Ortho addition

That this difference in (4+2)-cycloaddition behavior most likely has steric origins—the methyl groups in 150 or the derived monoadduct preventing an ortho -addition of two equivalents of the dienophile—is supported by the observation that permethyl[6]radialene 95 is inert even towards the extremely reactive dienophile 4-phenyl-1,2,4-triazolinedione68. 

Figure 10.35 is the GC-MS m/z 247 profile of the nitrofluoranthenes and nitropyrenes in an extract of an ambient particle sample collected at night (Arey et al., 1988b). The high ratio of 2-nitrofluoranthene to 2-nit-ropyrene observed in this nighttime sample is indicative of nighttime gas-phase NO, radical reactions (for a review, see Kwok et al., 1994b). An NO, radical initiated mechanism for atmospheric formation of 2-nitrofluoranthene is shown in Fig. 10.36 (Atkinson and Arey, 1997 Arey, 1998a, and references therein). Analogous to the OH reaction, NO, is proposed to add to the ring to form a fluoranthene-NO, adduct, followed by ortho addition of N02 and subsequent loss of HNO,. This reaction is noteworthy because of its selectivity i.e., only 2-nitrofluoranthene is formed, and in high yield (24%) compared to the OH-initiated daytime reaction (3%).

Addition of silyl enol ethers to nitroarenes2 In the presence of 1 equiv. of TASF, silyl enol ethers add to nitroalkenes to form unstable ortho and/or para nitronates, which are oxidized in situ by Br2 or DDQ to nitroaryl carbonyl compounds. The position of substitution depends on the substitution pattern of the arene and the size of the silicon reagent. With less hindered silyl derivatives ortho addition is strongly favored. 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

Section V describes ortho photocycloadditions of mostly simple alkenes that do not form ground-state complexes with arenes, do not absorb light in the presence of the arenes, and add to the arene in its singlet excited state. Mechanistic investigations, including the search for intermediates (ground-state complexes, excited states, exciplexes, zwitterions), the formulation of empirical rules, and theoretical descriptions of the reaction, have mostly been concerned with this type of ortho addition. Therefore, this section is divided into a number of subsections, each describing a particular aspect of ortho photocycloaddition. 

Bryce-Smith and Lodge [3] have discovered that methyl propiolate, dimethyl acetylenedicarboxylate, and phenylacetylene add to benzene upon irradiation at 50°C. The products are cyclooctatetraenes, formed via initial ortho addition of the acetylene to benzene followed by ring opening (Scheme 9). 

Sket and coworkers [65,66] have irradiated l-phenyl-2-alkylacetylenes (Ph—C=C—R R = H, CH3, -C3H7,1-C4H9) in the presence of hexafluoroben-zene. They have succeeded in isolating the primary ortho addition products,... 

Atkinson et al. [73] have described the photochemical addition of 3-hexyne and 5-decyne to benzonitrile. The products were 2,3-diethylcyclooctatetraene-l-carbonitrile and 2,3-n-butylcyclooctatetraene-l-carbonitrile, respectively. The ortho addition apparently takes place at positions 1 and 2 of benzonitrile. Subsequent ring opening of the initial bicyclo[4.2.0]octa-2,4,7-trienes leads to the 1,2,3-trisubstituted cyclooctatetraenes. 

This reaction proceeds only upon sensitization, preferably by acetophenone. The initial reaction is ortho addition of triplet excited dichlorovinylene carbonate to benzene, leading to endo and exo adducts. The exo isomer is quite stable and can be isolated, whereas the endo isomer is very sensitive to further reactions. The authors have considered the possibility of a stepwise reaction, but they prefer a formulation of the reaction mechanism in which an adiabatic reaction leads to triplet excited products. These decay to the ground-state ortho adducts or may... 

When the substituent is CONH2, CN, or CH3, ortho addition occurs toward the substituent (Scheme 20). 

