Exo-cycloadduct

Again, it is noteworthy that 4-substituted 5-hydrdxythiazoles (24) react like 5-hydroxy-THISs with alkynes to give pyrroles and sometimes with alkenes to give exo-cycloadducts (Scheme 22). In the latter case other processes compete with the cycloaddition, becoming dominant when 24 is treated with azo-compounds, enamines, or heterocumulenes (31). 

Ni(C104)2 6H2O showed a litde better enantioselectivity than the anhydrous complex. Although the uncatalyzed reaction was highly exo selective (cis/trans=i 97), the catalyzed reactions were very poor in diastereoselectivity, a mixture of endo and exo cycloadducts being formed. We expected that this poor diastereoselectivity would not be a serious problem since the same enantioface should be involved at the 2-position of the diastereomeric cycloadducts (Scheme 7.27). The best enantioselectivity (cis > 99% ee, trans 94% ee) was observed when the reaction was catalyzed by l ,J -DBFOX/Ph-Ni(SbF6)2 (50 mol%). With the decreased amount of catalyst (10 mol%) still a satisfactory level of enantioselectivity was observed for the cis cycloadduct (94% ee). 

The Diels-Alder reaction of simple alkoxy alkenylcarbene complexes leads to mixtures of endo and exo cycloadducts, with the endo isomer generally being the major one [96,97]. Asymmetric examples of endo Diels-Alder reactions have also been reported by the use of chiral auxiliaries both on the carbene complex and the diene. Thus, the reaction of cyclopentadiene with chiral alkenylcarbene complexes derived from (-)-menthol proceeds to afford a 4 1... 

Titanoxy alkenylcarbene complexes have been used as dienophiles in their reaction with cyclopentadiene to give predominantly the exo cycloadduct in high yield. The unexpected formation of the exo isomer is attributed to the... 

The cycloaddition of glyoxylic acid with cyclopentadiene in water at pH 6 and 60 °C is slow and occurs with low yield and low diastereoselectivity [18] (Scheme 6.17). Proton (pH = 0.9) [18], copper salts [27] and Bi(OTf)3 [28] accelerate the reaction and increase the diastereoselectivity. The lactones 28 and 29 originate from endo and exo cycloadducts 27, respectively. The proposed rearrangement is depicted in Scheme 6.17 for the major endo adduct 30. A competitive ene reaction that originates 28 and 29 cannot be excluded [28]. 

The intramolecular cycloaddition of the norbornadiene-tethered nitrile oxides 110 (Eq. 11 and Table 11) was reported to be highly regio- and stereoselective, providing the exo cycloadduct 111 as the exclusive product out of the four possible regio/stereoisomers [36]. The cycloadduct 111 provides a stereoselective entry into tricyclic (e.g., 112) and spirocyclic (e.g., 113) frameworks. 

GuoetaLhavereported Diels-Alder reaction of differently substituted2-acetyl-[l, 2,3] diazaphospholes, 6 with cyclopentadiene and obtained both endo and exo cycloadducts in moderate yields depending on the reaction conditions (Scheme 28). By quenching the room temperature reaction after only 5 min, endo product 89 was obtained exclusively in 65-75% yields, while prolongation of reaction time to 3 days led to the isolation of only exo product 90 in 50-75% yields [19]. 

Analogues endo and exo cycloadducts have been observed in the reactions of cyclopentadiene (6) with 21 or methoxybicyclo[3.1.0]hex-l-ene (23) (Scheme 5) [11]-... 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Reactions of methoxycarbonylformonitrile, furonitrile and substituted benzoni-trile oxides (4-Me, 4-OMe, 3-OMe, 4-C1, 3-C1, 2,4-di-Cl, 4-F as substituents) with dimethyl 7-(diphenylmethylene)bicyclo[2.2. l]hept-2-ene-5,6-dicarboxylate led exclusively to exo cycloadducts 82 (R = C02Me, 2-furyl, substituted phenyl), which, on irradiation with a low-pressure mercury lamp, afforded 3-azabicyclo [4.3.0]nonadiene-7,8-dicarboxylates 83 as the only products. The 1,3-dipolar cycloaddition, followed by a photorearrangement, provides a new method for obtaining tetrahydro-27/ -pyridine derivatives from cyclopentadiene (245). 

The chiral Lewis acid catalyzed cycloaddition of methacrolein 310 to cyclopentadiene predominantly affording exo cycloadduct 322 together with some 323 has been extensively investigated. The application of menthoxyaluminum dichloride (324) as the chiral catalyst in this reaction represents one of the earliest examples of a chiral Lewis acid catalyzed Diels-Alder reaction206 (equation 90). The authors confirmed their results in 1987, but the ee was revised from 72% to 57%207. 

Mahon and colleagues297 studied the cycloaddition reactions of substituted cis-1,2-isopropylidenedioxycyclohexadienes. The reaction of tropone (471) with cyclohexadiene 472, for example, afforded the expected exo cycloadduct 473 with good yield (equation 140). 

