Photochemical electrocyclization

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

The cyclohexadiene-hexatriene system seems to be less complicated than the cyclobutene-butadiene system. Cyclohexadiene undergoes photochemical electrocyclic ring opening ... 

The photocyclization of N-aryl enamines derived from cyclic or acyclic ketones proceeds under mild conditions to produce 2,3-dihydroindole derivatives (178b). The stereochemistry of the products is predominantly trans, which follows from a photochemical electrocyclic process which should take place in a conrotatory manner (178c,I78d). However, the presence of some cis products is not as easily explained. 

Thermal and photochemical electrocyclic reactions always take place with opposite stereochemistry because the symmetries of the frontier orbitals are always different. Table 30.1 gives some simple rules that make it possible to predict the stereochemistry of electrocyclic reactions. 

The other commonly quoted industrial photochemical process is the production of vitamin D3 involving a photochemical electrocyclic ring opening followed by a thermal 1,7-hydride shift (Scheme 7.2). This is a further example of a successful low quantum yield process in this case there is no viable thermal alternative. Vitamin A acetate has also been produced commercially using a photochemical isomerization process to convert a mixed tetra-alkene precursor to the all-trans form. 

Electrocyclic Reaction of Radicals Metal Catalysed Electrocyclic Reactions Photochemical Electrocyclic Reactions... 

Thermal and photochemical electrocyclic reactions are both stereospecific, with the two processes giving rise to stereospecific reactions in the opposite sense. 

For the photochemical electrocyclic reaction of the diene, irradiation promotes one electron from n2 to n and the disrotatory mode of reaction gives the cis isomer (Scheme 8.4). 

The photochemical electrocyclization of conjugated iminium salts 160, formed by protonation of 2-azadienes 159, led to isoquinolin-4-ones 162, presumably through hydrolysis and oxidation of the dihydroisoquinoline intermediates 161 (85TL5213) (Scheme 39). A closely related reaction served as the key step for a short synthesis of the pentacyclic marine alkaloid ascididemin as reported by Moody, Rees, and Thomas [90TL(31)4375 92T3589] the central reaction involves a 67r-electron pho-tocyclization of a syn- aza stilbene in sulfuric acid. 

Figure 14.6. (ia) Orbital correlation diagram for the photochemical electrocyclic reaction of butadienes. (b) Orbital correlation diagram for for the photochemical electrocyclic reaction of hexa-trienes. Solid lines and S, A denote correlation for conrotatory motion dashed lines and S, A denote correlation for disrotatory motion. 

Several thermal as well as photochemical electrocyclizations have been reported, which involve the 2,3-double bond of the nucleus in addition to the side-chain 7r-systems. The new ring formed can be either homocyclic or heterocyclic. 

Photochemistry is used commercially in the synthesis of Vitamin A and Vitamin D3, Figure 3.14. Vitamin A is formed via a photochemical isomerisation process and the synthesis of Vitamin D3 involves a photochemical electrocyclic ring-opening step. The industrial relevance of this process is due to the lack of a viable thermal alternative and therefore, if unusual and useful chemistry is only possible via photochemistry, an industrial process may result, due to the high intrinsic value of the chemical product. 

The standard observation that thermal and photochemical electrocyclic and cycloaddition reactions always take place by opposite stereochemical pathways [96] is explained directly by the unit of angular momentum carried by a photon. Photochemical activation disturbs the balance between angular-momentum vectors and dictates a different molecular conformation. 

Several examples pertaining to the photochemical electrocyclization of compounds possessing an aromatic moiety and an olefinic substituent are also known [69, 70]. For example, one of the earliest reports in this series was concerned with the photocyclization-rearrangement of a-(N-methylanilino) styrene (139) which, on irradiation in the absence of oxygen, produced l-methyl-2-phenyl-2,3-dihydroindole (140) in 73% yield, as depicted in Scheme 8.40. 

The photochemical electrocyclic reaction of acrylamides represents a versatile strategy for alkaloid synthesis. Thus, (S)-pipecoline has been synthesized using the photochemical cyclization of enantiomerically pure acrylamide derivatives in the presence of NaBH4, which causes reduction of the imonium intermediate. The lactam may then easily be transformed into the desired heterocyclic compound (Scheme 9.26) [38]. 

After your experience with cycloadditions and sigmatropic rearrangements, you will not be surprised to learn that, in photochemical electrocyclic reactions, the rules regarding conrotatory and disrotatory cyclizations are reversed. 

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