Cyclopentanone enol form

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... 

The enol form (8) of the highly fluorinated cyclopentanone (7) is more stable than the keto form (Scheme 1.15), demonstrating the powerful fluorine effect on enolization [6]. It is well known that the transformation of the enol form (3) to the corresponding keto form was found not to be easy [2]. We all know that hemiacetals of ketones and aldehydes and enols of common ketones can exist only as intermediates and cannot be isolated as their stable form. However, the chemical nature of the highly fluorinated aliphatic carbonyl compounds is totally different from that of the nonfluorinated ones. 

The size of each of the rings present in steroids was established by serial oxidation reactions starting with what would later be dubbed ring A. The empirical, so-called Blanc, rule holds that oxidation of a cyclohexanone (4-1) (Scheme 1.4) proceeds to afford a dicarboxylic acid (4-3), likely through the enol form, 4-2. Heating the diacid 4-3 with acetic anhydride proceeds to cyclopentanone 4-4 with loss of one carboxyl carbon. Repeated oxidation of that intermediate again results in a dicarboxylic acid, in this case adipic acid (4-5). Exposure to hot acetic anhydride leads to anhydride... 

In another approach, cyclopentanone enol ether reacts with a pentacarbonyldiphen-ylcarbene complex to give an unsaturated carbene, X (the metathesis product) and a cyclopentanone derivative formed by rearangement of the cyclopropane intermediate, both coming from the nonisolated tungstacyclobutane intermediate ... 

Ionic strength and specific ion effects have been investigated in the oxidation of mandelic acid by cerium(iv) sulphate. Unlike the reaction in HCIO4 where there is spectrophotometric and kinetic evidence for complex formation, under these conditions there is a first-order rate dependence of both oxidant and reductant. The replacement of H+ by Li+, Na+, or K+ produces only a minor change in rate and has no effect on the activation parameters. Rate laws which are essentially similar have been established in the reactions with cyclohexane-1,4-diol cyclopentanone, and methyl isopropyl ketone. The enol form of the substrate is favoured as the active reagent in the latter two reactions. 

Non-fluxional vinylic boranes do not react with carbonyl compounds. Nevertheless, the vinylic borane 29 reacts with acetone (2 h under reflux) yielding the Z-isomer of the homoallylic borinic ester 30b. The cw-configuration of the reaction product 30b corresponds to the following sequence of transformations (Scheme 2.11). The [1,7]-H shift in the vinylic borane 29 gives the allylic Z, Z-isomer 28d which immediately reacts with acetone before the equilibrium among the allylic isomers is established. On the other hand, cyclopentanone reacts directly with 29 under mild conditions yielding Z, Z-1,3,5-heptatriene 31 and borinic ester 32 (Scheme 2.12). Apparently 29 reacts with the enol form of cyclopentanone, and a direct splitting of the B-Q ,2 bond takes place. Similar reaction of 29 with acetic acid was used for the preparative synthesis of previously unknown hydrocarbon 31 (Scheme 2.12) [35]. 

Cyclobutanone i Cyclopentanon is Enol form of diketones Quinnnes... 

Only the a hydrogens are replaced by deuterium m this reaction The key intermediate IS the enolate ion formed by proton abstraction from the a carbon atom of cyclopen tanone Transfer of deuterium from the solvent D2O to the enolate gives cyclopentanone containing a deuterium atom m place of one of the hydrogens at the a carbon... 

In a related study the adduct of the lithium enolate of methyl bis(trimethylsilyl)acetale and ( —)-(/J)-2-(4-methylphenylsulfinyl)-2-cyclopentanone was transformed to ( — )-methyl jasmonate in > 99% ee. In contrast to the previous study described in this section, addition of the enolate proceeded apparently through a chelated form of the enone15. 

Finally, Lipshutz and co-workers developed catalytic copper(i)-assisted polyfunctionalizations of zirconacyclopen-tenes of type 93 by trapping the intermediary zirconium enolates 94 with an aldehyde to form the corresponding 2,3-disubstituted cyclopentanones 95 (Scheme 40).146... 

A new piperidine alkaloid Adalinine 352 was prepared in racemic form, using a rearrangement as a key step (equation 134). Enolate chemistry allowed double a-alkylation of cyclopentanone, producing 350 after oxime formation. Rearrangement provided a clear conversion into the lactam 351, easily converted to racemic Adalinine 352. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

Baldwin and Kruse (57) have found that the enolate salts 196A-B (M=Li or K) give the enol-ether 197 and no cyclopentanone 198. In contrast to this result, the enolates 199A-B (M=Li or K) under the same conditions gave only the cyclohexanone 201. In this case, the enol-ether 200 was not formed. 

