<title>Background</title> <p>Enantioselective electrophilic fluorination represents an important and straightforward strategy for C-F bond formation at a carbon stereocenter, providing easy access to chiral fluoro-organic compounds [##UREF##0##1##–##UREF##1##2##]. Due to the significance of chiral fluoro-organic compounds, such as fluorinated quinolones [##REF##7932562##3##–##UREF##2##4##] and liquid crystals [##UREF##3##5##], in pharmaceutical and material sciences considerable effort has been dedicated to this issue for decades [##REF##15584697##6##–##REF##18197348##17##]. As a consequence, a variety of procedures have been developed to increase the yields and enantioselectivities of electrophilic fluorination reactions. Stoichiometric approaches based on cinchona alkaloid/Selectfluor® combinations [##UREF##12##18##–##UREF##22##32##], chiral ligand/metal-catalyzed [##UREF##23##33##–##UREF##40##57##] or organocatalytic [##REF##11843587##58##–##REF##16789058##64##] procedures for enantioselective fluorination are major advances in recent years. The discovery that chiral ligands/metals can catalyze electrophilic fluorination with conventional fluorinating reagents has had a large impact on synthetic organic chemistry, because of the availability of commonly used classes of ligands for asymmetric catalysis, such as, TADDOLs [##UREF##27##37##,##REF##12735758##39##,##REF##15071186##41##,##UREF##31##47##], BINAPs [##REF##12465951##38##,##REF##12943393##40##,##REF##16028916##43##–##UREF##29##44####REF##15932185##46##,##UREF##33##49##,##UREF##35##51##,##REF##17194106##53##,##UREF##38##55##–##UREF##40##57##] and bis(oxazoline) [##UREF##23##33##–##UREF##24##34####UREF##26##36##,##UREF##28##42##,##UREF##30##45##]. Of particular importance are BINAP ligands. Sodeoka et al. have used the latter ligands in asymmetric fluorination of a wide range of substrates, including β-keto esters, β-keto phosphonates, oxindoles [##REF##12465951##38##,##REF##12943393##40##,##REF##16028916##43##,##UREF##35##51##,##REF##17194106##53##,##UREF##39##56##–##UREF##40##57##]. They have also recently reported the enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with their extended catalytic system, NiCl<sub>2</sub>-BINAP/R<sub>3</sub>SiOTf-lutidine with high enantioselectivities [##UREF##40##57##]. This study is useful because, up until now, the fluorinated products obtained by Sodeoka's method have been prepared by diastereoselective methods [##UREF##45##65##–##UREF##47##67##]. Independently, our group has focused on the development of enantioselective fluorination and related reactions using bis(oxazoline) ligands, Box-Ph [(<italic>S</italic>,<italic>S</italic>)-2,2<sup>'</sup>-isopropylidene-bis(4-phenyl-2-oxazoline)] and DBFOX-Ph [(<italic>R</italic>,<italic>R</italic>)-4,6-dibenzofurandiyl-2,2'-bis(4-phenyloxazoline)] [##UREF##23##33##–##UREF##24##34####UREF##26##36##]. As an extension of this study, we herein evaluate our DBFOX-Ph/metal catalysis for the enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with N-fluorobenzenesulfonimide (NFSI) (##FIG##0##Figure 1##).</p>
<title>Results and Discussion</title> <p>Our previous studies of the DBFOX-Ph/Ni(II)-catalyzed enantioselective fluorination of β-keto esters have shown that the optimal reaction conditions require NFSI as the fluorine source and a catalytic amount of Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O in CH<sub>2</sub>Cl<sub>2</sub> at room temperature. Therefore, we first attempted the reaction of <bold>1a</bold> with the same conditions and found that the desired fluorinated product <bold>2a</bold> was obtained in 42% yield with 69% ee (##TAB##0##Table 1##, entry 1). The reaction at higher temperature (40 °C) improved the yield to 62% with slightly lower enantioselectivity (63% ee, entry 2). The reaction time in these experiments was shortened by the addition of 1 equiv of 2,6-lutidine and <bold>2a</bold> was obtained in 87% yield with 66% ee at room temperature (entry 3). Both yield and selectivity were improved to 90% and 74% ee when the reaction was performed at 0 °C (entry 4). The highest ee value of <bold>2a</bold> was obtained at −20 °C, but resulted in a decrease in yield (24%, 79% ee, entry 5). Changing the metal salts did not improve the results (entries 6 and 7). The absolute stereochemistry of <bold>2a</bold> was determined by comparing the optical rotation and HPLC analysis with the literature values [##UREF##40##57##]. Although the enantioselectivities are moderate to good in these examples (63–79% ee), the results are quite