Photochemically controlled cyclization reactions

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. 

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. 

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 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... 

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. 

Electrocyclization provides an efficient way to synthesize a large variety of heterocyclic compounds. Among the many photocyclization reactions of aromatic compounds, electrocyclization is among the most frequently studied. An example of this is that illustrated in Scheme 1. This involves cyclization between the arene moieties of the protonated azobenzene 1, which reacts from the jtJt state reaction and is controlled by the Woodward-Hoffmann rules. Six rr-electrons are involved in the conrotatory cyclization. The reaction was not observed when unprotonated azobenzene was irradiated because in this case, the ntt state is populated. Since the photochemical electrocyclization is reversible, a consecutive trapping reaction is needed to obtain the final products in good yields. In the present case, as in many other reactions, a rearomatization step via oxidation took place to afford the final product 2. In the same way, the imine 3 can be cyclized to the phenanthridine derivative 4. In this case, the oxidation of the... 

---