Cyclopentanoid

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. 

An illustrative example for the usefulness of the Weiss reaction for the construction of complex cyclopentanoid carbon skeletons is the synthesis of the all -cis [5.5.5.5]fenestrane 7 after Cook et al., starting from the a-diketone ... 

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. 

Scheme 14 Some applications of 5-amino-3-ethoxycyclopentadienes 66 to the syntheses of cyclopentanoid skeletons [44,63,64,70-72]...

There is another type of multiple thermal Diels Alder reaction in which the initial monoadduct is involved, either directly or after one transformation, in a second cycloaddition that affords the final polycyclic compounds. These methodologies have been used especially in the synthesis of polycyclic cage compounds. Paquette was the first to report the conversion of 9,10-dihydroful-valene into polyfused cyclopentanoid systems [124],... 

Helmchen G., Goeke A., Kreisz S., Krotz A Lauer H., Linz G. Cyclopentanoid Natural Products Via Asymmetric Diels-Alder Reactions Stud. Nat. Prod. Chem. 1991 8 139-158... 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

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. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

Hubbard and Miller87 used a Lewis acid catalyzed Diels-Alder reaction between y.y-disubstituted o. /i-unsaluralcd esters and cyclopentadiene in their approach toward oligomeric cyclopentanoids. In order for the reaction to proceed, they needed to add trimethylaluminum as a desiccant prior to addition of the Lewis acid catalyst aluminum trichloride. The endo/exo selectivity of the reaction with 97, depicted in equation 29, increased from 98/99 = 75/25 to 88/12 when the reaction temperature was dropped from room temperature to —20 °C. 

H. Hemmerle, H. J. Gais, Asymmetric Hydrolysis and Esterification Catalyzed by Esterases from Porcine Pancreas in the Synthesis of Both Enantiomers of Cyclopentanoid Building Blocks , Tetrahedron Lett. 1987, 28, 3471-3474. 

Harney JW, Barofsky IM, Leary JD. (1978). Behavioral and toxicological studies of cyclopentanoid monoterpenes from Nepeta cataria. Lloydia. 41(4) 367-74. 

Ni-cyclam, Ni(CR), or Ni(tet a) can be used efficiently as catalyst in DMF, and in the presence of NH4CIO4 as proton source [71-74]. Ni species generated electrochemically react rapidly with organic halides to generate alkyl, alkenyl, or aryl radicals which add intramolecularly to a double or triple bond, then leading to cyclopentanoids (Table 7, entries 3-7a). 

Khand annulations (extremely efficient in the synthesis of polyquinanes and cyclopentanoid sesquiterpenes -triquinacene, coriolin, etc.-, among many others). 

Goldsmith and Soria (6b) reported a novel approach to a synthesis of the cyclopentanoid ring system 25 based on the 1,3-dipolar cycloaddition of p-bromobenzenesulfonyl azides with the electron-rich 1,4-cyclohexadienol ether 22 and subsequent ring contraction at moderate temperature (Scheme 9.6) (6a). 

Bobbitt J.M., Segebarth K.P. The Iridoid Glycosides and Similar Substances. In Bat-tersby A.R. and Taylor W.I. (eds.) Cyclopentanoid Terpene Derivatives. New York Marcel Dekker 1969. p25-31. 

The bicyclo[3.3.0]octene skeleton is of interest due to its potential use as an intermediate in the synthesis of cyclopentanoid natural and nonnatural compounds. The bicyclo[3.3.0]octene skeleton can be prepared by asymmetric elimination of the corresponding alcohols on treatment with a variety of chiral amines80, S1. Bicyclic trifluoromethanesulfonales 1 on treatment with (5)-Ar,Ar-dimethyl-l-phenylethylaminc give the corresponding bicyclo[3.3.0]octenes 2 with 15,5/ -configuration with up to 89% enantiomeric excess in high yield. 

The alkylation of cyclopentanoid enolate groups, which are part of polycyclic systems, is a common step in natural product syntheses, particularly in the synthesis of terpenoids and steroids. A high degree of stereoselectivity is usually encountered in such reactions, for example, in the preparation of the bicyclic compounds 17-2054 59. Steric, rather than electronic, control elements determine the diastereoselectivity. 

In the cyclopentanoid monoterpene family, compounds containing an iridoid-structure exhibit various bioactivities in Nature. For example, dehydroiridodiol, isolated from dry leaves of the cat-attracting plant Actinidia polygama Miq., is known to be an attractant for the male adults of the Chrysopidae and shows activity in amounts as small as lO"" pg [35]. Dehydroiridodial, a more oxidized product, was isolated as a pungent principle of Actinidia polygama Miq. and was characterized by T. Sakan et al. in 1978 [36]. 

Besides the synthesis of racemic dehydroiridodiol [37], some ex-chiral-pool syntheses using (S)-limonene have been described [38]. Dehydroiridodial was synthesized in the same manner [39]. Since the increasing number of cyclopentanoid natural products and their interesting biological activity has stimulated considerable interest in the synthesis of such compounds, we have used our methodology to provide a new asymmetric synthesis of dehydroiridodial, dehydroiridodiol, as well as analogues [40]. 

---