1,3-Dienes, photocycloaddition

With conjugated dienes, photocycloaddition of carbonyl compounds occurs at one of the double bonds to give vinyloxetanes. An interesting example is the reaction of acetone with 2-methyl-l,3-butadiene, which gave the two oxetanes (60) and (61) in a ratio of 3 1 and a total yield of about 20% (72JA8761). Other alkenes which have been used for photosynthesis of oxetanes include enol ethers, ketene acetals, enamines, allenes and diketene, with the reaction of the last compound with benzaldehyde illustrated in equation (105) (75CPB365). 

Irradiation of benzothiazoline-2-thiones (34) and acrylonitrile affords 2-alkyhdenethiazoles (35) (Scheme 6). On the other hand, two products (36,37) are formed by the photoaddition of (34) with 1,1-disubstituted alkenes such as methacrylonitrile and methyl methacrylate. Aminothietanes (38) is proposed as intermediates in these photoreactions. Thioformaldehyde formed by the decomposition of the intermediate has been detected by its trapping by a diene. Photocycloaddition reaction of N-unsubstituted... 

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

Preparation of oxetanes by [2- -2]-photocycloaddition reactions of ketones and dienes 98S683. 

The thermal addition of dimethyl acetylenedicarboxylate to indoles, unlike the photocycloaddition (see Section 3.2.1.4.1.1.), proceeds via a polar stepwise process to yield, initially, 3,4-benzo-2-azabicyclo[3.2.0]hepta-3,6-dienes which in some cases are isolable,13 141 but which, in general, ring open in situ to give the indolylacrylates 3 and/or undergo electrocyclic ring expansion to 1-benzazepines.21... 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

Intermolecular photocycloadditions of alkenes can be carried out by photosensitization with mercury or directly with short-wavelength light.179 Relatively little preparative use has been made of this reaction for simple alkenes. Dienes can be photosensitized using benzophenone, butane-2,3-dione, and acetophenone.180 The photodimerization of derivatives of cinnamic acid was among the earliest photochemical reactions to be studied.181 Good yields of dimers are obtained when irradiation is carried out in the crystalline state. In solution, cis-trans isomerization is the dominant reaction. 

Intramolecular [2 + 2] photocycloadditions of alkenes is an important method of formation of compounds containing four-membered rings.184 Direct irradiation of simple nonconjugated dienes leads to cyclobutanes.185 Strain makes the reaction unfavorable for 1,4-dienes but when the alkene units are separated by at least two carbon atoms cycloaddition becomes possible. 

The literature of diene and polyene photochemistry provides many cases of synthetically useful reactions. As a result, certain arbitrary decisions have been made regarding what is covered in this chapter. For example, intramolecular [2 + 2]-photocycloaddition reactions of a, >-dienes can be formally included under the general rubric of diene photochemistry. However, we have chosen to restrict our discussion to dienes and polyenes which constitute a self-contained chromophore, viz. conjugated, cross-conjugated and 1,4-diene systems. Likewise, arene-olefin photocycloadditions will not be considered. These two broad classes of photoreactions have been applied extensively in synthesis, and have been the subject of recent reviews3,4. 

III. PHOTOCYCLOADDITIONS INVOLVING DIENES AND POLYENES A. [2 + 2]-Photodimerization of 1,3-Dienes... 

The [2+2]-photocycloaddition of carbonyl groups with olefins (Paterno-Buchi reaction) is one of the oldest known photochemical reactions and has become increasingly important for the synthesis of complex molecules. Existing reviews have summarized the mechanistic considerations and defined the scope and limitations of this photocycloaddition73. Although this reaction likely proceeds via initial excitation of the carbonyl compound and not the excited state of the diene, the many examples of this reaction in natural product synthesis justify inclusion in this chapter. 

