Salsolene oxide

The [4+ 4]-cycloaddition reaction of tethered bis-dienes has been used by Wender and co-workers in total synthesis as exemplified in syntheses of ( )-salsolene oxide and (-l-)-asteriscanolide (Scheme 28). In the synthesis of ( )-salsolene oxide, a nickel(0)-catalyst cleanly effects the cycloaddition of the two conjugated dienes in compound 93 to afford the bicyclo[5.3.1]undecadiene in a good yield and with moderate selectivity.99 The first synthesis of (-l-)-asteriscanolide was accomplished in only 13 steps. The key [4+ 4]-cycloaddition reaction efficiently set the requisite eight-membered ring of (-l-)-asteriscanolide in good yield and with excellent diastereoselectivity.100 The diastereoselective [4 + 4]-cycloaddition has also been applied to the synthesis of the core ring system found in several sesterterpenes such as the ophiobolins (Scheme 28).101... 

In the total synthesis of (—)-salsolene oxide (17), an architecturally unusual sesquiterpene with an unsaturated bicyclo[5.3.1]undecane core and trisubstituted... 

A type II cycloaddition was employed to synthesize ( )-salsolene oxide, as depicted in Scheme 3. Upon treatment with a nickel(O) catalyst, pentaene substrate 8 is converted to bicyclic systems 9a and b (3 7) in 80% yield. The major isomer (9b) is converted in two subsequent steps to ( )-salsolene oxide 10. 

Scheme 3. Synthesis of salsolene oxide via metal-catalyzed [4+4] cycloaddition.

Hypsicity profile (Salsolene oxide-Wender plan)... 

Wender (2006) plan for ( )-salsolene oxide step 6 (intramolecular zipper)... 

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