Cyclopentanone derivatives

The addition of diphenylcyclopropenone to pyrrolidinocyclohexene and ring expansion of the adduct gave an aminocyclononadicnone (330,331), A hereas the corresponding cyclopentanone derived enamine yielded a bieyclic enone. 

Feringa s group has demonstrated that cyclopentene-3,5-dione monoacetals as 2-47 can also be successfully applied as substrates in an asymmetric three-component domino Michael/aldol reaction with dialkyl zinc reagents 2-48 and aromatic aldehydes 2-49 [17]. In the presence of 2 mol% of the in-sitw-generated enantiomeri-cally pure catalyst Cu(OTf)2/phosphoramidite 2-54, the cyclopentanone derivatives 2-51 were formed nearly exclusively in good yields and with high ee-values (Scheme 2.11). 

The approach to cyclopentanone derivatives from oxaspirohexanes can be appropiately demonstrated by the following examples S7). 

Recently, an enantioselective total synthesis of ( )-18,19-dihydroantirhine has been reported by Kametani s group (140). They started from the chiral cyclopentanone derivative 211, obtained from the previously prepared (/ )-1,2-isopropylideneglyceraldehyde (141). Utilizing a number of reaction steps, 211 was transformed to 215 with the desired stereochemistry at the future C-15 and... 

Reaction of 4a with TiCl4 was carried out in the presence of siloxyalkene 3 as nucleophile and the results are summarized in Table III. In the reaction with ketene silyl acetals 3a and 3e at -78 °C, y-ketoesters 15a and 15e were obtained instead of chloride product 8 which is a major product in the absence of 3. Formation of product 15 is likely to result from trapping of alkylideneallyl cation 5 with 3 at the sp2 carbon. In contrast, the reactions with silyl enol ethers 3f and 3g gave no acyclic product 15, but gave cyclopentanone derivatives 16-18. The product distribution depends on the mode of addition of TiCl4 (entries 4-7). 

From an exhaustive retrosynthetic analysis and from the experimental work performed by Curran [29] [32], it was clear that the synthesis of modhephene required an elaborate strategy. In the first place, the tandem radical cyclisation should be conducted individually rather than just in one step since it allows more flexibility. In the second place, Curran s observation that the precursor of modhephene (54) could be the olefmic exocyclic derivative 55 allows the application of a series of heuristic principles already familiar to us, which greatly simplifies the retrosynthetic analysis and leads to diquinane and, finally, through a second radical retroannulation to the very simple cyclopentanone derivative (Scheme 7.24). 

Addition reactions of cyclopentanone derivatives, where the reagent is directed to the opposite ring face by a vicinal substituent. 

Ketones are most widely represented and include cyclopentanone derivatives, such as the jasmin fragrance substances, and cyclic ketones with 15-17-membered carbon rings, such as muscone and civetone, which are constituents of the extremely expensive animal products, musk and civet. Cyclopentadecanone, a natural musk fragrance, and the unsaturated 5-cyclohexadecen-l-one, which has not yet been found in nature, have odor characteristics similar to those of muscone and civetone and are more easily synthesized. They are, therefore, often used as substitutes. 

Pinacol rearrangement driven by the release of the ring strain of a cyclobutane ring has been employed in an extremely efficient manner to form cyclopentanone derivatives. Experimentally. the Lewis acid mediated aldol condensation of benzaldehyde with l,2-bis(trimethyl-siloxy)cyclobutcne at —78 C gave the pinacol 1 in its silylated form.35,36 Subsequent treatment of this pinacol with trifluoroacetic acid at room temperature afforded 2-phenyl-cyclopentane-l,3-dione (2) in 97% yield.35,36... 

Morpholinocyclohex-l-ene is smoothly acylated by diketene to give a fused pyranone (61CB486, B-68MI22400). The initially formed diketone ring-closes and the pyranone results from elimination of morpholine. Using the cyclopentanone-derived enamine, much resinous material is formed and the yield of pyranone is reduced. 

The reaction of nonconjugated dienes such as 1,4-pentadiene and 1,5-hexadiene yields cyclopentanone derivatives, while 1,6-heptadiene gives only traces of ketone (equation 47). -2 80 The yields in these reactions are low, 1,4-pentadiene giving only 10% of cyclic ketone product. 

The Lewis acid-mediated domino reaction between cyclohex-2-enone and methyl azide has been investigated at the B3LYP/6-31G and B3LYP/6-31-G //B3LYP/ 6-31G levels of theory. A domino process comprising three consecutive reactions yields a cyclopentanone derivative as the product.31 The Cp RuCl(PPh3)2-catalysed 1,3-dipolar cycloaddition of organic azides with terminal alkynes produces 1,5-disub-stituted 1,2,3-triazoles.32... 

