Cycloadduct 2+2 Cyclobutane formation

Various photochemical (2 + 2)-cycloadditions of heteroaromatic compounds have been reported in which an enone moiety is incorporated either into the olefinic reagent or into the heteroaromatic compound. Both furan and thiophene have been found to give cycloaddition reactions with maleic anhydride derivatives in the presence of a sensitizer.202 213 The cycloadducts (185 and 186) were formed in high yield, but in the case of 2,5-dimethylthiophene, cyclobutane formation was the minor pathway, as oxetane formation predominated.210 Cyclic enones, such as 2-cyclopenten-l-one and 2-cyclohexen-l-one reacted with furan to afford mixtures of (2 + 2)-cycloadducts (187a, R = H) and (188),... 

Many examples of cyclobutane formation involving cyano-substituted alkenes or enone components have been reported over the years. Some of these reactions arise as a result of SET to an electron-accepting sensitizer such as 1,4-dicyanonaphthalene. One such reaction among the many reported involves the photoreaction of the diene 244 in benzene solution. Under these conditions the (2 + 2)-cycloadduct 245 is formed in reasonable yields ca 70%). In acetonitrile, however, a different reaction occurs leading to the allylation of the sensitizer affording 246, which undergoes (2 + 2)-cycloaddition to yield the cyclobutane 247 ". Other intramolecular cycloadditions have also been reported, such as the formation of the cage compound 248 from irradiation of the pentaene 249 " ". ... 

Cyclobutane formation was first observed in our studies of the cycloadditions between an electron-deficient NBD 19 (Y = COOMe) and dimethyl meleate. A small amount of [2 + 2] cycloadduct accompanies the expected [2 + 2 + 2] adduct (ratio 1 4.5). When the more reactive olefin N-phenylmaleimide (NPM) is used, the major product isolated is cyclobutane exo-39 (34%) accompanied by ew cyclobutane endo-39 (17%) and two [2 + 2 + 2] adducts 40 (14%, exo/endo = 2.5 1) (Scheme 22). l th electron-deficient 2,3-disubstituted NBD 41, cycloaddition with NPM affords exo-cyclobutane 42 (Eq. 17). No other [2 + 2] or [2 +... 

Acetone-sensitized [2+2]-photocycloaddition of 2(3//)-oxazolones 247a to maleic anhydride and dimethylmaleic anhydride gives the corresponding anti-cyclobutane cycloadducts 253 as the major products. Similar photoreaction of 2(37/)-oxazolones with 1,6-anhydro-4-(9-benzyl-2,3-dideoxy- 3-D-e 7t/ira-2-hex-enopyranose 254 results in the exclusive formation of the anh-cyclobutane-type adduct 255 (Fig. 5.61). ... 

The sensitizer-dependence of these product ratios has been attributed to triplet energies that differ for the s-cis and s-trans conformers (Sch. 6). Conversion of the dienes to triplet biradicals 24 and 25 lock in the initial conformations. Subsequent bond formation with a second diene leads to two allylic radicals 26 and 27, again preserving the geometries. Spin inversion and bond formation then forms the cyclobutane 6 from 26 and the cyclohexene 7 from 27. The higher population of s-cis conformer for isoprene 16 is reflected in the higher proportion of [4+2] cycloadducts 20 and 21 as well as the appearance of [4+4] cycloadducts 22 and 23 in the product mixture (Sch. 5) [32]. 

In our simplified scheme, there are four possibilites to form cycloadduct from donor olefins and acceptor olefins (1) concerted reaction of the partners, (2) the partners form an exciplex, which collapses to cyclobutanes directly, (3) the exciplex collapses to tetramethylene diradical, which then close to cyclobutanes, and (4) direct formation of diradical from donor/acceptor pair and then cyclization. 

Reaction of benzynes with acyclic dienes generally gives Diels-Alder products in poor yields because of competitive [2 + 2] cycloadditions and ene-type processes (Scheme 113). The product distribution, obtained from 2,3-dimediyl-l,3-butadiene (484)," is more characteristic of a two-step mechanism than of a concerted addition. Widiout pursuing this argument, it tqrpears diat the extremely poor yield of [4 + 2] cycloadduct (485) results from die very fast reaction of benzyne with the transoid diene (484). Bond formation at C-1 coupled with a hydrogen transfer (- 487) or cyclobutane ring closure (-> 486) seems to occur rapidly before diene (484) can adopt the s-cis conformation. 

The formation of cyclobutanes starting from a,P-unsaturated carbonyl compounds and olefins is referred to as the de Mayo reaction. The carbonyl component is excited upon irradiation by ti <—ti transition. The regioselectivity is determined by orbital coefficients and polarity effects that depend on the solvent, but the stereochemical information of the olefin is not preserved in intermolecular processes, indicating the non-concerted character of a triplet reaction. In this case 1,4-biradical intermediates are formed and the most stable one determines the stereochemistry of the main product. The cycloadducts of pentanones are most often cis-fused while hexanones preferentially give transcycloadducts. ... 