impressive because the fluorination proceeds even in the absence of base (entries 1 and 2). That is, both Ni(ClO<sub>4</sub>)<sub>2</sub>-DBFOX-Ph (unary system, entries 1 and 2) and Ni(ClO<sub>4</sub>)<sub>2</sub>-DBFOX-Ph/lutidine (binary system, entries 3–6) are moderately effective in the enantioselective fluorination of <bold>1a</bold>. According to the report by Sodeoka using their NiCl<sub>2</sub>-BINAP/R<sub>3</sub>SiOTf-lutidine (trinary system, up to 88% ee obtained), the reaction requires both R<sub>3</sub>SiOTf and lutidine [##UREF##40##57##]. They mentioned in the paper that a binary system consisting of Ni(OTf)<sub>2</sub>–binap complex and 2,6-lutidine failed to promote asymmetric fluorination. We also briefly attempted the fluorination of <bold>1a</bold> using the (<italic>S</italic>,<italic>S</italic>)-Box-Ph ligand instead of DBFOX-Ph. While the Box-Ph/Cu(OTf)<sub>2</sub> catalyst was not effective (run 8), the Box-Ph/Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O catalyst gave the desired product <bold>2a</bold> in 33% yield with low enantioselectivity (15% ee, entry 9).</p> <p>The DBFOX-Ph/Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O catalysis for fluorination showed high generality for various 3-(2-arylacetyl)-2-thiazolidinones <bold>1a</bold>–<bold>k</bold> in good to high yields with moderate to good enantioselectivities. The results are summarized in ##TAB##1##Table 2##. The fluorination reaction was not very sensitive to substitution in the position of the phenyl group and the desired products with methoxy or methyl groups at the <italic>o</italic>-, <italic>m</italic>-, or <italic>p</italic>-position of the benzene ring were obtained in 65–78% ee (entries 2–7). The reactions of fluoro or bromo-substituted <bold>1h</bold>, <bold>i</bold> and bulky-substituted <bold>1j</bold>, <bold>k</bold> afforded the desired products <bold>2h</bold>–<bold>k</bold> in good yields with slightly lower enantioselectivities (56–62% ee, entries 8–11).</p> <p>The <italic>R</italic>-enantioselection of <bold>2</bold> can be explained by assuming an octahedral complex coordinated with a water molecule for DBFOX-Ph/Ni(II)/<bold>1</bold> as shown in ##FIG##1##Scheme 1##. In the complex, the <italic>Si</italic> face is shielded by one of the phenyl groups of DBFOX-Ph so that NFSI approaches from the <italic>Re</italic> face of the substrates (##FIG##1##Scheme 1##). Since a major difference in ee values of <bold>2</bold> was not observed for the fluorination reaction of <bold>1</bold> with NFSI in the presence or absence of 2,6-lutidine (entries 1–3, ##TAB##0##Table 1##), 2,6-lutidine presumably just accelerates the tautomerization of <bold>1</bold> to its enol form.</p>
<title>Results and Discussion</title> <p>Our previous studies of the DBFOX-Ph/Ni(II)-catalyzed enantioselective fluorination of β-keto esters have shown that the optimal reaction conditions require NFSI as the fluorine source and a catalytic amount of Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O in CH<sub>2</sub>Cl<sub>2</sub> at room temperature. Therefore, we first attempted the reaction of <bold>1a</bold> with the same conditions and found that the desired fluorinated product <bold>2a</bold> was obtained in 42% yield with 69% ee (##TAB##0##Table 1##, entry 1). The reaction at higher temperature (40 °C) improved the yield to 62% with slightly lower enantioselectivity (63% ee, entry 2). The reaction time in these experiments was shortened by the addition of 1 equiv of 2,6-lutidine and <bold>2a</bold> was obtained in 87% yield with 66% ee at room temperature (entry 3). Both yield and selectivity were improved to 90% and 74% ee when the reaction was performed at 0 °C (entry 4). The highest ee value of <bold>2a</bold> was obtained at −20 °C, but resulted in a decrease in yield (24%, 79% ee, entry 5). Changing the metal salts did not improve the results (entries 6 and 7). The absolute stereochemistry of <bold>2a</bold> was determined by comparing the optical rotation and HPLC analysis with the literature values [##UREF##40##57##]. Although the enantioselectivities are moderate to good in these examples (63–79% ee), the results are quite impressive because the fluorination proceeds even in the absence of base (entries 1 and 2). That is, both Ni(ClO<sub>4</sub>)<sub>2</sub>-DBFOX-Ph (unary system, entries 1 and 2) and Ni(ClO<sub>4</sub>)<sub>2</sub>-DBFOX-Ph/lutidine (binary system, entries 3–6) are moderately effective in the enantioselective fluorination of <bold>1a</bold>. According to the report by Sodeoka