Cyclopentanone, -substituted

The prochiral meso form of 2-cyclopenlen-1,4-diol (101) reacts with the (Z)-alkenyl iodide 102 to give the 3-substituted cyclopentanone 103 with nearly complete diastereoselectivity (98 2)[92], The reaction is used for the synthesis of prostaglandin. The alkenyl iodide 102 must be in the Z form in order to obtain the high diastereoselectivity. The selectivity is low when the corresponding (Z)-alkenyl iodide is used[93]. 

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

Similar to cyclohexanones, substituted cyclopentanones also adopt a conformation with the substituents in a sterically favorable position. In the case of 2-substituted cyclopentanones 1 the substituent occupies a pseudoequatorial position and the diastereoselectivity of nucleophilic addition reactions to 1 is determined by the relative importance of the interactions leading to predominant fra s(equatorial) or cw(axial) attack of the nucleophile. When the nucleophile approaches from the cis side, steric interaction with the substituent at C-2 is encountered. On the other hand, according to Felkin, significant torsional strain between the pseudoaxial C-2—H bond and the incipient bond occurs if the nucleophile approaches the carbonyl group from the trans side. 

Precomplexation of 2-butylcyclopentanone with methylaluminum bis(2,6-di-hrt-butyI-4-methylphenoxide) (MAD), prior to the addition of methyllithium, leads to the exclusive formation of the equatorial alcohol via cis attack3 4. However, this methodology is apparently not applicable to 3-substituted cyclopentanones. Thus, addition of propylmagnesium bromide to... 

Generally, in contrast to 2-substituted cyclopentanones, the diastereoselectivity of addition reactions to 3-substituted cyclopentanones is nearly independent of the nucleophile and the substituent in the 3-position. Thus, addition of various Grignard reagents, including ethynyl reagents, to 3-methyl- and 3-ferf-butylcyclopentanone leads to almost the same ratio of diastereomers (Table 3)3,4 6, 27,2s... 

Exclusive trims attack of the nucleophile is also observed with 2,3-epoxycyclopentanones 1559. In contrast to 2-alkyl- and 2-methoxy-substituted cyclopentanones, preferential trans attack to 2,3-epoxycyclopenlanones occurs with alkyl, ethenyl, and ethynyl nucleophiles. Thus, there is no assistance by the epoxidic oxygen for cis attack. Due to the geometry of the molecule, chelation-controlled cis attack is not possible39 60. 

The intramolecular Michael addition of acyclic systems is often hampered by competing reactions, i.e., aldol condensations. With the proper choice of Michael donor and acceptor, the intramolecular addition provides a route to tram-substituted cyclopentanones, and cyclopentane and cyclohexane derivatives. Representative examples are the cyclizations of /3-oxo ester substituted enones and a,/J-unsaturated esters. 

In the case of 3-substituted cyclopentanones or cycloheptanones, derivatization with diamine is slower, and the reaction time ranges from a few minutes to several hours. This method is not applicable to acyclic ketones and enones. 

An interesting example of a facile anionic multi-step one-pot reaction is the condensation of 2-ethylpropenal with substituted cyclopentanones using DBU as base to give functionalized cyclohep-... 

However, the reactions of mono substituted cyclopentanone sometimes becomes so much stereodirected that a mixture of cis and trans isomers is obtained. For example the reduction of 2-alkyl cyclopentanone by LiAlH4 gives a mixture of cis-trans isomeric alkyl cyclopentanols. 

Continuing with the diastereomerically pure tricycle 56, an 11-step sequence consisting of redox and protective group chemistry was necessary to generate a / -hydroxy keton (58) suitable for a retro-aldol addition via an intermediate alkoxide to the highly substituted cyclopentanone 52 (Scheme 6). 

In conclusion, the longest linear sequence of Yamada s (-)-claenone (42) synthesis consist of 40 steps (6 C/C connecting transformation) with an overall yield of 2.1%. The centrepiece of Yamada s synthetic strategy is the sequence of two Michael additions and a retro-aldol addition to provide a highly substituted cyclopentanone building block (52). 

The structural similarity between claenone (42) and stolonidiol (38) enabled Yamada to exploit an almost identical strategy for the total synthesis of (-)-stolonidiol (38) [40]. A short retrosynthetic analysis is depicted in Fig. 12. An intramolecular HWE reaction of 68 was successfully applied for the macrocyclization. The highly substituted cyclopentanone 69 was made available by a sequence that is highlighted by the sequential Michael-Mi-chael addition between the enolate 53 and the a, -unsaturated ester 70 followed by a retro-aldol addition. However, as is the case for the claenone (42) synthesis, the synthesis of stolonidiol (38) is characterized by numerous functional and protecting group transformations that are a consequence of Yamada s synthetic strategy. 

