Prolinol tert-Butyldiphenylsilyl Ether as Organocatalyst for the Asymmetric Michael Addition of Cyclohexanone to Nitroolefins

Abstract

The direct Michael additions of cyclohexanone to nitro­olefins catalyzed by prolinol tert-butyldiphenylsilyl ether were ­conducted successfully in good yields (up to 99%) and high stereoselectivities (up to 98:2 diastereomeric ratio and 95% enantiomeric excess).

asymmetric - organocatalyst - Michael addition - cyclohexanone - nitroolefin

References and Notes

1a Perlmutter P. Conjugate Addition Reactions in Organic Synthesis   Pergamon; Oxford: 1992. 

1b Sundén H. Ibrahem I. Zhao GL. Eriksson L. Córdova A. Chem. Eur. J.  2007,  13:  574 

1c Inokuma T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc.  2006,  128:  9413 

1d Ibrahem I. Zou WB. Xu YM. Córdova A. Adv. Synth. Catal.  2006,  348:  211 

1e Wang J. Li H. Zu LS. Wang W. Org. Lett.  2006,  8:  1391 

1f Marigo M. Bertelsen S. Landa A. Jørgensen KA. J. Am. Chem. Soc.  2006,  128:  5475 

1g Lattanzi A. Tetrahedron: Asymmetry  2006,  17:  837 

1h Bartoli G. Bosco M. Carlone A. Cavalli A. Locatelli M. Mazzanti A. Ricci P. Sambri L. Melchiorre P. Angew. Chem. Int. Ed.  2006,  45:  4966 

1i Wu FH. Li HM. Hong R. Deng L. Angew. Chem. Int. Ed.  2006,  45:  947 

1j Xie JW. Yue L. Xue D. Ma XL. Chen YC. Wu Y. Zhu J. Deng JG. Chem. Commun.  2006,  1563 

1k Hayashi Y. Gotoh H. Tamura T. Yamaguchi H. Masui R. Shoji M. J. Am. Chem. Soc.  2005,  127:  16028 

1l Mitchell CET. Brenner SE. Ley SV. Chem. Commun.  2005,  5346 

1m Yang JW. Fonseca MTH. List B. J. Am. Chem. Soc.  2005,  127:  15036 

1n Chi YG. Gellman SH. Org. Lett.  2005,  7:  4253 

1o Herrera RP. Sgarzani V. Bernardi L. Ricci A. Angew. Chem. Int. Ed.  2005,  44:  6576 

1p McCooey SH. Connon SJ. Angew. Chem. Int. Ed.  2005,  44:  6367 

1q Hoashi Y. Okino T. Takemoto Y. Angew. Chem. Int. Ed.  2005,  44:  4032 

2a Ono N. The Nitro Group in Organic Synthesis   Wiley; New York: 2001. 

2b Calderari G. Seebach D. Helv. Chim. Acta  1995,  58:  1592 

2c Czekelius C. Carreira EM. Angew. Chem. Int. Ed.  2005,  44:  612 

3a Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 

3b Seayad J. List B. Org. Biomol. Chem.  2005,  3:  719 

3c Berkessel A. Groger H. Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in Asymmetric Synthesis   Wiley-VCH; Weinheim / Germany: 2005. 

3d Tsogoeva SB. Eur. J. Org. Chem.  2007,  11:  1701 

4a McCooey SH. Connon SJ. Org. Lett.  2007,  9:  599 

4b Tsogoeva SB. Wei SW. Chem. Commun.  2006,  1451 

4c Liu K. Cui HF. Nie J. Dong KY. Li XJ. Ma JA. Org. Lett.  2007,  9:  923 

4d Huang HB. Jacobsen EN. J. Am. Chem. Soc.  2006,  128:  7170 

4e Lalonde MP. Chen YG. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  6366 

4f Xu YM. Córdova A. Chem. Commun.  2006,  460 

4g Xu YM. Zou WB. Sundén H. Ibrahem I. Córdova A. Adv. Synth. Catal.  2006,  348:  418 

