Cycloaddition-ortho intramolecular

The reaction is illustrated by the intramolecular cycloaddition of the nitrilimine (374) with the alkenic double bond separated from the dipole by three methylene units. The nitrilimine (374) was generated photochemically from the corresponding tetrazole (373) and the pyrrolidino[l,2-6]pyrazoline (375) was obtained in high yield 82JOC4256). Applications of a variety of these reactions will be found in Chapter 4.36. Other aspects of intramolecular 1,3-dipolar cycloadditions leading to complex, fused systems, especially when the 1,3-dipole and the dipolarophile are substituted into a benzene ring in the ortho positions, have been described (76AG(E)123). 

Trimethyl-2-azidobiphenyl thermolyzed in n-hexadecane gave only 4% 2,4,9-trimethylcarbazole, that is, the product of nitrene insertion into the ortho C-methyl bond the main products were 2 -amino-2,4,6-trimethyl-biphenyl and 250 (R = Me). An intramolecular dipolar cycloaddition com-... 

Conformational constraints induced by various ortho-substitutents in 1-aUyloxy-2-azidomethylbenzenes (97) were used to accelerate intramolecular cycloadditions of the azide group to alkenes (21) (Scheme 9.21). For the unsubstituted azide 96, high temperature was required for the cycloaddition and the yield of the cycloadduct 100 was low. The monosubstituted azide 97 underwent cycloaddition in refluxing benzene in 10 h to give the cycloadduct 101 in good yield. Disubstituted azides 98 and 99 underwent 1,3-dipolar cycloaddition in 5-7 h to give the triazolines 102 and 103. 

Intramolecular Cycloaddition Reactions of ortho-Quinodimethanes in Organic Synthesis W. Oppolzer, Synthesis, 1978, 793-802. 

The method of formation of complicated polycyclic compounds by an intramolecular cycloaddition in 1,4-dihydropyridines containing ortho-aikcny-laryl substituents is very common and is also observed in many other cases. For instance, treatment of dihydropyridines 361 with titanium tetrachloride in... 

Most compounds studied have a carbonyl group conjugated with the benzene ring and nearly all reactions are intramolecular cycloadditions. In most cases, the alkenyl moiety is connected to the arene ring via an oxygen atom, ortho or para with respect to the carbonyl group. 

The initial photochemical reaction is intramolecular ortho cycloaddition leading to bicyclo[4.2.0]octa-2,4-diene derivatives. These normally are not detected because they undergo rapid thermal disrotatory ring opening to all-cis cyclooctatrienes which have large extinction coefficients and absorb a second photon to undergo electrocyclic ring closure to the photostable bicyclo[4.2.0] octa-2,7-dienes. 

Wagner and McMahon [101] have irradiated compounds bearing chiral auxiliaries and observed that high diastereoselectivity can be achieved with photoinduced intramolecular ortho cycloaddition (Scheme 26). Carbon atom 8 is the only permanent new stereocenter created by the ortho photocycloaddition. WhenX = (2R,5R)-( )-2,5-dimethylpyrrolidine or(7/ )-H Fcamphorsultam, di-astereomeric excesses as high as 90% are obtained. The (85)-cyclooctatriene-sul-tam derivative could be isolated as a single diastereomer after one recrystallization. 

The formation of the cyclooctatrienes was quenched in the presence of low concentrations of 2,5-dimethylhexa-2,4-diene or 2,3-dimethylbuta-l,3-diene. The photocyclization of the trienes was, however, unaffected by the presence of the dienes. The authors conclude that the primary photoreaction of intramolecular ortho cycloaddition involves the 3 tt, tt state of the arene and the subsequent cyclization of the cycloocta-l,3,5-triene arises from the singlet state. 

In the formation of tetraenes from bicyclo[4.2.0]octa-2,4-dienes, two bonds are broken. This may occur in one concerted reaction which can be regarded as a retro [2 + 2] cycloaddition. It is also possible that the central bond, being part of a cyclohexadiene system, is the first one to break in a thermal, concerted disrota-tory process that leads to a 1,3,5-cyclooctatriene derivative. Ring opening of the cyclooctatriene then might take place photochemically, again disrotatory, to produce a tetraene. This two-step sequence was first observed by Mirbach et al. [114] in their study of the photocycloaddition of the two parent molecules benzene and ethene. The same explanation for the formation of a tetraene was given by Nuss et al. [160] in their report on the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile (see Scheme 40). 

