Cyclization, photocyclization

The photocyclization of iV-vinylanilines is an e.xarnple of a general class of photocyclizations[l]. If the vinyl substituent has a potential leaving group or the reaction is carried out so that oxidation occurs, the cyclization intermediate can aromatize to an indole. 

The most widely exploited photochemical cycloadditions involve irradiation of dienes in which the two double bonds are fairly close and result in formation of polycyclic cage compounds. Some examples of alkene photocyclizations are given in Scheme 6.9. Entry 1 is a transannular cyclization. The preference for the observed product over tricyclo[4.2.0.02,5]octane does not seem to have been analyzed in detail. Entries 2, 3, and 4 involve photolysis in the presence of Cu03SCF3. Entries 5 and 6 are cases in which the double bonds are in close proximity and can cyclize to caged structures. 

Likewise, Sheridan s group developed a photoassisted twofold [6jt + 2ji] cyclization generating tetracycloundecadienes [35], while Dittami s group has reported on several impressive domino photocyclization/pericyclic processes of substrates of type 5-104, which are represented in Scheme 5.20 [36]. 

The photocyclization of enamides has been the subject of detailed study and provides a valuable approach to the synthesis of alkaloids. A comprehensive review has been published.31 A variety of reaction types has been reported. The N-benzoylenamine 33, for example, is converted on irradiation to the trans-lactam 34 by a process involving conrotatory photocyclization followed by a thermally allowed [l,5]-suprafacial hydrogen migration.32 The influence of substituents on this transformation has been studied.33 The enacylamine 35 undergoes an analogous cyclization to give a mixture of cis- and trans-lactams 36, the ratio of which is solvent... 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

Norrish Type II photocyclizations have been employed in many instances in the synthesis of nitrogen heterocycles. Type II cyclizations are the result of an intramolecular hydrogen abstraction by an excited carbonyl group followed by cyclization of the resulting biradical. Hydrogen abstraction from the y-carbon atom is normally preferred. The introduction of a nitrogen atom... 

A wide variety of other photocyclizations have been reported, but only a few of these have any general application. The unsaturated amine 366 undergoes cyclization in cyclohexane to give the 7-azabicyclo[4.3.0]nonan-2-one 367.303 The formation of pyrrolidine derivatives by photocyclization has also been observed in JV-alkyl-2-allylanilines,304 and imidazoles have been obtained by irradiation of 2-amino-1-dialkylaminoanthraquinones.30 5... 

The photocyclization of cis-diaminomaleonitrile (372) to 4-amino-5-cyanoimidazole (373) has been shown to proceed via the trans isomer 374.308 4-Amino-3-cyanopyrazole does not seem to be an intermediate in this transformation.309 Analogous cyclizations have been reported in the imidazole 373 which undergoes further photoreaction to yield the bicycle 375, and in o-aminobenzonitrile which is converted into indazole.310 This photocyclization has been extended to include enaminonitriles 376 spectroscopic evidence for the intermediacy of iminoketenimes 377 in this311 and other similar transformations312 have been reported. 

Coumestrol has been prepared via a photocyclization of the glyoxylate ester shown below through consecutive 5-hydrogen abstraction and cyclization processes, and is followed by... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Like the cyclization of the parent system, the photocyclization of hetero analogues of norbornadiene was reported many years ago. Recent interest in this area will serve to illustrate the potential of the conversions. Thus the irradiation of the oxanorbomadiene system 259 brings about conversion to the oxepine 260138. The formation of 260 presumably arises by quadricyclane 261 formation, followed by secondary photolytic ring-opening. Other research has shown that irradiation of the oxanorbomadiene 262 follows the same reaction mode and it undergoes (2 + 2)-cycloaddition to the quadricyclane derivative 263. Apparently, in this instance, cycloreversion affords the ylide 264 that can be trapped by suitable addends, giving the adducts illustrated in Scheme 3139. 