5a Luo SZ. Xu H. Mi XL. Li JY. Zheng XX. Cheng JP. J. Org. Chem.  2006,  71:  9244 

5b Yan ZY. Niu YN. Wei HL. Wu LY. Zhao YB. Liang YM. Tetrahedron: Asymmetry  2006,  17:  3288 

6a Cobb AJA. Longbottom DA. Shaw DM. Ley SV. Chem. Commun.  2004,  1808 

6b Cobb AJA. Shaw DM. Longbottom DA. Gold JB. Ley SV. Org. Biomol. Chem.  2005,  3:  84 

6c Mitchell CET. Cobb AJA. Ley SV. Synlett  2005,  611 

7a . Singh VK. Org. Lett.  2007,  9:  1117 

7b Pansare SV. Pandya K. J. Am. Chem. Soc.  2006,  128:  9624 

7c Mase N. Watanabe K. Yoda H. Takabe K. Tanaka F. Barbas CF. J. Am. Chem. Soc.  2006,  128:  4966 

7d Mase N. Thayumanavan R. Tanaka F. Barbas CF. Org. Lett.  2004,  6:  2527 

7e Betancort JM. Barbas CF. Org. Lett.  2001,  3:  3737 

7f Betancort JM. Sakthivel K. Thayumanavan R. Tanaka F. Barbas CF. Synthesis  2004,  1509 

7g Zhu MK. Cun LF. Mi AQ. Jiang YZ. Gong LZ. Tetrahedron: Asymmetry  2006,  17:  491 

8a Mossé S. Alexakis A. Org. Lett.  2006,  8:  3577 

8b Andrey O. Alexakis A. Tomassini A. Bernardinelli G. Adv. Synth. Catal.  2004,  346:  1147 

8c Andrey O. Alexakis A. Bernardinelli G. Org. Lett.  2003,  5:  2559 

8d Alexakis A. Andrey O. Org. Lett.  2002,  4:  3611 

8e Andrey O. Vidonne A. Alexakis A. Tetrahedron Lett.  2003,  44:  7901 

9 Ishii T. Fujioka S. Sekiguchi Y. Kotsuki H. J. Am. Chem. Soc.  2004,  126:  9558 

10a Zu LS. Wang J. Li H. Wang W. Org. Lett.  2006,  8:  3077 

10b Wang J. Li H. Lou BS. Zu LS. Guo H. Wang W. Chem. Eur. J.  2006,  12:  4321 

10c Wang J. Li H. Zu LS. Wang W. Adv. Synth. Catal.  2006,  348:  425 

10d Wang W. Wang J. Li H. Angew. Chem. Int. Ed.  2005,  44:  1369 

10e Diez D. Gil MJ. Moro RF. Marcos IS. García P. Basabe P. Garrido NM. Broughton HB. Urones JG. Tetrahedron  2007,  63:  740 

11a Cao CL. Ye MC. Sun XL. Tang Y. Org. Lett.  2006,  8:  2901 

11b Cao YJ. Lai YY. Wang X. Li YJ. Xiao WJ. Tetrahedron Lett.  2007,  48:  21 

11c Cao YJ. Lu HH. Lai YY. Lu LQ. Xiao WJ. Synthesis  2006,  3795 

12a Hayashi Y. Gotoh H. Hayashi T. Shoji M. Angew. Chem. Int. Ed.  2005,  44:  4212 

12b Albertshofer K. Thayumanavan R. Utsumi N. Tanaka F. Barbas CF. Tetrahedron Lett.  2007,  48:  693 

12c Zu LS. Li H. Wang J. Yu XH. Wang W. Tetrahedron Lett.  2006,  47:  5131 

12d Li YW. Liu XY. Zhao G. Tetrahedron: Asymmetry  2006,  17:  2034 

13a Palomo C. Vera S. Mielgo A. Gómez-Bengoa E. Angew. Chem. Int. Ed.  2006,  45:  5984 