using their NiCl<sub>2</sub>-BINAP/R<sub>3</sub>SiOTf-lutidine (trinary system, up to 88% ee obtained), the reaction requires both R<sub>3</sub>SiOTf and lutidine [##UREF##40##57##]. They mentioned in the paper that a binary system consisting of Ni(OTf)<sub>2</sub>–binap complex and 2,6-lutidine failed to promote asymmetric fluorination. We also briefly attempted the fluorination of <bold>1a</bold> using the (<italic>S</italic>,<italic>S</italic>)-Box-Ph ligand instead of DBFOX-Ph. While the Box-Ph/Cu(OTf)<sub>2</sub> catalyst was not effective (run 8), the Box-Ph/Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O catalyst gave the desired product <bold>2a</bold> in 33% yield with low enantioselectivity (15% ee, entry 9).</p> <p>The DBFOX-Ph/Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O catalysis for fluorination showed high generality for various 3-(2-arylacetyl)-2-thiazolidinones <bold>1a</bold>–<bold>k</bold> in good to high yields with moderate to good enantioselectivities. The results are summarized in ##TAB##1##Table 2##. The fluorination reaction was not very sensitive to substitution in the position of the phenyl group and the desired products with methoxy or methyl groups at the <italic>o</italic>-, <italic>m</italic>-, or <italic>p</italic>-position of the benzene ring were obtained in 65–78% ee (entries 2–7). The reactions of fluoro or bromo-substituted <bold>1h</bold>, <bold>i</bold> and bulky-substituted <bold>1j</bold>, <bold>k</bold> afforded the desired products <bold>2h</bold>–<bold>k</bold> in good yields with slightly lower enantioselectivities (56–62% ee, entries 8–11).</p> <p>The <italic>R</italic>-enantioselection of <bold>2</bold> can be explained by assuming an octahedral complex coordinated with a water molecule for DBFOX-Ph/Ni(II)/<bold>1</bold> as shown in ##FIG##1##Scheme 1##. In the complex, the <italic>Si</italic> face is shielded by one of the phenyl groups of DBFOX-Ph so that NFSI approaches from the <italic>Re</italic> face of the substrates (##FIG##1##Scheme 1##). Since a major difference in ee values of <bold>2</bold> was not observed for the fluorination reaction of <bold>1</bold> with NFSI in the presence or absence of 2,6-lutidine (entries 1–3, ##TAB##0##Table 1##), 2,6-lutidine presumably just accelerates the tautomerization of <bold>1</bold> to its enol form.</p>
<title>Conclusion</title> <p>This research has demonstrated that DBFOX-Ph/Ni(II) catalysis can be used for the catalytic enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with or without 2,6-lutidine to afford chiral 2-fluoro-2-arylacetate derivatives in good to high yields with moderate to good enantioselectivities of up to 78% ee. The Box-Ph ligand was not effective for this reaction. Our best ee value is slightly lower than that of Sodeoka's report [##UREF##40##57##]; this is presumably due to the low activity of our catalyst system which requires higher reaction temperature conditions (0 °C vs. −20 °C [##UREF##40##57##]). Racemization of the products <bold>2</bold> during the fluorination reaction was ruled out since no racemization was observed when <bold>2a</bold> was stirred overnight under the same fluorination conditions. Further studies to improve the enantioselectivity of DBFOX-Ph/metal catalysis in enantioselective fluorination are under way.</p>
<p>We examined the catalytic enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones <bold>1</bold> with <italic>N</italic>-fluorobenzenesulfonimide (NFSI) by DBFOX-Ph/metal complexes under a variety of conditions. After optimization of the metal salts, solvents and additives, we found that the fluoro-2-thiazolidinones <bold>2</bold> were obtained in good to high yields with moderate to good enantioselectivities (up to 78% ee) when the reaction was carried out in the presence of DBFOX-Ph (11 mol%), Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O (10 mol%) and 2,6-lutidine (0 or 1.0 equiv) in CH<sub>2</sub>Cl<sub>2</sub>.</p>
<title>Supporting Information</title>
<p>Support was provided by KAKENHI (19390029), by a Grant-in-Aid for Scientific Research on Priority Areas "Advanced Molecular Transformations of Carbon Resources" from the Ministry of Education, Culture, Sports, Science and Technology Japan (19020024).</p>
<fig id="F1" position="float"><label>Figure 1</label><caption><p>Structures of DBFOX-Ph, Box-Ph and NFSI.</p></caption></fig> <fig id="C1" position="float"><label>Scheme 1</label><caption><p>Transition-State Structure for the DBFOX-Ph/Ni(II) Catalyzed Enantioselective Fluorination of <bold>1</bold> to <bold>2</bold>.</p></caption></fig>