The Ferrier (II) reaction is quite efficient to form six membered carbocycles, but is unsuitable to prepare cyclopentitols. Five membered enollactone 14 was converted to the cyclopentanone derivative 16 as a single epimer upon treatment by LiAlH(OtBu)3 (Scheme 4) [41]. Spectroscopic studies established some mechanistic details. Accordingly, the hydride of the reducing agent rapidly added to the carbonyl and formed with the metal a stable alu-minate complex. The carbocydization occurred by protonation followed by fragmentation and aldol type cyclization process. 

Intramolecular Carbon-Hydrogen Insertion. The advantages of rhodium(II) catalysts for carbenoid transformations are nowhere more evident than with carbon-hydrogen insertion reactions. Exceptional regio- and diastereocontrol has been observed for Rh2(OAc)4 catalyzed transformations of a broad selection of diazoketones, a-diazo-p-ketoesters, a-diazo-P-keto-sulfones and -phosphonates which yield cyclopentanone derivatives in moderate to good yields (57-54). In contrast, poor yields and low regioselectivities characterize the corresponding copper catalyzed reactions. Applications of dirhodium(II) catalysts for C-H insertion reactions have even been extended to the synthesis of y-lactones (55), 3(2//)-furanones (56,57), P-laetones (58), and P-lactams (59,60). 

Demethyldeoxynupharidine (5) was synthesized from (—)-castoramine (59) in six steps (Scheme 6) (26). Syntheses of ( )-nupharolutine (50) and of ( )-7-epinupharolutine (60) were completed from cyclopentanone derivative 61 (Scheme 7) (62). A stereocontrolled synthesis of ( )-anhydronupharamine (62) was achieved in six steps from cyclopentanone derivative 63 (Scheme 8) (63). Tufariello (64) pointed out the possibility of synthesizing of 7-demethylodeoxy-nupharidine (5) from nonfunctionalized nitrones such as 64 (Scheme 9). Compound 65, after cyclization and removal of the ketone group, would furnish a synthesis of alkaloid 5. 

Scheme 8. Synthesis of ( )-anhydronupharamine (62) from cyclopentanone derivative 63.

Bayer-Villager oxidation of the cyclopentanone derivative (442 R = chiral auxiliary) with MCPA gives the saturated pyranopyridone derivative (443) which has been used in the total synthesis of the heteroyohimbine alkaloid, 3-isorauniticine (444) <9iJA966o>. 

An earlier synthesis of the piperidine alkaloid anhydronupharamine by Beckmann rearrangement of a cyclopentanone derivative has now been extended to... 

C-Alkyl glycosides are useful carbohydrate mimetics, commonly employed as enzyme inhibitors. The formation of various C-alkyl glycosides was evaluated with phosphates 9 and 12 (Table 3). Mannosyl phosphate 9 was activated with TMSOTf and coupled to allyltrimethylsilane to provide a-allyl glycoside 2 (18) in excellent yield (93%). Coupling of 9 to the cyclopentanone derived trimethylsilyl enol ether 35 afforded 34 as a mixture of diastereomers in 84%... 

Scheme IX/3. Formation of seven-membered ring compounds from cyclopentanone derivatives [7].

Reaction of a-ketoenamines with a series of cyclic and acyclic nitroolefins gave aminocyclopentene derivatives with high diastereoselectivity, as products of kinetic control instead of the expected 1,2-oxazine N-oxides (see Section III.D.2)45,46. For example, ketoenamine 62 when reacted with cyclic nitroalkene 61 afforded 65 as a single diastereoisomer46, first through the dipolar intermediate 63 and later through the betaine-type intermediate 64. Hydrolysis of this enamine furnished the cyclopentanone derivative 66, also as a single diastereoisomer (equation 11). 

Chiral imines have proved to be useful reagents in the synthesis of cyclic systems. For example, imines derived from (S)-( — )- and (R)-( + )-l-phenylethylamine 412 have been used in the preparation of optically pure polysubstituted cyclopentanone derivatives 414 (equation 87)252 and in enantioselective steroid synthesis (equation 88)253. 

They found that at room temperature using benzene as the solvent only 3% consisted of the diketone 25 and mainly the ring-contracted products were obtained 33% of keto aldehyde 24 and 28% of ketone 26. From an industrial point of view the desired compound is the keto aldehyde 24, which is an interesting intermediate for the synthesis of other cyclopentanone derivatives with floral and fruity smells. The acid catalyzed reaction mechanism leading to the synthesis of keto aldehyde 24 had been discussed earlier (25). Therefore, it is of interest whether the product distribution changes in the presence of a heterogeneous catalyst system and also whether the decarbonylation of the compound 24 to compound 26 can be suppressed. 

Mash has recently employed a methylcerium reagent in the synthesis of (-)-chokol The reagent reacts with the readily enolizable cyclopentanone derivative (4) to give (-)-chokol A in 80% yield, as shown in Scheme S. 

An example of the reaction of an alkenylcerium reagent with a cyclopentanone derivative has been reported. As shown in Scheme 20, the ( )-cerium reagent adds to the ketone to provide a single adduct in modest yield. However, the (Z)-cerium reagent did not react, presumably due to steric effects. 

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