Cyclization photochemical

It was found that cyclization of benzannulated enediynes can be initiated by irradiation to give the same products as were obtained by thermal Bergman cyclization [238]. Photo-Bergman cyclization, which is also related to the chemistry of benzyne, has not been so extensively investigated. Terminal acyclic enediynes capable of cycloaromatization by thermal C -C route do not undergo photochemical initiation. However, introduction of one or two phenyl substituents in the acetylenic branches facilitates the C -C photocyclization of acyclic enediynes, but any increase in steric hindrance raises the activation barrier and the photochemical yield is significantly lower than in the case of their cyclic 

The enediyne structure in anticancer drugs, that act via DNA cleavage, is caused by a diradical formed in cyclo-aromatization. Thus a triggering mechanism was required to initiate the cyclization of stable precursors under physiological conditions (temperature about 37°C). Photochemical triggering is one approach used for this purpose. In some cases, it was achieved by photochemical synthesis of reactive enediynes that then readily undergo cyclo-aromatization [244]. 

P-ketoenediynes 3.475 proceeds via tautomerization to give the more reactive enyne-allenes 3.476, which then undergo Myers-Saito cycliza-tion via diradical 3.477 to give anthracene derivatives 3.478. The rate determining step of this reaction is the enolization of the ketone. Since enolization of carbonyl compounds depends on the pH, solvent, and other factors, this opens diverse approaches to the design of reactive enediynes [244]. 

Photochemical Generation of Enediynes from the Compounds with a Triple Bond Masked by a Cyclopropenone Ring 

Irradiation of cyclic enediyne precursor 3.483, which, has a cyclopropenone group instead of one of the triple bonds, produces 

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The same isomerization also occurs with diarylthiazoles, but when two adjacent phenyl groups are present, even in the final product, a photochemical cyclization gives rise to a polycyclic benzothiazole (Scheme 3) (213,218,219). 

A -Bridgehead compounds have been obtained from the photochemical cyclization of cfi-1-styrylimidazoles. For example, irradiation of the imidazole (532) in methanol in the presence of I2 resulted in cyclization at the 2-position of the imidazole ring with the formation of an imidazo[2,l-a]isoquinoline (533) (76JCS(Pl)75). Isomerization of the trans-to the c/i-styrylimidazole was followed by photodehydrocyclization, trans- 1-Styrylbenzimidazole (534) was isomerized under Pyrex-filtered light in the presence of one molar equivalent of I2. The resulting cis isomer on irradiation through quartz gave the benzimidazo[2,l-a]isoquinoline (535) in 53% yield. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

The photochemical cyclization of anthranilonitriles (190 Section 4.04.2.1.2) yields indazoles (72CC126). Reduction of o-benzonitrile with lithium aluminum hydride yields indazole (75ACS(B)1089). 2-Aminoindazole (576) has been prepared in 94% yield from (574) via the o-phthaloyl derivative (575 = o-phthaloyl) (72JOC2351). Similarly, treatment... 

However, all attempts to isomerize vm-alkynylnitropyrazole into A-oxide in conditions of thermal, catalytic, or photochemical cyclization failed (86MI1) (Scheme 114). 

Figure 30.7 Photochemical cyclizations of conjugated dienes and trienes. The two processes occur with different stereochemistry because of their different orbital symmetries.

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

Another approachl2a e makes use of bilenimincs which can be photochemically cyclized to isobacteriochlorins. A plausible mechanism for this ring-closure process involves the formation of an enamine tautomer from the imine at the 1-position, which is then cyclized in a photochemical 1 STc-n-isomcrization process followed by elimination of the leaving group at the 19-... 

Scheme 9 Photochemical cyclization of diethynylmethanes. Although this reaction is topologically analogous to the cyclization reactions discussed earlier, it does not lead to an aromatic product.

In a combination of photochemical cyclization and a radical reaction Yoshimatsu et al synthesized 2-azabicyclo[33.0locta-3,7-diene 169 from the trienal hydrazone 166.1891 The domino process was initiated by irradiation of 166 at 400-500 nm in benzene. The transformation may include an intermolecular [2+2]-cyclization, followed by ring opening to give... 