Photoinduced electron transfer promoted cyclization reactions of a-silyl-methyl amines have been described by two groups. The group of Pandey cyclized amines of type 135 obtaining pyrrolidines and piperidines 139 in high yields [148]. The cyclization of the a-silylated amine 140 leads to a 1 1 mixture of the isomers 141 and 142 [149]. The absence of diastereoselectivity in comparison to analogous 3-substituted-5-hexenyl radical carbocyclization stereochemistry [9] supports the notion that a reaction pathway via a free radical is unlikely in this photocyclization. The proposed mechanism involves delocalized a-silylmethyl amine radical cations as reactive intermediates. For stereochemical purposes, Pandey has investigated the cyclization reaction of 143, yielding... 

Anderson and Lavton in 1977 described vinyl modification of the Witkop cyclization to give azecino[4,5,6-cd]indole 79 from tryptophane 78. But later it was proven that the product was, indeed, azocino[4,5,6-cd]indole 80 (99TL8443). The same photocyclization has been used for trichlorobutenamide 81 with the resulting formation of azocinoindole 82 instead of the expected 83 (Scheme 24). 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

While the photocyclization of most cis-diarylethylenes takes place from the I st excited singlet state, there are two related systems which probably undergo cyclization from the first triplet state. 

In addition to the extensive information on the excited state cyclization reactivity summarized in Tables 1 -9, a wide body of reactivity data is available from studies of the direct photoaromatization process (D), the rate limiting step in such cases being the photocyclization process itself. This wealth of systematic and rather detailed excited state reactivity data is undoubtedly unique, providing numerous opportunities for theoretical studies of excited state reactivity some of which will be reviewed in Sect. VI. D. 

The same inertness holds for many inoperative cyclization paths that would have given highly quinoid systems such as 104 (cf 44 and 45), 105 (cf 86). 106(cf 87) and 107 c 88). Under certain circumstances such topological factors can not only modify the AO coefficients at the reacting atoms but can also result in an interchange of the usual topmost occupied MO and lowest unoccupied MO with other orbitals which prevent the photocyclization altogether. This situation has been deduced for the pentahelicenes series (Table In this series, (Table 20) benzo... 

The influence of steric effects on the photocyclization process is clearly discernible for the ortho and meta substituted stilbenes. In these cases steric repulsion intervenes as the two C atoms forming the new bond approach. This steric repulsion opposes the stabilizing interactions which promote the cyclization process. As a result the reactivity is decreased. Other consequences of such superimposed steric... 

Early studies of photocyclization reactivity using Coulson s Free Valence Numbers (Ff) were carried out by Scholz, Dietz and Miihlstadt and by Laarhoven et al. Relatively good reactivity predictions for several parallel cyclization paths were obtained taking the sums of excited state Free Valence numbers for the reacting C atom pair (S F ) as reactivity measure In this sense a threshold value of 2 F = 1 was assumed, 2F < 1 implying lack of reactivity (cf also Ref. ). 

Considerable effort has been expended on elucidating the mechanism of the photocyclizations. Di-p-tolylamine can be cyclized to 3,6-dimethylcar-bazole either photolytically in petrol or thermally at 880°C. Each process was viewed as electrocyclic, proceeding via cis and trans versions of 312 (R = Me, = H) produced by dis- or conrotatory processes, respectively. ... 

Dittami et al. (170,171) was able to generate a carbonyl ylide via photocycliza-tion of an aryl vinyl ether (Scheme 4.85). The photocyclization proceeded through a six-electron rearrangement providing initially the carbonyl ylide, then subsequent to the cyclization, a dipolar cycloaddition takes place with a pendant olefinic tether. 

Hosomi H, Ohba S, Tanaka K, Toda F (2000) The first in situ observation of intramolecular rotation and cyclization of anilide by an X-ray study partial single-crystal to single-crystal photocyclization of A-methyl-A- ( )-methylmethacrolyl anilide in inclusion crystals. J Am Chem Soc 122 1818-1819... 

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