The literature of mechanistic aromatic photochemistry has produced a number of examples of [4 + 4]-photocycloadditions. The photodimerization of anthracene and its derivatives is one of the earliest known photochemical reactions of any type97. More recently, naphthalenes98, 2-pyridones" and 2-aminopyridinium salts100 have all been shown to undergo analogous head-to-tail [4 + 4]-photodimerization. Moreover, crossed [4+4]-photocycloaddition products can be obtained in some cases101. Acyclic 1,3-dienes, cyclohexadienes and furan can form [4 + 4]-cycloadducts 211-214 with a variety of aromatic partners (Scheme 48). 

It is apparent from the quantity of material included in this chapter that there is an extensive body of work concerning the utilization of diene and polyene photochemistry in a synthetic setting. The unique behavior of the excited chromophores permits the application of powerful new methods for the construction of complex molecules. Unusual photochemical rearrangements and photocycloaddition pathways often lead to substantial increases in molecular complexity, allowing such processes to serve as key strategic steps in target oriented syntheses. 

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... 

Only a trace of the corresponding cubane 167 is formed on irradiation of the tricy-clooctadiene 168 in pentane at ambient temperatures using a 125-watt mercury arc lamp. The principal product 169 is the result of rearrangement within a biradical intermediate79. A review of the synthetic approaches to cubane and to its reactions has been published77. The diene 170 photochemically converts on irradiation in pentane solution at 254 nm to yield a photostationary mixture of the cubane 171, the starting material 170 and the isomeric diene 17280. Other additions of this type have been used for synthesis of the propellaprismane 173, essentially a heavily substituted cubane, by the intramolecular (2 + 2)-photocycloaddition of the diene 17481. 

The first total synthesis of a racemic dolastane (rac-llO) was apparently published by Pattenden as a short communication 1986 followed in 1988 by a full paper [77, 78]. Pattenden s strategy is based on an intramolecular [2+2]-photocycloaddition/cyclobutane fragmentation to transform the diene 133 into the hydroazulene 136 (Scheme 20). In between the cycloaddition... 

Photocycloaddition of thiones to alkenes is the most popular and fruitful method for the preparation of the thietane system. In analogy to the formation of the oxetanes by cycloaddition of the electronic excited ( ,tc ) carbonyls, thietanes can be expected to arise photochemically from aromatic thioketones and substituted olefins as well as 1,2- and 1,3-dienes. ° Thiobenzophenone serves as a source of a sulfur atom and, because of its blue color, which disappears on photocycloaddition, permits exact control over the reaction time. A mixture of thiobenzophenone and a-phellandrene must be irradiated for 70 hr before the blue color disappears (Eq. 2) and... 

One of the limitations of the photocycloaddition reaction is that the unsaturated system may itself act as a quencher. Conjugated dienes fall within this category since they quench the n,ir triplet of some carbonyl compounds. For the photoreduction of benzophenone in benzhydrol, the ratio, kqlka, for m-piperylene is 750 (Table II), which indicates that this diene is indeed an efficient quencher for the reaction. 

Irradiation of carbonyl compounds in the presence of dienes usually leads to the isomerization38 and dimerization39 (in concentrated diene solutions) of the dienes, but no photocycloaddition products. These reactions indicate that the dienes have quenched the carbonyl triplet. It is also known from spectroscopic studies that the triplet... 

Thus, the observations that (a) dienes quench the photoreduction reaction (b) the isomerization and dimerization of dienes is sensitized by the it,n carbonyl triplet and (c) there is a lack of photocycloaddition products with dienes, taken in conjunction with the relative energy levels of carbonyl compounds and dienes, form a consistent picture. 

If the triplet energy of the carbonyl compound is below that of the diene, triplet-triplet transfer will become inefficient and photocycloaddition may occur. For example, the triplet energy of 1,4-benzo-quinone is about 50 kcal mole - V41 and photocycloaddition to dienes can indeed occur.42 The products are spiro-pyrans 13 (not vinyl oxetanes), which may arise via the allylic radical intermediate 12. 

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