Stork isoxazole annelation

A new and highly stereoselective total synthesis of the 13 -ethyl gonane (448) which used a Stork isoxazole annelation sequence on the diene (449) has been intimated. 

Sandmeyer synthesis (isatin) 145 Schmidt-Druey synthesis (pyridazine) 461 Schollkopf synthesis (oxazole) 173 Sharpless-Katsuki epoxidation 24 Shaw synthesis (pyrimidine) 468 Skraup-Doebner-Miller synthesis (quinoline) 400 Smiles rearrangement 446 Sommelet-Hauser rearrangement 136 Staudinger reaction 53 Steglich reagent (DMAP) 348 Stork isoxazole annelation 191... 

A fuller account of Stork s synthesis of the unsaturated tricyclic diketone [see (7) on 1, 277] is given in a communication of 1967.3 Another communication4 discusses the mechanism of the isoxazole annelation. 

The 4-(chloromethyl)isoxazole 13, which is readily accessible from 3,5-dimethyloxazole, serves as a C4-building-block in annulations to cycloalkanones (isoxazole annelation according to Stork). The primary step is alkylation leading to product 14, a masked triketone. On hydrogenation, the isoxazole ring is reductively opened and cyclization via the enaminone 15 leads to the enamine 16. On treatment with sodium hydroxide, this is converted into the bicycloenone 17 by hydrolysis, acid fission of the y dicarbonyl system and an intramolecular aldol condensation (analogous to a Robinson annu-lation) ... 

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