Cyclohexadienones. 2 + 2 intramolecular

The monolithium salt of 4-hydroxy-4-(phenylethynyl)-2.5-cyclohexadienone (12), prepared in situ by the addition of lithium acetylide to /7-benzoquinone, was treated with methylmagnesium chloride in l HF-TMEDA or in THF —DMPU. The syn-, 4-addition adduct 13, derived from intramolecular delivery of the carbon nucleophile by the hydroxy oxygen, as well as the <7s-1,4-diol 14, obtained via intermolecular 1,2-addition, were obtained in varying amounts depending on the conditions. The selectivity on 1,4- to 1,2-addition increased by the addition of cation chelating agents such as DMPU, TMEDA, and 15-crown-5. Although the 1,4 to 1,2... 

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

Very recently, Cook and Danishefsky [24] reported an interesting regioselectivity of intramolecular Diels-Alder reactions reversed by the change in the dienophihc moieties from vinyl to allenyl group (Scheme 19). For R = 2-propenyl group, C is bonded to the methyl substituted carbon Cj of the cyclohexadienone ring. For R = 2,3-butadienyl, C is bonded to Cy... 

Rovis and co-workers have applied the asymmetric intramolecular Stetter reaction to the desymmetrisation of cyclohexadienones 140, generating a quaternary stereocentre and forming hydrobenzofuranones 141 in excellent yields and enantiose-lectivities. Substitution at the two, four and six-positions is tolerated, and even substitution at the three-position is accommodated (Scheme 12.29) [65]. 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

An unusual one-pot intramolecular sulfoxide alkylation-elimination reaction was found by Gibson et al. <2001SL712>. These authors found that treatment of 459 with potassium bis-trimethylsilylamide resulted in a ring closure to 460 in acceptable yield. Furthermore, Batori and Messmer found an effective method for preparation of [l,2,3]triazolo[l,5- ]pyrimidinium salts <1994JHC1041> oxidative cyclization of hydrazones 461 by 2,4,4,6-tetrabromo-2,5-cyclohexadienone gave rise to the quaternary salts 462. Under certain reaction conditions, the formation of 6-bromo-salts 462 (R6 = Br) was also experienced. As neither the starting compound nor the quaternary triazolopyridinium salt underwent bromination in this position, the authors assumed that this bromination process occurred on one of the intermediates in the course of the above-mentioned cyclization reaction. 

In a novel total synthesis of the tricyclic sesquiterpene (—)-longifolene, an intramolecular diazoalkane cycloaddition to a cyclohexadienone ring followed by thermal ring contraction of the resulting pyrazoline gave the tricychc vinylcyclo-propane 261 and this constitutes the key steps in this synthesis (314) (Scheme 8.63). The interesting features of this sequence are the separation of dipole and dipolarophile by five atoms and the formation of a seven-membered ring in the cycloaddition step. 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

The intramolecular [2 + 2] photocycloaddition of cyclohexadienone derivative 51, which is substituted with chiral piperidine ring in the solid state, proceeds enantioselectively and optically active products 52 and 53 were obtained [28], Two crystal modifications of 51, the a-form (mp 102-104°C) and (3-form (mp 127-128°C), gave optically active 52 and 53, respectively, upon irradiation in the solid state. 

The cyclohexadienone 10 undergoes an intramolecular asymmetric Heck reaction in the presence of a chiral monodentate phosphoramidate ligand to give the benzo[c]chromene derivative 11 with excellent enantioselectivity and conversion <02JA184>. 

Liu Q, Rovis T (2006) Asymmetric synthesis of hydrobenzofuranones via de-symmetrization of cyclohexadienones using the intramolecular Stetter reaction. J Am Chem Soc 128 2552-2553... 

CTOSs-conjngated Dienones.—Photochemical rearrangement of dienones of the type shown in (227) is a well known process and leads to bicyclo[3.1.0]hexenones. These compounds are also photoreactive and ring-open to give zwitterions [e.g., (228)]. Schultz et al." have used this rearrangement process and have successfully trapjjed the zwitterion (228) [from (227)] by an intramolecular thermal reaction with the azide group of the side-chain to afford the adduct (229). The cyclohexadienone (230) is photochemically rear-... 

The intramolecular chemical titration is conceptually and experimentally simple and convenient, but it requires that a particular dioxetane must be made that chemi-energizes the photochemically active carbonyl product K. This is usually a formidable and challenging synthetic problem. Representative intramolecularly chemienergized photochemical transformations include Norrish Type I cleavage (Eq. 44), Norrish Type II (Eq. 45a, b, c) cleavages, cyclohexadienone rearrangement (Eq. 46), and cyclopentenyl ketone rearrangement (Eq. 47). 

