2-Cyclohexenones isomeric

Although 2-substituted 2-cyclopentenones are in a base-catalyzed equilibrium with their 5-substituted 2-cyclopentenone isomers (Problem 22.38). the analogous isomerization is not observed for 2-subslitutcd 2-cyclohexenones. Explain. 

A comparison of the configuration of the substrates and reaction products shows that the oxiranyl anions arc configurationally stable under the reaction conditions. Only one example is known in which isomerization was observed. When the ci.v-tm-butyl-substituted epoxysilane27 was metalated and quenched with 2-cyclohexenone, addition product 27 was obtained under inversion of the anionic center. Presumably the strain created in forcing the ter/-butyl and the trimethylsilyl group cis on the oxirane ring facilitates the isomerization process13. 

Investigation of the photochemistry of protonated durene offers conclusive evidence that the mechanism for isomerization of alkyl-benzenium ions to their bicyclic counterparts is, indeed, a symmetry-allowed disrotatory closure of the pentadienyl cation, rather than a [a2a -f 7r2a] cycloaddition reaction, which has been postulated to account for many of the photoreactions of cyclohexadienones and cyclohexenones (Woodward and Hoffmann, 1970). When the tetramethyl benzenium ion (26) is irradiated in FHSO3 at — 90°, the bicyclo[3,l,0]hexenyl cation (27) is formed exclusively (Childs and Farrington, 1970). If photoisomerization had occurred via a [(r2a-t-772 ] cycloaddition, the expected... 

In the synthesis shown in Scheme 13.15, racemates of both erythro- and threo-juvabione were synthesized by parallel routes. The isomeric intermediates were obtained in greater than 10 1 selectivity by choice of the E- or Z-silanes used for conjugate addition to cyclohexenone (Michael-Mukaiyama reaction). Further optimization of the stereoselectivity was achieved by the choice of the silyl substituents. The observed stereoselectivity is consistent with synclinal TSs for the addition of the crotyl silane reagents. 

Epoxides are reactive substrates, which can easily be isomerized to give aldehydes or ketones. Kulawiec and coworkers have combined a Pd-catalyzed isomerization of mono and diepoxide 6/1-348 or 6/1-349 and 6/1-352 or 6/1-353, followed by an aldol condensation to give either cyclopentenones or cyclohexenones 6/1-350, 6/1-351, 6/1-354 and 6/1-355, respectively (Scheme 6/1.89) [165]. 

An interesting synthesis of enantiopure cu-decahydroquinolines, which involves enol ether hydrolysis, double bond isomerization, and intramolecular 1,4-addition of an amino group across a cyclohexenone has been reported <06T9166>. The process is stereoselective, with the exclusive formation of both cu-isomers 176 (43% over 3 steps) and 177 (17% over 3 steps) of the decahydroquinoline ring. 

The foregoing stabilizing 1,3-diaxial interaction was shown to have potentially useful applications for stereochemical control of addition reactions56. The /l-trimethylstannyl cyclohexenone ketal 65 affords a nearly 1 1 mixture of isomeric c/s-diols 66 and 67 when hydroxylated with OsC>4 (equation 25). However, the chlorostannane 68 upon hydroxylation with OSO4, then Sn methylation, yields a 94 6 mixture favoring the a,a,-diol 66. Evidently, the conformational change induced by the 1,3-diaxial donor-acceptor... 

Hayashi et al. proposed a catalytic cycle for the rhodium-catalyzed 1,4-addition of phenylboronic acid to 2-cyclo-hexenone (Scheme 28), which was confirmed by NMR spectroscopic studies.96 The reaction presumably involved three intermediates, phenylrhodium a, oxa-7r-allylrhodium b, and hydroxorhodium c complexes. Complex a reacted with 2-cyclohexenone to give b by insertion of the carbon-carbon double bond of enone into the phenyl-rhodium bond followed by isomerization into the thermodynamically more stable complex. Complex b was converted to c upon addition of water, liberating the phenylation product. Transmetallation of the phenyl group from phenylboronic acid to rhodium took place in the presence of triphenylphosphine to regenerate a. 

Although the enones (15) underwent [2 + 2]cycloaddition with (16) with complete regiospecificity, the reaction between cyclohexenone (19) and (16) yielded the isomeric inseparable (20) and (21) in 3 1 ratio. Compound (20) and (21), upon... 

Conjugated silyl ketones are likewise converted to acylcyclopentenes (Eq. 9.64) [64], In some additions an isomeric cyclohexenone is formed (Eq. 9.65). This latter product is postulated to arise from ring expansion of the initial acylcyclopentene as illustrated in Scheme 9.15. 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

The reaction of simple ketones such as 2-butanone or phenylacetone with ,/<-unsaturated ketones gives cyclohexenones when the reaction is effected by heating in methanol with potassium methoxide. Explain how the cyclohexenones are formed. What structures are possible for the cyclohexenones Can you suggest means for distinguishing between possible isomeric cyclohexenones ... 

