<title>Introduction</title> <p>The cycloadditions of anthrones <bold>1</bold> and <italic>N</italic>-substituted maleimides <bold>2</bold> are prominent examples of asymmetric catalysis exerted by chiral Brønsted bases. Moderate to excellent stereoselectivities of products <bold>3</bold> have been reported using pyrrolidines <bold>4</bold> [##UREF##0##1##–##UREF##1##2##], cyclic guanidine <bold>5</bold> [##REF##17044689##3##], or cinchona alkaloids <bold>6</bold> [##UREF##2##4##] as catalysts. Recently, we could promote this type of cycloaddition by metal-free bisoxazolines <bold>7</bold> in up to 70% <italic>ee</italic>, in spite of their limited Brønsted-basicity [##UREF##3##5##] (##FIG##0##Scheme 1##).</p> <p>Our study was motivated by the structural similarity of bisoxazolines <bold>7</bold> and bisamidines <bold>8</bold>. Bisamidines <bold>8</bold>, readily accessible from malonodinitrile in two steps, prefer the conjugated tautomeric form (enamine-imine) in the monoprotonated state, which is characterised by an almost planar structure [##REF##17585816##6##] (##FIG##1##Scheme 2##).</p> <p>The aqueous p<italic>K</italic><sub>a</sub> of <bold>8</bold>·H<sup>+</sup> is approximately 11, sufficient to allow deprotonation of anthrones <bold>1</bold> (p<italic>K</italic><sub>a</sub> around 10, [##UREF##4##7##–##UREF##5##8##]) by bisamidines to a significant extent. Here we report on the use of neutral bisamidines <bold>8</bold> as asymmetric Brønsted base catalysts in the cycloaddition of anthrones <bold>1</bold> and maleimides <bold>2</bold>.</p>
<title>Results and Discussion</title> <p>Analogous to the synthesis of compound <bold>8a</bold> [##REF##17585816##6##], the other bisamidines were prepared as hydrochlorides in 60–79% yield from the corresponding chiral diamines <bold>9</bold> and bisimidate <bold>10</bold> in refluxing ethanol. Simple extraction in the presence of Na<sub>2</sub>CO<sub>3</sub> afforded the neutral bases <bold>8b</bold>–<bold>c</bold> and <italic>ent-</italic><bold>8d</bold> in almost quantitative yield. The <italic>S</italic>,<italic>S</italic> configurated diamines <bold>9b</bold> and <bold>9c</bold> were prepared from L-(+)-tartaric acid (<italic>R,R</italic>) via the vicinal diazide using Saalfrank's procedure [##UREF##6##9##]. <bold>9d</bold> was purchased as the dihydrochloride salt and then deprotonated by aqueous sodium hydroxide. As an “artefact” of the sequence rule, the <italic>S</italic>,<italic>S</italic> configurated diamine <bold>9d</bold> leads to bisamidine <italic>ent</italic>-<bold>8d</bold> (##FIG##2##Scheme 3##).</p> <p>The anthrones <bold>1b</bold> (R<sup>1</sup>: H; R<sup>2</sup>: Cl) and <bold>1c</bold> (R<sup>1</sup>: Cl; R<sup>2</sup>: H) resulted from regioselective reductions of 1,8-dichloroanthraquinone [##UREF##7##10##–##REF##11667122##11##]. Aliphatic side chains of compounds <bold>2</bold> could be introduced by a Mitsunobu alkylation of maleimide [##UREF##8##12##]. Alternatively, substituted maleimides were prepared by reaction of maleic anhydride with the corresponding amines followed by ring closure [##UREF##9##13##–##UREF##10##14##].</p> <p>Cycloaddition kinetics of <bold>1a</bold> and <bold>2a</bold> was examined first by <sup>1</sup>H NMR in CD<sub>2</sub>Cl<sub>2</sub> at room temperature. In the absence of catalyst, no product could be observed after 4 days. 5 mol% of the bisamidinium salt <bold>8a</bold>·H<sup>+</sup> with tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (TFPB<sup>-</sup>) as weakly coordinating anion resulted in 7% yield of <bold>3a</bold> after 4 h. In contrast, only 1 mol% of the free Brønsted base <bold>8a</bold> led to a high rate increase in the first 30 min. After 90 min no further conversion was observed indicating product inhibition (##FIG##3##Figure 1##). Accordingly, the reaction runs best in the base-catalyzed mode. Compared to the bisoxazolines <bold>7</bold>, bisamidines <bold>8</bold> as stronger Brønsted bases induced much higher rates in all subsequent experiments.