Electrocyclic reactions photochemical cyclization

Brief Review of Molecular Orbitals 25. ELECTROCYCLIC REACTIONS Thermal Cyclization of 4n + 2 n Systems Photochemical Cyclization of 4n + 2 n Systems Thermal Cyclization of 4n n Systems Photochemical Cyclization of 4n n Systems Summary of Electrocyclic Reactions... 

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. 

The cyclization step of Equation 28-8 is a photochemical counterpart of the electrocyclic reactions discussed in Section 21-10D. Many similar photochemical reactions of conjugated dienes and trienes are known, and they are of great interest because, like their thermal relatives, they often are stereospecific but tend to exhibit stereochemistry opposite to what is observed for formally similar thermal reactions. For example,... 

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. 

It would be a good point here to remind you that, although all electrocyclic reactions are allowed both thermally and photochemically pro viding the rotation is right, the steric requirements for con- or disrotatory cyclization or ring opening may make one or both modes impossible. 

Four electron pairs undergo reorganization in this electrocyclic reaction. The thermal reaction occurs with conrotatory motion to yield a pair of enantiomeric rra/w-7,8-dimethyI-1,3,5-cyclooctatrienes. The photochemical cyclization occurs with disrotatory motion to yield the cis-1,8-dimethyl isomer. 

Similarly, the photochemical opening of cannabinol (256) to (257) was followed by ring closure and dehydration to the hydroxyphenanthrene (258), elimination of H2O being the internal tn of the initial cyclization product (257). ° Note that the initial ring opening of (256) is an example of a photo-induced hetero electrocyclization reaction (Section 6.2.4.2). 

A third and critical advance in the development of the Nazarov cyclization was the demtmstration that it belongs to the general class of cationic electrocyclic reactions (Scheme 4). This broadened its definition to include reactions which involve pentadienylic cations or equivalents and thus expanded the range of precursors for cyclopentenones. Further, the stereochemical features of electrocyclization enhanced the utility of the reaction and, in addition, stimulated the development of a photochemical variant. 

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). 

Classical methods rely on electrocyclization reactions promoted by heat or, especially, by photochemical means, usually followed by an oxidation to deliver the aromatic compound. One of the most prominent routes is also known as the Mallory reaction, first reported in 1964 [84, 85]. Since then it has been further optimized [86] and applied, especially in the synthesis of helicenes [87], but also in a number of syntheses of graphene-type structures. Zhang et al. recently combined the Mallory reaction with a Scholl cyclization to access tetrabenzocoronene 135 (Scheme 33) [88]. A similar approach has been reported for the preparation of hexabenzocoronene [62]. 

The effect of the number of n electrons upon the stereochemistry of a reaction is illustrated by the cyclization of a diene system compared to a triene system, as shown above. Although the methyl groups in both compounds have the E configuration, the products have different stereochemistry. Although both reactions are thermal, only the trans isomer results from the diene and only the cis isomer results from the triene. Thermal electrocyclic reactions of systems with 4 n electrons have the opposite stereochemistry to structurally related systems with 4 + 2 ti electrons. Furthermore, the stereochemistry of the thermal and photochemical pericyclic reactions is opposite. Photochemically initiated cychzation of the triene gives the trans isomer, whereas the ds isomer forms in the thermal cyclization. 

Vitamin D2 is produced by two pericyclic reactions. One of them is photochemicaUy initiated the second thermally initiated. The first step is a photochemical electrocyclic reaction in which a cyclohexadiene of the B ring is isomerized to a triene. The reaction involves six k electrons and is the reverse of the photochemical cyclization reaction discussed in Section 28.4. Thus, by the principle of microscopic reversibility, this photochemicaUy allowed ring opening involving a 4 +2 71 system must occur by a conrotatory process. 

H.l According to the Woodward-Hoffhiann rule for electrocyclic reactions of 4 r-electron systems (Section H.2A), the photochemical cyclization of cis, trani -2,4-hexadiene should proceed with disrotatory motion. Thus, it should yield trani -S,4-dimethylcyclobutene ... 

Photochemical conversion of stilbenes to phenanthrenes via a six 7t-elec-tron conrotatory cyclization according to an electrocyclic mechanism to the dihydrophenanthrenes and subsequent dehydrogenation is a very famous and useful synthetic reaction (103). 

In recent years the group of C. A. Merlic has reported photochemically induced cyclizations of dienyl carbene complexes of type 39 to produce phenol derivatives 40 [19]. In these very intelligently designed reactions, which are related to the Dotz reaction, the primary, photochemically generated intermediates of type 41 undergo a (formal) electrocyclic ring-closure to form linear, conjugated cyclohexadienones 42, which then tautomerize to the phenols (Scheme 12). 

This electrocyclization leading to a 1,6-fused cyclohexadiene also takes place with polyenes. A photochemical example from the vitamin A field is exemplified by the conrotatory phot clization of the (7Z)-isomer (IW) of retinal (185) to the bicyclic derivative (187). The photocyclization procedure has also been used in the aromatic series. - Thus the photocyclization-oxidation reaction of l-phenyl-4-(2 -thienyl)-1,3-butadiene (188) gave 4-phenylbenzo[b]thiophene (189). Similarly, the 3 -thienyl analogue (190) afforded 7-phenylbenzo[b]thiophene (191), the reaction exhibiting high selectivity for cyclization to the logically more reactive thiophene nucleus. ... 

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