<table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Optimisation of the Conditions for DBFOX-Ph/Ni(II)-Catalysed Enantioselective Fluorination of 3-(2-Phenylacetyl)-2-thiazolidinone (<bold>1a</bold>)<sup>a</sup>.</p></caption><table frame="hsides" rules="groups"><tr><td align="left" colspan="7" valign="middle" rowspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Run</td><td align="center" valign="middle" rowspan="1" colspan="1">Metal salt</td><td align="center" valign="middle" rowspan="1" colspan="1">2,6- Lutidine (equiv)</td><td align="center" valign="middle" rowspan="1" colspan="1">Temp (°C)</td><td align="center" valign="middle" rowspan="1" colspan="1">Time</td><td align="center" valign="middle" rowspan="1" colspan="1">Yield (%)</td><td align="center" valign="middle" rowspan="1" colspan="1">ee (%)</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="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">none</td><td align="center" valign="middle" rowspan="1" colspan="1">rt</td><td align="center" valign="middle" rowspan="1" colspan="1">6 d</td><td align="center" valign="middle" rowspan="1" colspan="1">42</td><td align="center" valign="middle" rowspan="1" colspan="1">69</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">2</td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">none</td><td align="center" valign="middle" rowspan="1" colspan="1">40</td><td align="center" valign="middle" rowspan="1" colspan="1">4 d</td><td align="center" valign="middle" rowspan="1" colspan="1">62</td><td align="center" valign="middle" rowspan="1" colspan="1">63</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">3</td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">rt</td><td align="center" valign="middle" rowspan="1" colspan="1">17 h</td><td align="center" valign="middle" rowspan="1" colspan="1">87</td><td align="center" valign="middle" rowspan="1" colspan="1">66</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4</td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">0</td><td align="center" valign="middle" rowspan="1" colspan="1">20 h</td><td align="center" valign="middle" rowspan="1" colspan="1">90</td><td align="center" valign="middle" rowspan="1" colspan="1">74</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">5</td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">−20</td><td align="center" valign="middle" rowspan="1" colspan="1">4 d</td><td align="center" valign="middle" rowspan="1" colspan="1">24</td><td align="center" valign="middle" rowspan="1" colspan="1">79</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">6</td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(OAc)<sub>2</sub>·4H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">rt</td><td align="center" valign="middle" rowspan="1" colspan="1">4 d</td><td align="center" valign="middle" rowspan="1" colspan="1">55</td><td align="center" valign="middle" rowspan="1" colspan="1">72</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">Zn(OAc)<sub>2</sub></td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">rt</td><td align="center" valign="middle" rowspan="1" colspan="1">3 d</td><td align="center" valign="middle" rowspan="1" colspan="1">NR</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">8<sup>b,c</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">Cu(OTf)<sub>2</sub></td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">0</td><td align="center" valign="middle" rowspan="1" colspan="1">2 d</td><td align="center" valign="middle" rowspan="1" colspan="1">NR</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">9<sup>b</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">Ni(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0</td><td align="center" valign="middle" rowspan="1" colspan="1">0</td><td align="center" valign="middle" rowspan="1" colspan="1">2 d</td><td align="center" valign="middle" rowspan="1" colspan="1">33</td><td align="center" valign="middle" rowspan="1" colspan="1">15<sup>d</sup></td></tr></table></table-wrap> <table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Enantioselective Fluorination Reaction of 3-(2-Arylacetyl)-2-thiazolidinones with NFSI Catalyzed by DBFOX-Ph/Ni(II)<sup>a</sup>.