DBFOX-Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

DBFOX-Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones Takehisa Ishimaru, Norio Shibata*, Dhande Sudhakar Reddy, Takao Horikawa, Shuichi Nakamura and Takeshi Toru* Preliminary Communication Address: Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan Email: Norio Shibata* - ; Takeshi Toru* Open Access Beilstein Journal of Organic Chemistry 2008, 4, No. 16. doi:10.3762/bjoc.4.16 Received: 06 February 2008 Accepted: 16 May 2008 Published: 20 May 2008 © 2008 Ishimaru et al; licensee Beilstein-Institut. License and terms: see end of document. * Corresponding author Keywords: fluorination; enantioselective; nickel; Lewis acid; catalyst Abstract We examined the catalytic enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones 1 with N-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 2 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(ClO4)2·6H2O (10 mol%) and 2,6-lutidine (0 or 1.0 equiv) in CH2Cl2. Background Enantioselective electrophilic fluorination represents an important and straightforward strategy for C-F bond formation at a carbon stereocenter, providing easy access to chiral fluoroorganic compounds [1,2]. Due to the significance of chiral fluoro-organic compounds, such as fluorinated quinolones [3,4] and liquid crystals [5], in pharmaceutical and material sciences considerable effort has been dedicated to this issue for decades [6-17]. 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 [18-32], chiral ligand/metal-catalyzed [33-57] or organocatalytic [58-64] 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 [37,39, 41,47], BINAPs [38,40,43,44,46,49,51,53,55-57] and bis(oxazoline) [33,34,36,42,45]. Of particular importance are Page 1 of 5 (page number not for citation purposes) Beilstein Journal of Organic Chemistry 2008, 4, No. 16. Results and Discussion Figure 1: Structures of DBFOX-Ph, Box-Ph and NFSI. 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 [38,40,43,51,53, 56,57]. They have also recently reported the enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with their extended catalytic system, NiCl2-BINAP/R3SiOTf-lutidine with high enantioselectivities [57]. This study is useful because, up until now, the fluorinated products obtained by Sodeoka's method have been prepared by diastereoselective methods [65-67]. Independently, our group has focused on the development of enantioselective fluorination and related reactions using bis(oxazoline) ligands, Box-Ph [(S,S)-2,2'-isopropylidene-bis(4phenyl-2-oxazoline)] and DBFOX-Ph [(R,R)-4,6-dibenzofurandiyl-2,2'-bis(4-phenyloxazoline)] [33,34,36]. As an extension of this study, we herein evaluate our DBFOX-Ph/metal catalysis for the enantioselective fluorination of 3-(2arylacetyl)-2-thiazolidinones with N-fluorobenzenesulfonimide (NFSI) (Figure 1). 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(ClO4)2·6H2O in CH2Cl2 at room temperature. Therefore, we first attempted the reaction of 1a with the same conditions and found that the desired fluorinated product 2a was obtained in 42% yield with 69% ee (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 2a 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 2a 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 2a was determined by comparing the optical rotation and HPLC analysis with the literature values [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(ClO4)2-DBFOX-Ph (unary system, entries 1 and 2) and Ni(ClO 4 ) 2 -DBFOX-Ph/lutidine (binary system, entries 3–6) are moderately effective in the enantioselective fluorination of 1a. According to the report by Sodeoka using their NiCl2-BINAP/R3SiOTf-lutidine (trinary system, up to 88% ee obtained), the reaction requires both R 3 SiOTf and Table 1: Optimisation of the Conditions for DBFOX-Ph/Ni(II)-Catalysed Enantioselective Fluorination of 3-(2-Phenylacetyl)-2-thiazolidinone (1a)a. Run Metal salt 2,6- Lutidine (equiv) Temp (°C) Time Yield (%) ee (%) 1 2 3 4 5 6 7 8b,c 9b Ni(ClO4)2·6H2O Ni(ClO4)2·6H2O Ni(ClO4)2·6H2O Ni(ClO4)2·6H2O Ni(ClO4)2·6H2O Ni(OAc)2·4H2O Zn(OAc)2 Cu(OTf)2 Ni(ClO4)2·6H2O none none 1.0 1.0 1.0 1.0 1.0 1.0 1.0 rt 40 rt 0 −20 rt rt 0 0 6d 4d 17 h 20 h 4d 4d 3d 2d 2d 42 62 87 90 24 55 NR NR 33 69 63 66 74 79 72 15d aFor detailed reaction conditions, see Supporting Information File 1. Enantioselectivity was determined by chiral HPLC analysis. The absolute config- uration of 2a was determined by comparison with the optical rotation and HPLC analysis in the literature [57]. NR: No reaction. b(S,S)-Box-Ph (11 mol%) was used instead of (R,R)-DBFOX-Ph. cEther was used as solvent. d(S)-2a was obtained. Page 2 of 5 (page number not for citation purposes) Beilstein Journal of Organic Chemistry 2008, 4, No. 16. Table 2: Enantioselective Fluorination Reaction of 3-(2-Arylacetyl)-2-thiazolidinones with NFSI Catalyzed by DBFOX-Ph/Ni(II)a. Entry 1 Ar 2 Time (h) Yield (%) ee (%) 1 2 3 4 5 6 7 8 9 10 11 1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k Ph C6H4-o-OMe C6H4-m-OMe C6H4-p-OMe C6H4-o-Me C6H4-m-Me C6H4-p-Me C6H4-p-F C6H4-p-Br 1-Naphthyl 2-Naphthyl 2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 2k 20 48 24 24 48 48 48 48 48 48 48 90 96 94 90 69 75 (...truncated)