</p> <p>In the next series of experiments, bisamidines <bold>8a</bold>–<bold>c</bold> and <italic>ent</italic>-<bold>8d</bold> were compared as catalysts of the cycloaddition forming <bold>3a</bold> from <italic>N</italic>-phenylmaleimide (<bold>2a</bold>) and anthrone (<bold>1a</bold>). Using 0.25 equiv of catalyst at room temperature, isolated yields between 71% and 86% were obtained after 30 min. The best enantioselectivity, albeit low, was induced by amidine <bold>8c</bold> (24% <italic>ee</italic>). As expected, in the presence of catalyst <italic>ent</italic>-<bold>8d</bold> product <italic>ent</italic>-<bold>3a</bold> was formed preferentially (##TAB##0##Table 1##).</p> <p>In a solvent screening using 10 mol% of TBDPS-protected bisamidine <bold>8c</bold>, best results were obtained in dichloromethane (84% yield; 30% <italic>ee</italic>). Even higher yields were accessible in aromatic solvents, however, at the price of reduced stereoselectivity (##TAB##1##Table 2##).</p> <p>Lowering the reaction temperature from 23 to −20 °C (<bold>8c</bold>, dichloromethane) retarded the cycloaddition but did not change enantioselectivities. After extended reaction times, excellent yields were still observed. Up to 39% <italic>ee</italic> was finally obtained at −70 °C. However, such conditions resulted in lower yields, even with increased catalyst loads and further extended reaction times. Best results, 96% yield and 36% <italic>ee</italic> with only 10 mol% of catalyst, were found at −40 °C (##TAB##2##Table 3##).</p> <p>Having identified suitable experimental conditions, we explored the scope of the bisamidine-catalyzed Diels-Alder reaction. The results are summarized in ##TAB##3##Table 4##. Both electron-donating and electron-withdrawing substituents were tolerated and furnished products in good to excellent yields and with moderate values of <italic>ee</italic>. A remarkable increase in enantioselectivity was observed using maleimide <bold>2i</bold>. The steric hindrance imposed by the large 2,6-diisopropylphenyl moiety of <bold>2i</bold> resulted in 76% <italic>ee</italic> at −70 °C but also lowered reaction rates.</p> <p>Only 13% yield could be obtained under such conditions. Yields rose to 65% at room temperature (51% <italic>ee</italic>; entries 11 and 12). With other sterically hindered dienophiles such as <italic>N</italic>-<italic>tert</italic>-butylmaleimide (<bold>2c</bold>), the level of <italic>ee</italic> remained low (entry 4). The halogen-substituted anthrones <bold>1b</bold>–<bold>c</bold> did not react with <bold>2i</bold> at −70 °C. At room temperature, however, <bold>1b</bold> and <bold>2i</bold> were efficiently transformed into <bold>3m</bold> by catalyst <bold>8a</bold> with 76% yield and 54% <italic>ee</italic>. A single recrystallisation step afforded an almost enantiopure product (96% <italic>ee</italic>). The <italic>R</italic>,<italic>R</italic> configuration of compound <bold>3m</bold> was determined by anomalous X-ray diffraction using a single crystal of <bold>3m</bold> with 96% <italic>ee</italic> (##FIG##4##Figure 2##).</p> <p>A mechanistic rationalisation is proposed in ##FIG##5##Scheme 4##. The catalyst deprotonates the anthrone in the initial step. This assumption is supported by the p<italic>K</italic><sub>a</sub> values of compounds <bold>2a</bold> (10, [##UREF##4##7##–##UREF##5##8##]) and <bold>8</bold>·H<sup>+</sup> (~11, [##REF##17585816##6##]). Furthermore, the appearance of the yellow color of enolates (<bold>1</bold>·H<sup>+</sup>) shows significant proton transfer when bisamidine <bold>8a</bold> is added to anthrones <bold>1a</bold>, <bold>1b</bold>, or <bold>1c</bold>. A chiral contact ion pair <bold>A</bold> is formed and controls the stereochemical course of the Diels-Alder reaction with maleimides. In the last step, the catalyst-product-complex <bold>B</bold> dissociates and regenerates the unprotonated bisamidine.</p>