</p></caption><table frame="hsides" rules="groups"><tr><td align="left" colspan="7" valign="middle" rowspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Entry</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">Ar</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Time (h)</td><td align="center" valign="middle" rowspan="1" colspan="1">Yield (%)</td><td align="center" valign="middle" rowspan="1" colspan="1">ee (%)</td></tr><tr><td align="left" colspan="7" valign="middle" rowspan="1"><hr/></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">1</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1a</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">Ph</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2a</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">20</td><td align="center" valign="middle" rowspan="1" colspan="1">90</td><td align="center" valign="middle" rowspan="1" colspan="1">74</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">2</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1b</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>o</italic>-OMe</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2b</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">96</td><td align="center" valign="middle" rowspan="1" colspan="1">78</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1c</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>m</italic>-OMe</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2c</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">24</td><td align="center" valign="middle" rowspan="1" colspan="1">94</td><td align="center" valign="middle" rowspan="1" colspan="1">66</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">4</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1d</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>p</italic>-OMe</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2d</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">24</td><td align="center" valign="middle" rowspan="1" colspan="1">90</td><td align="center" valign="middle" rowspan="1" colspan="1">65</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">5</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1e</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>o</italic>-Me</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2e</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">69</td><td align="center" valign="middle" rowspan="1" colspan="1">76</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">6</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1f</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>m</italic>-Me</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2f</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">75</td><td align="center" valign="middle" rowspan="1" colspan="1">73</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">7</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1g</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>p</italic>-Me</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2g</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">75</td><td align="center" valign="middle" rowspan="1" colspan="1">77</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">8</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1h</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>p</italic>-F</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2h</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">62</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">9</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1i</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">C<sub>6</sub>H<sub>4</sub>-<italic>p</italic>-Br</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2i</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">77</td><td align="center" valign="middle" rowspan="1" colspan="1">56</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">10</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1j</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">1-Naphthyl</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2j</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">85</td><td align="center" valign="middle" rowspan="1" colspan="1">59</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">11</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>1k</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">2-Naphthyl</td><td align="left" valign="middle" rowspan="1" colspan="1"><bold>2k</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">90</td><td align="center" valign="middle" rowspan="1" colspan="1">60</td></tr></table></table-wrap>
<supplementary-material content-type="local-data" id="SD1"><label>File 1</label><caption><p>Experimental methods. General methods, general procedure for the enantioselective catalytic fluorination, spectral data of <bold>2</bold>, copies of <sup>1</sup>H, <sup>13</sup>C and <sup>19</sup>F-NMRs and HPLC charts of <bold>2</bold></p></caption></supplementary-material>