Irradiation of cyclohexenes or cyclohexenones leads to valence isomerization with the formation of vinylcyclobutane derivatives85 (see Houben-Weyl, Vol. 4/4, p 108). 

Similar reactions with 3-(o-bromoarylamino)cyclohexenones yield carbazole derivatives.77 Spiro pyrrolidinones are obtained from N-(cyclohexylcarbonyl)-o-iodoaniline derivatives.66 The use of silver nitrate in reactions significantly reduces the amount of double-bond isomerization observed. This system is useful for preparing six- and seven-membered ring analogs, also. Even quaternary centers can be... 

Substrates A3 (Q = O) have been employed not only as starting materials for fragmentation reactions but also to probe novel stereoselectivity concepts. The photochemical transformation of axial chirality into central chirality was achieved by Carreira et al., who employed chiral, enantiomerically pure allenes in intramolecular [2 + 2]-photocycloaddition reactions (Scheme 6.27) [79]. The reaction of enantiomerically pure (99% ee) cyclohexenone 71, for example, yielded the two diastereomeric products 72a and 72b, which differed only in the double bond configuration. Apparently, the chiral control element directs the attack at the allene to its re face. The double bond isomerization is due to the known configurational liability of the vinyl radical formed as intermediate after the first C—Cbond formation step (see Scheme 6.2, intermediate C). 

The first such reaction published in 1908 by Ciamician and Silber was the light induced carvone —> carvonecamphor isomerization, corresponding to type b [1]. Between 1930 and 1960 some examples of photodimerizations (type c) of steroidal cyclohexenones and 3-alkylcyclohexenones were reported [2-5]. In 1964, Eaton and Cole accomplished the synthesis of cubane, wherein the key step is again a type b) photocycloisomerization [6]. The first examples of type a) reactions were the cyclopent-2-enone + cyclopentene photocycloaddition (Eaton, 1962) and then the photoaddition of cyclohex-2-enone to a variety of alkenes (Corey, 1964) [7,8]. Very soon thereafter the first reviews on photocycloaddition of a,(3-unsaturated ketones to alkenes appeared [9,10]. Finally, one early example of a type d) isomerization was communicated in 1981 [11]. This chapter will focus mainly on intermolecular enone + alkene cycloadditions, i.e., type a), reactions and also comprise some recent developments in the intramolecular, i.e., type b) cycloisomerizations. 

Amino-Claisen rearrangement of propargylamino-cyclohexenone and cyclopentenone is reported to proceed with ring closure to quinoline and pyridine derivatives (equation 82). The isomeric 2-propynylenaminone gave an indolone in good yield118 (equation 83). 

Isomerization of a 2-substituted 2-cyclohexenone to a 6-substituted 2-cyclohexenone requires removal of a proton from the 5-position of the 2-substituted isomer. Since protons in this position are not acidic, double bond isomerization does not occur. 

A 4,4-disubstituted cyclohexenone synthesis has been developed by Holmes and Madge. The procedure is based upon PAA oxidation of anisole-derived bicyclo[2.2.2]oct-S-en-2-ones, followed by acid-catalyzed isomerization of the products (Scheme 21). 

Catalyst for DIels-Alder reaction of ynamlnes. A zero-valent iron species prepared by reduction of iron(III) chloride with isopropylmagnesium chloride serves as a unique catalyst for cycloaddition of butadiene and ynamines (1) to form 1,4-cyclohexadienamines (2). These products are hydrolyzed by mild acid treatment to (3,y-cyclohexenones (3), which are isomerized to either 4 or 5 by catalytic amounts of rhodium catalysts. 

The stereospecific rearrangement of cyclohexenones to isomeric bicyclohexanones (74 78) has a close formal parallel in the likewise... 

The best control of addition of these organometallics at the C-1 site of enones is achieved by performing the reaction in a less basic solvent, such as ether or THF, at a lower temperature (-110 or -78 °C), and within a shorter time, so that not only the formation of the C-1 adducts is favored, but also there is a lower chance of them isomerizing to the more stable C-3 adducts (Scheme 152, compare f to g Scheme 153, compare a with b-d Scheme 154, compare c to a). This control is particularly efficient with cyclohexenone (Scheme 153, a and b)" and straight chain enones (Scheme 152, e)" and particularly poor with cyclopentenone (Scheme 154, a and b). Such control cannot be achieved with chal-cone (Scheme 152, a-d)." ... 

Nonconjugated /3,y-unsaturated ketones, such as 3-cyclohexenone, are in an acid-catalyzed equilibrium with their conjugated o,/3-unsaturated isomers. Propose a mechanism for this isomerization. 

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