Pyrex-filtered irradiation of methanol solutions of the pyridone (94) results in the formation of the (2+2)-cycloadduct (95). The route to (95) is thought to involve (4+4)-photocycloaddition to yield the adduct (96) which is thermally unstable and undergoes a facile Cope rearrangement to yield the cyclobutane isomer (95). A full account has been published of the photo-induced mixed addition between (97) and (98). A 1 1 ratio of these compounds yields the two adducts (99) and (100) in a 6 22 ratio. A 1 4 ratio of the reactants gives the same products but in a respective ratio of 21 6. 

The formation of a cyclobutane introduces a large strain in the cycloadducts, and cis configurations of the bicyclic molecules are selectively obtained. When asymmetric centers are present in the starting material, the stereochemistry of the products is controlled by the relative rates of cyclization and of cleavage of these biradicals. For intermolecular processes, it is well established that steric... 

Two reports have dealt with the result of the photoaddition of ethyne to the hexenulose 70. This reaction occurs stereo-specifically to afford the adduct 71. The adduct can be readily reduced to the corresponding cyclobutane derivative or can be elaborated into optically active tricothecene derivatives. Acetone-sensitized irradiation of the pyrone 72 in the presence of ethyne affords the adduct 73 and the rearrangement product 14 . The formation of this latter adduct presumably involves cyclobutene ring-opening followed by crossed addition of the diene. Cycloaddition of but-l-yne to the quinolone 75 affords the head-to-tail (2 + 2)-cycloadduct 76 while addition to hex-3-yne yields 77 h The route using the adducts 76 has been developed as a synthetic path to 3-substituted quinolones. 

Photolysis of 1 in the presence of hexa-2,4-diyne gave two compounds in high yield, of which one was easily identified as the propynylsilirene 13 (Scheme 4). Elucidation of the constitution of the 2 1 cycloadduct of the disilene 3 and hexa-2,4-diyne was more difficult finally use of a combination of NMR methods and X-ray crystallography demonstrated the formation of the bicyclic product 12. The mechanism of formation of 12 presumably begins with the addition of two molecules of disilene 3 to the C=C triple bond, followed by a thermally allowed sigmatropic 1,5-hydrogen shift. Silyl radicals could be formed by homolysis of the thus-formed cyclobutane ring and then two consecutive cyclization steps would furnish the isolated bicyclic product 12 [8]. 

Irradiation of 3-(alk-l-ynyl)cyclohept-2-en-l-ones (32) leads to selective formation of tricyclic head-to-head dimers. However, in the presence of 2,3-dimethylbuta-1,3-diene, [2 + 2], [4 + 2] or [4 + 4] cycloadducts can be obtained, depending on the enone structure. In the case of cyclohex-2-enones, photocycloaddition to the diene leads to cyclobutane adducts. A special case are 3-(alk-l-ynyl)-cyclohex-2-enones, which undergo [2 + 2] cycloaddition exclusively at the C=C bond to afford 3-cyclobutenylcyclo-hex-2-enones (33). ... 

A proposed mechanism for the formation of cycloheptanone 228 is illustrated in (Scheme 102). The reaction is believed to proceed through precoordination of the metal to the double bond of the allene that is proximal to the cyclobutane. Insertion and C—C bond cleavage leads to metallacycle P-II. CO insertion gives either intermediate P-III or P-IV, and reductive elimination provides the [6-1-1] cycloadduct 228. 

The use of Bu2BOTf or AICI3 led to increased yields of the cyclobutane product 2a, but production of the desilylated alcohol 2b was also observed with these catalysts (entries 2 and 3). Broad screening of a number of Lewis acids showed that EtAlCL and TiCL were the optimal catalysts, both serving to promote formation of cycloadduct 2a in 76 and 61% yields, respectively (entries 4 and 5). Diastereoselective formation of 2a occurred in these reactions, as was seen in the stoichiometric reactions reported earlier [10b]. Several Lewis acids, including Et2AlCl, Sn(OTf)2, SnCLt, TMSI, and InCL, were found to catalyze the formation of 2a and/or 2b, but in low yields (not shown in Table 4.1). On the contrary, no cyclobutane product is produced in reactions catalyzed by lanthanide Lewis acids and transition metal Lewis acids starting enol ether 1 or desilylated ketone 3 were recovered in these cases. Thus, these results indicated that EtAlCla is an efficient catalyst for catalytic [2+2] cycloaddition reaction. 

When enol esters derived from P-diketones are used in the photocycloaddition reaction with an alkene (de Mayo s reaction), a hydrolysis of the ester group of the cyclobutyl intermediate allows opening of the cyclobutane ring by a retro-Aldolization process and the formation of medium-ring cychc compounds. Similarly, hydrolysis of the cycloadduct obtained by irradiation of 3-carbomethoxycyclopentenone in the presence of a P-ketoester allowed facile access to ( )-norasteriscanoHde (Scheme 18). 

The formation of cycloadducts by photochemical [2-1-2]-, [4-1-2]-, and [4-1-4]-cycloaddition reactions of 2-pyrones shows considerable potential. The addition reactions can provide adducts that can undergo ring transformations to natural products, among other compounds of interest. Cyclobutanes can often be used to enhance the reactivity of the heterocyclic rings in the adducts. This path usually uses the... 

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