Cyclopentanone aldol reaction

It is often said that the property of acidity is manifest only in the presence of a base, and NMR studies of probe molecules became common following studies of amines by Ellis [4] and Maciel [5, 6] and phosphines by Lunsford [7] in the early to mid 80s. More recently, the maturation of variable temperature MAS NMR has permitted the study of reactive probe molecules which are revealing not only in themselves but also in the intermediates and products that they form on the solid acid. We carried out detailed studies of aldol reactions in zeolites beginning with the early 1993 report of the synthesis of crotonaldehyde from acetaldehyde in HZSM-5 [8] and continuing through investigations of acetone, cyclopentanone [9] and propanal [10], The formation of mesityl oxide 1, from dimerization and dehydration of... 

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). 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

Figure 1. Kinetic parameters for the selection of antibody-catalyzed aldol and retro-aldol reactions, reflecting the biocatalyst s ability to accept substrates that differ clearly with respect to their molecular geometry. No background reaction was observed for the self-condensation of cyclopentanone. The indicated value for cyclopentanone addition to pentanal was estimated using the published kuncat value of 2.28 X 10 M s for the aldol addition of acetone to an aldehyde. Reproduced with permission of the authors and the American Association for the Advancement of Science.

Munson and Haw (151) reported the first in situ NMR study of acetaldehyde in a zeolite. Figure 27 shows 13C spectra of this species reacting on HZSM-5 in the presence of water to form crotonaldehyde with high selectivity (an example of aldol condensation). We later reported a very detailed study of the aldol reactions of acetone and cyclopentanone on various zeolites (Scheme 4) (147). Dimerization of acetone followed by dehydration gives mesityl oxide (31), and the I3C isotropic shifts of this conjugated ketone are strongly dependent on state of protonation. Farcasiu and Ghen-ciu (152,153) have reported extensive measurements of the 13C shifts of 31... 

They are useful for ketones too. Disconnection of the enone 99 reveals an aldol reaction between cyclopentanone 74 and the enolisable ketone 100. Control is needed solely to prevent self-condensation of the aldehyde. 

S)-Proline-catalyzed aldol reactions involving 2-butanone afforded the products of C-C bond formation at the methyl group, the less substituted a-position of the ketone as the major regioisomers (Fig. 2.1) [6, 9]. The regioselectivity of the aldol reaction of 2-butanone was reversed using a proline amide derivative as the catalyst, as shown in Scheme 2.2 [13]. The (S)-proline-catalyzed aldol reactions of cyclohexanone and of cyclopentanone afforded both anti- and syn-products (anti syn 2 1) with moderate enantioselectivities (63-89% ee) [6]. The selectivity... 

Table 5 Stereochemistry of Aldol Reactions of Cyclopentanone with Aliphatic Aldehydes (equation 93)...

Zirconocene dichloride. 14. 12 Aldol reaction. Zirconiu amides derived from (- >-ps< corresponding lithium enolates ( Cyclopentanones.- C ck) valuable method for the prep application is found in a symhei... 

One of the simplest aldol condensations is the reaction of benzaldehyde with acetophenone. Iron(iii) chloride hexahydrate in [BMIM][BF4] catalyzes this reaction to give chalcone [239]. This same ionic liquid catalyst combination can also be used in the reaction of benzaldehyde with cyclopentanone and cyclohexanone [240]. The aldol reaction can also be base promoted in ionic liquids such as [BMIM][PF6]. An example is the reaction of benzaldehyde with l,3-thiazolidine-2,4-dione. The authors follow this reaction with methylation of the imide with methyl iodide (Scheme 5.2-104) [241],... 

In the third case, the cyclopentanone has self-condensed and ignored the enone. The answer again is to use a specific enolate, such as the easily made P keto-ester below. The six-membered ring is then easily formed by intramolecular aldol reaction. These two reactions together make a Robinson annelation. Finally the C02Me group must be removed by hydrolysis and decarboxylation. 

The term condensation is often used for reactions like this. Condensations are reactions where two molecules combine with the loss of another small molecule—usually water. In this case, two ketones combine with the loss of water. This reaction is called an aldol condensation and chemists may say two molecules of cyclopentanone condense together to give a conjugated enone. You will also find the term condensation used for ail aldol reactions whether they occur with dehydration or not. The distinction is no longer important. 

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