Catalytic Asymmetric Electrophilic α-Amination of α-Cyanoketones in the Presence of Chiral Palladium Complexes

Abstract

The catalytic enantioselective electrophilic α-amination promoted by chiral palladium complexes is described. Treatment of α-cyanoketones with azodicarboxylates as electrophilic amination reagents under mild reaction conditions afforded the corresponding α-amino α-cyanoketones with excellent enantiomeric excesses (81-95% ee).

Key words

electrophilic amination - asymmetric catalysis - chiral palladium catalysts - α-cyanoketones

References and Notes

• 1 Enders D. Shilvock JP. Chem. Soc. Rev.  2000,  29:  359 
• For reviews on α-amino acids, see:
• 2a Williams RM. Synthesis of Optically Active α-Amino Acids   Pergamon; Oxford: 1989. 
• 2b Duthaler RO. Tetrahedron  1994,  50:  1539 
• 2c Hanessian S. McNaughton-Smith G. Lombart H.-G. Lubell WD. Tetrahedron  1997,  53:  12789 
• 2d Arend M. Angew. Chem. Int. Ed.  1999,  38:  2873 
• 2e Kotha S. Acc. Chem. Res.  2003,  36:  342 
• 2f Maruoka K. Ooi T. Chem. Rev.  2003,  103:  3013 
• 3a Matier WL. Owens DA. Comer WT. Dietchman D. Ferguson HC. Seidehamel RJ. Young JR. J. Med. Chem.  1973,  16:  901 
• 3b Weinstock LM. Davis P. Handelsman B. Tull R. J. Org. Chem.  1967,  32:  2823 
• 4 Lucet D. Le Gall T. Mioskowski C. Angew. Chem. Int. Ed.  1998,  37:  2580 
• See, for example:
• 5a Sigman MS. Vachal P. Jacobsen EN. Angew. Chem. Int. Ed.  2000,  39:  1279 
• 5b Takamura M. Hamashima Y. Usuda H. Kanai M. Shibassaki M. Angew. Chem. Int. Ed.  2000,  39:  1650 
• 5c Corey EJ. Grogan MJ. Org. Lett.  1999,  1:  157 
• 5d Ishitani H. Komiyama S. Hasegawa Y. Kobayashi S. J. Am. Chem. Soc.  2000,  122:  762 
• 5e Ooi T. Uematsu Y. Maruoka K. J. Am. Chem. Soc.  2006,  128:  2548 
• For reviews on asymmetric α-amination reactions, see:
• 6a Genet J.-P. Greck C. Lavergne D. Modern Amination Methods   Ricci A. Wiley-VCH; Weinheim: 2000.  Chap. 3.
• 6b Greck C. Drouillat B. Thomassigng C. Eur. J. Org. Chem.  2004,  1377 
• 6c Erdik E. Tetrahedron  2004,  60:  8742 
• 6d Janey JM. Angew. Chem. Int. Ed.  2005,  44:  4292 
• For 1,3-dicarbonyl compounds, see:
• 7a Juhl K. Jørgensen KA. J. Am. Chem. Soc.  2002,  124:  2420 
• 7b Marigo M. Juhl K. Jørgensen KA. Angew. Chem. Int. Ed.  2003,  42:  1367 
• 7c Ma S. Jiao N. Zheng Z. Ma Z. Lu Z. Ye L. Deng Y. Chen G. Org. Lett.  2004,  6:  2193 
• 7d Pihko PM. Pohjakallio A. Synlett  2004,  2115 
• 7e Xu X. Yabuta T. Yuan P. Takemoto Y. Synlett  2006,  137 
• 7f Kang YK. Kim DY. Tetrahedron Lett.  2006,  47:  4565 
• 7g Terada M. Nakano M. Ube H. J. Am. Chem. Soc.  2006,  128:  16044 
• 7h Comelles J. Pericas A. Moreno-Manas M. Vallribera A. Drudis-Sole G. Lledos A. Parella T. Roglans A. Garcia-Grands S. Roces-Fernandez L. J. Org. Chem.  2007,  72:  2077 
• 7i Mashiko T. Hara K. Tanaka D. Fujiwara Y. Kumagai N. Shibasaki M. J. Am. Chem. Soc.  2007,  129:  11342 
• For β-ketophosphonates, see:
• 8a Kim SM. Kim HR. Kim DY. Org. Lett.  2005,  7:  2309 
• 8b Bernardi L. Zhuang W. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  5772 
• For α-cyanoacetates, see:
• 9a Saaby S. Bella M. Jørgensen KA. J. Am. Chem. Soc.  2004,  126:  8120 
• 9b Liu X. Li H. Deng L. Org. Lett.  2005,  7:  167 
• 9c Liu Y. Melgar-Fernandez R. Juaristi E. J. Org. Chem.  2007,  72:  1522 
• 9d Hasegawa Y. Watanabe M. Gridnev ID. Ikariya T. J. Am. Chem. Soc.  2008,  130:  2158 
• For catalytic asymmetric reactions of α-cyanoketones, see:
• 10a Wang Y. Liu X. Deng L. J. Am. Chem. Soc.  2006,  128:  3928 
• 10b Wang B. Wu F. Wang Y. Liu X. Deng L. J. Am. Chem. Soc.  2007,  129:  768 
• 10c Nojiri A. Kumagai N. Shibasaki M. J. Am. Chem. Soc.  2008,  130:  5630 
• 11a Kim DY. Park EJ. Org. Lett.  2002,  4:  545 
• 11b Kim DY. Choi YJ. Park HY. Joung CU. Koh KO. Mang JY. Jung K.-Y. Synth. Commun.  2003,  33:  435 
• 11c Park EJ. Kim MH. Kim DY. J. Org. Chem.  2004,  69:  6897 
• 11d Park EJ. Kim HR. Joung CW. Kim DY. Bull. Korean Chem. Soc.  2004,  25:  1451 
• 11e Kim DY. Huh SC. Bull. Korean Chem. Soc.  2004,  25:  347 
• 11f Kang YK. Cho MJ. Kim SM. Kim DY. Synlett  2007,  1135 
• 11g Cho MJ. Kang YK. Lee NR. Kim DY. Bull. Korean Chem. Soc.  2007,  28:  2191 
• 11h Kim SM. Kang YK. Cho MJ. Mang JY. Kim DY. Bull. Korean Chem. Soc.  2007,  28:  2435 
• 12a Fujii A. Hagiwara E. Sodeoka M. J. Am. Chem. Soc.  1999,  121:  5450 
• 12b Hamashima Y. Yagi K. Takano H. Tamas L. Sodeoka M. J. Am. Chem. Soc.  2002,  124:  14530 
• 12c Li K. Hii KK. Chem. Commun.  2003,  1132 
• 12d Li K. Horton PN. Hursthouse MB. Hii KK. J. Organomet. Chem.  2003,  665:  250 
• 12e Kim SM. Kim HR. Kim DY. Org. Lett.  2005,  7:  2309 
• 12f Kim HR. Kim DY. Tetrahedron Lett.  2005,  46:  3115 
• 12g Kim SM. Kang YK. Lee K. Mang JY. Kim DY. Bull. Korean Chem. Soc.  2006,  27:  423 
• 12h For an aquapal-ladium complex, see: Shimada T. Bajracharya GB. Yamamoto Y. Eur. J. Org. Chem.  2005,  59 ; and references cited therein
• 12i Vicente J. Arcas A. Coord. Chem. Rev.  2005,  249:  1135 
• 12j For Pd(II) chemistry, see: Tsuji J. Palladium Reagents and Catalysts: New Perspectives for 21st Century   John Willey and Sons; Chichester: 2004. 

