Diene generation

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Subsequently, other publications have appeared involving the DA reactions of porphyrins with other dienes. For instance, the reaction of meso-tetrakis(pentafluorophenyl)porphyrin Id with the diene generated from pyrrole-fused 3-sulfolene gave rise to the isoindole-fused chlorin derivative 8 accompanied by a mixture of stereoisomeric bacteriochlorins 9 (Scheme 2) <98CC2355>. 

Dienes generated in this fashion can be trapped with dienophiles, either intramolec-ularly or intermolecularly, and this strategy has been exploited for the synthesis of natural products (equations 85 and 86)135,136. 

Enyne metathesis using ruthenium catalyst 52a was developed by Mori and Kinoshita [18]. When enyne 62a was treated with Grubbs s ruthenium catalyst 52a in benzene at room temperature for 22 h, the cyclized product 63a was obtained in only 13% yield (Eq. 29). It seems that the catalyst was coordinated by the diene generated in this reaction. This problem was overcome by the study of... 

Reduction of the metal dimer [CpMo(NO)l2]2 with Na/Hg in the presence of a variety of acyclic dienes generates the (diene)MoCp(NO) complexes in moderate to low isolated yield (equation 8)12,31,89. For the majority of diene ligands, complexes 60 are formed exclusively as the s-trans isomers as evidenced by NMR spectroscopy and single-crystal X-ray diffraction analysis. In comparison, complexation of the 2,3-dimethyl-l,3-butadiene initially gives a separable mixture of the s-trans (60) and s-d.v-complex (61). The s-cis isomer isomerizes to the more thermodynamically stable s-trans isomer in solution (THF, 1/2 = 5 min C6H6, ti/2 = 24 h). 

In contrast, exposure of 14-VE (diene)MCp Cl complexes (M = Zr, Hf) to CO (1 atm) results in the formation of cyclopentadienes70. The mechanism proposed for this transformation was elucidated with a carbon labeled CO ( CO) as requiring an initial coordination of CO to generate a (diene)MCp (CO)Cl complex 153 (Scheme 37). For the hafnium complex, the intermediate 153 (M = Hf) was observed by infrared spectroscopy. Insertion of CO into the a2, jt diene generates a metallacyclohexenone, which undergoes reductive elimination to generate the dimeric metallaoxirane species 154. -Hydride elimination from 154 (M = Zr, Hf) followed by 1,2-elimination produces substituted cyclopentadienes and the polymeric metal-oxide 155. Treatment of (diene)TiCp Cl with CO leads to isolation of the metallaoxirane complex 154 (M = Ti). 

For the first time, application of sequential Diels-Alder reactions to an in situ-generated 2,3-dimethylenepyrrole was shown with various dienophiles 548 to afford 2,3,6,7-tetrasubstituted carbazoles (549). This novel tandem Diels-Alder reaction leads to carbazole derivatives in two steps, starting from pyrrole 547 and 2 equivalents of a dienophile, and is followed by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) oxidation of the intermediate octahydrocarbazole. Mechanistically, the formation of the intermediate octahydrocarbazole appears to involve two sequential [4+2] cycloadditions between the exocyclic diene generated by the thermal elimination of acetic acid and a dienophile (529) (Scheme 5.17). 

Tricyclic P-lactams not having a bridgehead nitrogen atom have been obtained by intramolecular Friedel-Crafls reactions <99T5567> and from the intramolecular Diels-Alder reactions of 1,3-dienes generated from a mesylate 79 <99TL1015>. Other tricyclic P-lactams e.g., 80 have been obtained by intramolecular nitrone-alkene cycloaddition <99TL5391>. 

The hydroformylation of conjugated dienes with unmodified cobalt catalysts is slow, since the insertion reaction of the diene generates an tj3-cobalt complex by hydride addition at a terminal carbon (equation 10).5 The stable -cobalt complex does not undergo facile CO insertion. Low yields of a mixture of n- and iso-valeraldehyde are obtained. The use of phosphine-modified rhodium catalysts gives a complex mixture of Cs monoaldehydes (58%) and C6 dialdehydes (42%). A mixture of mono- and di-aldehydes are also obtained from 1,3- and 1,4-cyclohexadienes with a modified rhodium catalyst (equation ll).29 The 3-cyclohexenecarbaldehyde, an intermediate in the hydrocarbonylation of both 1,3- and 1,4-cyclo-hexadiene, is converted in 73% yield, to the same mixture of dialdehydes (cis.trans = 35 65) as is produced from either diene. 

Reactions of halides with 1,2-, 1,3- and 1,4-dienes generate 7i-allylpalladium intermediates, which react further with nucleophiles. The reaction of 1,3-dienes with aryl and alkenyl halides is explained by the following mechanism. The insertion of 1,3-diene to the aryl or alkenylpalladium bond generates 7r-allylpalladium complexes 54, which react further in several ways. As expected, nucleophiles such as carbon nucleophiles, amines, and alcohols attack the 7i-allylpalladium 54 to form the 1,4-... 

