Cyclohexenones. cycloaddition

The cyclooctenonecarboxylate 169 undergoes smooth cycloaddition with 154 to give 170 in a good yield, but no reaction takes place with cyclooctenone (171)[111], Cyclohexenone behaves similarly. Cycloheptatrienone (172) undergoes [6-1-3] cycloaddition to form the nine-membered carbocycle 173[112],... 

The parent TMM precursor (1), now commercially available, has played a pivotal role in the execution of many synthetic plans directed at natural and unnatural targets. Reaction of (1) with 2-(methoxycarbonyl)cyclohexenone (14, R=C02Me) in the presence of palladium acetate and triethyl phosphite produced the adduct (15) in near quantitative yield. This cycloadduct is a critical intermediate in the total synthesis of a hydroxykempenone (16), a component of the defensive substances secreted by termites (Scheme 2.5) [12]. In accord with a previous observation by Trost that unactivated 2-cyclohexenone reacts poorly with TMM-Pd [13], the substrate (14, R=Me) was essentially inert in the cycloaddition. 

Stable cA-1-phenyl-1-cyclohexene 24 photodimeiizes via Diels Alder cycloaddition to trans adduct 25 (Equation 1.33) [66] and the photoexcitation of dihydrobenzofuran-fused cyclohexenone 26 in net furan gives the trans fused Diels-Alder adduct 27 (Equation 1.34) [67]. 

Conjugated cyclohexenones [6] have also been easily prepared by combining the cycloaddition of dimethylaminobutadiene 4 and several cyclic and acyclic dienophiles followed by the elimination of the amino group from the cycloadducts under acidic conditions. Scheme 2.3 summarizes some of these results. 

A broad study of aluminum chloride-induced cycloadditions of cyclopente-nones, cyclohexenones and cycloheptenones with 1,3-butadiene (1), isoprene... 

Highly uMtr-diastereofacial selective cycloaddition of isoprene (2) with 4-isopropyl-2-cyclohexenone allowed a short regiocontrolled and stereocon-trolled synthesis [13] of jS-cadinene and (y2-cadinene, Scheme 3.3). High anti-diastereofacial selectivity also occurs in the Diels-Alder reaction of optically active cyclohexenones 6-9 (Figure 3.2), readily available from the chiral pool, with open chain dienes [14-16]. Their cycloadducts are valuable intermediates in the synthesis of optically active sesquiterpenes in view of the easy conversion of the gem-dimethylcyclopropane and gem-dimethylcyclobutane in a variety of substituents. 

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... 

Similarly, cycloaddition of the cyclohexenone-like dienophile 40 with 2-tri-methylsilyloxy-1,3-butadiene (41) allowed [7] the regio- and stereoselective synthesis of tetracyclic compound 42, in high yield (Equation 5.5). 

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... 

Nitroethene undergoes rapid cycloaddition to 1,3-dienes the subsequent Nef reaction gives cyclohexenones, which are formally produced by the Diels-Alder reaction of ketene with... 

While doubly activated dienophiles gave moderate to good yields under thermal conditions (Table 11), mono activated alkenes such as cyclohexenone (123) failed to react at temperatures up to 150 °C but underwent cycloaddition under Lewis-acid catalysis even if with poor yields (Table 12, entries 1-3) [32],... 

An useful intermediate for the preparation of 1,4-cyclohexanediones is obtained by cycloaddition of 6-isopropyl-3-methyl-2-cyclohexenone to a cyclobutanediol derivative (4.59) 470>. 

H)-furanones undergo efficient cycloadditions as oxa-enones 450). The cycloadducts have been successfully utilized as synthetic precursors for 8-valerolactones 473) (4.62) or for 2-cyclohexenones (4.63)474>. 

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... 

Intramolecular [2 + 2]-cycloadditions of allenes and enones occur with fair to good site- and regioselectivities. Thus, cyclohexenone 40 bearing an allenic side-chain at the C3 position was irradiated and a single product 41 was isolated in 95% yield [45],... 

The reaction of allenylsilanes with a,/8-unsaturated acylsilanes presents a new [3 + 3]-cycloaddition approach to a six-membered carbocycle [189]. Lewis acid-promoted ring expansion of the [3 + 2]-annulation product 260 is followed by a second cationic 1,2-silyl migration to produce the cyclohexenone 261 after desilylation. 

