Meta addition

Polyhalogenated arenes can function as diaryne equivalents via the tandem sequence illustrated in Scheme lO.90-91 The predominant meta addition to aryne (59) can be ascribed to steric hindrance, while in addition to (58) both steric and electronic effects favor the observed regioselectivity. 

This process has been coupled with meta addition of a carbonyl anion equivalent and the controlled exo addition of the incoming nucleophile to generate acorenone and acorenone B stereospecifically from [(o-methylanisole)Cr(CO)3] (63 Scheme 14).123 The first step is addition of a cyanohydrin acetal anion (64) to the less-hindered meta position in [(o-methylanisole)Cr(CO)3]. Addition of allylMgBr to the resulting ketone, anti-Markovnikov addition of HBr to the alkene, substitution for Br by CN, and coordina-... 

In benzene derivatives, electron-donating substituents direct into the ortho-and para-positions, while in the case of the electron-withdrawing substituents considerable meta-addition is observed (Table 3.1) otherwise a more equal distribution is established [reactions (6)-(9) and Table 3.1]. In agreement with the pronounced regioselectivity, ipso-addition at a bulky substituent such as the chlorine substituent in chlorobenzene is disfavored. Evidence for this is the low HC1 yield in the case of chlorobenzene, the low yield of para adduct in 4-methyl-phenol (Table 3.1), or the decarboxylation in the case of benzoic acid [reactions (6) and (10)]. 

As in the case of the ortho photocycloaddition, the first examples of the meta addition were followed by hundreds of others. A comprehensive review summarizing the state of the art up to 1993 has appeared [6],... 

Although the relative orientations of the two addends must be different for ortho and meta addition, it is conceivable that both processes should proceed via the same exciplex. One may speculate that the exciplex does not have one favorite rigid geometry, but that it is in a double-minimum energy well on the excited-state potential-energy surface, with the minima separated by a small barrier. 

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]. 

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). 

For photocycloaddition, to benzene the following conclusions were drawn from this empirical correlation [124], Olefins with poor electron-donor or poor electron-acceptor abilities yield mainly meta adducts with benzene (i.e., if AG > 1.4-1.6 eV, all other olefins yield mainly ortho adducts). Even ethene, which had seemed to behave exceptionally, fits into this correlation provided that it acts as the acceptor. The transition area from ortho to meta cycloaddition (i.e., the AG region where ortho meta = 1 1) is relatively large ( 0.2 eV). This is considered not to be surprising because the AG correlation is based on many different types of olefins. When only AG values for derivatives of 1,3-dioxole and for 1,4-dioxene were used, the transition area was narrowed to 0.03 eV. Not only ethene but also vinylene carbonate now fit into the correlation. According to the ionization potential rule, this compound should give only ortho photocycloaddition with benzene. Mattay s empirical rule predicts mainly meta addition, which is indeed found experimentally. 

Several reviews have been appeared about the synthetic utility and mechanistic details of photocycloadditions to aromatic rings [18,20-23], In this subsection, we will deal with mainly the examples of last two decades. Photocycloaddition of alkenes to benzene rings proceeds at ortho, meta, and para positions as described earlier. It has been suggested that alkenes and arenes having either electron-releasing or electron-accepting substituents favor the ortho process, whereas relatively simple alkenes and arenes undergo meta addition [24,44],... 

To clarify the effects of linking chains, Gilbert et al. investigated the photocycloaddition of 163-180, which produce various types of adducts [231,234-237] (Scheme 53). In some cases, not only the meta addition but also ortho and para addition and ene reaction took place. The observed regiochemistry was rationalized in terms of the stabilization of zwitterionic intermediates and the steric constraints. 

These intramolecular meta-addition processes were utilized in the key steps for the total synthesis of a-cedrene [245], isocomene [246], hirsutene [247], coriolin [248], silphinene [249], rudmollin [250], laurenene [251], and fenestranes [252-254], which were synthesized by Wender s and Keese s groups (Scheme 58). 

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). 

The reaction appears to be general, although a limited number of examples have been reported. A particularly useful process begins with meta addition to anisole-Cr(CO)3, followed by protonation and hydrolysis of the enol ether unit. The result is a 5-substituted cyclohex-2-en-l-one. This dienol ether can be isolated in high yield before the aqueous hydrolysis. 

Altogether, one arrives at the prediction that for the addition of ethylene to the S ( B2u) state of benzene, whose wave function can be written as (d>s a - d>a s )/V2, comparable amounts of ortho and meta adducts should be formed, while the meta addition should dominate whenever the alkene MOs JI and ji are close in energy to the benzene MOs and... 

Irradiation of (164) in a matrix of frozen benzene and THE brings about different photochemical results from those obtained from irradiation in solution phase. The solution phase reaction was carried out in benzene with added trifluoroacetic acid. This treatment yielded only the cyclooctatriene derivative (165). In the frozen system meta addition to the benzene ring results in the formation of the three products (166), (167) and (168). The photochemical reaction of the same chlorouracil (164) in the presence of p-xylene results in the... 

Intermolecular photocycloaddition also occurs between alkenes and simple phenols. The swing from meta addition illustrated above in the [3 + 2]-mode to ortho-addition is a result of charge-transfer interactions between the alkene and the phenol and a greater charge transfer favours the ortto-addition mode. These aspects have been the subjects of reviews . This reaction mode is exemplified by the addition of acrylonitrile... 

The regioselectivity of the addition with respect to the arene has been interpreted in terms of both meta addition of the alkene to the Sj arene via an exciplex followed by formation of the vinylcyclopropane system,and initial rearrangement of the arene to a prefulvene species which then undergoes concerted alkene addition (see below). The orientation of the substituents on the wcfa-cycloadducts from some systems requires that both mechanisms operate in competition. The reaction shows no apparent regioselectivity with simple alkenes thus 2-methylpropene gives both wc/a-cycloadduct isomers in approximatively equal amounts. ... 

The effect of substituents on the regiochemistry of the intramolecular meta photocycloaddition of the l-(3-butenyl)indanes (49)-(54) has been examined by Keese and coworkers.In the methoxy-substituted compounds (49)-(51) meta addition of the side chain alkene occurs across the 1,5-positions of the benzene ring while for (52)-(54) addition occurs across the 1,3-positions. 

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