Ring systems containing cyclohexadienones spiro-linked to a cyclic ether can be constructed by oxidative C—O bond connection in the intramolecular mode. Five-membered ring formation is well documented, and the reactions may be efficient. For example, the linked bisnaphthols (230), (231) and (232)... 

Thus, the formation of symmetrical (caused by perpendicular arrangement of the naphthalene and cyclohexadienone ring systems) cyclohexadienone 215 proceeds not as a [4 + 2]-cycloaddition of two carbocation species but rather as a two-step electrophilic substitution, the first stage of which is intermolecular and the second intramolecular. The reasons for the different direction of the cyclodimerisation reactions of carbocation 211 in protic media and in the presence of Lewis catalysts have been discussed elsewhere29,207. 

In 2009, the Magnus group disclosed the synthesis of racemic codeine [50]. In their synthesis (1) an intramolecular phenol alkylation generating an A-C bicyclic ring system with a quaternary carbon, (2) a stereo-controlled, one-pot formation of a B-ring by way of the combination of Henry reaction and Michael addition of nitromethane with a cyclohexadienone-aldehyde, and (3) an introduction of the requisite functionalities in the C-ring by the epoxide-mediated selenylation followed by oxidation, were employed as the key transformations. 

Photolysis of benzene solutions of l-methoxycarbonyl-2-naphthylmethyl 2,6-di-methyl substituted phenyl ethers induces C-O cleavage with formation of 2,4-cyclohexadienone intermediates which are subsequently photo-rearranged into meta substituted phenols. In methanol, 9-anthrylmethoxy-pyrid-2-one or l-pyrenylmethoxypyrid-2-one undergo photoheterolysis to give the C-O heterolysis products l-hydroxypyrid-2-one and the arylmethyl methyl ether, together with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from homolysis of the N-O bond. Evidence shows that an intramolecular exciplex plays a crucial role in C-O bond heterolysis. 

Cross-conjugated Dienones.- The isomers (254) and (255) axe obtained from the direct irradiation of the cyclohexadienone (256) in benzene. Prolonged irradiation of the mixture results in the photoisomerization of (254) into (255). The irradiation of (255), however, does not bring about isomerization. The study of enantiomerically pure (256) was also carried out and from this it was found that the starting material isomerized into a mixture of enantiomers. The photochemical rearrangement of the cyclohexadienone (257) in methanol occurs in a stereospecific fashion and yields the adduct (258) whose structure was proven by X-ray crystallographic analysis. Cyclohexadienone (259) is photochemically reactive and can be converted in two steps into the adduct (260) as shown in Scheme 8. This process represents the intramolecular trapping of the zwitterionic intermediate (261). ... 

During the following step the cyclohexadienone 2 isomerizes to tetrachlororophenol in an intramolecular way. This last point was perfectly demonstrated by heating a mixture of tetrachlorocyclohexadienone 2 (1 mM) and 2,3,4,6-tetrachlorophenol (10 mM) in the presence of A1C13, at a temperature of 70°C for 8 hours. 

As opposed to this, the transformation process of the same cyclohexadienone 2 (1 mM) under the same conditions with trifluoromethanesulphonic acid produces a mixture of 2,3,4,6-tetrachlorophenol and pentachlorophenol, by intermolecular and intramolecular processes. 

The intramolecular asymmetric Heck reaction has featured in the synthesis of complex heterocyclic compounds. Bidentate ligands, such as diphosphines (especially BINAP) and phosphine—oxazolines, have been used as a chiral ligand of the asymmetric Heck reaction. Imbos et al. demonstrated that the mono-dentate phosphoramidite 513 was an effective ligand for the asymmetric Heck reaction of the prochiral cyclohexadienone 511 (Scheme 153).227 The reaction of 511 in the presence of catalytic amounts of Pd-(OAc)2 and the chiral phosphoramidite 513 gave the 4a-methoxy-4a//-benzo[c]chromen-2(6E/)-one 512 in 71% yield with 96% ee. By contrast, the reaction of... 

Cyclohexadienones of the type IV (n = 0, 1, 2)29 are formed from 2,2 -bi-phenyldiols, 2,2 -methylenebisphenols or 2,2 -ethylenebisphenols via intramolecular C-0 coupling. 5, 7, 3 , 5 -Tetra-tert-butylspiro [2,3-dihydrobenzofuran-2,P-cyclohexa-3 , 5 -diene-2 -one] (IV, R1 = R2 = tert-Bu, n = 1) is stable. The similar compound IV (R1 = tert-Bu, R2 = Me, n = 1), prepared from the technically important antioxidant 2,2 -methylenebis (4-methyl-6-tert-butylphenol) by oxidation with sodium hypochlorite30 is oily and crystallizes in the form of Diels-Alder addition compound V. 

Scheme 38. Enantioselective and solid state [2 -1- 2] intramolecular photocycloadditions of alkenyl cyclohexenones or cyclohexadienones, in chiral inclusion complexes.

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