<table-wrap-foot><fn id="TFN1"><p><bold><sup>a</sup></bold>For detailed reaction conditions, see ##SUPPL##0##Supporting Information File 1##. Enantioselectivity was determined by chiral HPLC analysis. The absolute configuration of <bold>2a</bold> was determined by comparison with the optical rotation and HPLC analysis in the literature [##UREF##40##57##]. NR: No reaction. <sup>b</sup>(<italic>S</italic>,<italic>S</italic>)-Box-Ph (11 mol%) was used instead of (<italic>R</italic>,<italic>R</italic>)-DBFOX-Ph. <sup>c</sup>Ether was used as solvent. <sup>d</sup>(<italic>S</italic>)-<bold>2a</bold> was obtained.</p></fn></table-wrap-foot> <table-wrap-foot><fn id="TFN2"><p><sup>a</sup>For detailed reaction conditions, see ##SUPPL##0##Supporting Information File 1##. Enantioselectivity was determined by chiral HPLC analysis. The absolute configuration of <bold>2a</bold> was determined by comparison with the optical rotation and HPLC analysis in the literature [##UREF##40##57##]. Others were tentatively assigned by comparing the signs of their optical rotations to that of <bold>2a</bold>.</p></fn></table-wrap-foot>
<graphic xlink:href="Beilstein_J_Org_Chem-04-16-g002"/> <inline-graphic xlink:href="Beilstein_J_Org_Chem-04-16-i001.jpg"/> <inline-graphic xlink:href="Beilstein_J_Org_Chem-04-16-i002.jpg"/> <graphic xlink:href="Beilstein_J_Org_Chem-04-16-g003"/>
<media mime-subtype="msword" mimetype="application" xlink:href="Beilstein_J_Org_Chem-04-16-s001.doc" xlink:type="simple" id="d39e1196" position="anchor"/>
[{"label": ["1"], "surname": ["Soloshonok"], "given-names": ["V A"], "source": ["Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Stereochemical Challenges and Biomedical Targets"], "year": ["1999"], "publisher-loc": ["Chichester"], "publisher-name": ["John Wiley & Sons"]}, {"label": ["2"], "surname": ["Kirsch"], "given-names": ["P"], "source": ["Modern Fluoroorganic Chemistry"], "year": ["2004"], "publisher-loc": ["Weinheim"], "publisher-name": ["Wiley-VCH"]}, {"label": ["4"], "surname": ["Takemura", "Takahashi", "Kawakami", "Namba", "Tanaka", "Miyauchi"], "given-names": ["M", "H", "K", "K", "M", "R"], "article-title": ["(Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan) Anti-acid fast bacterial agents containing pyridonecarboxylic acids as the active ingredient"], "source": ["European Patent Application EP"], "patent": ["1262477A1"], "year": ["2002"], "month": ["12"], "day": ["4"]}, {"label": ["5"], "surname": ["Kusumoto", "Hiyama", "Soloshonok"], "given-names": ["T", "T", "V A"], "article-title": ["Fluorine-Containing Chiral Liquid Crystals: Syntheses and Properties"], "source": ["Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Stereochemical Challenges and Biomedical Targets"], "year": ["1999"], "publisher-loc": ["Chichester"], "publisher-name": ["John Wiley & Sons"], "fpage": ["535"], "lpage": ["556"]}, {"label": ["7"], "surname": ["Ibrahim", "Togni"], "given-names": ["H", "A"], "source": ["Chem Commun"], "year": ["2004"], "fpage": ["1147"], "lpage": ["1155"], "pub-id": ["10.1039/b317004g"]}, {"label": ["8"], "surname": ["Oestreich"], "given-names": ["M"], "source": ["Angew Chem, Int Ed"], "year": ["2005"], "volume": ["44"], "fpage": ["2324"], "lpage": ["2327"], "pub-id": ["10.1002/anie.200500478"]}, {"label": ["9"], "surname": ["Pihko"], "given-names": ["P M"], "source": ["Angew Chem, Int Ed"], "year": ["2006"], "volume": ["45"], "fpage": ["544"], "lpage": ["547"], "pub-id": ["10.1002/anie.200502425"]}, {"label": ["11"], "surname": ["Hamashima", "Sodeoka"], "given-names": ["Y", "M"], "source": ["Synlett"], "year": ["2006"], "fpage": ["1467"], "lpage": ["1478"], "pub-id": ["10.1055/s-2006-941578"]}, {"label": ["12"], "surname": ["Shibata"], "given-names": ["N"], "source": ["J Synth Org Chem, Jpn"], "year": ["2006"], "volume": ["64"], "fpage": ["14"], "lpage": ["24"]}, {"label": ["13"], "surname": ["Shibata", "Ishimaru", "Nakamura", "Toru"], "given-names": ["N", "T", "S", "T"], "source": ["J Fluorine Chem"], "year": ["2007"], "volume": ["128"], "fpage": ["469"], "lpage": ["483"], "pub-id": ["10.1016/j.jfluchem.2006.12.014"]}, {"label": ["14"], "surname": ["Hamashima", "Sodeoka"], "given-names": ["Y", "M"], "source": ["J Synth Org Chem, Jpn"], "year": ["2007"], "volume": ["64"], "fpage": ["1099"], "lpage": ["1107"]}, {"label": ["15"], "surname": ["Brunet", "O'Hagan"], "given-names": ["V A", "D"], "source": ["Angew Chem, Int