Cycloaddition reactions of enones

Scheme 6.8. Photochemical Cycloaddition Reactions of Enones with Alkenes and Alkynes... 

Intermolecular.- Reviews have described some of the photochemical (2+2)-cycloaddition reactions of enones used in the synthesis of natural products. Other reports have also focussed on such additions as key steps in the design of natural products. Thus the photoadducts obtained by the cycloaddition of the enone (61) to the alkene (62) have been used as the starting materials for the synthesis of terpenoid intermediates. ... 

Intramolecular [2+2] cycloaddition reactions of enones D. Becker, N. Haddad, Organic Photochemistry 1989,10, 1- 162. 

Intermolecular [2+2] cycloaddition reactions of enones S. W. Baldwin, Organic Photochemistry 1981,5,123 - 226. 

A study of the intramolecular (2+2)-addition in the enones (77) has been reported. The outcome of the addition is both temperature and substituent dependent. Thus irradiation of the enone (77a) at 0°C in acetonitrile with benzophenone as the sensitizer yields a single adduct (78) in 90% yield after only 35 min. irradiation. The photocycloaddition of the enone (77b) at lower temperatures yields a mixture of (78) and (79) in a ratio of 1.8 1. The other derivatives (77c,d) afford only one product identified as (79). The products obtained from the cycioaddition can be cleaved to spiroacetals. The synthetic potential of the intramolecular (2+2)-cycloaddition reaction of enones continues to be exploited. In a recent example example the cycioaddition of the enone (80) affords the product (81) which is then subjected to ring-opening and further transformation to provide a path to the natural product (+)-ligudentatol (82). " ... 

Several reviews have been devoted to the subject of, among other cycloaddition reactions, (2 + 2)-cycloaddition reactions to enones. Within these articles the additions of alkynes has been dealt with. Specifically, a short review has discussed the cycloaddition reactions of enones with alkynes. ... 

The two-step formal [3-1-2] cycloaddition reactions of enones or enals with allenylethers afford cyclopentenone derivatives. For example, reaction of the masked enalallene 342 at room temperature in the presence of a gold catalyst affords the bicycUc aldehyde 343 in 90 % yield... 

Bauslaugh, P. G., Photochemical cycloaddition reactions of enones to alkenes synthetic applications, Synthesis, 287,1970. 

Cyclopropyl ketones 32 and cyclopropyl imines 33 can also undergo [3+2] cycloaddition reactions with enones 34 in presence of NHC-Ni complexes to afford the corresponding cyclopentane compounds 35 (Scheme 5.9) [11]. The catalytic system is prepared in situ from the use of [Ni(COD),], SIPr HCl salt and KOBu, the reaction also required the use of Ti(O Bu) as an additive to improve yields and increase reactions rates. In most of the cases, th products 35 were obtained in good to excellent diastereoselectivities. 

Scheme 5.9 NHC-Ni catalysed [3-I-2] cycloaddition reaction of cyclopropyl ketones or cyclopropyl imines with enones...

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

Orbital Symmetry Conservation in Bimolecular Cycloadditions. The cycloaddition reactions of carbonyl compounds to form oxetanes with ethylenes, as well as those of enones and their derivatives to form cyclobutanes, are examples of reactions which originate from triplet excited states and lead in the first step to biradical intermediates. Such reactions are of course not concerted, and they show little or no stereo-specificity. 

The intramolecular 1,3-dipolar cycloaddition reaction of azides has become an increasingly useful process for the construction of natural products and molecules of theoretical interest.192 193 For example, 2-substituted azido enone (238) was prepared from the corresponding bromide by treatment with sodium azide. Thermolysis of this material afforded aziridinyl ketone (240) presumably via a transient dipolar cycloadduct (239).193 Ketone (240) was subsequently converted to an intermediate previously used to prepare histrionicotoxin (241 Scheme 56). 

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

Despite the fact that the [2 + 2] -photocycloaddition reaction of enones has a history of more than 100 years, it has remained a vital and attractive reaction. The continuing interest and many applications to increasingly more complex targets not only bear testimony to its utility but also contradict the myth that photochemical reactions are nonselective and unpredictable. It would be desirable if this most useful chemistry could also be appreciated in the life sciences industry. The first blockbuster drug to be synthesized via a [2 + 2]-photocycloaddition is yet to be developed. Apart from the conventional evolution of the reaction, which involves an increase in scope and an improvement in its practical execution [154], it is expected that sensitization - as a means of catalyzing photochemical reactions in general [155-157] - will become a dominant factor in the development of catalytic enantioselective [2 + 2]-photo-cycloaddition variants. 

Cycloaddition reactions of a,p-unsaturated carbonyl compounds to olefins have been studied in detail. Cyclic enones, undergo rapid and efficient intersystem crossing thereby providing easy access to the triplet state through direct excitation. The following cycloaddition reaction is proposed to involve a diradical intermediate formed directly or from an exciplex [102, 103] (see (29)). 

A2-Isoxazolines are readily available from the 1,3-dipolar cycloaddition of nitrile JV-oxides with alkenes and from the condensation reaction of enones with hydroxylamine. Therefore, methods of conversion of A2-isoxazolines into isoxazoles are of particular interest and of synthetic importance. 

The stannaphosphenes 21-48 and 21-49 are formed by lit.hia.tion of the FSn-PH unit to give FSn-PLi, followed by the elimination of LiF. Methanol adds across the Sn=P double bond in the same way as with the Sn=N structure, and 21-49 shows cycloaddition reactions with enones and orthoquinones.83"86 No X-ray diffraction study of a stanna-phosphene has yet been reported... 

