Electrocyclization conrotatory

Upon treatment of a divinyl ketone 1 with a protic acid or a Lewis acid, an electrocyclic ring closure can take place to yield a cyclopentenone 3. This reaction is called the Nazarov cyclization Protonation at the carbonyl oxygen of the divinyl ketone 1 leads to formation of a hydroxypentadienyl cation 2, which can undergo a thermally allowed, conrotatory electrocyclic ring closure reaction to give a cyclopentenyl cation 4. Through subsequent loss of a proton a mixture of isomeric cyclopentenones 5 and 6 is obtained ... 

Compound 6 is a pivotal intermediate in Schreiber s synthesis. It was hoped that the conspicuous and strained bridgehead cyclobutene substructure in 6 would undergo a conrotatory electrocyclic ring opening upon thermolysis to give an isomeric 1,3-diene (8, Scheme 1). In the event, when a solution of cyclobutene 6 in toluene is confined to a sealed tube and heated to 180°C for 12 h, a stereoisomeric mixture of 1,3-dienes 7 and 8 is produced in an excellent yield of 95% (7 8 ca. 5 1). Finally, irradiation of the 5 1 mixture of cis-7 and trans-8, or of each independently, establishes a photostationary state in which the desired trans isomer 8 predominates (8 7 ca. 10 1). 

The acid-catalysed ring-closure of divinyl ketones to cyclopentenones (equation 6), the Nazarov reaction6-8, represents a conrotatory electrocyclization of 4jr-cyclopentadienyl cations. The conrotatory course of the reaction was confirmed for the case of the dicyclo-hexenyl ketone 7, which yielded solely the tricyclic ketone 8 on treatment with phosphoric acid (equation 7)3b. Cycloalkanocyclopentenones 10 with c/s-fused rings are obtained from the trimethylsilyl-substituted ketones 9 (n = 1, 2 or 3) and iron(III) chloride and... 

In practice, the equivalent synthon of 2 was l-cyano-4,5-dimethoxybenzocyclobutene 22 (Scheme 3.7) which on heating generates a reactive o-quinodimethane by a conrotatory electrocyclic ring opening process (Cf. Scheme 3.7) and reacts, at 150-160 °C, with the 3,4-dihydroisoquinoleine 23 to give 80-88%yield of 13-cyanoprotoberberine 24. A simple reductive decyanation with lithium in liquid ammonia in the presence of isopropyl alcohol afforded xylopinine (19) in 84.6% yield [19]. 

The first example illustrates how a 1,4-dehydroaromatic system with cyclohexane ring having two double bonds may be also disconnected according to a retro-Diels-Alder to give a diene and an acetylene as the dienophile [25]. The second example makes clear that even an aromatic double bond may be -in some instances-involved in a retrosynthetic pericyclic disconnection [26]. In the synthetic direction, the polycyclisation involves a conrotatory electrocyclic cyclobutene ring opening, (16 15) followed by an intramolecular Diels-Alder addition (see Scheme... 

The Nazarov reaction [196] is a conrotatory electrocyclization involving four electrons over a five-carbon span. Usually, a more highly substituted cyclopentenone is obtained. However, contrathermodynamic products may be generated by placing a silyl group at the p-position of a bare vinyl moiety in the cross-conjugated dienone [197]. The acceptor facilitates and controls the regiochemistry of the cyclization process. 

Figure 14.2. a) Conrotatory electrocyclic reaction showing preservation of a C2 axis of symmetry. (b) Disrotatory ring closure showing preservation of a mirror plane of symmetry. 

Orbital Correlation Diagrams—The Conrotatory Electrocyclic Reaction... 

Intermediates (6) can yield to the corresponding [3-lactams via conrotatory electrocyclic closures (Fig. 3). The main features of these transition structures closely resemble those found for the thermal electrocyclic ring opening of cyclobutenes [34]. 

