Six-membered a, P-unsaturated ketone

Base value for acyclic (or six-membered) a ,P-unsaturated ketone 215 nm... 

Michael addition of cyclohexanones to methyl vinyl ketone followed by intramolecular aldol condensation to afford six-membered a, p-unsaturated ketones. 

The irreversible elimination drives the reversible aldol reaction and gives a favourable conjugated ketone in a favourable six-membered ring. On paper, one could also draw an acceptable mechanism in which the order of events was reversed. This is not so neat, and would require generating an enolate anion y to the a,P-unsaturated ketone formed by the first aldol-dehydration sequence. 

Heterocyclizations of a,p-unsaturated ketones are the most widely investigated reactions leading to six-membered heterocycles. For convenience these processes can be separated into three large groups (Scheme 3.1) ... 

A severe limitation of this method, however, is the failure of the ylide 103 to yield oxaspiropentanes vide supra) from a,p-unsaturated ketones and the poor yields of vinylcyclopropanes obtained from its reactions with hindered ketones or with con-formationally rigid six-membered rings. Moreover, attempts to extend the oxaspiro-pentane ring opening to compounds containing an adjacent tertiary center have failed thus, oxaspiropentane 110 did not lead to 111, Eq. (33) 57). 

A popular and useful application of the conjugate addition reaction is the combined conjugate addition-intramolecular aldol strategy, commonly known as the Robinson annulation. When the Michael donor is a ketone and the Michael acceptor an a,p-unsaturated ketone, the product is a 1,5-diketone which can readily undergo cyclization to a six-membered ring. Typical Michael donor substrates are 2-substituted cyclohexanones, which condense with alkyl vinyl ketones to give the intermediate conjugate addition products 42 (1.52). The subsequent intramolecular... 

Reduction of cyclic a,p-unsaturated ketones in which there are substituents on the (3- and y -carbon atoms could give rise to two stereoisomeric products. In many cases one isomer is formed predominantly, generally the more stable of the two. The guiding principle appears to be that protonation of the intermediate anion takes place orthogonal to the enol double bond (axially in six-membered rings). Thus,... 

Wang et al. further used pyrrolidine-sulfonamide 3a to develop a highly enantioselective Michael reaction of cyclic ketones to a,p-unsaturated ketones (chalcones). The synthetically useful 1,5-dicarbonyl compounds were obtained in good yields and with high stereoselectivities (>40 1 dr, up to 97% ee). The most satisfactory results were achieved for six-membered cyclic ketones, whereas cyclopentanone appeared to be a more challenging substrate for this reaction (Scheme 9.26). A possible transition-state model was presented to rationalise the stereochemical outcome in which hydrogen-bond formation between the NH in 3a and the carbonyl group of chalcone caused the increase in reactivity. 

The electron-rich end of the diene reacts regiospecifically with the more electron-deficient part of the dienophile to give the 1,2-product. After the addition is complete, the functionalities are easily removed by acid hydrolysis to generate an a, p-unsaturated ketone in a six-membered ring... 

The Robinson annulation forms a six-membered ring and three new carbon-carbon bonds—two a bonds and one 7t bond. The product contains an a,P-unsaturated ketone in a cyclohexane ring—that is, a 2-cyclohexenone ring. To generate the enolate component of the Robinson annulation, OH in H2O and "OEt in EtOH are typically used. 

The enone system itself is usually part of a five- or six membered ring, although acyclic a,(3-unsaturated ketones and enols of P-diketones are also found to undergo cycloadditions under certain conditions. For seven- and higher membered rings the primary photochemical event is Z—E isomerization around the C—C double bond, the E-isomer then eventually undergoing further thermal reactions. 

The mechanism of the Robinson annulation consists of two parts a Michael addition to the a,p-unsaturated carbonyl compound to form a 1,5-dicarbonyl compound, followed by an intramolecular aldol reaction to form the six-membered ring. The mechanism is written out in two parts (Mechanisms 24.7 and 24.8) for Reaction [2] between methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. 

Ge, Sn) double-bond compounds, while benzaldehyde or benzophenone react with M=N double bonds to give the corresponding [2 + 2] adducts regioselectively with the formation of M-0 bonds. In addition, the [4 + 2] cycloaddition reaction of azametallenes and phosphametallenes with a,p unsaturated aldehydes and ketones have been reported to give the six-membered ring compounds. Other cycloaddition using 1,3-dipoles such as nitrileoxide and azide derivatives were reported. The reactivities of M=E double bond are summarized in Scheme... 

The base value for the a,p-unsaturated six-membered ring ketone system is 215 nm. Extended conjugation adds an additional 30 nm. The presence of an exocydic double bond, marked a, extends the another +5 nm. There is asubstituent on the p-carbon atom (+12 nm) and on the 8-carbon atom (+18 nm). There is no solvent effect because the spectrum was obtained in ethanol (0 shift).The total is 215 + 30 + 5 + 12 + 18 = 280 nm ... 

Two-carbon ring expansions of the five-, six,- and seven-membered rings of P-indanone, P-tetralone, and P-suberone can be achieved via a sensitized [2-1-2]-photoaddition of the trimethylsilyl enol ethers of the cyclic ketones with acrylonitrile or methyl acrylate followed by P-fragmentation of the alkoxyl radicals generated from the hypoiodites of the resulting cyclobutanols and mercury(ll) oxide-iodine, as outlined in Scheme 72. The ring expansion of the cyclobutanol derived from P-indanone enol ether and acrylonitrile gave an a,P-unsaturated nitrile. 

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