Cyanothioformamides NC-CS-NR1 -COR2 (R1 = Ph or 4-02NC6H4 R2 = CF3 or Ph) comprise another class of reactive dienophiles (e.g. equation 40)36. The trithiocarbon-ate 61 adds to cyclopentadiene to yield 62 (equation 41 )37. Trithiocarbonate. SVS-dioxidcs 63 (Ar1 = d-MeCgHa or 4-CIC6H4 Ar2 = Ph or 4-CIC6H4) react instantly with cyclopentadiene to afford mixtures of endo- and exo-cycloadducts 64 and 65, respectively, in which the former predominate (equation 42)38. The adducts produced from acyclic dienes are unstable they readily eliminate arylsulfinic acids to yield thiopyrans (equation 43)38. 

A simple preparation of electron-poor 2-azadienes and the preliminary study of their ability to participate in [4 + 2] cycloadditions was done almost simultaneously by out group (87CC1195) (Scheme 49). The preparation of 2-azadienes 212 with two appended methoxycarbonyl groups was achieved, in a multigram scale and in nearly quantitative yield, by the insertion reaction of N- trimethylsilyl imines 210 into the carbon—carbon triple bond of dimethyl acetylenedicarboxylate to give 211 followed by protodesilylation with CsF/MeOH. Azadienes 212 underwent at room temperature inverse-electron demand [4 + 2] cycloaddition with cyclic enamines to give exclusively exo-cycloadducts 213 in 82-95% yield. Acid hydrolysis of them resulted in their aromatization to yield 2-pyrindine (n = 1] and isoquinoline (n = 2) derivatives 214. 

The heavily annulated benzo- and furanothia[ll]annulenes depicted in 6182 and 6283 were synthesized by condensation of dialdehyde (47) with properly structured Wittig components. Further, treatment of 62 with maleic anhydride produced a mixture of endo and exo cycloadducts of general formula 63 whose hexatriene segment that was not directly bound to the heteroatom was found to be thermally labile, readily... 

Diels-Alder reactions of N-substituted benzo[4,5]thieno[2,3-c]pyrroles 149 [27] and benzo[4,5]furo[2,3-c]pyrroles 150 [26] with Af-phenylmaleimide and DMAD gave the corresponding exo cycloadducts 151-153 (Scheme 28). Oxidative extrusion of the nitrogen bridge in cycloadducts 152 and 153 via intermediates 154, 155 afforded derivatives of dibenzothiophene 156 [27] and diben-zofuran 157 [26],... 

This cycloaddition takes place to give the exo cycloadduct, rather than the more common endo cycloadduct, as the major product. Presumably this is a consequence of the intermediate munchnone 131 being locked in an anti orientation as compared to the commonly favored syn orientation (as in 24). 

The most recent report in this field is related to the use of optically pure 3-(2-exo-hydroxy-10-bornyl)propenamide 56 [43]. This compound reacted with cyclopentadiene under both atmospheric and high pressure conditions in CH2Cl2/methanol to give similar mixtures of endo and exo cycloadducts (de 80-88%). Reactions with furan and 2-methoxyfuran took place only under high pressure (12.6 kbar). With furan, the endo-adduct was obtained as a single diastereoisomer (82% yield), whereas with 2-methoxyfuran a 92 8 mixture of endo-57 and exo-57 adducts was obtained (Scheme 30). 

We examined the IMDA reaction of 62 under Lewis-acid-mediated conditions (Scheme 10). As in the case of the Lewis-acid-mediated IMDA reaction of the substrate 48, no good results were obtained (Table 3, Entries 1-3). Treatment of 62 with 5.0 M LiC104 in Et20 [81] resulted in the formation of a complex mixture (Entries 4, 5). We found that the IMDA reaction of 62 proceeded under thermal conditions as a 0.02 M toluene solution in a sealed tube in the presence of BHT (Entry 6). In contrast to the case of 48, the IMDA reaction of 62 required a longer heating time for completion. Two endo-cycloadducts 63-A and 63-B were isolated in 62% and 21% yields, respectively, after separation on silica gel. Furthermore, an exo-cycloadduct 63-D was isolated in a trace amount of 2%. The stereochemistries of the... 

With the complex [(indenyl)Ru(acetone)(Me4BIPHOP-F)]SbF6 as catalyst [22], the reaction afforded the exo cycloadduct as the major product for the reaction of acrolein with cyclopentadiene, whereas this noncatalyzed reaction is known to give the endo derivative as the major product. Analogously the catalyst 41 performed the asymmetric 1,3-dipolar addition of nitrones with enals [24]. 

Cationic ansa metallocenes can be utilized as chiral catalysts in Diels-Alder reactions. For example, in the presence of the cationic zirconocene complex [(ebthi)Zr(Ot-Bu) thf]+, the [4 + 2] cycloaddition of acrolein and cyclopentadiene proceeds efficiently to afford endo and exo cycloadducts (equation 71). In reactions in which methyl acrylate is used as the dienophile, cycloadditions occur with lower levels of enan-tioselection (23% ee), but with significantly higher degrees of diastereoselectivity (17 1 endo, exo). In these processes, recent studies demonstrated the great influence of chiral metallocene structure and the dramatic solvent effect. ... 

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