Solvent Diels-Alder cyclizations

The scope of the 2-azadiene intramolecular Diels-Alder cyclization, employed for the synthesis of the daphniphyllum alkaloids, has been further investigated by Heathcock et al.[76j. The protocol involves Moffatt-Swem oxidation of the 1,5-diol to the dialdehyde, and treatment of the crude methylene chloride solution with ammonia followed by solvent exchange from methylene chloride to a buffered acetic add solution. The cydopentyl ring, quaternary carbon and tertiary carbon centers in... 

A solvent-free procedure for the preparation of methylenedioxyprecocene (MDP), a natural insecticide, has been developed for use in the undergraduate organic chemistry laboratory a section of 15 students is being used as a test group. The synthesis involves, in tandem, electrophilic addition of 3-methyl-2-butenal to sesamol, followed by dehydration and an intramolecular hetero-Diels-Alder cyclization (Scheme 6.6). Montmorillonite-KlO, a commercially available basic clay, is used as a support... 

Wang recently reported [30] that thermolysis of carbodiimides 15 (Scheme 1.5) in aromatic solvents is an efficient route to indoloquinolines 18 used as precursors for synthesizing naturally occurring alkaloids [31], The cyclization is thought to occur through a two-step biradical Diels-Alder reaction that gives 17, which then tautomerizes to 18. 

Another strained alkylidenecyclopropane, 2-methylbicyclo[3.1.0]hex-l-ene (21), formed by cyclization of the carbenoid generated from dibromide 20 at 0 °C gave, in the presence of an excess of 1,3-diphenylisobenzofuran (10), a very small amount (5%) of a 2 1 mixture of diastereoisomeric Diels-Alder adducts 22 (Scheme 4) [11a]. The parent furan does not capture 21 even when used as solvent for the carbenoid cyclization. 

Rather large rate enhancements with increasing solvent polarity have also been found for intramolecular Diels-Alder reactions such as the cyclization of 2-furfuryl methyl fumarate shown in Eq. (5-42a) to yield lactone D. This first-order reaction is about 3200 times faster in dimethyl sulfoxide than in toluene as solvent [807]. 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

Asymmetric catalysis of ene reactions was initially investigated for the intramolecular examples, because intramolecular versions are much more facile than their inter-molecular counterparts. The first reported example of an enantioselective 6-(3,4) car-bonyl-ene cyclization employed a BINOL-derived zinc reagent [81]. This, however, was successful only when excess zinc reagent (at least 3 equiv.) was used. An enantioselective 6-(3,4) olefin-ene cyclization has also been developed which uses a stoichiometric amount of a TADDOL-derived chiral titanimn complex (Sch. 26) [82]. In this ene reaction, a hetero Diels-Alder product was also obtained, the periselectivity depending critically on the solvent system employed. In both cases, geminal disubstitution is required of high ee are to be obtained. Neither reaction, however, constitutes an example of a truly catalytic asymmetric ene cyclization. 

N,N-Dicyclohexyl-4-morpholinocarboxa-mjdine, 126 Dicyclohexylurea, 162 ( )-Didesoxyzearalone, 329 Dieckmann cyclization, 158 Diels-Alder catalyst, 21 Diels-Alder reactions, 94, 95, 206, 282, 324, 325, 332, 392, 396, 399 Diels-Alder solvents, 126... 

For a few combinations of less reactive dienes and dienophiles, transition metal catalyzed variants of the Diels Alder reaction have been developed. An example is the cycloaddition of an unpolar diene and an unactivated alkyne however, except when the reaction is catalyzed with iron, nickel, cobalt, or rho-dium(I) complexes, the temperature required often causes competing decomposition, even for the intramolecular version. [2] Wilkinson s catalyst [3] - tris(triphenylphosphane)rho-dium(I) chloride - frequently used for hydrogenations and for decarbonylations, permits the cyclization of 4 to the annelated cyclo-hexadiene 5 in excellent yield in only 15 minutes at 55 °C in trifluoroethanol as solvent (Scheme 2). [2c]... 

Quinones. - Goerner has demonstrated that the yield of semiquinone radicals is low in the absence of hydrogen donating solvents. He notes that the quantum yield for decomposition is substantial in aqueous solution. A detailed account of the photohydroxylation reactions of 1,4-benzoquinone in aqueous solution has been published.The photochemical cyclization of some Diels-Alder adducts of benzo-l,4-quinones has been described. This has provided a path to complex molecules such as 3-bromotetracyclo[5.3.1.0 . 0 ]undec-10(12)-ene-9,l 1-dione. A biradical has been identified as the key intermediate in the photocyclization of phenylbenzoquinone. " A charge-transfer complex is formed initially on irradiation of 2-chloro-5-methoxybenzo-l,4-quinone in the presence of triethylamine and various solvents.2-Chloro-5-methoxyben-zo-l,4-quinone also undergoes addition to arylalkynes to afford oxetenes. The mechanism of this addition reaction was studied.A hydrogen abstraction is involved in the photochemical reactions of chloranil with 3-diketones. ... 

Theoretical studies have been carried out on the conrotatory and disrotatory reaction pathways of hexa-l,3,5-triene to cyclohexadiene, and the effect of solvent and salt effects on the rates of the electrocyclic ring closure of (IZ, 3Z, 5 )-l,2,6-triphenylhexa-l,3,5-triene has been determined. An ab initio study of the electro-cyclization of (Z)-hexa-l,3,5-triene and its hetero-substituted analogues has been undertaken.The involvement of a lone pair on the nitrogen or oxygen atom appears to facilitate the interaction between the terminal atoms that bond to each other to close the ring. It has been reported that the intramoiecular aza-Diels-Alder reaction of an a./S-unsaturated hydrazones to a quinone, as in (197), is followed by an unprecedented rearrangement in which the aminoaryi moiety formally undergoes a 1,2-shift to yield benzo- or pyrido-[fc]acridine-6,11-dienes (198). 

Here, the initially formed endo adducts 4.50 and 4.51 spontaneously cyclize to the lactols 4.52 and 4.53. No exo adducts were obtained in this Diels-Alder reaction. While the observed diastereoselection is only modest in this case, it is better than that obtained in organic solvents and is consistent with a Felkin-Anh type of transition-state conformation. 

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