Cyclopropyl lactones

Tin(IV) chloride-catalyzed biomimetic transformation of allylic oxiranes with a tethered carboxyl group into 2-(hydroxymethyl)cyclopropyl lactones has been reported (equation 50)66. Essentially identical results are obtained from the ( )- and (Z)-isomers. 

Cyclopropyl lactones. Copper-catalyzed decomposition of unsaturated esters of dia-zoacetic acid can provide eyclopropyl lactones >2, 83). The soluble copper chelate 1 is superior for this purpose to copper powder or copper oxide. In a typical example, the lactone 3 is obtained from the diazo ester 2 in 92% yield. 

Herz et have isolated linearifolin-A (461) and -B (462) from Hymenoxys linearifolia Hook. New xanthanolides include apachin (463), acetylparthemollin (464), and ivambrin (465). Two groups have reported that photolysis of coronopilin (466) in benzene at 253.7 nm yields the cleaved product (467). Furthermore, Kagan et have shown that the major photolysis product of parthenin (468) is the cyclopropyl lactone (469). 

The method used by Coates and Robinson" involved the copper-catalysed decomposition of trans,trans-farnesyl diazoacetate (4) to the cyclopropyl-lactone (5) having the stereochemistry shown. This was transformed into the cis-aldehyde-ester (6) by standard methods. Base epimerization gave the more stable transcompound (7). A Wittig reaction between the trans-aldehyde-ester (7) and the phosphorane (8), followed by lithium aluminium hydride reduction, yielded presqualene alcohol (1) as the major product accompanied by the minor isomer (9). 

Conjugate addition to cyclopropyl lactones and fi-keto esters. (4, 219-220). The reaction of the cyclopropyl lactone (1) with 1.5 eq. of dimethylcopper-lithium at -30 to 0° gives the isomeric spirolactones (2) in high yield. The related cyclopropyl /34ceto ester (3) reacts similarly to give (4). 

There has also been a renewal of interest in reactions catalyzed by ru-thenium(II) porphyrin complexes, simultaneously with the development of new chiral ruthenium porphyrins [175-178]. Although these reactions focus mainly on asymmetric epoxidation of olefins [179,180], in some cases asymmetric cyclopropanations were very successful As a recent example, the intermolecular cyclopropanation of styrene and its derivatives with ethyl diazoacetate afforded the corresponding cyclopropyl esters in up to 98% ee with high trans/cis ratios of up to 36 and extremely high catalyst turnovers of up to 1.1 X 10 [140]. The structure of the metalloporphyrin is given in Fig. 2. Asymmetric intramolecular cyclopropanations were also reported with the same catalyst [140]. hi this case, the decomposition of a series of aUyhc diazoacetates afforded the cyclopropyl lactones in up to 85% ee. Both the inter-and intramolecular cyclopropanation were proposed to proceed via a reactive chiral ruthenium carbene intermediate. The enantioselectivities in these processes were rationahzed on the basis of the X-ray crystal structures of closely related stable chiral carbene complexes obtained from the reaction of the chiral complex with N2CPh2 and N2C(Ph)C02CH2CH = CH2. 

The quasi-Favorskii rearrangement has been used often in the synthesis of unnatural, conplex, polycyclic structures. Indeed, this method is uniquely suited for such targets. However, undesired side reactions can occur. An exanple, discussed here within its mechanistic context, is based on a report by Ueda and coworkers. They treated the polycyclic dibrominated diketone 37 with potassium hydroxide in the expectation of obtaining cubane-l,3-dicarboiq lic acid 38. Given what was known about quasi-Favorskii reactions at the time (vide supra), the plan made perfect sense. However, exposure of 37 to 5% KOH for 15 min at 80 °C afforded not 38 but the cyclopropyl lactone 43 fScheme 7.12). A proposed mechanism for the process began with a Haller-Bauer cleavage, always a potential risk in quasi-Favorskii... 

MoC15 promotes the ring-opening transformations of cyclopropyl ketones. Cyclopropyl phenyl ketone 251 is converted to 1-phenyl-1,2,4-trichloro-1-butene 252. Desilylative lactonization of propyl 2-(trimethylsilylmethyl)cyclo-propanecarboxylate 253 yields ds-2-chloro-4-pentanolide 254 stereoselectively [144]. (Scheme 100)... 

The availability of cyclopentenones from butanolides allows the lactone annulation to facilitate the synthesis of cyclopentyl natural and unnatural products. An example that highlights the latter is dodecahedrane (178) for which 179 constitutes a critical synthetic intermediate 136,137). Lateral fusion of cyclopentenones as present in 179 can arise by acid induced reorganization and dehydration of 180. While a variety of routes can be envisioned to convert a ketone such as 182 into 180, none worked satisfactorily137 On the other hand, the cyclobutanone spiro-annulation approach via 181 proceeds in 64 % overall yield. Thus, the total carbon cource of dodecahedrane derives from two building blocks — cyclopentadiene and the cyclopropyl sulfonium ylide. 

Deprotonation of (alkylcyclopropylidenemethyl)cyclopropanes (alkyl = methyl, cyclopropyl) with BuLi and subsequent reactions with various electrophiles afforded the corresponding ring-substituted methylenecyclopropanes (equation 295)365. When the lithiated compounds are treated with C02, carboxylic acids are obtained, together with isomeric lactones. These can be regarded as formal 3+2 adducts of the methylenecyclopropanes with C02 (equation 295)366. 

A few natural products which contain the cyclopropyl ring have been synthesized through metal catalysed cyclopropanation using dicarbonyl diazomethanes. ( )-Cycloeudesmol 63, isolated from marine alga Chondria oppositiclada, was synthesized via a sequence involving a copper catalysed cyclopropanation of a-diazo-/8-ketoester 61 to give the key intermediate 62 (equation 73)1 7,108. Similarly, the bicyclo[3.1.0]hexane derivative 65 was synthesized from the corresponding a-diazo-/8-ketoester 64 via the catalytic method and was converted into ( )-trinoranastreptene 66 (equation 74)109. Intramolecular cyclopropanation of -diazo-/i-ketoesters 67 results in lactones 68 which are precursors to 1-aminocyclopropane-l-carboxylic acids 69 (equation 75)110. 

A similar approach was also applied by the same authors [68], who addressed a series of carbocyclic cyclopropyl nucleosides of the L-series by utilizing L-gulonic y-lactone as the chiral source. 

The photochemistry of a,p nsaturated ketones has attracted much attention and is still a field cld of current interest. 1/Numer-ous examples of such photochemical transformations are well-documented for cyclic enones and dienones, including both cycloaddition ructions and rearrangements. For example, cyclopentenones / and/readily rearrange to cyclopropyl ketenes upon irra/idiation. Recently, the related cyclohexadienone/butadienyl ketene rearrangement has been shown to be a highly useful tool in the synthesis of natural products and macrocydic lactone /... 

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