Ed"], "year": ["2008"], "volume": ["47"], "fpage": ["1179"], "lpage": ["1182"], "pub-id": ["10.1002/anie.200704700"]}, {"label": ["18"], "surname": ["Shibata", "Suzuki", "Takeuchi"], "given-names": ["N", "E", "Y"], "source": ["J Am Chem Soc"], "year": ["2000"], "volume": ["122"], "fpage": ["10728"], "lpage": ["10729"], "pub-id": ["10.1021/ja002732x"]}, {"label": ["21"], "surname": ["Shibata", "Ishimaru", "Nakamura", "Toru"], "given-names": ["N", "T", "M", "T"], "source": ["Synlett"], "year": ["2004"], "fpage": ["2509"], "lpage": ["2512"], "pub-id": ["10.1055/s-2004-834810"]}, {"label": ["22"], "surname": ["Fukuzumi", "Shibata", "Sugiura", "Nakamura", "Toru"], "given-names": ["T", "N", "M", "S", "T"], "source": ["J Fluorine Chem"], "year": ["2006"], "volume": ["127"], "fpage": ["548"], "lpage": ["551"], "pub-id": ["10.1016/j.jfluchem.2006.01.004"]}, {"label": ["24"], "surname": ["Mohar", "Baudoux", "Plaquevent", "Cahard"], "given-names": ["B", "J", "J-C", "D"], "source": ["Angew Chem, Int Ed"], "year": ["2001"], "volume": ["40"], "fpage": ["4214"], "lpage": ["4216"], "pub-id": ["10.1002/1521-3773(20011119)40:22<4214::AID-ANIE4214>3.0.CO;2-B"]}, {"label": ["25"], "surname": ["Cahard", "Audouard", "Plaquevent", "Toupet", "Roques"], "given-names": ["D", "C", "J-C", "L", "N"], "source": ["Tetrahedron Lett"], "year": ["2001"], "volume": ["42"], "fpage": ["1867"], "lpage": ["1869"], "pub-id": ["10.1016/S0040-4039(01)00017-X"]}, {"label": ["26"], "surname": ["Baudequin", "Plaquevent", "Audouard", "Cahard"], "given-names": ["C", "J-C", "C", "D"], "source": ["Green Chem"], "year": ["2002"], "volume": ["4"], "fpage": ["584"], "lpage": ["586"], "pub-id": ["10.1039/b208817g"]}, {"label": ["27"], "surname": ["Baudequin", "Loubassou", "Plaquevent", "Cahard"], "given-names": ["C", "J-F", "J-C", "D"], "source": ["J Fluorine Chem"], "year": ["2003"], "volume": ["122"], "fpage": ["189"], "lpage": ["193"], "pub-id": ["10.1016/S0022-1139(03)00085-X"]}, {"label": ["29"], "surname": ["Mohar", "Sterk", "Ferron", "Cahard"], "given-names": ["B", "D", "L", "D"], "source": ["Tetrahedron Lett"], "year": ["2005"], "volume": ["46"], "fpage": ["5029"], "lpage": ["5031"], "pub-id": ["10.1016/j.tetlet.2005.05.074"]}, {"label": ["30"], "surname": ["Greedy", "Paris", "Vidal", "Gouverneur"], "given-names": ["B", "J-M", "T", "V"], "source": ["Angew Chem, Int Ed"], "year": ["2003"], "volume": ["42"], "fpage": ["3291"], "lpage": ["3294"], "pub-id": ["10.1002/anie.200351405"]}, {"label": ["31"], "surname": ["Wang", "Wang", "Shi", "Tu", "Fan", "Wang", "Hu", "Zhang"], "given-names": ["M", "B M", "L", "Y Q", "C-A", "S H", "X D", "S Y"], "source": ["Chem Commun"], "year": ["2005"], "fpage": ["5580"], "lpage": ["5582"], "pub-id": ["10.1039/b510004f"]}, {"label": ["32"], "surname": ["Ram\u00edrez", "Huber", "Togni"], "given-names": ["J", "D P", "A"], "source": ["Synlett"], "year": ["2007"], "fpage": ["1143"], "lpage": ["1147"], "pub-id": ["10.1055/s-2007-973897"]}, {"label": ["33"], "surname": ["Shibata", "Ishimaru", "Nagai", "Kohno", "Toru"], "given-names": ["N", "T", "T", "J", "T"], "source": ["Synlett"], "year": ["2004"], "fpage": ["1703"], "lpage": ["1706"], "pub-id": ["10.1055/s-2004-829571"]}, {"label": ["34"], "surname": ["Shibata", "Kohno", "Takai", "Ishimaru", "Nakamura", "Toru", "Kanemasa"], "given-names": ["N", "J", "K", "T", "S", "T", "S"], "source": ["Angew Chem, Int Ed"], "year": ["2005"], "volume": ["44"], "fpage": ["4204"], "lpage": ["4207"], "pub-id": ["10.1002/anie.200501041"]}, {"label": ["35"], "surname": ["Shibata", "Yasui", "Nakamura", "Toru"], "given-names": ["N", "H", "S", "T"], "source": ["Synlett"], "year": ["2007"], "fpage": ["1153"], "lpage": ["1157"], "pub-id": ["10.1055/s-2007-977429"]}, {"label": ["36"], "surname": ["Reddy", "Shibata", "Nagai", "Nakamura", "Toru", "Kanemasa"], "given-names": ["D S", "N", "J", "S", "T", "S"], "source": ["Angew Chem, Int Ed"], "year": ["2008"], "volume": ["47"], "fpage": ["164"], "lpage": ["168"], "pub-id": ["10.1002/anie.200704093"]}, {"label": ["37"], "surname": ["Hintermann", "Togni"], "given-names": ["L", "A"], "source": ["Angew Chem, Int Ed"], "year": ["2000"], "volume": ["39"], "fpage": ["4359"], "lpage": ["4362"], "pub-id": ["10.1002/1521-3773(20001201)39:23<4359::AID-ANIE4359>3.0.CO;2-P"]}, {"label": ["42"], "surname": ["Ma", "Cahard"], "given-names": ["J-A", "D"], "source": ["Tetrahedron: Asymmetry"], "year": ["2004"], "volume": ["15"], "fpage": ["1007"], "lpage": ["1011"], "pub-id": ["10.1016/j.tetasy.2004.01.014"]}, {"label": ["44"], "surname": ["Kim", "Kim"], "given-names": ["H