Both 2-cyanocycIohexanone and 2-cyanocyclopentanone give good yields of the CK-aicohol by reduction at a mercury cathode in aqueous alcohol at pH 8 [63]. Reduction of 2-carbethoxy substituted cyclopentanone and cyclohexanone under the same conditions favours the cfr-alcohol at -6° C but the thermodynamically preferred /ra 4-isomer at 80° C [64]. 

Cyclopenta-l,2,3-dithiazole 140 was formed through a reaction of 2-substituted cyclopentanone oximes and S2CI2 (Scheme 71 2001CC403). Exhaustive chlorination accompanied this reaction as in the case of other cyclopentadithioles (see above). 

As an example, this opening was applied to the synthesis of enantiopure 3-substituted cyclopentanones 506 from 2-norbornanones 505 ° (equation 220). The key step on this synthetic route was the Beckmann fragmentation of the oxime 505, promoted by TfaO/ pyridine. 

The title compound can be prepared by condensing an alkyl a-bromocaprylate with a trialkyl propane-1,1,3-tricarboxylate to give a substituted cyclopentanone. Hydrolysis, decarboxylation, and esterification of the resulting monocarboxylic... 

S)-(+) -2-(p-TOLU NESULFINYL)-2-CYCLOPENTENONE PRECURSOR FOR ENANTIOSELECTIVE synthesis OF 3-SUBSTITUTED cyclopentanones (2-Cyclopenten-l-one, 2-[(4-methylphenyl)sulfinyl>, (S)-)... 

Certain unsaturated aldehydes may be converted to cyclic ketones by a related mechanism. The formyl group reacts with Rh(I) complexes to form an acyl-Rh hydride species, which undergoes intramolecular reaction with the olefinic linkage present in the same molecule (117a). Asymmetric induction is observed with a chiral diphosphine ligand (Scheme 53) (117b-d). Enantioselective cyclization of 4-substituted 4-pentanals into 3-substituted cyclopentanones in greater than 99% ee is achieved with a cationic BINAP-Rh complex. 

Recent studies on radical-induced cyclisation reactions have led to a simple, one step method for the preparation of hydroazulenes from appropriately substituted cyclopentanone precursors. Treatment of 1, for example, with triphenyltin hydride and AH3N in refluxing toluene gave 2 in 79% yield. 

Nucleophilic attack occurs at C(2) of the diene. The 1,3-cyclohexadiene complex 66 is converted to the homoallyl anionic complex 67 by nucleophilic attack, and the 3-alkyl-1-cyclohexene 68 is obtained by protonation. Insertion of CO to 67 generates the acyl complex 69, and its protonation and reductive elimination afford the aldehyde 70 [20]. Reaction of the butadiene complex 56 with an anion derived from ester 71 under CO atmosphere generates the homoallyl complex 72 and then the acyl complex 73 by CO insertion. The cyclopentanone complex 74 is formed by intramolecular insertion of alkene, and the 3-substituted cyclopentanone 75 is obtained by reductive elimination. The intramolecular version, when applied to the 1,3-cyclohexadiene complex 76 bearing an ester chain at C(5), offers a good synthetic route to the bicyclo[3.3.1]nonane system 78 via intermediate 77 [21]. 

Comins, D. L. LaMunyon, D. H. Chen, X. Enantiopure N-acyldihydropyridones as synthetic intermediates asymmetric synthesis of indolizine alkaloids (-J-205A, (-J-207A, and (-J-235B./. Org. Chem. 1997, 62, 8182-8187. Padwa, A. Muller, C. L. Rodriguez, A. Watter-son, S. H. Alkylation reactions of3-(phenyl-sulfonyl) methyl substituted cyclopentanones. Tetrahedron 1998, 54, 9651-9666. 

Two different reports have illustrated that cationic Me-DuPhos-Rh complexes serve as excellent catalysts for asymmetric C-C bond-forming cyclization reactions. In the first example, Bosnich and co-workers discovered that valuable 3-substituted cyclopentanones can be prepared simply by treatment of 4-pentenal derivatives 68 with the Me-DuPhos-Rh catalyst.69 Asymmetric intramolecular hydroacylation furnished the product cyclopentanones 69 in high yield and with enantioselectivities ranging from 93% to 98% (Scheme 13.24). 

As you can see, reduction of 2-substituted cyclopentanones may not be very stereoselective. The substituent probably occupies a pseudo equatorial position and the two faces of the ketone are very similar. 

This is a good route to 2-substituted cyclopentanones and cyclohexanones. 

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