Synthesis of 4-aryl- and 4-alkyl-2-silyl-1,3-butadienes and their Diels-Alder/cross-coupling reactions

An ene-yne cross methasis of silyl-substituted alkynes and alkenes has been developed as a route to 4-aryl- and 4-alkyl-2-silyl-substituted 1,3-dienes. The dienes prepared were used to affect highly diastereoselective Diels-Alder reactions and then the silicon-substituted Diels-Alder cycloadducts were used in Hiyama cross-coupling reactions. The cross-coupling reactions enable these silicon dienes to be used as synthons for a variety of other dienes one might prepare and need access to. Two of the silicon-substituted Diels-Alder cycloadducts and one of the Hiyama cross-coupling products were also characterized by X-ray crystallography.     

Lewis Acid promoted tandem intermolecular Diels-Alder/intramolecular allylation reactions of silyl-substituted 1,3-butadienes leading to multisubstituted 7-norbornenones and related polycyclic compounds

7-Norbornenones of exo,exo-disubstituted patterns were formed highly selectively in good yields from Lewis acid-promoted tandem intermolecular Diels-Alder/intramolecular allylation reactions. The intermolecular Diels-Alder reaction between 1,4-bis(trimethylsilyl)-1,3-butadienes or 1-trimethylsilyl-1,3-butadienes with maleic anhydride in the presence of newly sublimed AlCl3 afforded their corresponding cycloaddition adducts, which underwent AlCl3-mediated intramolecular allylation of the carbonyl group by the in situ generated allylsilane moiety affording 7-norbornenones of exo,exo-disubstituted patterns.     

1-Phthalimido-4-(3-indolyl)-2-siloxy-1,3-butadienes: synthesis and Diels-Alder reactivity

New 1-phthalimido-4-(3-indolyl)-2-trialkylsiloxy-1,3-butadienes were easily prepared from 1,3-dichloropropanone and their configurations were established from NMR data. Their Diels-Alder reactivity with different maleimides and quinones was studied, high yields of the exo cycloadducts being obtained, as confirmed by X-ray diffraction studies.     

Synthesis and properties of 5-methylene-1,3-dioxolan-4-ones

A general method, which consists in the dehydroxypropanoic of 5-chloromethyl-1,3-dioxolan-4-ones, is proposed for the synthesis of 5-methylene-1,3-dioxolan-4-ones. With respect to their structure, the synthesized compounds are simultaneously derivatives of acrylic acid and vinyl ethers.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1316–1318, October, 1985.     

Formylation of 5-alkyl-3H-furan-2-ones

3-Formyl derivatives of 3H-furanones and 2-chlorofurans are formed in the reaction of 5-alkyl-3H-furan-2-ones with POCl₃ and DMF. The conditions for the purposeful synthesis of these compounds were found. The transformations of the formyl group in reactions with dinitrophenylhydrazine and aniline were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 456–458, April, 1993.     

Diastereoselective synthesis of the top half of kijanolide

A highly diastereoselective synthesis of the top half (4) of kijanolide is described. The key step is the exo and diastereoface selective Diels-Alder reaction of triene 6 and chiral dienophile 6.     

Synthesis and Diels-Alder reactions of 4-vinylimidazoles

[structure in text] The synthesis of several 4-vinylimidazoles via Stille cross-coupling reactions of the corresponding protected 4-iodoimidazoles with tributylvinylstannane is described. These heterocyclic dienes are shown to be effective partners in the Diels-Alder reaction, providing adducts in good yield and exhibiting useful levels of isomer selectivity and stereoselectivity (endo/exo).     

Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octa-5,7-dien-2-ones

The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13), bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a-d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl-2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5-diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively, in good overall yields.     

Regio- and stereoselective microwave-assisted synthesis of 5-alkyl-4-alkenyl-4-phenyl-1,3-oxazolidin-2-ones

Chiral symmetrical alk-2-yne-1,4-diols have been stereoselectively transformed into 5-alkyl-4-alkenyl-4-phenyl-1,3-oxazolidin-2-ones, which are precursors of quaternary α-amino β-hydroxy acids. The key step was the cyclization of the bis(tosylcarbamates) of 2-phenylalk-2-yne-1,4-diols, easily obtained from the starting chiral diols. These cyclizations were accomplished with complete regioselectivity and up to 92:8 dr in the presence of catalytic amounts of Ni(0) or Pd (II) derivatives under microwave heating.     

Selectivity in the electron transfer catalyzed Diels-Alder reaction of (R)-alpha-phellandrene and 4-methoxystyrene

Electron transfer catalysis is an effective method for the acceleration of Diels-Alder reactions between two substrates of similar electron density. The dependence of the selectivity of the Diels-Alder reaction between (R)-alpha-phellandrene and 4-methoxystyrene catalyzed by photoinduced electron transfer with tris(4-methoxyphenyl) pyrylium tetrafluoroborate is studied. Despite the fact that the radical ions involved are highly reactive species, complete regioselectivity favoring attack on the more highly substituted double bond is observed. The endo/exo selectivity and the periselectivity between [4 + 2] and [2 + 2] cycloaddition is found to be solvent-dependent. Stereochemical analysis showed that the periselectivity is correlated with the facial selectivity, with attack trans to the isopropyl group leading to the [4 + 2] product and cis attack leading to the formation of the [2 + 2] product. A good correlation between the dielectric constant of the solvent and the endo/ exo ratio is found, but more polar solvents lead to lower periselectivity. The effect of reactant and catalyst concentrations is found to be smaller. These results are rationalized in the context of the relative stability of the ion-molecule complexes and the singly linked intermediate of the reaction.     