<title>Results and Discussion</title> <p>Analogous to the synthesis of compound <bold>8a</bold> [##REF##17585816##6##], the other bisamidines were prepared as hydrochlorides in 60–79% yield from the corresponding chiral diamines <bold>9</bold> and bisimidate <bold>10</bold> in refluxing ethanol. Simple extraction in the presence of Na<sub>2</sub>CO<sub>3</sub> afforded the neutral bases <bold>8b</bold>–<bold>c</bold> and <italic>ent-</italic><bold>8d</bold> in almost quantitative yield. The <italic>S</italic>,<italic>S</italic> configurated diamines <bold>9b</bold> and <bold>9c</bold> were prepared from L-(+)-tartaric acid (<italic>R,R</italic>) via the vicinal diazide using Saalfrank's procedure [##UREF##6##9##]. <bold>9d</bold> was purchased as the dihydrochloride salt and then deprotonated by aqueous sodium hydroxide. As an “artefact” of the sequence rule, the <italic>S</italic>,<italic>S</italic> configurated diamine <bold>9d</bold> leads to bisamidine <italic>ent</italic>-<bold>8d</bold> (##FIG##2##Scheme 3##).</p> <p>The anthrones <bold>1b</bold> (R<sup>1</sup>: H; R<sup>2</sup>: Cl) and <bold>1c</bold> (R<sup>1</sup>: Cl; R<sup>2</sup>: H) resulted from regioselective reductions of 1,8-dichloroanthraquinone [##UREF##7##10##–##REF##11667122##11##]. Aliphatic side chains of compounds <bold>2</bold> could be introduced by a Mitsunobu alkylation of maleimide [##UREF##8##12##]. Alternatively, substituted maleimides were prepared by reaction of maleic anhydride with the corresponding amines followed by ring closure [##UREF##9##13##–##UREF##10##14##].</p> <p>Cycloaddition kinetics of <bold>1a</bold> and <bold>2a</bold> was examined first by <sup>1</sup>H NMR in CD<sub>2</sub>Cl<sub>2</sub> at room temperature. In the absence of catalyst, no product could be observed after 4 days. 5 mol% of the bisamidinium salt <bold>8a</bold>·H<sup>+</sup> with tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (TFPB<sup>-</sup>) as weakly coordinating anion resulted in 7% yield of <bold>3a</bold> after 4 h. In contrast, only 1 mol% of the free Brønsted base <bold>8a</bold> led to a high rate increase in the first 30 min. After 90 min no further conversion was observed indicating product inhibition (##FIG##3##Figure 1##). Accordingly, the reaction runs best in the base-catalyzed mode. Compared to the bisoxazolines <bold>7</bold>, bisamidines <bold>8</bold> as stronger Brønsted bases induced much higher rates in all subsequent experiments.</p> <p>In the next series of experiments, bisamidines <bold>8a</bold>–<bold>c</bold> and <italic>ent</italic>-<bold>8d</bold> were compared as catalysts of the cycloaddition forming <bold>3a</bold> from <italic>N</italic>-phenylmaleimide (<bold>2a</bold>) and anthrone (<bold>1a</bold>). Using 0.25 equiv of catalyst at room temperature, isolated yields between 71% and 86% were obtained after 30 min. The best enantioselectivity, albeit low, was induced by amidine <bold>8c</bold> (24% <italic>ee</italic>). As expected, in the presence of catalyst <italic>ent</italic>-<bold>8d</bold> product <italic>ent</italic>-<bold>3a</bold> was formed preferentially (##TAB##0##Table 1##).</p> <p>In a solvent screening using 10 mol% of TBDPS-protected bisamidine <bold>8c</bold>, best results were obtained in dichloromethane (84% yield; 30% <italic>ee</italic>). Even higher yields were accessible in aromatic solvents, however, at the price of reduced stereoselectivity (##TAB##1##Table 2##).</p> <p>Lowering the reaction temperature from 23 to −20 °C (<bold>8c</bold>, dichloromethane) retarded the cycloaddition but did not change enantioselectivities. After extended reaction times, excellent yields were still observed. Up to 39% <italic>ee</italic> was finally obtained at −70 °C. However, such conditions resulted in lower yields, even with increased catalyst loads and further extended reaction times. Best results, 96% yield and 36% <italic>ee</italic> with only 10 mol% of catalyst, were found at −40 °C (##TAB##2##Table 3##).</p> <p>Having identified suitable experimental conditions, we explored the scope of the bisamidine-catalyzed Diels-Alder reaction. The results are summarized in ##TAB##3##Table 4##. Both electron-donating and electron-withdrawing substituents were tolerated and furnished products in good to excellent yields and with moderate values of <italic>ee</italic>. A remarkable increase in enantioselectivity was observed using maleimide <bold>2i</bold>. The steric hindrance imposed by the large 2,6-diisopropylphenyl moiety of <bold>2i</bold> resulted in 76% <italic>ee</italic> at −70 °C but also lowered reaction rates.