Thus, ketenes (2) can react as dienophiles with (E)-l,3-diazabuta-l,3-dienes (E)-(25) to yield either [4 + 2] cycloaducts (26) or (27) depending on the participation of the C = C or C = O moieties of the ketenes (Scheme 7). Claisen rearrangement of 3,6-dihydro-2-methylene-2//-l,3,5-oxadiazines (27) yields the p-lactams (28). Alternatively, reaction between ketenes (2) and (Z)-l,3-diaza-buta-1,3-dienes (Z)-(25) leads to the usual zwitterionic intermediates (29), whose conrotatory electrocyclation leads to p-lactams (28). No computational data including solvent effects have been reported for these reactions. 

Scheme 29 Formation of intermediates (116) via conrotatory electrocyclization of homochiral azadiene (113)...

There is a general agreement on the stepwise nature of the [2+2] cycloaddition between ketenes and imines. The first step consists of a nucleophilic attack of the iminic lone pair on the v/ -hybridized atom of the ketene to form a zwitterionic intermediate. The subsequent four-electron conrotatory electrocyclization leads to the corresponding (3-lactam. The final stereochemical outcome of the reaction depends on the combination of the following features (1) endo/exo attack of the imine on the ketene (2) inward outward disposition of the substituents at the conrotatory transition structure and (3) relevance of the isomerization pathways, including those of the starting imines. 

In equation 128 it is shown that thiocarbonyl ylide 117 may undergo a conrotatory electrocyclic reaction leading to thiirane 118. Thiirane is the smallest sulfur heterocycle and the Munich group has thoroughly studied not only the construction of this system, but also its destruction455, since the elimination of sulfur converts thiiranes into olefins 121 providing an important synthetic application for these molecules (equation 130). 

In addition to the above kinetics studies, the fluorene cyclization was studied using ab initio computational methods.323 It was found that the theoretically predicted barriers to the cyclizations for the dicationic intermediates agree well with the values obtained from the kinetic experiments. For example, geometry optimization and energy calculations at the B3LYP/6-31 level estimated that the activation energy (Ea) is 14.0 kcal/mol for the 4jt-electron conrotatory electrocyclization reaction involving compound 57 and the diprotonated intermediate (46, eq 13). 

The Nazarov Cyclization is a rare example of a Lewis acid-catalyzed 4-7t conrotatory electrocyclic reaction. Asymmetric... 

The ingenious solution was to isomerise the alkene and cyclise it in a single operation using light to catalyse both reactions. Cyclisation of Z-18 should give trans-27 by a conrotatory electrocyclic reaction but the reaction was conducted with diphenyldiselenide PhSe-SePh which oxidised it to the benzene 28 in the reaction mixture. So three steps were combined in one. 

The selection rules for conrotatory electrocyclic reactions are the opposite of those just listed that is, for a molecule with an even number of electron pairs, conrotation is thermally allowed, and for a molecule with an odd number of electron pairs, conrotation is photochemically allowed. 

An important group of conjugated diene/triene systems are those in the vitamin D series. The key reactions in the commercial manufacture of vitamin D (and probably also in its formation in skin exposed to daylight) are a photochemical, conrotatory electrocyclic ringopening in the provitamin, and a thermal 1,7-shift of hydrogen in the previtamin so formed (2.23). High conversions to the vitamin are not normally possible because all three species absorb appreciably at the... 

Reaction 2 Conrotatory electrocyclic opening of a cyclobutene ring ... 

For the synthesis of estradiol methyl ether 4-319, the cyclobutene derivative 4-317 was heated to give the orthoquinonedimethane 4-318 which cydized in an intramolecular Diels-Alder reaction [109]. The thermally permitted, conrotatory electrocyclic ring-opening of benzocyclobutenes [110] with subsequent intramolecular cycloaddition also allowed the formation of numerous complex frameworks (Scheme 4.70). 

Sorensen and coworkers used a domino conrotatory electrocyclic ring-opening/ 6it-disrotatory electrocyclization for the formation of ring C in the total synthesis of ( )-viridin (4-327) (Scheme 4.72) [112]. Heating 4-325 in the presence of a base followed by in-situ oxidation with DDQ afforded the tetracycle 4-326 in 83% yield. 

The biosynthesis of vitamin D3 (8.24) involves the thermal [1,7]-sigmatropic rearrangement of pre-vitamin 8.23, which is obtained by conrotatory electrocyclic ring opening of 7-dehydrocholesterol (8.22) (Scheme 8.3). 

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