R", "D Y"], "source": ["Tetrahedron Lett"], "year": ["2005"], "volume": ["46"], "fpage": ["3115"], "lpage": ["3117"], "pub-id": ["10.1016/j.tetlet.2005.02.164"]}, {"label": ["45"], "surname": ["Bernardi", "J\u00f8rgensen"], "given-names": ["L", "K A"], "source": ["Chem Commun"], "year": ["2005"], "fpage": ["1324"], "lpage": ["1326"], "pub-id": ["10.1039/b415568h"]}, {"label": ["47"], "surname": ["Perseghini", "Massaccesi", "Liu", "Togni"], "given-names": ["M", "M", "Y", "A"], "source": ["Tetrahedron"], "year": ["2006"], "volume": ["62"], "fpage": ["7180"], "lpage": ["7190"], "pub-id": ["10.1016/j.tet.2005.12.071"]}, {"label": ["48"], "surname": ["Bonaccorsi", "Althaus", "Becker", "Togni", "Mezzetti"], "given-names": ["C", "M", "C", "A", "A"], "source": ["Pure Appl Chem"], "year": ["2006"], "volume": ["78"], "fpage": ["391"], "lpage": ["396"], "pub-id": ["10.1351/pac200678020391"]}, {"label": ["49"], "surname": ["Kim", "Kang", "Lee", "Mang", "Kim"], "given-names": ["S M", "Y K", "K S", "J Y", "D Y"], "source": ["Bull Korean Chem Soc"], "year": ["2006"], "volume": ["27"], "fpage": ["423"], "lpage": ["425"]}, {"label": ["50"], "surname": ["Suzuki", "Furuno", "Yokoyama", "Inanaga"], "given-names": ["S", "H", "Y", "J"], "source": ["Tetrahedron: Asymmetry"], "year": ["2006"], "volume": ["17"], "fpage": ["504"], "lpage": ["507"], "pub-id": ["10.1016/j.tetasy.2005.12.029"]}, {"label": ["51"], "surname": ["Hamashima", "Suzuki", "Takano", "Shimura", "Tsuchiya", "Moriya", "Goto", "Sodeoka"], "given-names": ["Y", "T", "H", "Y", "Y", "K", "T", "M"], "source": ["Tetrahedron"], "year": ["2006"], "volume": ["62"], "fpage": ["7168"], "lpage": ["7179"], "pub-id": ["10.1016/j.tet.2005.12.070"]}, {"label": ["52"], "surname": ["Althaus", "Becker", "Togni", "Mezzetti"], "given-names": ["M", "C", "A", "A"], "source": ["Organometallics"], "year": ["2007"], "volume": ["26"], "fpage": ["5902"], "lpage": ["5911"], "pub-id": ["10.1021/om700714u"]}, {"label": ["54"], "surname": ["Shibatomi", "Tsuzuki", "Nakata", "Sumikawa", "Iwasa"], "given-names": ["K", "Y", "S", "Y", "S"], "source": ["Synlett"], "year": ["2007"], "fpage": ["551"], "lpage": ["554"], "pub-id": ["10.1055/s-2007-970746"]}, {"label": ["55"], "surname": ["Kang", "Cho", "Kim", "Kim"], "given-names": ["Y K", "M J", "S M", "D Y"], "source": ["Synlett"], "year": ["2007"], "fpage": ["1135"], "lpage": ["1138"], "pub-id": ["10.1055/s-2007-977436"]}, {"label": ["56"], "surname": ["Moriya", "Hamashima", "Sodeoka"], "given-names": ["K", "Y", "M"], "source": ["Synlett"], "year": ["2007"], "fpage": ["1139"], "lpage": ["1142"], "pub-id": ["10.1055/s-2007-977437"]}, {"label": ["57"], "surname": ["Suzuki", "Hamashima", "Sodeoka"], "given-names": ["T", "Y", "M"], "source": ["Angew Chem, Int Ed"], "year": ["2007"], "volume": ["46"], "fpage": ["5435"], "lpage": ["5439"], "pub-id": ["10.1002/anie.200701071"]}, {"label": ["59"], "surname": ["Park", "Kim", "Joung", "Kim"], "given-names": ["E J", "H R", "C U", "D Y"], "source": ["Bull Korean Chem Soc"], "year": ["2004"], "volume": ["25"], "fpage": ["1451"], "lpage": ["1452"]}, {"label": ["60"], "surname": ["Enders", "H\u00fcttl"], "given-names": ["D", "M R M"], "source": ["Synlett"], "year": ["2005"], "fpage": ["991"], "lpage": ["993"], "pub-id": ["10.1055/s-2005-864813"]}, {"label": ["61"], "surname": ["Marigo", "Fielenbach", "Braunton", "Kj\u00e6rsgaard", "J\u00f8rgensen"], "given-names": ["M", "D", "A", "A", "K A"], "source": ["Angew Chem, Int Ed"], "year": ["2005"], "volume": ["44"], "fpage": ["3703"], "lpage": ["3706"], "pub-id": ["10.1002/anie.200500395"]}, {"label": ["62"], "surname": ["Steiner", "Mase", "Barbas"], "given-names": ["D D", "N", "C F"], "suffix": ["III"], "source": ["Angew Chem, Int Ed"], "year": ["2005"], "volume": ["44"], "fpage": ["3706"], "lpage": ["3710"], "pub-id": ["10.1002/anie.200500571"]}, {"label": ["65"], "surname": ["Davis", "Han"], "given-names": ["F A", "W"], "source": ["Tetrahedron Lett"], "year": ["1992"], "volume": ["33"], "fpage": ["1153"], "lpage": ["1156"], "pub-id": ["10.1016/S0040-4039(00)91883-5"]}, {"label": ["66"], "surname": ["Davis", "Qi"], "given-names": ["F A", "H"], "source": ["Tetrahedron Lett"], "year": ["1996"], "volume": ["37"], "fpage": ["4345"], "lpage": ["4348"], "pub-id": ["10.1016/0040-4039(96)00825-8"]}, {"label": ["67"], "surname": ["Davis", "Kasu"], "given-names": ["F A", "P V N"], "source": ["Tetrahedron Lett"], "year": ["1998"], "volume": ["39"], "fpage": ["6135"], "lpage": ["6138"], "pub-id": ["10.1016/S0040-4039(98)01296-9"]}]
Beilstein J Org Chem. 2008 May 20; 4:16