In one of the earliest reports on ortho photocycloaddition, in which the reaction of benzonitrile with 2-methylbut-2-ene is described, a diradical (triplet) intermediate was proposed [73], The structure of the product corresponds to the most stable of the four possible diradical intermediates. When benzophenone was added as a sensitizer in an attempt to increase the yield of the photoadduct, only 0.05% of ortho adduct was isolated along with 54% of an oxetane formed by the addition of benzophenone to 2-methylbut-2-ene. In the absence of benzophenone, the ortho adduct was isolated in 63% yield. It is, however, thermally as well as photochemically unstable and reverts to starting materials, supposedly also via a biradical. The authors propose that benzophenone catalyzes bond cleavage of the adduct more efficiently than ortho addition and this would account for the low yield of photoadduct in the presence of benzophenone. From these experiments, no conclusion about the identity of the reactive excited state can be drawn. 

Collapse of the polarized diradical/zwitterion would lead to the ortho cycloadduct. Stereospecificity in ortho addition by this route would then be governed not by concertedness in the usual sense, but rather by coulombic interaction between the charged centers [38],... 

On the basis of these observations, Bryce-Smith et al. [115] introduced a rule stating that for addition to benzene, Pmeta when 9.6 eV < IP (alkene) <8.65 eV. They concluded that if this rule is correct, ortho addition of ethylenes to Si benzene necessarily involves an element of charge transfer to or from the ethylene. Indeed, a marked effect of polar solvents (methanol or acetonitrile) in promoting the ortho addition of benzene to ethyl vinyl ether and tetramethylethene was observed (portho increased by 20-50%, whereas cpmeta was unaffected. One exception to this rule was found by Heine and Hartmann [10], who discovered that vinylene carbonate (IP = 10.08 eV) undergoes mainly meta photocycloaddition to benzene, accompanied by some para addition. Bryce-Smith and Gilbert [46] commented that their rule referred to quantum yields and not chemical yields, whereas no quantum yields were given for the vinylene carbonate additions. Moreover, quantum yield measurements should be made at low conversions because most ortho cycloadducts are photolabile. 

The ionization potential of 1,3-dioxole is 8.56 eV and thus outside the region where meta addition is expected to dominate over ortho addition. Yet, the quantum yield of meta addition (exo + endo) is 0.38 and that of ortho addition 0.21. With 2-methyl-1,3-dioxole and benzene, 40% meta adducts, 40% ortho adducts, and 16% para adduct are found [13]. 

Ohashi et al. [128] found that the yields of ortho photoaddition of acrylonitrile and methacrylonitrile to benzene and that of acrylonitrile to toluene are considerable increased when zinc(II) chloride is present in the solution. This was ascribed to increased electron affinity of (meth)acrylonitrile by complex formation with ZnCl2 and it confirmed the occurrence of charge transfer during ortho photocycloaddition. This was further explored by investigating solvent effects on ortho additions of acceptor olefins and donor arenes [136,139], Irradiation of anisole and acrylonitrile in acetonitrile at 254 nm yielded a mixture of stereoisomers of l-methoxy-8-cyanobicyclo[4.2.0]octa-2,4-diene as a major product. A similar reaction occurred in ethyl acetate. However, irradiation of a mixture of anisole and acrylonitrile in methanol under similar conditions gave the substitution products 4-methoxy-a-methylbenzeneacetonitrile (49%) and 2-methoxy-a-methylbenzeneacetonitrile (10%) solely (Scheme 43). 

Mattay et al., having discovered exciplex emission from solutions of benzene and 1,3-dioxole [122], continued their investigations with a study on selectivity and charge transfer in photoreactions of a,a,a-trifluorotoluene with 1,3-dioxole and some of its derivatives, and with vinylene carbonate and dimethylvinylene carbonate [15,143,144], a,a,a-Trifluorotoluene and 1,3-dioxole upon irradiation yield three types of products ortho cycloadducts, meta cycloadducts, and so-called substitution products (Scheme 44). The products are formed in the ratio ortho adductsimeta adducts substitution products = 0.8 1.7 0.3. The substitution reaction (which is really an addition of a C—F bond to the double bond of 1,3-dioxole, but named substitution in order to distinguish it from the ortho addition [186] is supposed to start with electron transfer from 1,3-dioxole to excited a,a,a-trifluorotoluene. The radical anion then releases a fluoride ion, which adds to the 1,3-dioxole radical cation. Radical combination then leads to the product. 

In view of the occurrence of electron transfer and also in view of the observations made by Bryce-Smith and Gilbert (on which the ionization potential rule is based), Mattay et al. [15,143,144] have proposed a relationship between the mode of reaction (ortho addition, meta addition, substitution) and the free enthalpy of electron transfer between the reaction partners. The free enthalpy was calculated using the Rehm-Weller equation... 

