Cyclopentane annulations

One way of achieving the synthesis of annulated cyclopentanes is via the intramolecular cycllzation of a variety of silicon and tin derivatives. For instance the enol ether (47) has been shown to... 

Most of the trends which were apparent in previous years have continued to manifest themselves. The feverish activity directed towards the synthesis of the hirsutane class of sesquiterpenes has not abated and other natural products containing annulated cyclopentane rings have also proved popular synthetic targets. In the field of steroid synthesis. Stork and his co-workers have developed an outstandingly elegant approach to 11-oxygenated steroids. 

Danishefsky and his co-workers have also achieved a total synthesis of quadrone (103), another interesting synthetic target containing annulated cyclopentane rings. Conjugate addition, followed by enolate trapping served to convert (99) to (100). Further elaboration including Aldol cyclization yielded the key intermediate (101), which underwent base-induced cyclization to (102), which in turn was converted to ( )-quadrone (103). 

Reaction of the imine moiety of 278 with excess ethyl diazoacetate in the presence of Cu(acac)2 led to the cyclopentane-annulated product 279 the structure of which was confirmed by an X-ray analysis 262. It is assumed that 279 results from reaction between a carbene dimer (diethyl fumarate) and an intermediate N-ylide or the... 

The vinylcyclopropane rearrangement is particularly valuable for cyclopentane synthesis. Aphidicolin (187), a most unusual antitumor agent, yields nicely to an analysis based on the concept of cyclopentanone annulation as outlined in Scheme 9... 

In practice, however, the annulation does not take place because the aldol condensation is essentially a reversible reaction and strain between the two cyclopentane rings shifts the equilibrium towards the reactants rather than towards the products. In order to overcome this difficulty, the synthetic scheme was substantially modified and 3-acetoxy-2-ethoxypropene (4) was used as the umpoled C3 fragment and the aldol condensation was substituted by a Wittig reaction, as... 

Reaction of linear conjugated dienes with la at —10 °C in hydrocarbon solvent in the presence of McsSiCl/AlCls affords stereospecific tra i-l-silyl-3-vinyl-cyclopentanes, indicating a [3 + 2] cycloaddition of the allyl group of la with a carbon arbon double bond of the diene [Eq. (9)]. In the [3 + 2] annulation reaction, of greater significance is the tram conformation of the trimethylsilyl group and vinyl groups. 

The product in entry 1 of Scheme 2.10 is commonly known as the Wieland-Miescher ketone and is a useful starting material for the preparation of steroids and terpenes. The Robinson annulation to prepare this ketone can be carried out enantioselectively by using the amino acid L-proline to form an enamine intermediate. The 5-enantiomer of the product is obtained in high enantiomeric excess.89 This compound and the corresponding product obtained from cyclopentane-1,3-dione90 are key intermediates in the enantiose-lective synthesis of steroids.91... 

The procedure described here serves to illustrate a general [3+2] annulation method for the synthesis of cyclopentane derivatives. A unique feature of this one-step annulation is its capacity to generate regio-specifically five-raembered rings substituted at each position, functionally equipped for further synthetic elaboration. As formulated in the following equation, the reaction proceeds with remarkably high stereoselectivity via the effective suprafacial addition of the three-carbon allene component to an electron-deficient olefin ("allenophile"). ... 

The reaction pathway may be supported by the observations with 4,4-dimethyl-5-trimethylsilyloxyhept-l-en-6-yne and its positional isomer 4,4-dimethyl-3-trimethylsilyloxyhept-l-en-6-yne. These react with Me2PhSiH to give the corresponding aldehydes, 280 and 282, respectively, as a mixture of two diastereomers under the conditions similar to mode 1 in Scheme 13 (Equations (47) and (48)). In the reaction of 281, an appreciable amount of 283 is formed concomitantly, which implies that the trimethylsilyloxy group at an allylic position likely retards the cyclopentane annulation step. 

I. Marco-Contelles and J. Ruiz-Caro, Iridoids from carbohydrates via Pauson-Khand reaction synthesis of advanced highly oxygenated cyclopentane-annulated pyranosides from D-glucal derivatives,. /. Org. Chem., 64 (1999) 8302-8310. 

I(Cyclopentadienyl)dicarboayM phate, Cp(CO)2Fe+=CHSC H, phenylthio iron carbene is obttii C1CH2SC6H3 and then with (C H Cyclopentane annulation.2 by insertion into C-H bonds. Thi... 

Cyclopentane annulation.2 This complex is useful for cyclopentane annulation by insertion into C-H bonds. Thus reaction of 1 with the enolate of ketone 2 provides... 

Fig. 1.42. Cyclization of a 5-hexenyl radical intermediate from a Barton-McCombie defunctionalization as a method for cyclopentane annulation (cyclizing defunctionalization, in terms of Figure 1.2 this means a "substitution including a fragmentation and an addition ).

Similar cyclopentane annulations of allylsilanes with benzotropylium salts149,150, tetracyanoethylene151, benzyl cations152 and l,2,4-triazoline-3,5-diones had been reported153. 

Cyclopentane ring annulation by a 3 + 2 radical cycloaddition reaction of 3-alkenyl type radicals 68 and 69 to electron-deficient olefins like 70-71, represents a useful methodology for the construction of polysubstituted cyclic molecules 72, 73 etc.2-4,46-48 Cekovic and coworkers have exercised... 

The 4,5-threo-thiobutenolide 91 thus obtained was then reduced and shortened by one carbon atom to arrive at aldehyde 92 onto which a highly stereoselective cyclopentane-forming annulation was performed via a TBSOTf/DIPEA-promoted silylative protocol. In the event, a major 2,3-cA-configured bicycle educt 94 was isolated in a 82% yield, accompanied by only 7% of fram-isomer 93. Completion of the synthesis entailed the reductive cleavage of the thiolactone bond within 93 and 94, followed by acidic deprotection, giving l-deoxy-l-thio-4a-carba-[ -D-... 

Fig. 1.35. Cyclization of a 5-hexenyl radical intermediate from a Barton-McCombie defunctionalization as a method for cyclopentane annulation.

Scheme 18). The formation can be explained by the initial conjugate umpolung of the aldehyde and subsequent 1,4-addition to the unsaturated ketone. After proton transfer, an intramolecular aldol-type addition results in the formation of the aforementioned zwitterions. Nucleophilic displacement of the imidazolium moiety by the alkoxide provides the p-laclonc, which exhibits increased strain, since it is annulated to a cyclopentane ring. Consequently, the P-lactone breaks apart and liberates CO2 and the observed cyclopentene products (Scheme 19). 

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