Aldol reaction cyclopentenones from

A combination of an anionic oxy retro-ene and an aldol reaction to give annulated cyclopentenones 4-361 from 4-358 was described by Jung and coworkers (Scheme 4.80) [126]. It can be assumed that, in the presence of KH, the potassium alkoxide 4-359 is first formed this leads to 4-360 and finally to 4-361 in an intramolecular aldol reaction. 

The central bond in (photochemically) easily accesible bicyclo[n.2.0]-alkan-2-ones (n = 3,4) can be cleaved by retro-aldol reaction (cf. Sch. 2), but also by treatment with Broenstedt- and Lewis-acids. This is shown in Sch. 16 for the synthesis of (i)descarboxyquadrone (55) starting from indenone 56 via the cycloadduct 57 which reacts with HC1 to 58 [69], or by the preparation of the AB-ring core of Taxol 59 from cyclopentenone 60 via cycloadduct 61 which rearranges to 62 in the presence of TiCl4 [70]. 

Asymmetric Michael reactions have heen conducted with assistance of C2-symmetric malonamides derived from (5)-ptohne esters/ 2-Methyl-3,4,5,6-tetrahydropyridine and 2-cyclopentenone are condensed to afford a tricyclic alcohol. The reaction starts from Michael reaction of the endocychc enamine isomer and as the double bond shifts to the exo-cychc position an intramolecular aldol reaction follows. If the imine is hthiated, the initial Michael reaction (CuBr-catalyzed) then involves the exocyclic carbon. ... 

The cyclopentenone 19 can be prepared by an intramolecular aldol reaction from the diketone 18. This reaction is best achieved with a base such as KOH in MeOH and heat. The diketone 18 can be prepared by Wacker oxidation of the alkene 17. Standard conditions for the Wacker oxidation are 10 mol% PdCla, CuCl, O2, DMF, H2O (see Scheme 5.115). The alkene 17 is prepared by allylation of the enamine of cyclohexanone. See J. Tsuji, I. Shimizu and K. Yamamoto, Tetrahedron Lett. (1976), 2975. 

Catalytic, enantioselective Michael reactions of cyclopentenones have attracted particular attention in recent years. Ben L. Feringa, Albert S. C. Chan, Andreas Pfaltz and Amir H. Hoveyda described various hgand systems for stereoselective addition of organo-zinc reagents to cyclopentenones. With the aid of a phos-phoramidite derived from BINOL, Feringa developed an enantioselective, catalytic domino-Michael/aldol reaction for the preparation of (+)-PGEi methyl ester. [223]... 

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

Intramolecular versions of reactions other than aldols can also be considered as useful options to prepare five- or six-membered rings from their corresponding bifunctional precursors. Several examples to illustrate the diverse approaches to construct five-membered rings are given in Scheme 2.110. A high-yield method to prepare cyclopentenone 284 is given in the sequence (i) alkylation of formyl-anion equivalent 285 to give 286 (ii) Michael addition of the latter to methyl vinyl ketone (iii) removal of the carbonyl protection and (iv) intramolecular cyclization of the 1,4-diketone, 287. 

The Wittig reaction was carried out by the Schlosser method - the ylid was generated with PhLi and the aldehyde added at low temperature (-70 °C). A second equivalent of PhLi was added and the intermediates allowed to equilibrate at -30 °C. Elimination of Ph3P=0 occurred under these conditions to give the E-alkene. Deprotection and aldol condensation gave the cyclopentenone in a very impressive 46% yield over the five steps from the original aldehyde. 

Punaglandin 4 (208) is an example of a C-10 chlorinated prostanoid isolated from the Hawaiian octocoral telesto riisei. Its potent antitumor activity has attracted considerable synthetic interest. Characteristic of the a-chain is the same familiar dihydroxy stereochemistry found in (7, 7 )-tartaric acid. Wittig reaction of 167 with the phosphorane of [2-(l,3-dioxan-2-yl)ethyl]triphenylphosphonium bromide (205) followed by catalytic reduction and simultaneous debenzylation affords a primary alcohol, which is converted to aldehyde 206 in two oxidative steps. Aldol coupling of 206 with racemic cyclopentenone 207 (R=MOM) provides a statistical mixture of all four possible diastereomers. After chromatographic purification and protective group transformations, the target molecule 208 is obtained in 30—40% yield. The remaining three aldol products have been similarly converted to the diastereomers of 208 [75] (Scheme 47). 

Whereas in principle the reaction of (487) with alkali may give rise to either tetra-substituted (488) or trisubstituted (489) enones, the latter have not been obtained from such a reaction in the cyclopentenone series. This could arise if (488) is the kinetic product or if (489) is formed reversibly with (488) as the kinetic product. When (489 R = Pr") was exposed to reaction conditions which convert (487) into (488) the starting material was recovered unchanged. Also, under cyclization conditions aldol (490) gave only (489 R = Pr") (487 R = Pr") was cyclized to a 94 6 mixture of (488 R = Pr") and (489 R = Pr"). Reversibility of enolate formation was demonstrated by quenching a reaction run in deuteriated solvent, when [ Hg] (487 R = Pr ) was recovered. It was concluded that under the reaction conditions kinetic control operates at the aldol step, with the transition state for cyclization of the eno-... 

Although problems of regiochemistry are inherent, the aldol condensation of diketones has found vide application. Typical examples are syntheses of cyclopentenones and cyclohexenones from 1,4- and 1,5-diketones, respectively. The concept is illustrated by a synthesis of jasmone 12 (Eq. (12)) [28] and of the homosteroid derivative 13, the latter arising under thermodynamic control in a Robinson annelation reaction (Eq. (13)) [29]. 

The reaction is a unique method for the one-step synthesis of ketones from alkenes, and allows alkenes to be regarded as masked ketones which are stable to acids, bases, and nucleophiles. Particularly useful is the oxidation of terminal alkenes, which provides methyl ketones (eq 3). As a typical application, the allylation of a ketone, followed by the oxidation, affords a 1,4-diketone. A cyclopentenone can then be prepared by an aldol condensation (eq 4). The annulation method has widespread uses in the synthesis of natural products such as pentalenene, muscone, and coriolin. 1,5-Diketones are prepared by 3-butenylation of a ketone followed by the oxidation. This process has been used to prepare cyclohexenones (eq 5). ... 

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