Wender’s synthesis

Although Wender s synthesis was completed prior to Hudlicky s, it was published later [65]. It utilized the technique of mefa-photocycloaddition of arenes that Wender developed into a general method of synthesis for both angular and linear triquinanes. The overall strategy was centered around an intramolecular Diels-Alder cycloaddition for construction of the internal six-membered ring of the target. 

Scheme 10.14 Wender s synthesis of triquinane part of retigeranic acid by meta-photocycloadditon...

Zero-valent nickel is especially effective for the cyclization of (7j5(allyl) bromides.2 4 295 Corey used this technique to cyclize 450 to 451. Subsequent photolysis in the presence of diphenyl disulfide (PhSSPh) gave humulene, 452. 94 Wender et al. reported a novel [4+4]-cycloaddition reaction in which two diene moieties are coupled with a nickel(O) catalyst to form eight-membered rings. In Wender s synthesis of asteriscanolide,... 

In Holton s and Wender s work, the total synthesis was achieved by sequentially forming the AB ring through the fragmentation of epoxy alcohols derived from (—)-camphor and a-pinene. Nicolau s, Danishefsky s, and Kuwa-jima s total syntheses involved B ring closure connecting the A and C rings, whereas in Mukaiyama s synthesis, the aldol reaction was extensively applied to construct the polycyclic system. 

As an application of this procedure, Snapper succeeded in the formal total synthesis of (+)-astericanolide. Treatment of iron complex 62, which is prepared from cyclopentenol derivative 60 and iron complex 61, with MeaNO gives fused cyclobutene derivative 63. ROM of cyclobutene of 63 using Ig under ethylene gas smoothly proceeds to produce an eight-membered ring of 64 via Cope rearrangement. The resulting product 64 is converted into Wender s intermediate for the synthesis of (+)-astericanolide ... 

These intramolecular meta-addition processes were utilized in the key steps for the total synthesis of a-cedrene [245], isocomene [246], hirsutene [247], coriolin [248], silphinene [249], rudmollin [250], laurenene [251], and fenestranes [252-254], which were synthesized by Wender s and Keese s groups (Scheme 58). 

The first naturally occurring member of the class of fenestranes is the diterpene lauren-l-ene (27), isolated in 1979 from the essential oil of Dacrydium cupressinum. The intermediate (26) for Wender s stereocontrolled synthesis of (27) is readily accessible by attack of KOH on the tosyloxy ketone (25) to give, via fragmentation, a carboxylate anion which undergoes immediate ring closure to the lactone (26 Scheme 12). 

Wender s construction of the A/B ring system [8a] in principle resembles the Holton synthesis, but makes use of the 4/6 precursor... 

The more convergent routes of Nicolaou et al. and Danishefsky et al. with B ring closure from a tethered A-C precursor are clearly the least efficient with respect to total yield (about 0.01 % starting from commercially available materials) if directly compared to the other two routes. Additionally the Nicolaou route needs enantiomer separation or a -presumably less favorable - asymmetric synthesis, whereas the Danishefsky route addresses absolute stereochemistry but involves more steps. Holton s synthesis shows quite good yields throughout with a total one of approximately 0,1 %, but has less room for improvements and is based on a not readily available starting material. The best synthesis in all respects to date is the one of Wender and coworkers, which is about 1-2 orders of magnitudes better in total yield (ca. 0.8%),... 

Scheme 8.2 Wender s comments regarding an ideal synthesis...

The method of synthesis of ten-membered rings by olefin metathesis, involving tricyclo[4.4.0.0 ]decane intermediates, is also popular, and this year is illustrated by Wender and Lechleiter s synthesis of isabelin (165) (see also Section 2). 

Wender s group was able to streamline the synthesis considerably (Scheme... 

Wender and Aube have independently described the use of the Bischler-Napieralski reaction in the synthesis of Yohimban alkaloids. Aube s approach involved the cyclization of indole 50 followed by reduction of the resulting dihydroisoquinoline... 

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