Under acidic conditions enamines such as compound A in Figure 12.18 and aldehydes undergo condensation to form the conjugated iminium ions D. These will be deprotonated by the concomitantly formed hydroxide ions, In this way dienamines of type F are formed, which will then be hydrolyzed upon acidic workup to give a carbonyl group. The generation of the a,/i-unsaturated ketones E is thus completed. You will learn about type E compounds in Section 13.4.1 in connection with the so-called crossed aldol condensation products. It should be noted that it is not possible to form the same unsaturated ketone by reacting cyclopentanone or its equilibrium fraction of enol with an aliphatic aldehyde. Instead, a cyclodehydration of... 

Most of these methods are unable to distinguish between enol and another fast-reacting species and, as stressed by Dubois and Barbier, results are highly dependent on the purity of the carbonyl compound. Another procedure which apparently does not suffer the same drawback was more recently suggested by Bell and Smith and was applied to cyclopentanone and cyclohexanone (Bell and Smith, 1966) and to acetophenone (Novak and Loudon, 1977) ketone solutions were pretreated with bromine and the enol content was measured by potentiometry after allowing the enol to form. This method was also used for determining the acidity constants of ends. 

OL-Methylenecyclohutanones. The reagent reacts regioselectively with activated alkenes (vinyl ethers, silyl enol ethers) to give cyclobutanones. These products undergo ring expansion with diazomethane to cyclopentanones. Both products undergo desilylative elimination in the presence of fluoride ion to form a-methylene ketones. 

Trapping of the Beckmann intermediates with enol silyl ethers affords facile entry to a variety of en-amino ketones. This condensation takes place with retention of regiochemical integrity in both oxime sulfonates and enol silyl ethers. Reaction of 6-methyl-l-(trimethylsiloxy)-l-cyclohexene (41) or 1-methyl-2-(trimethylsiloxy)-l-cyclohexene (42) with cyclohexanone oxime mesylate furnishes (43) or (44), respectively, as the sole isolable products (equation 25). Another striking feature of the reaction is the high chemospecificity. The condensation of the enol silyl ether (45), derived from p-acetoxyaceto-phenone, occurs in a chemospecific fashion with cyclododecanone oxime mesylate, the acetoxy moiety remaining intact (equation 26). Oxime sulfonates of aromatic ketones and cyclopentanones are not employable since complex reaction mixtures are formed. 

The use of -fhio- and -silylacryloylsilanes switches the reaction mode from [2-1-1] to ]3-i-2] armulation to form cyclopentanone silyl enolates (Scheme 10.226) [588]. The annulation wifh /i-lhioacryloylsilaries might proceed via the delocahzed allylic carbanion 159 whereas a reaction pathway through 1,3-sigmatropic rearrangement of the vinylcyclopropane intermediate 160 has been proposed for/fsilylacryloylsilaries [589]. 

Only in modern times has aldol stereochemistry seemed a subject worth studying, or indeed even accessible to chemists. Formerly it was left to look after itself. Then Dubois carried out some simple experiments on the condensations between cyclic ketones and aldehydes in base.3 Though largely neglected at the time, these results showed that if LiOH (not NaOH) was used as the base, the anti aldol predominated. Indeed, with cyclopentanone and /-PrCHO, >95% anti-5 was formed, and syn-5 could not be detected. Later Heathcock4 showed that the lithium enolate of the open chain ketone 6 condensed with PhCHO to give >98 2 syn ami aldol 7. 

It is all very well knowing what enolates give rise to what aldol products, but this is not much use unless we can choose to have cis or trans enolates. Clearly with cyclopentanone there is no option but to form a trans enolate. But with an acyclic ketone we will need a little more care. Boron enol ethers provide an answer. Two common boron reagents used are 9-BBN chloride 46 (derived from 9-BBN 45) and another is dicyclohexylboron chloride 47. Other reagents include the corresponding triflates. There are also the chiral boron reagents that we shall meet later chapters. 

Cyclopentanones. The synthon reacts with sodium enolates of acetoacetic esters (2) in THF (65°) to form cyclopentenyl sulfides (3), which are hydrolyzed by 20% HCl—dioxane to keto acids (4). 

---