Cyclization reactions pericyclic

Norrish reaction Pericyclic elimination Tandem cationic cyclization Bergmann cycloaromatization... 

More importantly from a preparative viewpoint, pericyclic reactions, such as the Claisen rearrangement [569,570] or the Diels-Alder reaction [571,572], have been catalyzed by antibodies, which were raised against bicyclic and tricyclic transition-state mimics (Scheme 3.44). The latter reactions normally cannot be catalyzed by enzymes. Also cationic cyclization reactions [573, 574] and an enantioselective Robinson annulation were achieved [575]. 

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. 

The participation of the lone-pair orbital in the cyclization process allows its classification as a so-called pseudopericyclic reaction (76JA4325 97JA4509), which is a subset of a general type of pericyclic reactions... 

A trifold anionic/pericyclic domino reaction was used for the synthesis of the dioxapyrrolizidine 2-655 combining a nitro aldol condensation, SN-type cyclization, SN-type etherification, and an intramolecular 1,3-dipolar cyclization as described by Rosini and coworkers (Scheme 2.148) [339]. 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,8 ene reactions,9 [3+2]10 and [2+2]11 cycloadditions), in aldol12 and Wittig as well as Friedel-Crafts reactions.13 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions14 and electrophilic cyclizations.15... 

FIGURE 7 Pericyclic reactions in the biosynthesis of giffordene and 7-methyl-cyclooctatriene. (a) The [1.7]-hydrogen shift of the thermolabile undeca-(1,3Z,5Z,8Z)-tetraene generates undeca-(2Z,4Z,6E,8Z)-tetraene (giffordene), the major product of the brown alga G, mitchellae. (b) The thermolabile nona-(l,3Z,5Z,8E)-tetraene cyclizes at ambient temperature rapidly to 7-methylcy-cloocta-l,3,5-triene. At ambient temperature, the bicyclic isomer does not contribute to the equilibrium (requires s=80°C). 

In addition to the numerous pericyclic aromatic TSs, other reactions deserve attention. These include the Cope and Claisen rearrangements, the pericyclic reactions with Mobius TSs, the Bergman cyclizations [77,116], and the TSs for 1,5-H shifts [100,117],... 

The proposed mechanism involves either path a in which initially formed ruthenium vinylidene undergoes nonpolar pericyclic reaction or path b in which a polar transition state was formed (Scheme 6.9). According to Merlic s mechanism, the cyclization is followed by aromatization of the ruthenium cyclohexadienylidene intermediate, and reductive elimination of phenylruthenium hydride to form the arene derivatives (path c). A direct transformation of ruthenium cyclohexadienylidene into benzene product (path d) is more likely to occnir through a 1,2-hydride shift of a ruthenium alkylidene intermediate. A similar catalytic transformation was later reported by Iwasawa using W(CO)5THF catalyst [14]. 

Ab initio and density functional calculations have been carried out on the mechanism of the 1,5-electrocyclization reactions of conjugated nitrile ylides (190). The results indicate that vinyl-conjugated systems (306) (X = CH2) cyclize via the classical electrocyclization pathway—a pericyclic, monorotatary process with a relatively early transition state in which there is substantial torsion of the vinyl group as well as pyramidalization at C(5). In contrast, systems with a heteroatom at the cyclization site 306 (X=NH, O) react via a pseudo-pericyclic process that is characterized by the in-plane attack of the lone pair of the heteroatom on the nitrile ylide. Such reactions have a lower activation energy. 

Intramolecular reactions that differ from the 1,3-dipolar type are also known for olefinic diazo compounds. a,(3-Unsaturated diazo compounds are known to undergo 1,5-cyclization to give pyrazoles. This reaction type may be considered as a variant of an intramolecular [3 - - 2] cycloaddition. A recent ab initio and DPT study classified the cyclization of vinyldiazomethane to 3//-pyrazole as a monorotatory pericyclic process (318). 

The factors that control if and how these cyclization and rearrangement reactions occur in a concerted manner can be understood from the aromaticity or lack of aromaticity achieved in their cyclic transition states. For a concerted pericyclic reaction to be thermally favorable, the transition state must involve An + 2 participating electrons if it is a Hiickel orbital system, or 4 electrons if it is a Mobius orbital system. A Hiickel transition state is one in which the cyclic array of participating orbitals has no nodes (or an even number) and a Mobius transition state has an odd number of nodes. 

Experimental and computational studies of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of A-propargyl morphol i nc N-oxide revealed a novel inverse secondary kinetic isotope effect (kn/kD 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) to C(sp2) change in hybridization at the reaction center (Scheme 3).5... 

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