Use of the Rehm-Weller equation made it possible to predict the direction of charge transfer in a given system and to establish empirical correlations between the AG value for electron transfer and the mode of the photoreaction (meta addition, ortho addition, and/or substitution). 

Orbital-symmetry relationships for thermal and photochemical concerted cycloadditions to the benzene ring were published in 1969 by Bryce-Smith [81], From correlations between low-lying excited states of starting materials and products, it was concluded that photochemical ortho addition is allowed ... 

The ortho cycloaddition is thermally forbidden in a suprafacial-suprafacial manner and the photochemical reaction is forbidden with S benzene and ground-state alkene. On the basis of these considerations, it could be understood that the ortho addition had only been observed with systems where the alkene is the lowest excited singlet species (as with maleimides [37,74,75] or where either the alkene or the arene has marked acceptor properties (the only examples known at that time were benzene-acrylonitrile [127] and benzonitrile + a mono-olefin [1,73], Benzene-acrylonitrile and benzonitrile-olefin systems do not display charge-transfer absorption, but charge transfer could well follow excitation. Bryce-Smith further stated that irradiation of benzene in the presence of simple mono-olefins normally provides B2u (Si) benzene as the lowest excited singlet species, which leads to meta rather than ortho addition, but the latter process might, in principle, be able to occur under conditions where a Biu (S2) state of benzene is populated. 

The correlation diagram [38,46,187] for ortho addition of benzene to ethene is given in Fig. 4. Orbital symmetries are with respect to a plane of symmetry (from benzene plus ethene to bicy-clo[4.2.0]octa-2,4-diene. 

Houk concluded on the basis of this frontier orbital theory that the ortho addition is favored when the alkene is either a better donor or a better acceptor than benzene. The author qualifies this conclusion as simply the Bryce-Smith generalization, derived in a slightly different way [188],... 

The 1,2 and 3,4 regioselectivity of the ortho addition of an alkene to an arene substituted with a strong donor substituent is, according to Houk, dominated by interaction of the benzene S orbital with the alkene -tt HOMO, because the A -tt interaction would result in a 2,3 ortho adduct. For an arene substituted with a strong donor, the donor substituent, rather than the approaching alkene, will determine the symmetry of the orbitals [188],... 

Figure 7 Natural molecular orbital correlation diagram for the ortho addition of benzene...

Coulombic forces will determine the regioselectivity of the ortho addition [189], In the charge-transfer complexes of monosubstituted benzenes with alkenes, the charge (positive or negative) on the arene is largely located at the carbon atoms ipso and (to a lesser extent) para to the substituent. The carbon atoms of the alkene double bond will preferentially be located in the neighborhood of either the ipso carbon or (to a lesser extent) the para carbon atom of the monosubstituted benzene. This would explain the 1,2 and 3,4 selectivity in the ortho photocycloaddition. 

Compounds in which the hydroxyl group at the meta position is replaced by an alkoxy group also undergo photochemical ortho addition and acid-catalyzed rearrangement of the adducts [168],... 

Prinzbach and co-workers studied the photocycloaddition of a rigid compound in which naphthalene and alkene were placed [294], Distances between naphthyl (3-carbons and olefinic carbons of 272 are 2.911 and 2.944 A. Direct or acetone-sensitized photoexcitation induced an efficient meta addition to the naphthalene ring to give 273, the ortho addition did not occur, although it is not clear whether the ortho process occurred (Scheme 76). 

At the singlet excited state, ortho and meta photocycloadditions are often competitive processes and physicochemical investigations were carried out to rationalize the modes of cycloaddition of arenes with alkenes. In the context of the study of photochemical electron transfer reactions, it has been proposed that the difference of the redox potentials of the reaction partners might play an important role in this competition [10]. Such a discussion involves the intervention of an exciplex as intermediate. The Rehm-Weller equation [11] was used to quantify the relationship. When an electron transfer process is strongly endergonic (AG>1.5eV), the meta cycloaddition should be favored. When such a process is less endergonic (1 < AG< 1.5 eY), the ortho addition dominate [12]. This means that the... 

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