Wender synthesis, Cope rearrangement

A new multistep synthesis of ( )-reserpine (109) has been published by Wender et al. (258). The key building block of the synthesis is cw-hexahydroiso-quinoline derivative 510, prepared by the extension of the previously elaborated (259) Diels-Alder addition-Cope rearrangement sequence. Further manipulation of 510 gave 2,3-secoreserpinediol derivative 512, which already possesses the required stereochemistry in ring E. Oxidative cyclization of 512 yielded 3-isoreserpinediol (513), which was transformed by the use of simple reaction... 

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 ... 

An alternative approach to these systems, developed by Wender and his co-workers,utilizes the rearrangement of 2-(2-vinylcyclopropyl)cyclopent-2-enones as the key step [e.g. (217) — (218)]. An interesting feature of this route is the photochemical conversion of the tra 5-isomer (216) into the desired cis-isomer (217). A similar Cope rearrangement has been utilized in a recent synthesis of ( )-B-Himalchene (219). 

Oxy-Cope rearrangements (95, 98, 99) have been extensively used in natural product synthesis to generate l-oxo-hexa-l,5-diene systems which are then elaborated to introduce the functionality presented in the selected targets. Wender and his coworkers have utilized this methodology in a key step in the synthesis of reserpine (36, 37). They envisioned that the DE-ring precursor 128 could arise from the hydroisoquinoline 129 which could be generated by oxy-Cope rearrangement of isoquinuclidene 130 (Scheme 3.20). This key intermediate, in turn, could be prepared by Diels-Alder reaction of dihydropyridine 131 with an appropriately substituted dienophile 132. 

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