Radical cationic species of dienes, generated by photosensitized electron transfer, are known to exhibit an enhanced reactivity for [4 + 2] cycloaddition with... 

Reactions of 4-amino-l-metalla-l,3-dienes, generated from (1-alkynyl) carbene complexes 1 by addition of secondary amines (Scheme 32), with alkynes may lead to production of different compounds, depending on the substitution pattern as well as on the reaction conditions employed.3r Whereas successive addition of a secondary amine and one molecule of a terminal alkyne to a (l-alkynyl)carbene complex lj affords cyclopentadi-enes (Scheme 35), addition of two molecules of a terminal alkyne to complex lj yields cyclopenta[h]pyrans (Scheme 36). In an extension of this reaction sequence, (methylene)cyclopent-2-enones 103 are obtained from (1-alky-nyl)carbene chromium compounds 1 (R = rc-Pr, Ph, CH2CH2CH2OTBDS) by addition of secondary amines (NR) = NMe2, morpholino) and disubsti-tuted alkynes (Scheme 37).9e... 

Free radical addition to conjugated dienes involves addition of a radical at position 1 of the diene, generating a resonance-stabilized radical A which will attack other molecules, e.g. X-Y via its 2- or 4-position, yielding 1,2- and 1,4-addition products B and C, respectively (Scheme 2.45). 

The possibility of using porphyrins as dienophiles in DA reactions emerged in 1997 when Cavaleiro and coworkers <97CC1199> found that meio-tetraarylporphyrins la-d can behave as dienophiles in the presence of o-benzoquinodimethane, a highly reactive diene generated in situ by the thermal extrusion of SO2 from a sulfone by refluxing in 1,2,4-trichlorobenzene, TCB, giving chlorins 2a-d in moderate yields (Scheme 1). 

A number of other unsaturated poiyhydrocarbons have practical applications. These include poiy(phenyl acetylene) and poly((E,E)-[6.2]paracyclophane-1,5-diene), which have been studied as photoconducting polymers. The thermal decomposition of polyacetylenes and of poly((E,E)-[6.2]paracyclophane-1,5-diene) generates fragments summarized in Table 7.1.8 [19]. 

Diels-Alder adducts have also been prepared from tricyclo[4.1.0.0 ]hept-l(7)-ene and ben-zo[c]tricyclo[4.1.0.0 ]hept-l(7),3-diene, generated in situ by treating dimethyl sulfoxide... 

Dicyanobuta-l,4-diene, generated by thermolysis of 1,2-dicyanocyclobutene, reacted with bicyclopropylidene at 140°C in a [2 + 2] cycloaddition to give 7-(l-cyanovinyl)dispiro[2.0.2.2]oc-tane-7-carbonitrile in 28% yield. ... 

Diene generation followed by a Diels-Alder reaction can be carried out as a one-pot reaction. Methyl 9-(3-cyclopropylcyclobut-2-enyl)nonanoate was heated with dimethyl acetylenedicarboxylate, ring opening of the cyclobutene resulted followed by cyclohexene formation due to dienophile trapping of the buta-1,3-diene intermediate giving methyl 9-[5-cyclo-propyl-2,3-bis(methoxycarbonyl)phenyl]nonanoate after oxidation. ... 

A highly endo-selective Diels-Alder reaction can be performed on dienes generated in situ upon oxidation of certain 3-vinyl-hydroquinone-l-methyl ethers (406) [328]. 

Addition to alkynes and dienes. Organozincation of alkynes and dienes generates new organozinc species that are exploited synthetically. Eor example, alkenylzincs derived from propargyltrimethylsilane are useful for the synthesis of 1,3-disubstituted 1,3-dienes. ... 

The cycloadduct 2 is formed by a Diels-Alder reaction of the dienophile methyl 2-ethylacrylate and the diene generated by photochemical activation of the aromatic aldehyde. Irradiation of an ortho alkyl aromatic aldehyde (or ketone) gives an intermediate orf/io-quinodimethane (see Section 3.1.2). Cycloaddition with an activated alkene dienophile then gives the tetrahydronaphthalene product 2. See K. C. Nicolaou and D. Gray, Angew. Chem. Int. Ed., 40 (2001), 761. 

The phenylpalladium halides 1 are living species and undergo several further transformations before termination. Insertion of unsaturated bonds is one of them, as summarized in Scheme 3.2. Alkene insertion is followed by /i-H elimination to yield arylalkenes 7. Insertion of 1,2- and 1,3-dienes generates the jr-allylpalladium... 

VinyUc substitution carbopalladation can also be employed to synthesize dienes (Scheme 7). Bionnide 44 and the protected allylic amine 45 efficiently couple to yield diene 46 stereoselectively.t " Diene 46 has been used to build a C23-C29 fragmeut of the cytotoxic maCTOcycle iejimalide A (47). Diels-Alder reactions of dienes generated by similar reactions can also be envisioned to be useful in complex molecule synthesis. 

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