from the cyclopentenylpropionic acid 432. This yielded the tricyclic ketone 421, but as a mixture of both possible isomers. On treatment with formic acid and ketalization, the major product obtained was 433. The fact that the hydroxyl group is present as both stereoisomeric forms is unimportant, because oxidation and treatment with methyllithium yielded ( )-404, also prepared by Trost (see... 

This new cyclization method was used as the key step in the synthesis of a substance containing the bridged-ring system of the gibberellin family of plant hormones.4 The tricyclic keto ketal (3) was used to supply final rings A, B, and C. 

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