Introduction of an alkylthio group on the allene system increased the reactivity of the allene moiety in [2 + 2] cycloaddition reactions. It proved possible to conduct reactions of this allene at much lower temperatures. By adding Lewis acids, the reaction temperature could be decreased even more, as was illustrated by the Lewis acid catalyzed [2-1-2] cycioadditions of l-trimethylsilyl-l-methylthio-l,2-propadiene with a variety of electron-poor alkenes, including cyclic and non-cyclic enones, acrylates, methyl fumarate and acrylonitrile. When a chiral diol 21 based titanium catalyst was employed, the [2-1-2] cycloaddition reactions of /-acryloyl-l,3-oxazolidin-2-ones 17a and 17b with allenyl sulfides 18 yielded methylenecyclobutanes 19 and 20 with high optical purities (equation The highest yields were obtained with electron-poor allenophile 17b. 

The Hantzch-Panek condensation of ethylpyruvate with acrylamide followed by treatment with trifluoroaceticanhydride (TFAA) provided 2-vinyloxazole-4-ethylcarboxylate 37 in good yield [57]. The Stille coupling of 2-chlorooxazole-4-ethylcarboxylate with vinyltrimetbylstannane also provided 2-vinyloxazole 37 [26]. The reactivity of 37 towards cycloaddition reactions with enone and coupling reactions with aryl halides were explored [57]. Heck reaction of vinyloxazole with p-iodoanisole gave the cinnamyl oxazole 97 in 71% yield [57]. 

Hastings, D. J., Weedon, A. C., Origin of the Regioselectivity in the Photochemical Cycloaddition Reactions of Cyclic Enones with Alkenes Chemical Trapping Evidence for the Structures, Mechanism of Formation, and Fates of 1,4 Biradical Intermediates, J. Am. Chem. Soc. 1991, 113, 8525 8527. 

A preliminary examination of asymmetric induction in photochemical [2 + 2] cycloaddition reaction of an enone to an alkene employed a chiral auxiliary attached to the alkene component74. The photocycloaddition of 2-cyclopentenone to the optically active ketene acetal 1 led both to oxetanes and cyclobutanes in the ratio 6.5 3.5 with a total yield of 60%. The m-[2C + 2C] addition of the chiral alkene I to 2-cyclopentenone was completely regioselective and gave four diastereomeric head-to-tail cycloadducts 2-4 in the ratio 6 29 33 32. 

The intermolecular (2 + 2)-cycloaddition reactions of heterocyclic compounds can be divided into two groups, depending on whether the heterocycle contains an enone moiety or not. 

Reactions of some heterocycles with cyclic enones have also been reported154 as well as (2 + 2)-cycloaddition reactions of heterocycles having an enone moiety with olefins. In general it is assumed that the reactive species in these reactions are excited triplet states (ET 70 kcal/mol),123 but in some instances excited singlet states have also been proposed.155... 

Earlier work by Wiesner proposed a set of empirical rules to account for the outcome of cycloaddition reactions to enones. Wiesner et al. have now examined the photoaddition of allene to the sterically hindered system (61). This work has... 

As in past years this chapter describes the photochemistry of those carbonyl compounds where the reaction type is dictated by the carbonyl function. Thus Norrish Type I and II reactions, rearrangements, and cycloadditions are dealt with in this chapter, but reductions and reactions of enones will be covered in later chapters in Part III. The shift in emphasis away from the study of simple carbonyl compounds which was pointed out in Volume 6 has been noticeable throughout this year. 

Intermolecular Additions to Cyclopentenones and Related Systems. Mehta and co-workers have described the photochemical addition of 1,2-dichloroethene to the enone (12). This affords the adduct (13), which can be transformed into the protoilludane-type molecule shown in Scheme 4. A further study related to the (2 + 2)-cycloaddition reactions of compounds such as (14) and (15) has determined the crystal structures of these compounds. The... 

Inter molecular Additions to Cyclohexenones and Related Systems. Calculations have been reported that deal with a transition state analysis of the regioselectivity encountered in triplet-state (2 + 2)-cycloaddition reactions of cyclohex-2-enone. Diastereoselective (2 + 2)-cycloaddition of ethene to cyclohexenone carboxylates in the presence of chiral auxiliaries has been described. Yields of bicyclo[4.2.0]octanone derivatives can be obtained with de as high as 81%. The enone (16) can be tethered to a polymer substrate via the tether group R. Irradiation of this material in toluene with ethene at —78°C gives a 68% yield of the adduct (17). The de of the product is reasonable at 72%. Addition of 1,1-diethoxyethene to the cyclohexenone (18, R = Ph) results in the formation of the two stereoisomeric head-to-tail regioisomers (19) and (20). The outcome of the reaction is dependent on the rate of formation of 1,4-biradical intermediates. This can be seen in the dependence of the cisjtrans ratio on the solvent and on the temperature at which the reaction is carried out. Thus with enone (18, R = Ph) in acetone at 3°C, a cjt ratio of 4.4 is obtained, and this changes to 2.1 at —40°C. In acetonitrile the cjt ratio is only 1.9 at the same temperature. With the other derivative of (18), the cjt ratio is 1.3 in acetone and 0.8 in acetonitrile. Photoaddition of ethene to the enone carboxylate [21, R = (-)-8-(2-naphthyl)menthyl] results in the formation of the diastereoisomers (22) and (23) with a de of 56% at —78°C. The diastereo-selectivity can be enhanced by the addition of naphthalene derivatives to the solution. Thus with naphthalene, a de of 71% is obtained, and this can be increased to 83% with 1-phenylnaphthalene. ... 

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