Carbonylative [5 + l]-cycloaddition of allenylcydopropanes was successfully achieved by use of an Ir(I) catalyst to yield (2-alkylidene)cyclohexenones in good yields (Scheme 16.43) [43]. No carbonylative [5 + l]-cycloaddition was observed in the case of an allenylcyclopropane lacking substituents at the allenic terminus. It can be deduced that the metal is too distant to open the cyclopropane ring, probably owing to the preferred -coordination at the allenic Jt-bond distal to the cyclopropyl group. 

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. 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

Scheme 41 Mechanism of the aza-Diels-Alder-type reaction of cyclohexenone 2.3.12 1,3-Dipolar Cycloaddition...

The first stereocontrolled syntheses of juvabione are described in Schemes 13.11 and 13.12. Scheme 13.10 is a retrosynthetic analysis corresponding to these syntheses. These syntheses have certain similarities. Both start with cyclohexenone. There is a general similarity in the fragments that were utilized, but the order of construction differs. In the synthesis shown in Scheme 13.11, the crucial step for stereochemical control is step B. The first intermediate is constructed by a [2 + 2] cycloaddition between reagents of complementary polarity, the electron-rich enamine and the electron-poor enone. The cyclobutane ring is then opened in a process which corresponds to retrosynthetic step Ha => Ilia in... 

In early 1994, Padwa et al. (119) synthesized both mono- and bicyclic core skeletons of the illudins and ptaqualosins. By utilizing a 1,1-disubstituted cyclopropane as the core of the dipolar cycloaddition, Padwa was able to add a number of dipolarophiles including cyclopentenone and cyclohexenone to produce cycloadduct 233 amenable to subsequent transformations to form the illudins and ptaqualosins. The cycloaddition forms the bicyclic constrained ether in... 

In later work, Mioskowski and co-workers (320) used cyclohexenone 160 to prepare oxime 161 as part of a twofold nitrile oxide strategy to synthesize the basic taxol ring system. Cycloaddition of 161 was effected by means of sodium hypochlorite and gave tricyclic isoxazoline 162, which feamres rings A and C of taxol (320) (Scheme 6.79). Nagaoka and co-worker tried to apply a related intramolecular cycloaddition toward the synthesis of the taxane A/B ring but this approach failed, producing only the oxime derivative (248) (see Scheme 6.44, Section 6.3.1). 

Intramolecular nitrile oxide-alkene cycloadditions also provide efficient access to six-membered rings such as cyclohexanes or decalins that are heavily adorned with functional groups and side chains. For example, this strategy was used to prepare racemic hemaldulcin (213), which is a 3,6-disubstituted cyclohexenone found in a Mexican plant that possesses a strong sweet taste. Starting from (2Z,6E)-famesal (209) (328) (Scheme 6.88), the aldehyde was treated with hydroxylamine... 

Photochemical cycloaddition of ethene with racemic 4-/er -butyl-2-cyclohexenone yields three racemic diastereomers107. For configurational assignment, see pp 463 and 472. 

In principle, relative configurations can be determined directly by X-ray analysis (see Section A.4.2.). However, in cases where the compound of interest does not crystallize or does not give suitable crystals, it may be desirable to use crystals of a derivative. For example, photochemical cycloaddition of rac-4-tcrr-butyl-2-cyclohexenone and ethene yielded three stereoiso-meric products. The relative configuration of the (l, 55, 6 )-isomer (rac-6 on p 411) was determined by reduction and 4-bromobenzoate formation followed by an X-ray analysis107. 

If 2-methylenecyclobutanones, which themselves are not capable of this tautomerization and the following rearrangement, bear alkyl substituents with an a-hydrogen in the 3-position, still another rearrangement, a [1,3] shift, precedes the actual ring-enlargement step. This is important, because either 3-alkyl-2-methylene- or 2-alkylidenecyclobutanones or mixtures of both may be formed via [2 + 2] cycloaddition of allenes92 and can all be used as precursors for the same cyclohexenones. 

Cycloaddition to enones.1 The reagent undergoes photochemical cycloaddition to cyclopentenones and cyclohexenones to form cu-am/-cis-cycloadducts Selectively. The products can he converted into cu-hydrindancs and cis-dccaloncs. 

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