Cyclopentanoids fused

Hirsutene (1) and A9(,2,-capnellcnc (2), the parent members of the hirsutane and capnellane families of triquinane natural products, respectively, are isomeric molecules that possess four contiguous stereogenic centers, one of which is quaternary. The linearly fused tricyclopentanoid frameworks of compounds 1 and 2 are obviously very similar, differing only with respect to the positions of the three methyl groups. An asset of Curran s tandem radical cyclization strategy is that it provides a unified entry into a wide variety of linear condensed cyclopentanoid natural products. As a result, it is possible to devise nearly identical retrosynthetic pathways for these structurally related molecules. 

The synthesis of other angularly fused triquinanes as well as linearly fused sesquiterpenes such as hirsutene and capnellene quickly followed. Many general methods for the synthesis of cyclopentanoid natural products emerged as a result of the target-oriented effort [6]. These accomplishments have been reviewed extensively on numerous occasions [7]. This chapter reviews the history of retigeranic acid from its isolation and structure determination to published approaches to its synthesis and the four total syntheses accomplished to date. 

Where the diene function is attached to or is part of a carbocyclic system, the vinyl cyclopropane formation and subsequent rearrangement affords a reliable approach to the formation of tricyclic carbocycles. Some of the most elegant demonstrations of the use of this methodology in total synthesis of fused cyclopentanoid terpenes come from the work of Hudlicky and coworkers (equations 63-66)90 95"100. In these cases the diazoketones bear a carboxylate-substituted double bond of diene and the intramolecular cyclopropanation requires the combination of CuS04/Cu(acac)2 as catalyst. 

An elegant strategy for the synthesis of fused cyclopentanoids has been reported by Marino and coworkers (Scheme 21).38 Reaction of (104) with the phosphonium salt (105) generated the bicyclic system (106). Further conversion of (106) to (107) enabled the annulation sequence to be repeated to form tri-quinane derivatives such as (108). 

Fused Five-membered Rings.- Radical cyclizations continue to give ready access to fused cyclopentanoids. For example the stereo-controlled formation of (37) allows a radical-induced ring closure to the cyclopentanol (38) in a process which has been described as... 

Naturally Occurring Fused Cyclopentanoids.- An exceptional review on... 

Naturally Occurring Fused Cyclopentanoids.—Activity in this area continues to be intense. Little etal7 have used the rather low-yielding intramolecular 1,3-diyl trapping procedure in syntheses of A -capnellene (105) and the isomeric hirsutene (106), whereas in an alternative route to (105), sequential Nazarov and aldol cyclizations are used to build up the three ring system. Pyrolysis of the cage compound (107), derived from cyclopentadiene and 2,5-dimethylbenzo-quinone, leads to the hirsutene precursor (108) in high yield. The preparation of another potential precursor (110) to the hirsutanes by intramolecular [2 2]photoaddition of (109) has been detailed in full. ... 

Although synthetic activity towards natural fused-cyclopentanoid sesquiterpenes shows signs of abating, two new approaches to hirsutene (18) are worthy of mention. In one of these new approaches, Ley and Murray have demonstrated the use of intramolecular cyclization of the P-keto-ester (16), using A-phenyl-selenophthalimide and tin(iv) chloride to form the key tricyclieintermediate (17), and in the second approach Wender and Howbert have provided yet another example of the use of their intramolecular 1,3-photocycloaddition involving arenes and alkenes [viz. (19) -> (20)] to produce the central intermediate (21) on the road to hirsutene. 

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