Cyclization cyclopentanoid

This cyclization is a Level 1 intramolecular cyclization as described by Deslongchamps (sec. 10.6.C). In acyclic systems, the conformation required for cyclization may not be the low energy conformation assumed by the polyene. When the polyene is attached to a preformed ring, the conformational stability of that ring will stabilize the entire polyene system, usually in the lowest energy all chair conformation required for efficient cyclization. Cyclopentanoid derivatives were found to be very effective for this purpose. 

For the preparation of divinyl ketones, as required for the Nazarov reaction, various synthetic routes have been developed. A large variety of substituted divinyl ketones, including vinylsilane derivatives, can thus be prepared. The Nazarov cyclization, and especially the vinylsilane variant, has found application for the synthesis of complex cyclopentanoids. 

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 ozonolysis of cyclobutene derivatives in the preparation of 1,4-diketones was also applied to the total synthesis of cyclopentanoid antibiotics 161>162>. The oxidative cleavage of (470) by ozone and reductive work-up yielded the diketone (471) in 73 % yield. Diketone (471) underwent intramolecular aldol cyclization to give the key intermediate (472), which was used to synthesize ( )-xanthocidin161162>, (+)-epi-xanthocidin 162), ( )-P-isoxanthocidin 161 162) as well as ( )-desdihydroxy-4,5-didehydroxanthocidin 162). 

The previous examples rehed on a radical termination. Cationic termination could also be used, after suitable oxidation of the final radical (Scheme 75) [211]. Thus, ester 252 was treated with base and ethylchloro-formate to give anion 253, which was oxidized to malonyl radical 254 by the ferrocenium ion. Cyclization/oxidation gave cation 256, which yielded 93% of malonate 257 by loss of the TMS group. This adduct was further elaborated upon and led to a cyclopentanoid monoterpene, dihydronepetal-actone. 

The mechanism of cyclopentane ring formation of allosamizoline may take place via pathway A or B during inositol biosynthesis, whereas via pathway C during shikimic acid biosynthesis (Scheme 1). This was based on a study using [3- H]-, [4- H]-, [5- H]-and [6- H2]-D-glucosamine feeding in experiments which indicated that the cyclization to form the cyclopentanoid moiety of allosamizoline is presumed to proceed via a 4-keto or... 

Tsuji and his group have developed a palladium catalyzed cyclization reaction that has led to a simple synthesis of 2-carbomethoxy-3-vinylcyclopentanone 142, which they have utilized in syntheses of cyclopentanoid natural products. In the steroid field, 142 served as a ring D component in an orthoquinodimethane-based route to ( )-18-hydroxyestrone. The (-I-)-diastereomer is a component of pregnancy urine. ( )-Estradiol-3-methyl ether was also obtained (Scheme 19). ... 

The radical cyclization products derived from sugars are useful for the synthesis of cyclopentanoid natural products. For example, the unprecedented 1,5-trans stereochemistry seen in the case of 4,6-0-benzylidene-glucose-derived radicals can be used to prepare optically active prostaglandin intermediates such as Corey lactone 44 (Fig. 7.12) [23]. 

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... 

Feldman s group was one of the most active in this field, and published several applications of the synthesis of cyclopentanoid compounds via [3 + 2] annulation [60]. Thus, the PhS radical-catalyzed reaction of substituted vinylcyclopropanes with functionalized alkenes affords vinylcyclopentane derivatives (equation (24)). The reaction mechanism is shown in Scheme 9 [60, 61]. Initiation occurs by PhS radical addition to the vinylcyclopropane (step a), followed by three additional steps prior to termination via ejection of the PhS radical to afford the vinylcyclopentane product (step e). The intermediate steps include ring opening to afford the homoallylic radical (step b), bimolecular addition of the alkene to produce the 5-hexenyl radical (step c), and cyclization to cyclopentanyl carbinyl radical (step d). 

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. 

In the synthesis of lumisterin steroid a D ABCD approach was used [151]. A key step is the Co-induced cyclization of cyclopentanoid ene-diynes prepared by thioalkylation of 2,3-substituted cyclopentanone zinc enolates with a-chlorosulfides. 

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