</p> <p>Only 13% yield could be obtained under such conditions. Yields rose to 65% at room temperature (51% <italic>ee</italic>; entries 11 and 12). With other sterically hindered dienophiles such as <italic>N</italic>-<italic>tert</italic>-butylmaleimide (<bold>2c</bold>), the level of <italic>ee</italic> remained low (entry 4). The halogen-substituted anthrones <bold>1b</bold>–<bold>c</bold> did not react with <bold>2i</bold> at −70 °C. At room temperature, however, <bold>1b</bold> and <bold>2i</bold> were efficiently transformed into <bold>3m</bold> by catalyst <bold>8a</bold> with 76% yield and 54% <italic>ee</italic>. A single recrystallisation step afforded an almost enantiopure product (96% <italic>ee</italic>). The <italic>R</italic>,<italic>R</italic> configuration of compound <bold>3m</bold> was determined by anomalous X-ray diffraction using a single crystal of <bold>3m</bold> with 96% <italic>ee</italic> (##FIG##4##Figure 2##).</p> <p>A mechanistic rationalisation is proposed in ##FIG##5##Scheme 4##. The catalyst deprotonates the anthrone in the initial step. This assumption is supported by the p<italic>K</italic><sub>a</sub> values of compounds <bold>2a</bold> (10, [##UREF##4##7##–##UREF##5##8##]) and <bold>8</bold>·H<sup>+</sup> (~11, [##REF##17585816##6##]). Furthermore, the appearance of the yellow color of enolates (<bold>1</bold>·H<sup>+</sup>) shows significant proton transfer when bisamidine <bold>8a</bold> is added to anthrones <bold>1a</bold>, <bold>1b</bold>, or <bold>1c</bold>. A chiral contact ion pair <bold>A</bold> is formed and controls the stereochemical course of the Diels-Alder reaction with maleimides. In the last step, the catalyst-product-complex <bold>B</bold> dissociates and regenerates the unprotonated bisamidine.</p>
<title>Conclusion</title> <p><italic>C</italic><sub>2</sub>-symmetric bisamidines were shown to be potent chiral Brønsted base catalysts for the Diels-Alder reaction of <italic>N</italic>-substituted maleimides and anthrones. Compared to bisoxazolines <bold>7</bold>, much shorter reaction times under comparable conditions were sufficient with the more basic bisamidine catalysts <bold>8</bold> (~50-fold [##UREF##3##5##]). The higher intrinsic reactivity of the bisamidines allowed to run the reactions at lower temperatures. In both groups of catalysts, the phenyl substituted species induced the lowest enantioselectivities. Bisamidine <bold>8a</bold> performed better than the corresponding bisoxazoline. Increasing the size of substituents in catalysts <bold>8b</bold>–<bold>d</bold> also improved stereoselectivities, but not to high levels. This may be due to the flexible nature of the substituents present in bisamidines <bold>8b</bold> and <bold>8c</bold>. It is instructive, therefore, to compare with the bisoxazolines <bold>7</bold>. By far the best enantioselectivities were observed in this series with the <italic>t</italic>-Bu derivative (47% <italic>ee</italic> versus 3% for the phenyl analogue in the reaction of <bold>1a</bold> and <bold>2a</bold>). Keeping in mind that even the less selective bisamidine <bold>8a</bold> could induce up to 76% <italic>ee</italic> in favorable cases, replacing the phenyl moieties of <bold>8a</bold> by <italic>t</italic>-Bu is an attractive option for future studies on bisamidine-mediated organocatalytic transformations.</p>
<p><italic>C</italic><sub>2</sub>-symmetric bisamidines <bold>8</bold> have been tested as chiral Brønsted bases in the Diels-Alder reaction of anthrones and <italic>N</italic>-substituted maleimides. High yields of cycloadducts and significant asymmetric inductions up to 76% <italic>ee</italic> are accessible. The proposed mechanism involves proton transfer between anthrone and bisamidine, association of the resulting ions and finally a cycloaddition step stereoselectively controlled by the chiral ion pair.</p>
