2+2 Photocycloaddition

The strained undecacyclic pagodane framework was obtained in a series of 14 one-pot operations with an overall yield up to 24% from commercial isodrin. The key steps are (i) a benzene-benzene [6 -I- 6]photocycloaddition, and (ii) a domino Diels-Alder reaction. 

Photocycloaddition. Synthesis of the highly carcinogenic polycycHc hydrocarbons, eg (51) [72735-91-2] may be affected by photocycloaddition of 2-bromo-3-methoxy naphthoquinone [26037-61-6] with 1,1-diarylethylenes such as l,l-bis(p-methoxyphenyl)ethene (41). 

The benzo[Z)] fused systems participate in a number of [2 + 2] cycloaddition reactions (81JOC3939, 81TL521). The photocycloaddition products of benzo[Z)]thiophenes and DMAD are dependent on the irradiation wavelength (Scheme 56). 

Isothiazolidinones have been desulfurized by Raney nickel (74JOC1210). The 2,1-benzisothiazoline 2,2-dioxide (158) undergoes photocycloaddition with dimethyl acetyl-enedicarboxylate and loss of sulfur dioxide to give a compound of probable structure (168) (80CC471). 

Many [2 + 2] photocycloadditions have not been assigned a definitive mechanism, but they serve well as synthetic methods. Thiones add vinyl ethers to give thietanes in very good yields (Section 5.14.4.1.2), and interesting wavelength-stereochemistry relations were found in the photoaddition of 2-adamantanone to dicyanoethylene (Section 5.14.4.1.2). Diheterocyclobutanes can also be prepared by [2 + 2] photocycloadditions (Section 5.13.3.3). 

The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphosphonium salts and p-quinones. 

Whereas the cycloaddition of arylazirines with simple alkenes produces A -pyrrolines, a rearranged isomer can be formed when the alkene and the azirine moieties are suitably arranged in the same molecule. This type of intramolecular photocycloaddition was first detected using 2-vinyl-substituted azirines (75JA4682). Irradiation of azirine (54) in benzene afforded a 2,3-disubstituted pyrrole (55), while thermolysis gave a 2,5-disubstituted pyrrole (56). Photolysis of azirine (57) proceeded similarly and gave 1,2-diphenylimidazole (58) as the exclusive photoproduct. This stands in marked contrast to the thermal reaction of (57) which afforded 1,3-diphenylpyrazole (59) as the only product. 

The photochemical behavior of the isomeric 3-methyl-2-phenyl-2-allyl-l-azirine (66) system was also studied. Irradiation of (66) in cyclohexane gave a quantitative yield of azabicyclohexenes (67) and (68). Control experiments showed that (65) and (66) were not interconverted by a Cope reaction under the photolytic conditions. Photocycloaddition of (66) with an added dipolarophile afforded a different 1,3-dipolar cycloadduct from that obtained from (65). The thermodynamically less favored endo isomer (68b) was also formed as the exclusive product from the irradiation of azirine (66b). 

Photochemical [2 + 2] cycloaddition is a powerful way to produce cyclobutanes, which, in turn, are reactive synthesis intermediates. N-Methylpyrrole adds aldehydes via [2 -I- 2] photocycloaddition to give transient oxetanes with high regioselectivity Ring-opening produces 3-(oi-hydroxyalkyl)pyrroles which are oxidized easily to 3-arylpyrroles, such as 3-BUTYROYL-l-METHYL-PYRROLE. With a special apparatus, ethylene is conveniently added to 3-methyl-... 

In recent years the application of photocycloaddition reactions to organic synthesis has been growing in importance. - The procedure described is illustrative of a general method based on a photocycloaddition reaction for the introduction of an activated alkyl group specifically to the a-carhon atom of an a,/3-unsaturated cyclohexenone. Especially significant is the fact that the method is also applicable to... 

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

A second example of this strategy is the retrosynthetic simplification of 184 via the equivalent 185 by subsequent application of the tactical combination of retroaldol and [2 + 2] photocycloaddition transforms.50 Various targets which are structurally related to 184 have also... 

A which is not observed in individual solutions of the two enones at the same concentrations and may thus be indicative of a complex formation. However, the ratio of isomeric cyclobutane products resulting from such photocycloadditions is generally seen to be a quite sensitive function of steric effects and of the properties of the reaction solvent, of the excited state(s) involved (in some cases two different excited triplet states of the same enone have been found to lead to different adducts) and of the substituents of the excited enone and substrate. No fully satisfactory theory has yet been put forth to draw together all the observations reported thus far. 

The photochemical cycloadditions of alkenes and alkynes with aromatic compounds have received by far the most attention. Yields of [2+2] cydoadducts can be good, but reaction times are often long and secondary rearrangement products are common [139, 140, 141,142, 143,144, 145,146] (equations 63-65). The pioneering mechanistic and synthetic work on aromatic photocycloadditions has been reviewed [147],... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Stereoselective intermolecular [2- -2]-photocycloaddition reactions of unsaturated heterocycles with formation of fused systems 98S683. 

In this synthesis, we have witnessed the dramatic productivity of the intramolecular enone-olefin [2+2] photocycloaddition reaction. This single reaction creates three contiguous and fully substituted stereocenters and a strained four-membered ring that eventually provides the driving force for a skeletal rearrangement to give isocomene. 

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