Photochemically controlled cyclization

The Nazarov cyclization is an example of a 47r-electrocyclic closure of a pentadienylic cation. The evidence in support of this idea is primarily stereochemical. The basic tenets of the theory of electrocyclic reactions make very clear predictions about the relative configuration of the substituents on the newly formed bond of the five-membered ring. Because the formation of a cyclopentenone often destroys one of the newly created centers, special substrates must be constructed to aUow this relationship to be preserved. Prior to the enunciation of the theory of conservation of orbital symmetry, Deno and Sorensen had observed the facile thermal cyclization of pentadienylic cations and subsequent rearrangements of the resulting cyclopentenyl cations. Unfortunately, these secondary rearrangements thwarted early attempts to verify the stereochemical predictions of orbital symmetry control. Subsequent studies with Ae pentamethyl derivative were successful. - The most convincing evidence for a pericyclic mechanism came from Woodward, Lehr and Kurland, who documented the complementary rotatory pathways for the thermal (conrotatory) and photochemical (disrotatoiy) cyclizations, precisely as predicted by the conservation of orbital symmetry (Scheme 5). 

If the reaction is photochemically controlled, the excited butadiene now has an electron in a tt m.o. that was empty in the ground state. This m.o. was the LUMO of ground state butadiene depicted in the central part of Fig. 12.4. Now, a concerted closure (a net bonding interaction) can only be obtained by the disrotatory mode. As a result, the trans isomer (c) and not (b) is the product of cyclization. 

A similar reasoning can be applied to hexatriene to be converted into cyclohexadiene. The only significant change is that the number of tt electrons becomes six corresponding to six conjugated C atoms, and so there is one more node in the frontier orbitals. Accordingly, the symmetries of the HOMO and LUMO at the terminal C atoms are different from those for butadiene, and cyclization occurs by the disrotatory mode or by the conrotatory mode, respectively, for a thermally or a photochemically controlled reaction. The general rule is that the thermal cyclization reactions of a A 7r-electron system will be conrotatory for A =4 and disrotatory for A =4g-f-2 (g = 0,1,2,...). For photochemical cyclizations these relationships are reversed. 

In addition to the aforementioned transformations, the photo-induced Bergman cyclization was utilized by Zhu and coworkers to form intramolecular polymeric nanoparticles.The appropriate reactive diyne unit was incorporated into the polymer using both direct controlled radical polymerization and aHqme protection strategies. The resulting linear polymers were subjected to photochemical Bergman cyclization conditions using a continuous addition strategy, similar to the case previously discussed. ... 

For the thermal and photochemical cyclization of hexatriene, the controlling HOMO S are Vo and respectively. As shown in Fig. 3.5.9, the allowed... 

There are several reasons for the interest in controlled photocycloadditions. First, a cycloaddition (the 2+2, for example) allows access to the four-member ring system. Second, investigation of the regio- and stereochemical outcome of the cyclization process allows for a better understanding of the mechanistic pathway the reaction takes. The reaction is studied not only for synthetic exploitation, but for basic understanding of the photochemical process. 

The triplet state di-TC-methane reactivity of the methanoquinoline systems (61, 62) have been studied. The results of the irradiations are shown in Schemes 3 and 4 where it can be seen that each compound usually affords two products. The results indicate that the pyridine nitrogen does not manifestly alter the photochemical behaviour of the compounds. A detailed analysis of the reasons for the observed regioselectivity is made on the basis of molecular orbital theory. The di-ic-methane reactivity of the benzonorbornadienes (63) still excites considerable interest. Paquette and Burke have studied the triplet state reactivity of the derivatives (63) in an attempt to establish the influence of bridgehead substitution. Thus the irradiation of (63a) results in the formation of both isomers (64a) and <65a) in 42 and 58 It respectively. Similar yields are shown for the irradiation of (63b) when the two products are obtained in similar yields to the above. However, irradiation of the derivative (63c) results in the formation of only the cyclized product (64c) while the derivative with the bridgehead cyano (63d) yields both (64d) and (65d) but in 10 and 90 X yields respectively. The authors present arguments to explain the observed specificities leading to products of either bridgehead control or vinylic control of the biradical... 

The calix[4]arene-based 2-naphthoate 260 undergoes photochemical cyclization to afford 261. Hydrogen bonding controls the cyclization of 262 into 263. If the hydrogen bonding is broken by carrying out the reaction in methanol, the cyclization follows the path where attack occurs at the phenolic carbon. The stilbene derivatives 264 have also been investigated. This study was associated with work to establish why some phenolic... 

The influence of alkali metal perchlorates on the photocyclisation of (34) has also been studied. The quantum yield for cyclization is reduced from 0.21 for the free system to 0.17 for irradiations in the presence of sodium perchlorate. The effect is even more dramatic with potassium and rubidium perchlorates when (j) is reduced to 0.02. The crown ether systems are obviously important since the overall shape can be controlled by the photochemical ring closure. 