<title>Supporting Information</title>
<p>Financial support provided by the DFG (Priority Program “Organocatalysis” SPP1179) and by the FAZIT STIFTUNG is gratefully acknowledged.</p>
<fig id="C1" position="float"><label>Scheme 1</label><caption><p>Diels-Alder reaction of anthrones <bold>1</bold> and maleimides <bold>2</bold> catalyzed by chiral Brønsted bases <bold>4</bold>–<bold>8</bold>.</p></caption></fig> <fig id="C2" position="float"><label>Scheme 2</label><caption><p>Protonation states and tautomerism of <italic>C</italic><sub>2</sub>-symmetric bisamidine <bold>8a</bold> [##REF##17585816##6##].</p></caption></fig> <fig id="C3" position="float"><label>Scheme 3</label><caption><p>Synthesis of <italic>C</italic><sub>2</sub>-symmetric bisamidines <bold>8b</bold>–<bold>c</bold> and <italic>ent</italic>-<bold>8d</bold>.</p></caption></fig> <fig id="F1" position="float"><label>Figure 1</label><caption><p>Kinetic measurements of <bold>1a</bold> with <bold>2a</bold> catalyzed by 5 mol% of <bold>8a</bold>·H<sup>+</sup>·TFPB<sup>-</sup> (black line) and 1 mol% <bold>8a</bold> (free base; red line).</p></caption></fig> <fig id="F2" position="float"><label>Figure 2</label><caption><p>Molecular structure of <bold>3m</bold> (C: black; N: blue; O: red; Cl: green; hydrogen atoms are omitted for the sake of clarity).</p></caption></fig> <fig id="C4" position="float"><label>Scheme 4</label><caption><p>Proposed mechanism of the Diels-Alder reaction.</p></caption></fig>
<table-wrap id="T1" position="float"><label>Table 1</label><caption><p>First evaluation step of chiral bisamidine catalysts.</p></caption><table frame="hsides" rules="groups"><tr><td align="center" colspan="4" valign="middle" rowspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">entry<sup>a</sup></td><td align="right" valign="middle" rowspan="1" colspan="1">catalyst</td><td align="right" valign="middle" rowspan="1" colspan="1">yield [%]<sup>b</sup></td><td align="right" valign="middle" rowspan="1" colspan="1"><italic>ee</italic> [%]<sup>c</sup></td></tr><tr><td align="left" colspan="4" valign="middle" rowspan="1"><hr/></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">1</td><td align="right" valign="middle" rowspan="1" colspan="1"><bold>8a</bold></td><td align="right" valign="middle" rowspan="1" colspan="1">86</td><td align="right" valign="middle" rowspan="1" colspan="1">11</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">2</td><td align="right" valign="middle" rowspan="1" colspan="1"><bold>8b</bold></td><td align="right" valign="middle" rowspan="1" colspan="1">78</td><td align="right" valign="middle" rowspan="1" colspan="1">17</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">3</td><td align="right" valign="middle" rowspan="1" colspan="1"><bold>8c</bold></td><td align="right" valign="middle" rowspan="1" colspan="1">85</td><td align="right" valign="middle" rowspan="1" colspan="1">24</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4</td><td align="right" valign="middle" rowspan="1" colspan="1"><italic>ent</italic>-<bold>8d</bold></td><td align="right" valign="middle" rowspan="1" colspan="1">71</td><td align="right" valign="middle" rowspan="1" colspan="1">−17<sup>d</sup></td></tr></table></table-wrap> <table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Influence of the solvent on the bisamidine catalyzed Diels-Alder reaction.</p></caption><table frame="hsides" rules="groups"><tr><td align="left" valign="middle" rowspan="1" colspan="1">entry<sup>a</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">solvent</td><td align="right" valign="middle" rowspan="1" colspan="1">yield [%]<sup>b</sup></td><td align="right" valign="middle" rowspan="1" colspan="1"><italic>ee</italic> [%]<sup>c</sup></td></tr><tr><td align="left" colspan="4" valign="middle" rowspan="1"><hr/></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">1</td><td align="left" valign="middle" rowspan="1" colspan="1">dichloromethane</td><td align="right" valign="middle" rowspan="1" colspan="1">84</td><td