Eight-membered ring synthesis with dienes

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... 

The relative ease of ring formation from dienes decreases in the order six->seven->five-membered rings. Hoshi et al. [138] have recently reported the synthesis of a number of disilacycloalkenes via RCM of bis(allyldimethyl-silyl)substituted compounds, with the ruthenium vinylcarbene complex Cl2(PCy3)2Ru(=CHCH=CPh2) used as a catalyst. Successful formation of seven-and eight-membered rings has been achieved under mild reaction conditions. 

Eight-membered rings can be obtained by [4+4]-cycloadditions of 1,3-dienes [1] via diradicals or other intermediates. Synthesis of such compounds has been achieved by thermal, [2] photochemical, [3] and by metal-catalyzed [4] processes these reactions have been the subject of extensive mechanistic [5] and theoretical [5c] studies. Their strategic applications in natural product synthesis have been reviewed. [5d] The thermal version has generated little interest, except in orthoquino-dimethane dimerizations and in cycloreversions the Cope rearrangement of 1,2-divinyl-cyclobutanes [3] is more commonly used. [4+4]-Cycloadditions are also used with 1,3-dipoles or mesoionic heterocycles for the synthesis of six- and seven-membered rings. Sometimes also [6+4]-cycloadditions are... 

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,... 

Eight-membered rings are less commonly prepared by annulative RCM, with a number of reports of failure. Medium ring synthesis by RCM is often challenging, and has been the topic of a number of reviews. Grubbs reported the failure of dienes 108 and 109 to undergo RCM when conducted at an initial substrate concentration of 10 mmol (Scheme 2.43) the em-diester functionality is therefore not sufficient to achieve selective cyclization at this reaction concentration. Instead, dimeric species 110 and 111 were isolated and characterized, indicating that the EM was very low the EM is likely to be below 1 mmol as the desired cyclooctene products... 

Clark and co-workers used the olefin metathesis strategy pioneered by Rodriquez and co-workers for the synthesis of eight and nine-membered ring carbocycles, in their synthesis of the nine-membered carbocyclic core of a class of herbicidial nonadrides known as the comextins. Treatment of diene 381 with either catalytic 3 in refluxing dichloromethane, or 4 in... 

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