13

General Procedure for the Amination of α-Cyanoketone
To a stirred solution of α-cyanoketone 3 (0.2 mmol) and catalyst 1a (BF₄) (9.6 mg, 0.01 mmol) in acetone (2 mL) was added tert-butyl azodicarboxylate (4d, 46 mg, 0.2 mmol) at r.t. The reaction mixture was stirred for 10 min to 20 h at r.t. The mixture was diluted with sat. NH₄Cl solution (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried over MgSO₄, filtered, concentrated, and purified by flash chromatography (EtOAc-hexane, 1:3) to afford the α-aminated α-cyano-ketone 5. 2-Aminated 2-Cyano-1-indanone 5a
[α]_D ^²² -21.5 (c 1.45, CHCl₃, 92% ee). ^¹H NMR (200 MHz, CDCl₃): δ = 7.90-7.82 (m, 1 H), 7.74-7.66 (m, 1 H), 7.56-7.43 (m, 2 H), 7.01 (br s, 1 H), 4.07-3.83 (m, 2 H), 1.62-1.22 (m, 18 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 190.1, 155.5, 149.3, 136.9, 136.6, 132.2, 128.6, 126.5, 125.9, 115.6, 84.3, 82.2, 68.4, 40.9, 28.2, 27.8. MS (MSI): m/z
(%) = 387 [M⁺], 356 (10), 332 (70), 275 (32), 232 (8), 213 (12), 188 (7.5), 158 (8). ESI-HRMS: m/z calcd for C₂₀H₂₅N₃O₅ [M]⁺: 387.1794; found: 387.1802. HPLC (hexane-i-PrOH, 8:2, 254 nm, 1.0 mL/min, Chiralpak AD column): t _R = 5.8 min (minor), t _R = 7.7 min (major).