align="right" valign="middle" rowspan="1" colspan="1">30</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">2</td><td align="left" valign="middle" rowspan="1" colspan="1">chloroform</td><td align="right" valign="middle" rowspan="1" colspan="1">86</td><td align="right" valign="middle" rowspan="1" colspan="1">18</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">3</td><td align="left" valign="middle" rowspan="1" colspan="1">benzene</td><td align="right" valign="middle" rowspan="1" colspan="1">98</td><td align="right" valign="middle" rowspan="1" colspan="1">21</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4</td><td align="left" valign="middle" rowspan="1" colspan="1">toluene</td><td align="right" valign="middle" rowspan="1" colspan="1">99</td><td align="right" valign="middle" rowspan="1" colspan="1">16</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">5</td><td align="left" valign="middle" rowspan="1" colspan="1">α,α,α-trifluorotoluene</td><td align="right" valign="middle" rowspan="1" colspan="1">99</td><td align="right" valign="middle" rowspan="1" colspan="1">13</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">6</td><td align="left" valign="middle" rowspan="1" colspan="1">dibutyl ether</td><td align="right" valign="middle" rowspan="1" colspan="1">89</td><td align="right" valign="middle" rowspan="1" colspan="1">11</td></tr></table></table-wrap> <table-wrap id="T3" position="float"><label>Table 3</label><caption><p>Influence of temperature on the Diels-Alder reaction.</p></caption><table frame="hsides" rules="groups"><tr><td align="left" valign="middle" rowspan="1" colspan="1">entry<sup>a</sup></td><td align="right" valign="middle" rowspan="1" colspan="1">reaction temperature [°C]</td><td align="right" valign="middle" rowspan="1" colspan="1">reaction time [h]</td><td align="right" valign="middle" rowspan="1" colspan="1">yield [%]<sup>b</sup></td><td align="right" valign="middle" rowspan="1" colspan="1"><italic>ee</italic> [%]<sup>c</sup></td></tr><tr><td align="left" colspan="5" valign="middle" rowspan="1"><hr/></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">1</td><td align="right" valign="middle" rowspan="1" colspan="1">23</td><td align="right" valign="middle" rowspan="1" colspan="1">1</td><td align="right" valign="middle" rowspan="1" colspan="1">84</td><td align="right" valign="middle" rowspan="1" colspan="1">30</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">2</td><td align="right" valign="middle" rowspan="1" colspan="1">0</td><td align="right" valign="middle" rowspan="1" colspan="1">24</td><td align="right" valign="middle" rowspan="1" colspan="1">96</td><td align="right" valign="middle" rowspan="1" colspan="1">29</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">3</td><td align="right" valign="middle" rowspan="1" colspan="1">−20</td><td align="right" valign="middle" rowspan="1" colspan="1">24</td><td align="right" valign="middle" rowspan="1" colspan="1">98</td><td align="right" valign="middle" rowspan="1" colspan="1">31</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4</td><td align="right" valign="middle" rowspan="1" colspan="1">−40</td><td align="right" valign="middle" rowspan="1" colspan="1">48</td><td align="right" valign="middle" rowspan="1" colspan="1">96</td><td align="right" valign="middle" rowspan="1" colspan="1">36</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">5</td><td align="right" valign="middle" rowspan="1" colspan="1">−70</td><td align="right" valign="middle" rowspan="1" colspan="1">96</td><td align="right" valign="middle" rowspan="1" colspan="1">71</td><td align="right" valign="middle" rowspan="1" colspan="1">39</td></tr></table></table-wrap> <table-wrap id="T4" position="float"><label>Table 4</label><caption><p>Scope of the Diels-Alder-reaction.