Copper-Catalyzed Enantioselective Tandem Conjugate Addition/N-Nitroso Aldol Reaction

Yan-Jun Xu; Quan-Zhong Liu; Lin Dong

doi:10.1055/s-2007-968012

LETTER

Copper-Catalyzed Enantioselective Tandem Conjugate Addition/N-Nitroso Aldol Reaction

Yan-Jun Xu^a,b, Quan-Zhong Liu*^a, Lin Dong^b
^a College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002, P. R. of China
^b Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan Province and Union Laboratory of Asymmetric Synthesis, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China
e-Mail: quanzhongliu@cwnu.edu.cn;

Abstract

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Abstract

The first enantioselective tandem conjugate addition/N-nitroso aldol reaction catalyzed by copper and phosphoramidite is presented. The reactions proceeded smoothly furnishing the α-hydroxyamino carbonyl compounds in good yields with high enantioselectivity up to 95% ee.

Key words

tandem conjugate addition - N-nitroso aldol reaction - α-hydroxyamino carbonyl compounds - enantioselective - monophosphoramidite

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References

References and Notes

<A NAME="RW14706ST-1A">1a</A> Ho T.-L. Tandem Organic Reactions New York; Wiley: 1992.

<A NAME="RW14706ST-1B">1b</A> Tietze LF. Chem. Rev. 1996, 96: 115

<A NAME="RW14706ST-1C">1c</A> Nicolaou KC. Montagnon T. Snyder SA. Chem. Commun. 2003, 551

<A NAME="RW14706ST-2">2</A> Guo H.-C. Ma J.-A. Angew. Chem. Int. Ed. 2005, 44: 2

<A NAME="RW14706ST-3A">3a</A> Feringa BL. Acc. Chem. Res. 2000, 33: 346

<A NAME="RW14706ST-3B">3b</A> Krause N. Hoffmann-Röder A. Synthesis 2001, 171

<A NAME="RW14706ST-3C">3c</A> Alexakis A. Benhaim C. Eur. J. Org. Chem. 2002, 3221

<A NAME="RW14706ST-4A">4a</A> Alexakis A. In Transition Metal Catalysed Reactions Murahashi S.-I. Davies SG. IUPAC Blackwell Science; Oxford: 1999. p.303

<A NAME="RW14706ST-4B">4b</A> Ibuka T. Organocopper Reagents in Organic Synthesis Rose Press; Osaka: 2000.

<A NAME="RW14706ST-4C">4c</A> Krause N. Modern Organocopper Chemistry Wiley-VCH; Weinheim: 2002.

<A NAME="RW14706ST-4D">4d</A> Rathgeb X. March S. Alexakis A. J. Org. Chem. 2006, 71: 5737

<A NAME="RW14706ST-4E">4e</A> Li K. Alexakis A. Tetrahedron Lett. 2005, 46: 8019

<A NAME="RW14706ST-4F">4f</A> Li K. Alexakis A. Tetrahedron Lett. 2005, 46: 5823

For Co-catalyzed 1,4-addition/aldol and Michael cyclization, see:

<A NAME="RW14706ST-5A">5a</A> Baik T.-G. Luiz A.-L. Wang L.-C. Krische MJ. J. Am. Chem. Soc. 2001, 123: 5112

<A NAME="RW14706ST-5B">5b</A> Wang L.-C. Jang H.-Y. Roh Y. Schultz AJ. Wang X. Lynch V. Krische MJ. J. Am. Chem. Soc. 2002, 124: 9448

For Rh-catalyzed 1,4-addition/aldol cyclization, see:

<A NAME="RW14706ST-6A">6a</A> Jang H.-Y. Huddleston RR. Krische MJ. J. Am. Chem. Soc. 2002, 124: 15156

<A NAME="RW14706ST-6B">6b</A> Huddleston RR. Krische MJ. Org. Lett. 2003, 5: 1143

For PR₃-catalyzed 1,4-addition/Michael cyclization, see:

<A NAME="RW14706ST-7A">7a</A> Wang LC. Luiz A.-L. Agapiou K. Jang H.-Y. Krische MJ. J. Am. Chem. Soc. 2002, 124: 2402

<A NAME="RW14706ST-7B">7b</A> Agapiou K. Krische MJ. Org. Lett. 2003, 5: 1737

<A NAME="RW14706ST-8">8</A> For catalytic 1,4-addition/cycloallylation, see: Jellerichs BG. Kong J.-R. Krische MJ. J. Am. Chem. Soc. 2003, 125: 7758

<A NAME="RW14706ST-9">9</A> For Rh-catalyzed 1,4-addition/aldol cyclization, see: Cauble DF. Gipson JG. Krische MJ. J. Am. Chem. Soc. 2003, 125: 1110

<A NAME="RW14706ST-10A">10a</A> Feringa BL. Pineschi M. Arnold L. Imbos AR. de Vries AHM. Angew. Chem., Int. Ed. Engl. 1997, 36: 2620 ; Angew. Chem. 1997, 109, 2773

<A NAME="RW14706ST-10B">10b</A> Keller E. Maurer J. Naasz R. Schrader T. Meetsma A. Feringa BL. Tetrahedron: Asymmetry 1998, 9: 2409

<A NAME="RW14706ST-10C">10c</A> Arnold LA. Naasz R. Minnaard AJ. Feringa BL. J. Am. Chem. Soc. 2001, 123: 5841

<A NAME="RW14706ST-10D">10d</A> Mandoli A. Arnold LA. Salvadori P. Feringa BL. Tetrahedron: Asymmetry 2001, 12: 1929

<A NAME="RW14706ST-10E">10e</A> Arnold LA. Naasz RA. Minnaard J. Feringa BL. J. Org. Chem. 2002, 67: 7244

<A NAME="RW14706ST-11A">11a</A> Naasz R. Arnold LA. Pineschi M. Keller E. Feringa BL. J. Am. Chem. Soc. 1999, 121: 1104

<A NAME="RW14706ST-11B">11b</A> Pineschi M. Moro FD. Gini F. Minnaard AJ. Feringa BL. Chem. Commun. 2004, 1244

<A NAME="RW14706ST-12">12</A> Dijk EW. Panella L. Pinho P. Naasz R. Meetsma A. Minnaard AJ. Feringa BL. Tetrahedron 2004, 60: 9687

<A NAME="RW14706ST-13A">13a</A> Alexakis A. Trevitt GP. Bernardinelli G. J. Am. Chem. Soc. 2001, 123: 4358

<A NAME="RW14706ST-13B">13b</A> Knopff O. Alexakis A. Org. Lett. 2002, 4: 3835

<A NAME="RW14706ST-13C">13c</A> Alexakis A. March S. J. Org. Chem. 2002, 67: 8753

<A NAME="RW14706ST-14A">14a</A> Degrado SJ. Mizutani H. Hoveyda AH. J. Am. Chem. Soc. 2001, 123: 755

<A NAME="RW14706ST-14B">14b</A> Mizutani H. Degrado SJ. Hoveyda AH. J. Am. Chem. Soc. 2002, 124: 779

<A NAME="RW14706ST-15">15</A> Agapiou K. Cauble DF. Krische MJ. J. Am. Chem. Soc. 2004, 126: 4528

For the enantioselective nitroso aldol reaction and related papers, see:

<A NAME="RW14706ST-16A">16a</A> Momiyama N. Yamamoto H. J. Am. Chem. Soc. 2003, 125: 6038

<A NAME="RW14706ST-16B">16b</A> Momiyama N. Yamamoto H. J. Am. Chem. Soc. 2004, 126: 6498

<A NAME="RW14706ST-16C">16c</A> Momiyama N. Yamamoto H. J. Am. Chem. Soc. 2004, 126: 5360

<A NAME="RW14706ST-16D">16d</A> Momiyama N. Torii H. Saito S. Yamamoto H. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 5374