The photochemical reaction can also proceed via the triplet state and in this case no cyclization is observed. Especially when acetophenone is added as a triplet sensitizer, 41 is not formed. Remarkable is the observation that in the presence of anthracene or pyrene as triplet quencher, the yield of the cyclization product 41 was not enhanced and that nitrene insertion into CH bonds of anthracene or pyrene was observed. When the photochemical cyclization reaction was performed with the tosyl azide derivative 42a or the azido nitrile derivative 42b (Scheme 6), only low yields of the tricyclic amide 41 (32% from 42a, 9% from 42b, respectively) were obtained <2001JCS(PI)2476>. 

One of the exciting areas that has gained importance over the recent decade is the photochemical cyclization of non-conjugated dienes in the presence of species that can act as templates. One such species that has been used is copper(I) salts. The earliest example of the use of copper salts in the intramolecular photocycloaddition of non-conjugated dienes is that described for cycloocta-1,5-diene. When this is irradiated in the presence... 

An example of this type of ring system is given by the photochemical cyclization observed within the hydrocarbon 165. Irradiation converts it into the tetracyclic isomer 16678. 

Low-temperature photochemical cyclization of alkynes bearing a bulky substituent, mediated by CpCo(CO)2, proceeds with CO insertion to give cyclopentadienone complexes. Higher reaction temperatures lead to cyclotrimerization. The intramolecular variant of this reaction gives the bicyclic cyclopentadienones 139 and 139 (equation 19)142. Cyclization of unsymmetrically substituted diynes with the chiral R CpCo(CO)2 (R = 8-phenylmenthyl) leads to the formation of a mixture of diastereomers modest diastere-oselectivity was found. 

Photochemical cyclization of enones with olefins is followed by a retro-aldol reaction to give 1,5-diketones. 

It is possible, that some of the natural neutral cannabinoids (if not all of them) are artifacts formed by decarboxylation, photochemical cyclization (cannabicyclol), oxidation (cannabielsoic acid) or isomerization (A -THC and A -THC acid) of other constituents. 

Most mechanistic studies " have utilized lV,Al-diphenylmethyl-amine. With this substrate in the absence of oxygen, photochemical cyclization to the observable 312 (R = H, R = Me) is followed by disproportionation to the carbazole and to a tetrahydrocarbazole believed to be... 

As early as 1969, Block and Corey (73) observed the photochemical transformation of divinyl sulfide 37 to a mixture of isomeric cyclization products (39 and 40) (Scheme 5.13). A pathway involving the cyclic thiocarbonyl ylide 38 was proposed. A theoretical study concerning the nature of intermediates in the photochemical cyclization of divinyl sulfides was recently carried out (74). Several examples are known in which the vinyl group is part of an aromatic system. 

Alkyl- or 3-aryl-2,4-oxazolidinediones via photochemical cyclization, ° organonickel-mediated carbonylation, ° cyclization of A-alkenyl-a-acet-amides, ° carboxylation and cyclization of 2-propynamides, °" cyclization of (9-carbamates of a-hydroxy acetic acids and esters,cyclization of a-hydroxy acetamides,and catalytic asymmetric dihydroxylation (ADH) of A-alkenoyl-2-oxazolidinones. ... 

The quinoline (111) is obtained when the o-aminostyrene derivative (110) is cyclized by phosphoryl chloride (77HCA1644). Other syntheses involving a,(3-bond formation are the photochemical cyclization of the o-thiocarboxamidostyrene (112) (79CC499) and the acid-... 

Most coralyne analogs have been prepared by a suitable modification of the coralyne reaction (Scheme 102) although a patent (76JAP(K)7634200) has described a novel photochemical cyclization of an amide (230) to yield coralyne (Scheme 116). Evidence concerning the possible mode of action of coralyne is included in a recent reveiw (81JHC223). 

The alkaloids granulatamide 30 and isogranulatimide, isolated from marine invertebrates, have been synthesized from didemnimide A by a facile photochemical cyclization (Equation 120). It is unclear whether this is a biomimetic... 

The protoberberine alkaloid, xylopinine, has been synthesized in an optically active form by Kametani et al.22 ). A key reaction in this synthesis was the photochemical cyclization of the optically active amino acid derivative 1,2,3,4-tetrahydro-6,7-dimethoxy-3-methoxycarbonyl-1 -methylene-2-veratroylisoquinoline with 1,3... 

Photochemical cyclization of (78) with formation of the C(3)—N(4) bond leads to oxapenam (79) (78TL4233) (see also Section 5.12.3.4.2). Another method of oxapenam formation involves closure of the C(3)—N(4) bond by base-induced cyclization of a-bromoesters (77CC359, 77CC405). 

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