</p></caption><table frame="hsides" rules="groups"><tr><td align="center" colspan="7" valign="middle" rowspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">entry<sup>a</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1</bold> [R<sup>1</sup>, R<sup>2</sup>]</td><td align="left" valign="middle" rowspan="1" colspan="1">R<sup>3</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">condition<sup>b</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">yield [%]<sup>c</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>ee</italic> [%]<sup>d</sup></td></tr><tr><td align="left" colspan="7" valign="middle" rowspan="1"><hr/></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">1</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold> [H, H,]</td><td align="left" valign="middle" rowspan="1" colspan="1">Ph (<bold>2a</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">A</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">96</td><td align="left" valign="middle" rowspan="1" colspan="1">36</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">2</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1b</bold> [H, Cl]</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">A</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3b</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">95</td><td align="left" valign="middle" rowspan="1" colspan="1">41</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">3</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">iPr (<bold>2b</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3c</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">74</td><td align="left" valign="middle" rowspan="1" colspan="1">26</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>t</italic>-Bu (<bold>2c</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3d</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">45</td><td align="left" valign="middle" rowspan="1" colspan="1">30</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">5</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">Cy (<bold>2d</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3e</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">83</td><td align="left" valign="middle" rowspan="1" colspan="1">42</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">6</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1c</bold> [Cl, H]</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2d</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3f</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">90</td><td align="left" valign="middle" rowspan="1" colspan="1">19</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">7</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">Bn (<bold>2e</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">A</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3g</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">95</td><td align="left" valign="middle" rowspan="1" colspan="1">20</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">8</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">CHPh<sub>2</sub> (<bold>2f</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">A</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3h</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">85</td><td align="left" valign="middle" rowspan="1" colspan="1">26</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">9</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">4-Br-(C<sub>6</sub>H<sub>4</sub>)- (<bold>2g</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3i</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">70</td><td align="left" valign="middle" rowspan="1" colspan="1">13</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">10</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">4-MeO-(C<sub>6</sub>H<sub>4</sub>)- (<bold>2h</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">A</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3j</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">82</td><td align="left" valign="middle" rowspan="1" colspan="1">32</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">11</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">2,6-iPr<sub>2</sub>-(C<sub>6</sub>H<sub>3</sub>)- (<bold>2i</bold>)</td><td