Thio-Diels-Alder reactions

Mark6 and colleagues178 studied the Eu(hfc)3 catalyzed inverse electron demand Diels-Alder reactions between (—)-pantolactone derived chiral a-pyrones 279 and vinyl ethers and thio ethers 280. This auxiliary proved superior to other auxiliaries in these reactions. The reactions generally proceeded with high yields, affording the endo adducts 281 with de values generally above 95%. The de proved independent of the chirality or achirality of the Lewis acid employed, as (+)-Eu(hfc)3, (—)-Eu(hfc)3 and Eu(fod)3 all afforded the same diastereomer with >95% de (equation 78, Table 13). 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

When cyclic 1,3-dienes were employed, the reactions were found to be exo selective [Eq. (28)]. In contrast, the Diels-Alder reactions of free thio-and selenoaldehydes with cyclopentadiene occur with a preference for the endo isomer.235 Thus, coordination of thio- and selenoaldehydes to a penta-carbonylmetal fragment resulted in a reversal of the endo selectivity. The exo/endo product ratio of [W(CO)5 E = C(Ph)H ] was 7.3 1 (E = S) and 2.6 1 (E = Se), whereas the kinetically controlled exo/endo ratio of the cycloadducts obtained by trapping of the free heterobenzaldehyde with cyclopentadiene was reported to be 1 7236 and 1 4235 237 (E = S) and 1 2.6238 and 1 4239 (E = Se), respectively. 

Although a,/8-unsaturated thio- and selenoaldehyde complexes also seemed to behave as dienophiles in Diels-Alder reactions with cyclopentadiene, the products were too unstable for characterization. Therefore, it remains unknown which double bond (E=C or C=C) was involved in the cycloaddition.64... 

However, 2-nitrothiophene (176), but also 2-acetylthiophene and thio-phene-2-carbaldehyde, irradiated in the presence of phenylacetylene, gave the corresponding diphenyl derivative ortho substituted 177. The reaction is probably a photo Diels-Alder reaction with extrusion of sulfur from the adduct to give the observed product (95TL6567). 

In search for control of absolute stereochemistry, the reaction of thio-chalcones was investigated with unsaturated amides bearing an Evans chiral oxazolidinone [223] and dimenthyl fumarate [224, 225]. For the first time with thiocarbonyl compounds, the efficiency of Lewis acid addition was demonstrated, and reactions could be conducted at room temperature. With EtAlCl2 (Table 4, entry 2) or A1C13 (entry 3), levels of induction up to 92% were attained for the endo isomer. Yb(OTf)3 in DMSO also caused the acceleration of the reaction with chiral acrylamides with p-facial selectivity [226]. This group has also reported [227] an intramolecular hetero Diels-Alder reaction with divinyl thioketones and the double bond of an allyloxy group (Table 4, entry 4). 

Early attempts to prepare selenoaldehydes by treatment of aldehydes with H2Se under acidic conditions yielded oligomeric or polymeric sele-nides, possibly via self-condensation of selenoaldehydes [15JPR116 67JCS(B)117]. In 1988, Japanese workers reported that the reaction of aldehydes with bis(trimethylsilyl)selenide in the presence of a catalytic quantity of butyl lithium afforded selenoaldehydes (88JA1976). This novel method has been exploited for the first intramolecular Diels-Alder reactions of selenoaldehydes (88TL6965). Dienal (79) was converted into dienselenal (80) and then into a mixture of stereoisomeric adducts 81 and 82. The major product was as-fused isomer 81, derived from the endo transition state. These results compare favorably with intramolecular thio-aldehyde reactions (Section II,B). 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

DIELS-ALDER REACTIONS Bis(methyl-thio)-l,3-ketadiene. 1,3-Bis(trimethyl-silyloxy)-l,3-butadiene. 2,5-Bis(tri-methylsilyloxyjfuranes. 5,5-Dimethoxy-1,2,3,4-tetrachlorocyclopentadiene. Di-peroxo-oxohexamethylphosphoramido-molybdenum(VI). Ethynyl p-tolyl sullbnc. liirane. (li)-l-Mcthoxy-1.3-... 