The carbapenam (276) is formed with high diastereoselectivity and the regioselectivity of the cyclization can be controlled either by varying the initial concentration of the bromide (275) or by varying the cyclization conditions (thermal or photochemical). An alternative approach to the carbapenam derivative (279) has been described by Dumas et al. which utilizes an efficient base-catalysed intramolecular N-alkylation of the iodide (278).150 Interestingly, attempted cyclization of the epimeric (at C-3) iodide was unsuccessful. 

The keto ester (42) undergoes photochemical hydrogen abstraction reactions to afford a 1,8-biradical.Again, in this case, the regiochemistry is controlled by the presence of the hetero atom. The resultant biradical cyclizes to yield the azalactone (43), the structure of which was determined by X-ray crystallography. The cyclization process is not stereoselective. 

Reactions of 1,3-Diketones - Irradiation of the 1,3-diketone (238) in ethanol or benzene results in the formation of l-hydroxy-2-naphthaldehyde. The site of photochemical hydrogen abstraction reactions within the keto esters (239, X = S) is controlled by SET transfer reactions from the thio substituent to the excited carbonyl group. The usual reaction train following this event yields the biradical (240) which undergoes cyclization to yield (241) in modest to good yields. The involvement of an SET process is proven by the failure of the sulfone derivative (239, X = SO2) to undergo the same reaction. 

Lactams such as (258) can be synthesized from the phthalimides (259) by irradiation. Again the reactions are controlled by single electron transfer processes that are usually encountered in the photochemical reactions of phthalimides. The outcome of the reaction is a conventional proton transfer from the benzylic site within the zwitterionic biradical formed on irradiation. Cyclization within the resultant 1,5-biradical affords the final product. Griesbeck and his coworkers have studied the photochemical reactivity of the phthalimide derivatives (260). These compounds on irradiation under triplet sensitized conditions undergo decarboxylation and cyclization. The reaction involves SET and the key intermediates are shown as (261) and (262). The biradical anion (262) is the species that either cyclizes to afford (263) or abstracts hydrogen to yield (264). The reaction is controlled by a variety of factors that have been reported in some detail. Some photochemical reactions of phthaloylcysteine derivatives have been described. Typical of the processes are the decarboxylations of the derivative... 

Interest in photochromic systems other than those based on the hexa-fluorocyclopentene moiety continues to grow. The photochemical reactivity of the two photoswitches (35) is similar, and irradiation is efficient with conversions of 85% and quantum yields of around 0.6. The novel photo-chromic systems (36) undergo reversible ring closure in a reaction analogous to that observed in the bisthienyl system. Qin et al. have studied the novel pyridyl substituted cyclopentene system (37). This undergoes photocyclization with an enhanced quantum yield when the reactions are carried out in the presence of a metal. The pyridine units are capable of co-ordinating with the metal. The photochromic dithienylethene unit tethered to 3-cyclodextrin (38) has been used as a photoswitch to control the uptake of porphyrin. A series of new photochromic molecules (39) have been synthesized and studied. These exhibit the usual cyclization on irradiation. " The terthiophene derivatives (40) exhibit reversible photochemical cyclization (at 313 nm) and reversion (at wavelengths >460 nm) reactions. The cycles can be carried out many times... 

It should be pointed out that this reaction has been carried out photochemically (i.e., the photo-Nazarov cyclization Fi2) or under near-critical water conditions. More importantly, it has been improved to occur in a controllable fashion, through a directed Nazarov cyclization or an interrupted Nazarov reaction. It is worth noting that two practically directed Nazarov cyclizations have been developed, one by Denmark by using the jS-cation stabilizing effect and electrofuge of silicon (Scheme 2),2 > 2tt,6,i3 and the other from Ichikawa by application of a /3-cation destabilizing effect and the... 

Cariying out photochemical reaction in crystals offers unique synthetic possibihties, particularly for control of stereochemistry. For example, in solution the irradiation of a 2,4,6-triisopropylbenzophenone bearing the (S)-phenylethylamide group (162) gives approximately 1 1 mixture of the R,S (163) and S,S (164) diastereomers of the Norrish-Yang cyclization product (equation 12.96). However, irradiation of microcrystals of 162 led exclusively to the R,S) diastereomer (equation 12.97). This stereoselectivity was attributed to steric forces present in the chiral crystal. 

The Bergman cycloaromatization can be controlled by means of photochemical generation of enediynes that require keto-enol tautomerism for further cyclization, such as the 5,6-benzocyclodeca-3,7-diynones 3.475 (Scheme 3.16) [244]. The cyclization of the 10-membered... 

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