<A NAME="RW14706ST-16E">16e</A> Yamamoto Y. Momiyama N. Yamamoto H. J. Am. Chem. Soc. 2004, 126: 5962

<A NAME="RW14706ST-16F">16f</A> Mathew SP. Iwamura HD. Blackmond G. Angew. Chem. Int. Ed. 2004, 43: 3317

<A NAME="RW14706ST-16G">16g</A> Córdova A. Sundén H. Bøgevig A. Johansson M. Himo F. Chem. Eur. J. 2004, 10: 3673

<A NAME="RW14706ST-16H">16h</A> Hayashi Y. Yamaguchi J. Sumiya T. Hibino K. Shoji M. J. Org. Chem. 2004, 69: 5966

<A NAME="RW14706ST-16I">16i</A> Hayashi Y. Yamaguchi J. Hibino K. Sumiya T. Urushima T. Shoji M. Hashizumi D. Koshino H. Adv. Synth. Catal. 2004, 346: 1435

<A NAME="RW14706ST-16J">16j</A> Wang W. Wang J. Li H. Liao L. Tetrahedron Lett. 2004, 45: 7235

<A NAME="RW14706ST-16K">16k</A> Iwamura H. Wells DH. Mathew SP. Klussmann M. Armstrong A. Blackmond DG. J. Am. Chem. Soc. 2004, 126: 16312

<A NAME="RW14706ST-17">17</A> Yamamoto Y. Momiyama N. Yamamoto H. J. Am. Chem. Soc. 2004, 126: 5962

