Five-membered enone

The Larock modified Saegusa oxidation conditions were utilized in the total synthesis of ( )-8,14-cedranoxide by M. lhara et al. The main strategy was to apply an intramolecular double Michael addition reaction to assemble the tricyclic cedranoid skeleton. The precursor five-membered enone was prepared in high yield from the corresponding substituted cyclopentanone in two steps. 

Five-membered enone / -Ring residue 2 X 12 Exocyclic double bond ... 

The carbopalladation of allylamine with malonate affords the chelating complex 510, which undergoes insertion of methyl vinyl ketone to form the amino enone 511[463]. The allylic sulfide 512 has the same chelating effect to give the five-membered complex 513 by carbopalladation[463.464]. 

For his synthesis of the anti-tumour compound diketo-coriolin, Danishefsky needed (9) with its two fused five-membered rings, Enone disconnection suggests two possible precursors. 

Intramolecular enone-alkene cycloadditions are also possible. In the case of (3-(5-pentenyl) substituents, there is a general preference for exo-type cyclization to form a five-membered ring.195 This is consistent with the general pattern for radical cyclizations and implies initial bonding at the (3-carbon of the enone. 

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

The formation of a diverse array of five-membered ring heterocycles via the cycloaddition of isocyanides with furan- or pyrrole-based enones was reported. The reaction mechanism is discussed and an example is shown below <06OL3975>. 

Ramirez, F., Gulati, A.S., and Smith, C.P, Reactions of five-membered cyclic triaminophosphines with hexafluoroacetone, trifluoroacetophenone, and fluor-enone. Attack by phosphorus on carbonyl oxygen and isolation of crystalline 2,2,2-triamino-l,3,2-dioxaphospholanes, /. Am. Chem. Soc., 89, 6283, 1967. 

Cycloaddition of a-aryl-A-phenylnitrones to the C16-C17 n-bond in 16-dehydropregnenolone-3P-acetate (545) involves only the minor rotamer (A-form) of the nitrones. It proceeds regio-, stereo- and Jt-facial-selectively to give steroido[16,17-d]isoxazolidines (546) in high yield (Scheme 2.257), (Table 2.24) (760). Similarly the cycloaddition of a,N -diphenylnitrones proceeds with five-membered heterocyclic enones (761). 

The high enantioselectivity shown in the above reactions can be attributed to two important factors. First, coordination of the Lewis acid with the a-hydroxy ketone moiety of dienophile 17 or 19 leads to the formation of a rigid five-membered chelate 21. This chelate causes the differentiation of the two dia-stereotopic faces of the enone system. Second, arising from the established absolute configuration of 17 and 19, within 21, the Diels-Alder reaction proceeds with the enone fragment at its cisoid position (yyu-planar). 

Cyclic alkynyl carbonates undergo carbonylation in the presence of a palladium catalyst and carbon monoxide (5 MPa) in MeOH to give allenic carboxylates (Eq. 9.118) [92], Bu3P proved superior to Ph3P as the catalyst ligand. An enynyl cyclic carbonate underwent double vicinal carbonylation at 80 °C to produce a five-membered lactone product in 52% yield (Eq. 9.119). When the reaction was performed at 50 °C, the bicyclic enone lactone was produced in 75% yield along with 10% of the y-lactone. 

However, the reaction of ,/i-unsaturated enones, 1,2-allenylsilane and TiCl4 in CH2C12 afforded five-membered vinylic silanes 65 via the formation of 62, regiose-lective electrophilic addition and 1,2-shift of the trimethylsilany] group and cycliza-tion [34]. 

In almost the same manner, tandem hydroformylation/aldol condensation aldol condensation of ketoolefins, such as p,y-unsaturated ketones, gives a single cyclization product under acid catalysis. Similar to the stepwise reaction, the in situ generated aldehyde preferentially acts as the electrophilic carbonyl component, while the ketone acts as the nucleophilic enol to form the five-membered ring product. Subsequent dehydration and hydrogenation of the resulting enone readily occurs under the reductive reaction conditions used (Scheme 30) [84],... 

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

Substrates possessing an allene that participate in the Alder-ene reaction are less common, but a few examples are known. Malacria [11] and Livinghouse [12] have independently used cobalt to effect intramolecular allenic Alder-ene reactions but the scope of these reactions was not investigated. Sato has performed an allenic Alder-ene reaction to form five-membered rings, using stoichiometric amounts of titanium [13], and Trost has shown that 1,3-dienes can be prepared via an intermolecular Alder-ene reaction between allenes and enones using a ruthenium(II) catalyst [14]. 

The first naturally occurring tricyclo[6.3.0.0 ]undecane to be synthesized was isocomene (757), a colorless oily sesquiterpene hydrocarbon isolated from several plant sources. In 1979, Paquette and Han reported an efficient, stereospecific approach starting with a preformed bicyclic enone, to which the third five-membered ring was appended with proper attention to stereochemistry and position of unsaturation (Scheme LXXX) The pivotal steps are seen to be the stannic chloride-induced cyclization of aldehyde 732 and the conjugate addition of lithium dimethylcuprate to 733 which sets the stereochemistry of the last methyl group. 

A series of differently substituted cyclic enones was used as substrate. Using a seven-membered ring enone the enantioselectivity remained high, but for a five-membered ring analogue the ee dropped (Table 3). 

Other five-membered heterocyclic enones used in [2 + 2] photocycloadditions are 1//-pyrrole-2,3-diones86-88 and derivatives of maleic anhydride. Some cycloadducts of dimethylmaleic anhydride and unsaturated acid esters have been used as monomers for condensation polymers.89... 

The position of the E.T. band depends in a predictable manner upon the extent of conjugation, the degree of substitution, etc., and may be calculated following rules which are analogous to those available for the prediction of absorption characteristics of conjugated dienes and which are set out in Table 3.9. The base values selected are 215 nm for an enone in an acyclic or six-membered ring system, or 202 nm for an enone system in a five-membered ring, or 207 nm for an a,/ -unsaturated aldehyde. 

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