De Keukeleire, D., Bako, P., and Van der Eycken, E. (2000) Intramolecular ortho and meta photocycloadditions of 4-phenoxybut-l-enes substituted in the arene residue with carbomethoxy, carbomethoxymethyl, and 2-carbo-methoxyethyl groups. Journal of Photochemistry and Photobiology A Chemistry, 133, 135-146 (c) Wender, P.A. and Dore, T.M. (1995) Intra and inter-molecular cycloadditions of benzene derivatives, in CRC Handbook of Organic Photochemistry and Photobiology (eds W.M. Horspool and P-.S. Song), CRC Press, Boca Raton, pp. 280-290. 

Due to their reduced aromatic character, naphthalene derivatives also frequently undergo ortho cycloaddition with alkenes (Sch. 4). 1-Cyano-naphthalene 13 reacts with cyclohexadiene to yield the regioisomeric ortho adducts 14 and 15 in good yields [34]. Two regioisomers 17 and 18 were also obtained from the intramolecular reaction of the 1-cyanonaphthalene derivative 16 [35]. The proportion of the two isomers depends on the solvent polarity. 

Other intramolecular cyclization reactions involving arylcarbodiimides with an ortho vinyl group to form 2-aminoquinolines and pyrido[2,3-b]indoles are listed in Table 3.1. The latter reactions involve a [2-1-4] cycloaddition in which the carbodiimide intermediate acts as an azadiene and the bond of the ortho vinyl group acts as the dienophile. Calculated transition states for electrocyclization and cycloaddition reactions show that the mode of reaction depends on substituents, stereoelectronic, eutropic and steric factors." ... 

The next selectivity issue, exo/endo preferences, can be predicted for both the ortho and meta modes of cycloaddition on the basis of secondly orbital interactions (FMO treatment) and by electrostatic considerations involving polarized species (54) and (27). In general, intermolecular reactions with simple al-kenes proceed with endo selectivity. Heteroatom-substituted or polarized alkenes (equation 11) give exolendo mixtures, whose composition can be explained by electrostatic considerations. Intramolecular cycloadditions of simple alkenes and arenes joined by a three-atom tether generally proceed with high exo selectivity due in part to orbital alignment effects. In all cases, alkene geometry is preserved, except for sterically encumbered alkenes, in which case excitation transfer from the arene to the alkene can occur. 

Ortho addition to the arene ring also occurs in cage systems where geometrical constraints disallow other orientations of addition a common example is the intramolecular photochemical cycloaddition which can occur in... 

The enantioselective total synthesis of the 13-membered macrolide fungal metabolite (+)-brefeldin A was accomplished using a triple chirality transfer process and intramolecular nitrile oxide cycloaddition in the laboratory of D. Kim. To set the correct stereochemistry at C9, the stereoselective ortho ester Claisen rearrangement was applied on a chiral allylic alcohol precursor. The rearrangement was catalyzed by phenol and it took place at 125 °C in triethyl orthoacetate to give 84% isolated yield of the desired diester. 

Intramolecular ortho-cycloaddition of benzene-ethylene systems... 

In contrast to the preferred meta mode of intramolecular photoaddition of 5-phenyl-l-pentenes, where the alkene and benzene groups are separated by three atoms, irradiation of the styrene (64) yields a single stereoisomer of the ortho adduct (65). In (64), not only are the reacting units separated by 4 atoms, but also it is the styrene rather than the benzene which is excited. Comparable photoreactivity is seen for phenanthrene-styrene systems such as (66) which yield 2+2 adducts (67) along with products derived from competing Paterno-Btichi reaction of the ester carbonyl with the alkene side chain. The photochemical cycloaddition also proceeds in an intermolecular fashion between the ester of 9-phenanthrene carboxylic acid and para-methoxy-0-methylstyrene. The mechanism of this reaction is shown to involve addition of the styrene to the singlet excited state of the phenanthrene derivative. °... 

Tab. 8.6. Activation volumes, partial molar volumes of the reactant (Vsubstrate). the ortho product (Vo-Produci), and of the ortho transition state (Vts) and reaction volume (AVr = V substrate Ws) for the intramolecular cycloaddition of 48.

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