Ene diones

In another interesting turn of event, while we were attempting to add acetate anion in a 1,4-fashion into the enone system of 45, we isolated ene-dione 49b when using KOAc in the presence of 18-crown-6 (Scheme 8.11). While this was not what we had anticipated, it turned out to be a known protocol developed by Komblum and DeLaMare to ring-open endoperoxides through a deprotonation pathway [55]. It is noteworthy that ene-dione 49b did not equilibrate to the ene-trione 49b which could suffer from the aforementioned HDA pathway as we had also suffered from [47c],... 

In principle, the approach outlined above for the a-oxoamides can be applied to any reaction, ground or excited state, which converts an achiral reactant into a chiral product, and Toda, Tanaka, and coworkers have investigated a wide variety of such processes [ 15,16]. A complete discussion of their work is beyond the scope of this review, and we illustrate the general approach taken with one final example. As shown in Scheme 4, irradiation of crystalline complexes of ene-diones 20a-f with chiral host (R,R)-(-)-9b led to cyclized products 21a-f in the variable yields and ee values indicated in Table 1 [22]. Remarkably, for reasons that were not clear (there was no accompanying X-ray crystallography), the R=n-propyl derivative 20g was found to give a completely different photoproduct, spiro compound 22 (69% yield, 97% ee, stereochemistry unknown), a result that once again illustrates the rather capricious nature of the use of chiral hosts for asymmetric induction. 

Lacroix C, Fiet J, Benais JP, et al Simultaneous radioimmunoassay of progesterone, androst-4-ene-dione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone in specific regions of human brain. J Steroid Biochem 28 317-325, 1987... 

Cyclic ketones can also be formed by intramolecular aldol condensation. Roger C. Whitehead of the University of Manchester found (Tetrahedron Lett. 2005,46,2803) that the cis ene dione 4, available by oxidation of the corresponding furan 3, underwent highly diasteroselective aldol condensation, to give untenone A 5. 

Disconnection of both C-N bonds of a pyridine 50 gives an ene-dione 51 but the alkene has to be cis for cyclisation to be possible and conjugated m-enones are rather unstable. It is usually easier to remove the double bond to reveal the saturated 1,5-diketone 52 that can be made by the methods of chapter 21. This usually means conjugate addition of an enolate to an enone. 

Is the experiment wrong What have we neglected Let us return to the assumption of no destabilization due to the ene-dione and ene-diamine, and no stabilization due to the two aminoenal groups. The sole ene-dione (other than quinones) for which there are enthalpy of formation data is (solid) 1,2-dibenzoylethylene. Fortunately for us, there are also data on its solid, saturated, analog. More precisely, one can take the difference of the enthalpy of hydrogenation of the ene-dione (141 kJ mol"x) and that of other internal olefins (ca 120kJmol-1) and equate this 21 kJmol-1 with the desired ene-dione destabilization. This value is the 30 kJmol-1 destabilization of 1,2-dicyanoalkene interactions as found from the enthalpies of formation of fumaronitrile, acrylonitrile and ethylene (equation 16). 

In fact, the reaction of (33) with ene-dione (50), in the presence of diaza(l,3) bicyclo[5.4.0]undecane (DBU) as base, proceeds as depicted in Figure 2.15 as a tandem process in which a regioselective Michael addition (yielding 51) is presumably followed by the elimination of nitrous acid, to give the corresponding nitro-enone (52). 

Until recently, the preparation of the bicyclic ene-diones (47a,b), which are important intermediates in steroid total synthesis, has led only to racemic mixtures This deficiency has now been met as follows. Michael addition of the vinyl ketone (44) to the cyclic diketones (45a) and (45b) afforded the triketo-intermediates (46a) and (46b) in high yield, each containing a prochiral centre. Optically active amines and amino-acids were used as chiral reagents to... 

The cage compound (301) is formed efficiently on irradiation of the adduct (302).Irradiation of the ene dione (303) affords the cage compound (304) by a (6 + 2)-cycloaddition. The Diels-Alder adducts (305) are photochemically reactive. Irradiation of (305) affords either the cage compounds (306) by a (2+2)-cycloaddition reaction, a process favoured by the adducts (305 a,b), or the oxetanes (307). The structures (306, 307) were verified by 2L ray diffraction studies The quinone adduct (308) also undergoes photochemical cyclization to afford the cage diketone (309). This material was subjected to flash vacuum pyrolysis to yield the diketone (310) important in the synthesis of perhydroindacenes. ... 

FIGURE 18,2. The solid-state polymerization (at wavelengths greater than 340 nm). (a) The reaction occurring in the solid state, and (b) a diagram of the solid-state reaction. The ene dione double bonds of adjacent molecules in the crystal have a C C distance (indicated by hatched lines) of 3.62 A. Cyclobutane dimerization occurs across a center of symmetry. (Refs. 10 and 14). 

The amino nitrile 9 fulfils all these hopes. It is easily made, it can be alkylated to give 10, and the anion from removal of its second proton gives a clean Michael reaction to form 11. Finally, the amino-nitrile functionality is easily hydrolysed at room temperature and neutral pH (unlike so many such compounds see chapter 14) with Cu(II) catalysis to give the ene-dione 4 and hence ds-jasmone 1 by thermodynamically controlled cyclisation in weak base.1 This process of adding a new five-membered ring, not necessarily to give a cyclopentenone, is often called cyclo-pentannelation and there are now many such methods.3... 

The reaction of trimethylsilyl cyanide with the cis ene diones 12, produced photo-chemically from furans, provides 2-cyano-5-hydroxy-2,5-dihydrofurans, which can be oxidized to 4-cyanobutenolides33 (equation 25). 

Tandem oxidative cyclization of a-chloromalonate ester with Mn(OAc)3 and Cu(OAc)2 in EtOH at reflux affords 65% of lactone 124, analogously to the conversion of 35 to 36 and 37 [60]. Further elaboration yields estafiatin (125) (Scheme 39). Oxidation of 126 with Mn(OAc)3 and Cu(OAc)2 in AcOH at 50 °C results in hydrolysis to the ene dione, which is oxidized to the a-keto radical. Tandem cyclization and oxidation of the cyclopentanemethyl radical by Cu(II) affords 70-80% of 127, which was converted to tricycloillincinone (128) (Scheme 40) [61]. Oxidative cyclization of phenylmenthyl y -keto ester 129 with Mn(OAc)3 and Yb(OTf)3 in trifluoroethanol at -5°C provides 77% of 130 as a 38 1 mixture of diastereomers. 

Irradiation of the enedione (355) results in formation of the two acids (356a, b) and the lactone (357) when the reaction is carried out in benzene solution. The formation of the lactone is presumed to involve the intermediacy of the biradical (358) within which a 1,2-phenyl migration occurs to yield product (357). A biradical (359) is also proposed as the key intermediate to the formation of the acids by way of the ketene intermediate (360) which is trapped by adventitious water. Further proof of the involvement of a ketene was obtained from experiments in methanol when the esters (356c, d) are obtained. Behaviour analogous to the above is also encountered with the ene diones (361). When the bridging chain is reduced as in (362) the irradiation yields only the quadricyclane (363). An account of the photochemical cis-trans isomerization of (364) applied to an undergraduate experiment has been reported. ... 

---