Flash vacuum pyrolysis of a p-chlorobenzoate ester (35) has also led to useful chemistry <90TL1487>. The reaction produced oxazole-4,5-xylylene (36), which could be trapped with thio-phenol or SO2 to give the corresponding adducts in 39% and 25% yield, respectively (Scheme 5). The unstable intermediate also gave a Diels-Alder adduct with methyl acrylate. The o-xylylene oxazole derivative and the furan analogue were unique among those of several heterocycles studied in that they underwent Diels-Alder reactions instead of polymerization. 

A variety of 2-methylthio-5-amidofuran systems containing a tethered rc-bond on the amido nitrogen were prepared and utilized for a subsequent intramolecular Diels-Alder reaction (02JOC3412). Thus, exposure of imides 331 to DMTSF resulted in the formation of furans 332 in 40-70% yields (Scheme 62). Thermolysis of these furans in toluene at reflux initiated an intramolecular Diels-Alder reaction to first produce an intermediate oxabicyclo adduct. A subsequent fragmentation of the intermediate cycloadduct followed by a 1,2-thio shift provided the bicyclic amides 333 in good yields (ca. 70%). In an analogous manner, the cycloaddition chemistry of amidofurans 334 provided the azatricyclic products 335. Apparently, the rate of the 1,2-thio shift of the initially formed cycloadduct is much faster than the deprotonation/dehydration pathway previously described in Scheme 21. 

Complexes of metal + ligand + protein or DNA can also catalyze the Diels Alder cycloaddition or oxidations with hydrogen peroxide. Copper complexes bound to DNA catalyzed the Diels-Alder cycloaddition with up to 99% ee [15, 16], Cu(phthalocyanine) complexed to serum albumin also catalyzed the enantioselective (98% ee) Diels-Alder reaction, but only with very high catalyst loading (10 mol%) and only with pyridine-bearing dienophiles (presumably to complex the copper) [17]. Achiral Cr(III) complexes or Mn(Schiff-base) complexes inserted into the active site of apomyoglobin variants catalyzed the sulfoxidation of thio-anisole with up to 13 and 51% ee, respectively [18, 19]. A copper phenanthroline complex attached to the adipocyte lipid-binding protein catalyzed the enantioselective hydrolysis of esters and amides [20]. 

Extensive kinetic studies of normal, neutral, and inverse Diels-Alder reactions observed in [4+2] cycloadditions of some thio- and selenocarbonyl compounds to 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine prove the highly dienophilic activity of the C=S and C=Se bonds. Studies of the solvent and temperature dependence of the reaction rate indicate a concerted mechanism <1998EJ02875>. 

The pyranothiophenes (577), prepared in reasonable yields from commerically available thio-phene-3-acetic acid in a single step, are stable thiophene-2,3-quinodimethane equivalents <88TL5817, 90JCS(PI)68I>. Thus, they undergo Diels-Alder reaction with DMAD to give benzo[6]thiophenes (578) after loss of carhon dioxide, and with ethyl propiolate to give isomeric mixtures of (57 ) and... 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

A review of the asymmetric thia-Diels-Alder reactions of chiral dithioesters with dienes has been published. The asymmetric organocatalytic thio-Diels-Alder reac- 0 tion of thiocarbonyls with a-methylene carbonyl dienes produced dihydrothiopyrans in high yields and high to excellent selectivities. The inverse-electron-demand 0 hetero-Diels-Alder cycloadditions of norbomene (106) with 5-benzylidene-2-arylimino-3-aryl-thiazolidine-4-thiones (107) at 25 °C produced cycloadducts (108)... 

From a comparison of the REPE values, isobenzofuran appears to be nonaromatic, which corresponds with its reactive nature. Furan also has a very small REPE and behaves much like a polyene as it undergoes Diels-Alder reactions readily, while pyrrole and thiophene do not. Isothianaphthene has a REPE that is considerably lower than that of thiophene. As compared to thio-... 

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