align="left" valign="middle" rowspan="1" colspan="1">B</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3k</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">13</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>76</bold></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">12</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2i</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3k</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">65</td><td align="left" valign="middle" rowspan="1" colspan="1">51</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">13</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1c</bold></td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2i</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3l</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">77</td><td align="left" valign="middle" rowspan="1" colspan="1">34</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">14</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1b</bold></td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2i</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>3m</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">76</td><td align="left" valign="middle" rowspan="1" colspan="1">54 (<bold>96</bold>)<sup>e</sup></td></tr></table></table-wrap>
<supplementary-material content-type="local-data" id="SD1"><label>File 1</label><caption><p>Supporting information features characterisation data and copies of <sup>1</sup>H- and <sup>13</sup>C-NMR spectra of anthrones <bold>1</bold>, maleimides <bold>2</bold>, Diels-Alder adducts <bold>3</bold>, bisamidine hydrochlorides <bold>8b</bold>–<bold>d</bold>·H<sup>+</sup>·Cl<sup>-</sup>, neutral bisamidines <bold>8b</bold>–<bold>d</bold> and diamines <bold>9b</bold>–<bold>c</bold>, plus copies of chromatograms obtained with chiral columns.</p></caption></supplementary-material> <supplementary-material content-type="local-data" id="SD2"><label>File 2</label><caption><p>X-Ray data of compound <bold>3k</bold></p></caption></supplementary-material> <supplementary-material content-type="local-data" id="SD3"><label>File 3</label><caption><p>X-Ray data of compound <bold>3m</bold></p></caption></supplementary-material>
<table-wrap-foot><fn id="TFN1"><p><sup>a</sup>All reactions were carried out using 0.1 mmol maleimide <bold>2a</bold>, 1.1 equiv anthrone (<bold>1a</bold>) and 0.25 equiv of catalyst in 1 mL abs. dichloromethane at room temperature for 30 minutes. <sup>b</sup>Isolated yield after column chromatography. <sup>c</sup>The enantiomeric excess was determined by HPLC using a Chiralpak IA column. <sup>d</sup>A negative <italic>ee</italic> stands for an excess of <italic>ent</italic>-<bold>3a</bold>.</p></fn></table-wrap-foot> <table-wrap-foot><fn id="TFN2"><p><sup>a</sup>All reactions were carried out using 0.1 mmol maleimide <bold>2a</bold>, 1.1 equiv anthrone (<bold>1a</bold>) and 0.1 equiv of <bold>8c</bold> in 1 mL abs. solvent at room temperature for 60 minutes. <sup>b</sup>Isolated yield after column chromatography. <sup>c</sup>The enantiomeric excess was determined by HPLC using a Chiralpak IA column.</p></fn></table-wrap-foot> <table-wrap-foot><fn id="TFN3"><p><sup>a</sup>All reactions were carried out using 0.1 mmol maleimide <bold>2a</bold>, 1.1 equiv anthrone (<bold>1a</bold>) and 0.1 (entry 1–4) or 0.25 equiv (entry 5) of <bold>8c</bold> in 1 mL abs. dichloromethane. <sup>b</sup>Isolated yield after column chromatography. <sup>c</sup>Enantiomeric excess was determined by HPLC using Chiralpak IA column.</p></fn></table-wrap-foot> <table-wrap-foot><fn id="TFN4"><p><sup>a</sup>All reactions were carried out using 0.1 mmol maleimide, 1.1 equiv anthrone in 1 mL abs. CH<sub>2</sub>Cl<sub>2</sub>. <sup>b</sup>A = 10 mol% <bold>8c</bold>, −40 °C, 48 h; B = 25 mol% <bold>8a</bold>, −70 °C, 96 h; C = 25 mol% <bold>8a</bold>, r.t., 3 h. <sup>c</sup>Isolated yield after column chromatography. <sup>d</sup>The enantiomeric excess was determined by HPLC using a Chiralpak IA column. <sup>e</sup>Recrystallized from 2-propanol/<italic>n</italic>-hexane.</p></fn></table-wrap-foot>
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