Cyclopentenones aldol reaction

Figure 23.4 Intramolecular aldol reaction of 2,5-hexanedione yields 3-methyl-2-cyclopentenone rather than the alternative cyclopropene.

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

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. 

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. 

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]. 

Diketones also self-condense rather easily in an intramolecular aldol reaction to give a cyclopentenone with an all-carbon five-membered ring, til is too is a useful reaction but we need to know how to control it. The usual rule is ... 

The mechanism of intramolecular aldol reactions is similar to that of inter-molecular reactions. The only difference is that both the nucleophilic carbonyl anion donor and the electrophilic carbonyl acceptor are now in the same molecule. One complication, however, is that intramolecular aldol reactions might lead to a mixture of products, depending on which eiiolate ion is formed. For example, 2,5-hexanedione might yield either the five-membered-ring product 3-methyl-2-cyclopentenone or the three-membered-ring product (2-methyl-cyclopropenyl)ethanone (Figure 23.4). In practice, though, only the cycio-pentenone is formed. 

Treatment of this diketone with anhydrous acid would cause recyclization to the same furan (see Chapter 44) but it can alternatively be cyclized in base by an intramolecular aldol reaction (Chapter 27) to give a cyclopentenone. 

The aWol reactions we ve seen up to this point have all been intermSSm.-lar, That is, they have taken place between two different molecules. Wher certain dicarbonyl compounds are treated with base, however, an inframo lecuiar aldol reaction can occur, leading to the formation of a cyclic produc. For example, base treatment of a 1,4-diketone such as 2,5-hexanedioii yields a cyclopentenone product, and base treatment of a 1,6-diketone sue as 2,6-heptanedione yields a cyclohexenone. 

Based on these results, it might be concluded that, because of the high concentrations of carbohydrate degradation products in the HHP treated system, retro-Aldol reactions are favored, which could then lead to the formation of higher amounts of, in particular, the cyclopentenones. 

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. ... 

Aldol and Mannich reactions. Formation of cyclopentenones is readily achieved by a twofold Mukaiyama aldol reaction between l,3-bis(trimethylsiloxy)-1,3-dienes and 1,2-diketones. ... 

The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction (Robinson annulation - see Section 1.1.2) to give cyclopentenones. Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-aUyl ketone 115 gave the 1,4-diketone 116, which was converted to the cyclopentenone 117 (5.115). ... 

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. 

Shibasaki s heterobimetallic complexes, active in the asymmetric aldol reaction (see Section 7.1) provide the opportunity to activate both the nucleophile and Michael acceptor. Whilst the aluminium lithium bis-BlNOL complex (ALB) (11.28) does not catalyse conjugate addition of a-phosphonate ester (11.29) with cyclopentenone (11.30) by itself, addition of sodium terf-butoxide allows a highly enantioselective reaction to take place. A postulated model for enantioinduction in this process involves simultaneous binding of the metallated nucleophile and acceptor to the catalyst by interaction with a BINAP oxygen and the aluminium centre respectively. Heterobimetallic complexes have also been used to catalyse the addition of a-nitroesters and malonatesto Michael acceptors. 

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