Cyclopentenones functionalized

Other related examples are provided in the literature [KY3, NS5, SM8, TH2, WKl, YK6]. The reductions of substituted cyclopentenones, functionalized vi-nylketones, and carbacyclin precursors by NaBH4-CeCl3 in MeOH have also provided interesting stereoselectivities [BA4, GLl, Jl, MH5, SG3]. The asymmetric reduction of a-enones by oxazaborolidines-BH3 has been described in Section 3.2.3. 

Unique chemistry is associated with the cyclopentenone all five carbon atoms can be functionalized, and the endo-methyl groups of the acetonide assure clean stereoselective addition of the alkenylcopper reagent from the convex side. The use of the acetonide group to control enolate regioselectivity and to mask alcohols should be generally applicable. 

Sdieine 6.2. Diactereocelective addition of a functionalized cuprate to cyclopentenone 14 in the cynthecic of proctaglandin E (PCE ) (TBS = t-butyldimethylcilyl,... 

An entry to this network was obtained by starting from 7. The reaction most favored by the reactivity functions leads to 46, but this reaction is endothermic by 17.4 kcal/mol. The second best reaction leads from 7 to 47. In order to explore the chemistry of these systems further, structures 46 and 47 were also submitted to EROS. Starting from 46, the reaction predicted to be the best leads back to 7, the second best reaction to 47. Thus overall, rearrangement of 7 to 47 is expected, with 46 as a potential intermediate of this reaction. The most favored reaction of 47 leads to the cyclopentenone 8, a reaction which is also favored by its exothermicity (—14.8 kcal/mol). The second best reaction leads from 47 to 48. In a further study, 48 was also submitted to EROS. The two reactions evaluated to be best by the present reactivity functions lead to 49 and... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

In another example (Scheme 8), the intramolecular cycloaddition of an azido functionality onto an enone group afforded bicyclic derivatives with bridgehead iV atoms. The cyclopentenone derivative 28 afforded the indolizidinone 30 through the proposed compound 29 which might react through a diradical intermediate or through a betaine intermediate <2002TL5385>. 

Tius and co-workers investigated a number of cationic cyclopentannelations of allenyl ethers [113] and found that 1-lithio-l-alkoxyallenes 180 react with a,/3-unsatu-rated carbonyl compounds 181 leading to highly functionalized cyclopentenones 182 (Scheme 8.44). The primary products are a-allenyl ketones 183, which form pentadienyl cations 184 by protonation. The latter undergo a thermally allowed 4jt-conrotatory ring closure to intermediates 185, which with elimination of R1 finally lead to the expected products 182 (Scheme 8.45). 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

Similarly, a double functionalization can be reached when an activating group is present in close vicinity to the triple bond. Tsuji et al. have discovered that with a diphosphine palladium(O) complex, a carbonate function in the a-position of the alkyne provides by decarboxylation a palladium methoxy species on which the alkyne moiety can be isomerized into an al-lenyl a -bonded group. CO insertion in the Pd - C bond, reductive elimination with the methoxy group and further cyclization with incorporation of a second CO molecule give rise to the corresponding cyclopentenone as shown in Scheme 21 [127]. 

The Ir-tolBINAP catalyst also functions well in the desymmetrization of dienynes, where a highly enantioselective and diastereoselective Pauson-Khand-type reaction proceeded to give vinyl-substituted bicyclic cyclopentenones with two chiral centers (Scheme 11.19) [31]. 

This approach is related to Mehta s in so far as the carbon atoms and were connected to afford a desired hydroazulene (Eq. 2). Ensuing manipulation of functional groups led to the functionalized racemic hydroazulene 263. The cyclopentenone 261 was synthesized from an acyclic precursor by a Nazarov cyclization [134]. 

Disjoint functionalities also exist in chloral and this property has been exploited in the isomerization of 4-hydro xy-2-cyclopentenones [206]. 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

The addition of lithium alkoxydienolates to a,P-enones occurs exclusively in the l,4(a)-mode. For example, alkoxydienolate (202), obtained from ethyl senecioate, adds efficiently, in a tandem conjugate addition-allylation protocol, to cyclopentenone to afford the a,(3-functionalized cyclopentanone (203),153 In contrast, the lithium dienolate (204), from 5-methylbutenolide, affords exclusive y-alkylation,154 b while the analogous phthalide enolates (206) can be exploited to accomplish regiospecific polynuclear aromatic syntheses (Scheme 76).l54c ... 

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