Reactivity of 2-Methylene-1,3-dicarbonyl Compounds. Stereoselective and Asymmetric Diels-Alder Reactions

The Diels-Alder reaction of 1,1-dicarbonylethenes 1 with dienes was investigated. The adduct of the reaction of 1, whose two carbonyl groups were different, with cyclopentadiene showed moderate stereoselectivity and this was explained by FMO theory. However, in the Lewis acid-catalyzed addition, the reaction proceeded with high stereoselectivity to give the exo adduct 3x. This might be due to steric hindrance because the benzene ring cannot orient in the plane of the conjugated system in the metal-chelated enedione 6. Applying this principle to (1'R,2'S,5'R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate (1d), we achieved a diastereomeric Diels-Alder reaction to afford 3x-R, whose structure was confirmed by the X-ray crystal analysis.     

Diastereoselective Diels-Alder reactions of N-sulfonyl-1-aza-1,3-butadienes with optically active enol ethers: an asymmetric variant of the 1-azadiene Diels-Alder reaction

The first detailed study of a room-temperature asymmetric Diels-Alder reaction of N-sulfonyl-1-aza-1,3-butadienes is reported enlisting a series of 19 enol ethers bearing chiral auxiliaries, with many providing highly diastereoselective (endo and facial diastereoselection) reactions, largely the result of an exquisitely organized [4+2] cycloaddition transition state. Three new, readily accessible, and previously unexplored auxiliaries rationally emerged from the studies and provide remarkable selectivities (two of these give 49:1 endo:exo and 48:1 facial selectivity) that promise to be useful in systems beyond those detailed.     

Exo-selective Diels-Alder reactions of vinylazepines. Origin of divergent stereoselectivity in Diels-Alder reactions of vinylazepines, vinylpiperideines, and vinylcycloalkenes

Diels-Alder reactions of vinylazepines with N-phenylmaleimide afforded exclusively the exo cycloadduct, while high endo stereoselectivity was observed, as previously reported, in analogous reactions of vinylpiperideines. This curious contrast was confirmed by X-ray analysis of cycloadducts not susceptible to epimerization. The stereoselectivity of Diels-Alder reactions of vinylazepines, vinylpiperideines, and vinylcycloalkenes exhibits surprising divergence depending on the detailed diene structure, and DFT calculations (Becke3LYP) were undertaken to shed light on these observations. The model calculations correctly predict the major stereoisomers in these reactions, though they tend to significantly underestimate the stereoselectivity. The results suggest some general considerations in predicting or controlling the stereochemistry of this class of Diels-Alder reactions.     

Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3h-cycloheptimidazol-4-ones and 2-alkyl-3h-cycloheptimidazol-4-ones

Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2'-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2'-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu(4)NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.     

Diastereoselective Diels-Alder reactions of alpha-fluorinated alpha,beta-unsaturated carbonyl compounds: chemical consequences of fluorine substitution. 2

Two alpha-fluoro alpha,beta-unsaturated carbonyl compounds, i.e., benzyl 2-fluoroacrylate (3) and 2-fluorooct-1-en-3-one (4), as well as the corresponding nonfluorinated parent compounds, were synthesized and subjected to Diels-Alder reactions with cyclopentadiene. The cycloadditions were conducted thermally, microwave-assisted, and Lewis acid-mediated (TiCl(4)). The fluorinated dienophiles exhibited a lower reactivity and exo diastereoselectivity, while the corresponding nonfluorinated parent compounds reacted endo selectively. DFT calculations suggest that kinetic effects of fluorine determine the stereoselectivity rather than higher thermodynamic stability of the exo products.     

A new diene, 2-methoxy-1,3-pentadiene-5-ol. Synthesis and intramolecular diels-alder reactions

Reactions of the diene 1-benzyloxy-2-methoxy-1,3-pentadiene-5-ol in intramolecular Diels-Alder reactions using maleic anhydride or fumaric acid ethyl ester is described. The new reactive diene is prepared starting from 3-methoxypyridine. The structure of the diene was elucidated by a NOE nmr experiment.     

Dipolar addition of diazomethane to 5-methylene-1,3-dioxolan-4-one

The reactions of 1-pyrazoline-3-spiro-4-(1,3-dioxolan-5-one) were studied; this compound is the product of the 1,3-dipolar addition of diazomethane to 5-methylene-1,3-dioxolan-4-one. Depending on the conditions, thermolysis of the spiro compounds proceeds either with destruction of the pyrazoline ring, or with cleavage of the dioxolane ring, followed by rearrangement to give 1(2)-hydroxymethyl-3(5)-pyrazolecarboxylic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1182–1184, September, 1985.     

Total synthesis of (+/-)-alantrypinone by hetero Diels-Alder reaction

An efficient total synthesis of (+/-)-alantrypinone 4 by hetero Diels-Alder reaction of a novel pyrazine diene 9 with either a functionalized 3-alkylideneoxindole or 3-methyleneoxindole itself is described. The Diels-Alder reactions provide both the desired regiochemistry and exo selectivity. An interesting anionic equilibration between alantrypinone 4 and its epimer 31 or between its ester analogues 23 and 24 has been demonstrated, and a mechanism has been proposed.