Cyclohexenones fused

Trichodermatides A—D (66—69) have been characterized from the fungus Trichoderma reesei, obtained from marine sediments in China. Octaketide derivatives such as 67—69 with an 0 ,/ -unsaturated cyclohexenone fused to a pyran ring have repeatedly been reported from the genus Trichodermabut do not seem to occur elsewhere in nature. 66 is the first example of a pentacyclic polyketide with a ketal moiety. 66—69 exhibited weak cytotoxicity toward the A375-S2 human melanoma cell line. 

The synthesis of this series involved the reaction of disubstituted or benzo fused 6-keto(formyl)-2-cyclohexenones with hydroxylamine (Scheme 176), Base degradation gave a-cyanoketones which can be further degraded to diacids (67AHC(8)277, 80IJC(B)406). 

FUJIMOTO - BELLEAU Cyclohexenone Synthesis Synthesis of fused cyclohexenones from lactones (an alternative to the Robinson annulation). 

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]. 

A seven-membered ring is formed in the cyclization of 195 (equation 95)105. The homologue 196 affords the fused cyclooctane 197, together with the cis- and trans-decalinones 198 (equation 96)106. Six-, seven- and eight-membered rings are produced in Lewis acid-catalysed reactions of various cyclohexenones with side-chains terminating in allylic trimethylsilyl groups (equations 97 - 99)107. 

Occidentalol (628), a eudesmane-type sesquiterpene isolated from the wood of Eastern white cedar, was synthesized from a as-fused decalin system (627) prepared by cycloaddition of the a-pyrone (625) with 4-methyl-3-cyclohexenone (626 Scheme 140) (72TL4651). Derivatives of 2-pyrone have also been employed in syntheses of colchicine (629 Scheme 141) (59AG637) and barrelene (630 Scheme 142) (69JA2330). 

Several groups have prepared cyclopentane systems by intramolecular Michael addition.72 Reaction of the triester (292 Scheme 37) with phenyl vinyl ketone (293) and base produces the cyclopentane (295) in good yield via an intermolecular (giving 294) and subsequent intramolecular Michael addition.72 When the Michael acceptor is a cyclohexenone (Scheme 38), the c/s-fused hydrindanone is produced (298 or 297).72b 72f Spiro systems can also be formed by these reactions (300a,b equation 66) in which the Michael addition gives a spiro ring fusion. 

Cis,anti,cis products are favored in the intermolecular photocycloaddition of cyclopentenones with cyclic alkenes87 (Scheme 34). However, intermolecular photoaddition of some cyclohexenones provided preferred /raw. -fused product as the major product with cyclic alkenes60. From the large number of examples presented in Schemes 37, 42, 43, 45, 46, 48 and other examples, it could be concluded that cis -fused products are usually preferred. 

The new ring need not be fused to an old one and simple cyclohexenones can be made by Robinson annelation usually with the addition of a CC Et activating group. In the disconnection of cyclohexenone 78, you could add the CC Et to form 79 before the second disconnection, as we have done, after the second disconnection or while writing out the synthesis. 

Cyclopentenones and cyclohexenones react with 2-hydroxybenzaldehydes in presence of DABCO to afford cyclopentanone- and cyclohexanone-fused 2/7-chromenes (Equation 37) <2004AGE115>. 

A further example of the use of 2//-thiopyrans as surrogates for m-substituted dienes involves the use of the protected 3,4-dihydio-3-(3-oxobutyl)A//-thiopyranA-onc, 3-[2-(2-methyl-l,3-dioxolan-2-yl)ethyl]-4-[tris(l-methy-lethyl)silyl)oxy-2//-thiopyran 328 as an equivalent of l-ethenyl-2-methylcyclohexene in Diels-Alder reactions. The thiopyran reacted with various maleimides to yield the endo cycloadducts and with methyl propenoate to give the exo adduct under either thermal or Lewis-acid-catalyzed conditions. In the latter case concomitant release of the protected ketone functions occurs, acid-catalyzed cyclization of which generates a fused cyclohexenone ring (Scheme 67). Desulfurization, preferably before the aldol cyclization, leads to derivatives of 2,3,4,4a,5,6,7,8-octahy-dro-4a-methylnaphthalenes < 1997CJC681 >. 

The photocycloaddition of 1-alkenylboranes in cyclohexane provided m-fused head-to-head adducts for 2-cyclopen-tenone and a mixture of cis- and trans-isomer for 2-cyclohexenone (Equation (71)).397... 

Langer and coworkers reported on the [3+ 2]-type C,0-cyclodialkylation of cyclohexane-1,3-dione dianion with l,4-dibromo-2-butene (Scheme 25)39. The formation of the tetrahydrofuran-fused cyclohexenone can be explained by a regioselective attack of the terminal carbon of the dianion on the l,4-dibromo-2-butene and subsequent Sy2 -type cyclization. This reaction proceeded with a high degree of diastereoselectivity. An excellent review of this type of cyclization reaction is now available elsewhere40. 

A particularly short and efficient synthesis of the lycopodium al oid (+)-luciduline (303) features as the first step the [4 + 2] cycloaddition of butadiene to optically pure cyclohexenone (299) opposite to the homoallylic methyl group (Scheme 73). To achieve this excellent face discrimination the presence of SnCl4 was requir which, however, provoked an epimerization at C-8a yielding mainly the undesired rmns-fused product (301). Oximation, under epimerizing conditions, easily rectified this problem by channelling both isomers (300) and (301) to a single cij-fused oxime (302) which was converted to the enantiomerically pure alkaloid (303). 

Ligands of type 1 have also led to interesting results in kinetic resolutions during Cu-catalyzed reactions of dialkyIzinc with cycloalkene oxides (eq. (1)) [18] and cyclohexenones [19]. On the other hand, monophosphonites bearing a fused 1,4-dioxane ring behave moderately in the Rh-catalyzed hydrosilylation of ketones (up to ca. 56 % ee) [20] cf. Section 2.6 Finally, a phosphapallada-cyclic complex has been reported as an exceptionally fast catalyst for the hydroarylation of norbomene (TONs up to 10 °) but with low ees (< 25 %) [21]. 

The cyclohexenone 272, derived from L-alanine, was subjected to hydrogenation to give a 2 1 mixture of cis- and trara-fused perhydroquinolines 273 <05T8264> (Scheme 83). 

The titanium tetrachloride-promoted addition of allyltrimethylsilane to methylcyclohexenones and methylcycloheptenones has been explored (68,69) results are summarized in Eqs. [l]-[6] of Scheme 32. With the exception of 4-substituted cyclohexenones and cycloheptenones, good to excellent facial selection is observed (Eqs. [2], [5], and [6], Scheme 32). The major products obtained are those predicted by axial attack of the nucleophile on the more stable conformer of the acceptor. Although there are some similarities, the results show some significant deviations from the corresponding cuprate additions. Addition to the bicyclic enone 32.1 occurs from the convex face, producing exclusively the cis-fused decalone (Eq. [7], Scheme 32) (5). In this case, the product is formally the result of equatorial attack of the allylsilane on the a,/ -unsaturated ketone. 

Synthesis of fused cyclohexenones by reaction of cyclanones with vinyl ketones (base or acid catalyzed), a tandem Michael addition-aldol condensation (see 1st edition). 

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