Unsaturated Ring Ketones

Unsaturated Ring Ketones.—Acetylene hexacarbonyldicobalt complexes react with ethene, alkenes, and cycloalkenes to provide a general synthetic route to cyclopentenones. Unfortunately most monosubstituted ethenes react non-specifically. 2-Bromoethylallene gives 2-methylcyclopent-2-enone on treatment with Collman s reagent. 

Michelot, R. Lome, C. Huynh, and S. Julia, Bull. Soc. chim. France, 1976, 1445. 

Further work has been reported on the peracid oxidation of vinylallenes to cyclopentenones/  

The 2-substituted cyclopentenone (28) has also been prepared from 3-toluene-p-sulphonylpropanol by a longer reaction sequence.  

Reagents i, e, MeOH ii, Amberlite 120B resin iii, Na2C03, H2O 

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Five-ring ketones corresponding open-chain ketones 1750-1740 a,/3 Unsaturation, a,/3,a, /3 unsaturation, etc.. 

With cyclic ketones, the a-cleavage can also be followed by intramolecular bydn en abstraction that leads eventually to an unsaturated ring-opened aldehyde ... 

Another reaction that has potential is the intramolecular ene reaction, which preferentially results in five-membered rings Because fluorinated ketones have a propensity for undergoing intermolecular ene reactions [5S], this reaction has tremendous synthetic possibilities Only one example of an ene reaction of an unsaturated trifluoromethyl ketone has been reported, but it indicates the potential of the methodology [59] (equation 59)... 

Reduction of ketones other than 48 to dimers has been examined. Ethyl pyridyl ketone (51) gave a poor yield of the corresponding pinacol (52).79 Pinacols can also be made from crossed coupling of ketones with 3-(48).80 Finally, a study of the radical anions formed from the isomeric benzoylpyr-idines (53) was done, and the rates of rotation of the pyridyl ring were determined.81 The mechanism of reduction of the oxime and thiosemicar-bazone derivatives of 53 was determined by voltammetry techniques.82 The monoimine derivative of the pyridil 54 was reduced to the a-amino ketone 55 (Scheme 18).83 Unsaturated pyridyl ketones and heteroaryl pyridyl ketones have also been studied by voltammetry.84,85... 

For the puiposes of retrosynthetic analysis, a six-membered ring in a target can be related to a Robinson annulation of an existing ketone with an a,/3-unsamrated ketone. Normally cc,/3-unsaturated methyl ketones are used to facilitate the ring closure, but this is not an absolute requirement. Thus the target steroid S could potentially be constructed by a series of Robinson annulations as shown. The last retrosynthetic step (the first synthetic step) could be problematic as a mixture of regioisomers would be formed. 

Four-ring ketones cal 780 unsaturation, etc., have a similar effect on these values as on those of open-chain ketones. 

Remarkably, thermolysis of the Baylis-Hillman adducts 311 (R1 = alkyl or aryl Rz = Ac, CN, CC Me) in toluene at 210 °C in a sealed tube gave stereoselectively the cyclized product (+)-312, which included incorporation of the elements of the solvent and, when Rz = Ac, a single isomer was obtained (Equation 33). The yields were moderate (37-56%) and when RZ = CN and C02Me some racemization occurred. Similar results were obtained when either p-xylene or mesitylene was used but no reaction occurred when chlorobenzene or anisole was used. Unsaturated rings are obtained in similar yields and stereoselectivity if the N-substituent is an alkyne. In addition, benzene thiol reacted in boiling benzene in the presence of AIBN to give 313, which on ozonolysis yielded the cyclic ketones 314 ( = 1-3) in 52-70% yield <2001JOC1612>. 

Sanin etal. described the reaction of a,/3-unsaturated fluorinated ketones 88 with ammonium sulfide in ethanol, which led to the formation of thiopyran- Wdioxide derivatives 89 (Equation 28) <1996JOC1986>. However, one of the studied ketones (3-adamantan-2-ylidene-l,l,l-trifluoro-propan-2-one 90) demonstrated an unusual behavior in the course of this reaction, which led to the formation of the fused-ring thietane 31 in 86% yield (Equation 29) <1996JOC1986>. 

The anions of these mercaptans, successfully generated with steric hindered amines underwent smooth addition to the a,/3-unsaturated five membered ring ketones 201. Under defined reaction conditions we obtained 203 as a major product when... 

Compound A is a cyclic, nonconjugated keto alkene whose carbonyl infrared absorption should occur at 1715 cm-. Compound B is an a,B-unsaturated, cyclic ketone additional conjugation with the phenyl ring should lower its IR absorption below 1685 cm-1. Because the actual IR absorption occurs at 1670 cm-1, B is the correct structure. 

Compound A has 4 degrees of unsaturation and is a five-membered ring ketone. The 3C NMR spectrum has only three peaks and indicates that A is very symmetrical. 

The preparation of doubly unsaturated macrocyclic ketones is provided (3). The synthesis of functionalized macrocycles by ring closing metathesis methods are described (4). 

The construction of the tetracyclic diterpenoids has continued to attract attention. The intramolecular alkylation of an olefin by the acid-catalysed reaction of y5-unsaturated diazo-ketones has been used ° to generate ring D in the step (194)->(195) -i- (196). A benzocyclobutane route based on the thermal cyclization of (197) to (198) has been developed for the synthesis of the beyerane skeleton. A stereoselective synthesis of stachenone, based on a series of... 

Oxidation of a series of cyclobuxine-D derivatives with protected amino functions furnished compounds characterized as five-membered ring ketones by their IR-spectra and positive response to the Zimmer-mann test. When the protection of the nitrogen functions was omitted, the ketones arising from the oxidation readily eliminated methylamine on treatment with alkali to give cis- and trans-cisoiA a, -unsaturated ketones CCLXXX and CCLXXXI. Apart from its stereochemistry, the above results allowed the establishment of the structure of cyclobuxine-D as CCLXXXII 184,187). 

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