Cycloalkenone

In the case of cycloheptenone and larger rings, the main initial photoproducts are the -cycloalkenones produced by photoisomerization. In the case of the seven- and eight-membered rings, the double bonds are sufficiently strained that rapid reactions follow. In nonnucleophilic solvents dimerization occurs, whereas in nucleophilic solvents addition occurs. ... 

Another chiral cuprate that shows high diastereoselectivity on addition to cycloalkcnones is the dihydropyrazine derivative 12. The adducts 13 were obtained in good chemical yield with diastereoselectivities exceeding 90% A Lower diastereoselectivities resulted on addition of 12 to /(-substituted cycloalkenones or to acyclic ( )-enones. 

The addition reaction of the lithium salt of ( + )-3-[(7 )-4-methylphenylsulfinyl]-l-propene with various 2-cycloalkenones was examined at —78 DC in tetrahydrofuran17. 

The starting materials for annulative cyclization are cycloalkenones that contain the allylsilane side chain in the 4-position. Such starting materials can easily be prepared from vinylogous esters40. Furthermore, reactions of 3-alkoxy-2-cyclohexenones with functionalized iodides in the presence of lithium diisopropylamide provides an excellent route to such precursors41 34 35. 

Highly diastereoface selective Michael additions to chiral cycloalkenones and lactones have been developed264. The selectivity is, in general, due to the shielding of one of the diastereotopic faces by a substituent R at the stereogenic center in the y- or -position (steric effect). 

A diastereoselective route to d.v-2,3-disubstituted cyclohexanones is based on the kinetically controlled protonation of the enolate obtained via the addition of an arylacetonitrile to 2-sub-stituted 2-cycloalkenones in THF or in THF/HMPA mixtures at — 70-0 °C 299,30°, see also refs 301, 302 and 403. 

In related studies (S)-3-alkylcycloalkanones were obtained in moderate to high enantiomeric purity from the addition of dialkylmagncsium reagents to (,S)-2-(4-methylphenyl-sulfinyl)-2-cycloalkenones in dimethoxyethane at — 78 "C11. The addition of divinylmagne-sium and diphenylmagnesium occurred in the same stereochemical sense11. 

The addition of the lithium enolates of methyl acetate and methyl (trimelhylsilyl)acetate to ( + )-(S)-2-(4-methylphenylsulfinyl)-2-cycloalkenones gives, after desulfurization, (/ -substituted cycloalkenones. A higher level of selectivity is observed with the a-silyl ester enolate and in the cyclohexenone series13. The stereochemical outcome is rationalized by assuming attack on a ground-state conformation analogous to that in Section 1.5.3.2.1. 

Posner and coworkers have published a series of papers in which they described a successful application of the Michael reaction between a variety of carbanionic reagents and chiral cycloalkenone sulphoxides 557 to the synthesis of chiral organic compounds (for reviews see References 257, 649, 650). In several cases products of very high optical purity can be obtained. Subsequent removal of the sulphinyl group, serving as a chiral adjuvant, leads to optically active 3-substituted cycloalkenones 558 (equation 356 Table 27). 

TABLE 27. Michael additions to chiral cycloalkenone sulphoxides 557... 

In a conceptually similar fashion, camphor-derived hydroxysulfide 9 is oxidized diastereospecifically into hydroxysulfoxide 10 whose absolute configuration has been determined by X-ray crystallography48. Heating this diastereomer to 145 °C causes complete epimerization at sulfur to form diastereomer 11 in quantitative yield (equation 12). This type of allylic sulfoxide can be deprotonated and then added in a Michael fashion to cycloalkenones (see p. 834). 

Lewis acids can greatly accelerate the cycloaddition. Instructive examples are the AlQs-catalyzed reaction of cycloalkenones with 1,3-butadienes [12]. The catalytic effect is explained by FMO theory considering that the coordination of the carbonyl oxygen by Lewis acid increases the electron-withdrawing effect of the carbonyl group on the carbon-carbon double bond and lowers the LUMO dienophile energy. 

Highly thermally stable Diels-Alder adducts of [60]-fullerene with 2-cycloalkenones and their acetals [137]... 

CARBON DIELS-ALDER REACTION 3.2.1 Cycloadditions of Cycloalkenones... 

Diels-Alder reactions of conjugated cycloalkenones provide a very important method for rapidly constructing complex polycyclic molecules. Since cycloalkenones are very poorly reactive dienophiles, acceleration by special physical and catalytic methods is required in order to avoid high reaction temperatures and long reaction times which often lead to low product yields [8],... 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

Diels-Alder reactions of 2-bromo-2-cycloalkenones. A convenient approach to doubly cisoid fully conjugated dienone system [94]... 

Cycloalkenones and/or their derivatives can also behave as dienic partners in the Diels-Alder cycloaddition. It is well documented [41] that cyclic acetals, for example, can interconvert with ring-opened enol ether forms, in a reversible manner the latter compounds can then be trapped by various dienophiles. Thus dienes 119 and 120 reacted with [60]-fullerene (Ceo) at high pressure, affording highly thermally stable products [42] (Scheme 5.16). Ketones 123 and 124 could be directly obtained by cycloaddition of enol forms 121 and 122 of 2-cyclopen-ten-and 2-cyclohexen-l-one, respectively. 

Minuti L., Taticchi A., Costantini L. High Pressnre Diels-Alder Reactions of Cycloalkenones in Organic Synthesis Recent Res. Dev. Org. Chem. 1999 3 105-116 Keywords ketones, regiochemistry, stereoselectivity, reactivity... 

Reduction, carboxyl groups, 56,83 Reduction of a,0-unsaturated p-toluene-sulfonyl-hydrazones to alkenes, 59,42 Reductive alkylation, 56,52 Reductive cleavage, 56, 101 Resolution of amines, 55,80, 83 Rexyn 201,55,4 Rhodium(III) oxide, 57, 1 Ring contraction, 56, 107 Ring expansion of cycloalkanones to cycloalkenones, 59, 113... 

ONE-CARBON RING EXPANSION OF CYCLOALKANONES TO CONJUGATED CYCLOALKENONES 2-CYCLOHEPTEN-l-ONE... 

Preparation of 2-Cycloalkenones and Cycloalkane-1,3-diones BY Iron(III) Chloride-Induced Ring Opening of 1-Trimethyi,-siLYLOxY- AND 1,2-Bis(trimethylsilyloxy)bicyclo[w.1.0]alkanes... 

Dithioacetal monoxides undergo Michael addition to acrylonitrile. The addition products are easily converted into y-ketonitriles 382 (equation 221). Benzenesulphinyl allylic carbanions 383 derived from the corresponding allylic sulphoxides react selectively at the y-position with a variety of cycloalkenones to give the l,4-adducts " (equation 222). Recently, Nokami and coworkers have synthesized some prostaglandin analogues via a three-component coupling process involving 1,4-addition of phenylsul-phinyl allylic carbanion (equation 223) . ... 

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

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