<A NAME="RW14706ST-18">18</A> Bamberger E. Ber. Dtsch. Chem. Ges. 1894, 27: 1548

Copper-Catalyzed Enantioselective Tandem Conjugate Addition/ N -Nitroso-Aldol Reaction: Typical Procedure: Under an Ar atmosphere, a solution of Cu(OTf)₂ (3.6 mg, 0.010 mmol) and the monodentate phosphoramidite (0.020 mmol) in toluene (1 mL) was stirred at r.t. for 1 h. The colorless solution was cooled (-20 °C) and the ketone (0.50 mmol) and the diethylzinc solution (1.2 equiv) in hexane (1.0 M, 0.6 mL, 0.6 mmol) were added. After 3 h at -20 °C, PhNO (80.2 mg, 0.75 mmol, 1.5 equiv) in anhyd toluene (1.5 mL) was added. After stirring the mixture for 18 h, sat. aq NH₄Cl (10 mL) was added to the reaction mixture, and then the reaction mixture was extracted with EtOAc (3 × 10 mL). The combined organic phases were washed with brine and dried over Na₂SO₄. The solvent was then removed under vacuum. After purification by flash chromatography on silica gel (PE-EtOAc, 200:1), the addition product 2a was obtained in 86.4% yield as a 2:1 diastereomeric mixture. IR (KBr): 3413, 2956, 2825, 2871, 1677, 1637, 1594, 1489, 1452, 1377, 1362, 1257, 1222 cm^-1. MS: m/z = 345 [M⁺], 240 (47), 226 (80), 104 (53), 91 (44), 77 (100). 2a ^¹ (minor isomer); yellow solid; mp 117.9-119.6 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.78 (t, J = 7.3 Hz, 3 H), 1.82 (m, J = 7.3 Hz, 1 H), 2.43 (m, J = 7.3 Hz, 1 H), 3.50 (m, J = 10.3 Hz, 1 H), 5.27 (d, J = 10.3 Hz, 1 H), 6.79 (t, J = 7.1 Hz, 1 H), 6.97-7.34 (m, 15 H). ¹³C NMR (75 MHz, CDCl₃): δ = 11.7, 22.7, 48.2, 70.9, 114.9, 121.4, 126.9, 127.9, 128.1, 128.3, 128.4, 128.9, 129.1, 133.0, 137.2, 139.6, 151.3, 205.8. 2a ^² (major isomer): yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 0.72 (t, J = 7.2 Hz, 3 H), 1.62 (m, J = 7.2 Hz, 2 H), 3.61 (m, 1 H), 5.4 (d, J = 9.7 Hz, 1 H), 6.79 (t, J = 7.1 Hz, 1 H), 6.97-7.34 (m, 15 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.3, 26.2, 47.4, 71.5, 115.5, 121.5, 126.7, 128.3, 128.4, 128.5, 128.6, 128.8, 133.8, 137.8, 141.5, 151.2, 203.7.
The enantiomeric excess of 2a was determined according to the following procedure: EtOH (20 mL) and HCl (2 M, 20 mL) were added to 2a at r.t. and the mixture was stirred for 2 d. The solvent was evaporated under vacuum and to the residue was added H₂O (10 mL) and the resulting mixture was extracted with EtOAc (3 × 10 mL). The combined organic phase was washed with brine and dried over Na₂SO₄. The solvent was then removed under vacuum. Purification by flash chromatography on silica gel afforded 3a (PE-EtOAc, 200:1). IR (KBr): 3514, 3419, 2957, 2926, 2871, 1677, 1595, 1488, 1452, 1446, 1258, 1223, 1211, 750, 768, 696, 685 cm^-1. MS: m/z = 363 [M⁺], 258 (100), 244 (39), 105 (23), 91 (30), 77 (40). 3a ^¹: yellow solid; mp 99.1-102.5 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.67 (t, J = 7.3 Hz, 3 H), 1.75 (m, 2 H), 2.99 (q, J = 4.8 Hz, 1 H), 4.75 (d, J = 9.2 Hz, 1 H), 5.03 (q, J = 4.6 Hz, 1 H), 6.36 (q, J = 6.7 Hz, 2 H), 6.98 (q, J = 6.7 Hz, 2 H), 7.20-7.26 (m, 5 H), 7.43-7.48 (m, 2 H), 7.54-7.57 (m, 1 H), 7.85-7.88 (q, J = 10.0 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.1, 22.5, 50.9, 64.5, 115.4, 122.9, 127.1, 128.4, 128.7, 128.9, 129.1, 133.6, 135.8, 146.6, 200.6.
3a ^²: yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 0.84 (t, J = 7.3 Hz, 3 H), 1.90 (m, 2 H), 3.09 (m, 1 H), 4.31 (d, J = 9.2 Hz, 1 H), 5.16 (q, J = 4.4 Hz, 1 H), 6.57 (q, J = 6.8 Hz, 2 H), 6.98 (m, 2 H), 7.04 (q, J = 6.8 Hz, 2 H), 7.22-7.26 (m, 3 H), 7.48-7.62 (m, 3 H), 7.92-7.95 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.5, 25.4, 50.8, 62.9, 115.4, 122.9, 127.2, 128.4, 128.4, 128.7, 129.0, 129.1, 133.6, 136.0, 138.8, 146.4, 199.9. Enantiomeric excess: 87%, 87%, determined by chiral HPLC analysis [Daicel Chiralcel AS; hexane-i-PrOH = 99:1, flow = 1.0 mL/min, t_R(3a ^¹) = 12.49 min, 18.19 min; t_R(3a ^²) = 13.95 min, 22.65 min].

Crystal data of 3c: C₂₃H₂₁ClFNO, MW = 381.86, orthorhombic, space group P2(1)2(1)2(1), a = 9.682(2), b = 19.389(3), c = 21.673(4) Å, α = 90°, β = 90°, γ = 90°, V = 4068.5(13) Å³, T = 296(2) K, Z = 8, D _c = 1.247 mg/m³, µ = 0.208 mm^-1, λ = 0.71073 Å, F(000) = 464, crystal size: 0.60 × 0.50 × 0.36 mm³, 9078 reflections collected, 7582 independent reflections [R(int) = 0.0203]; refinement method: full-matrix least-squares on F²; goodness-of-fit on F ^² = 0.804, final R indices [I > 2σ(I)] R1 = 0.0419, wR2 = 0.0853 (CCDC no. 618359).