13b Clarke ML. Fuentes JA. Angew. Chem. Int. Ed.  2007,  46:  930 

13c Luo SZ. Mi XL. Zhang L. Liu S. Xu H. Cheng JP. Angew. Chem. Int. Ed.  2006,  45:  3093 

13d Luo SZ. Mi XL. Liu S. Xu H. Cheng JP. Chem. Commun.  2006,  3687 

13e Almasi D. Alonso DA. Nájera C. Tetrahedron: Asymmetry  2006,  17:  2064 

13f Reyes E. Vicario JL. Badia D. Carrillo L. Org. Lett.  2006,  8:  6135 

13g Barros MT. Phillips AMF. Eur. J. Org. Chem.  2007,  178 

13h Martin HJ. List B. Synlett  2003,  1901 

13i Mossé S. Laars M. Kriis K. Kanger T. Alexakis A. Org. Lett.  2006,  8:  2559 

13j Mossé S. Laars M. Kriis K. Kanger T. Alexakis A. Synthesis  2007,  1279 

14a Seebach D. Golinski J. Helv. Chim. Acta  1981,  64:  1413 

14b Blarer SJ. Schweizer WB. Seebach D. Helv. Chim. Acta  1982,  65:  1637 

15

Procedure for the Preparation of Catalyst 1a: To a DMF (10 mL) solution of prolinol (3.36 mmol) and imidazole (10.1 mmol) was added TBSCl (6.73 mmol) at 0 °C. The reaction mixture was stirred for 17 h at r.t. and quenched with aq NH₄Cl and the organic materials were extracted with EtOAc and the combined organic phase was washed with brine. Then the organic extracts were dried over anhyd Na₂SO₄ and concentrated in vacuo after filtration. Purification by silica gel column chromatography gave (S)-2-[(tert-butyldimethylsilyloxy)methyl]pyrrolidine (1a) in 77% yield; [α]_D ^r.t. -6.63 (c = 0.8, CHCl₃). IR (neat): 3406, 2929, 2857, 2738, 1680, 1460, 1394, 1255, 1100, 840, 775 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.10-0.12 (d, J = 4.6 Hz, 6 H), 0.90 (s, 9 H), 1.84-1.89 (m, 1 H), 1.93-2.11 (m, 3 H), 3.29-3.38 (m, 2 H), 3.76-3.81 (m, 2 H), 3.94-3.98 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = -5.5, -5.3, 24.0, 25.8, 26.8, 45.7, 60.0, 62.1. Preparation of catalyst (S)-2-[(tert-butyldiphenylsilyloxy)methyl]pyrrolidine (1b) was similar to that of catalyst 1a. 1b: 85% yield; [α]_D ^r.t. -5.8 (c = 0.94, CHCl₃). IR (neat): 3419, 2935, 2866, 2734, 1112, 708, 504 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.09 (s, 9 H), 1.80-1.99 (m, 1 H), 2.02-2.04 (m, 3 H), 3.30-3.35 (t, J = 6.5 Hz, 2 H), 3.71-3.79 (m, 1 H), 3.83-3.84 (m, 1 H), 3.91-3.96 (m, 1 H), 7.39-7.73 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 19.1, 23.8, 26.8, 45.6, 59.9, 63.0, 127.8, 129.9, 132.5, 135.6, 135.7.

16

General Procedure for the Asymmetric Michael Addition of Cyclohexanone 2 to Nitroolefin 3 Catalyzed by 1b: The catalyst 1b (0.1 mmol) and cyclohexanone 2 (0.5 mL) were mixed in hexane (2 mL) at r.t. After stirring for 20 min and then cooling to 10 °C, the nitroolefin 3 was added. The mixture was stirred at 10 °C for the specified time (Table [2] ) and then directly purified by silica gel column chromatography (PE and EtOAc as the eluent) to obtain the product 4,¹⁷ which was confirmed by the comparison of IR, ¹H NMR and ¹³C NMR data with that reported in the literature. The enantiomeric ratios were identified by HPLC analysis.

17

(S)-2-[(R)-2-Nitro-1-phenylethyl]cyclohexanone (4): mp 125-126 °C; [α]_D ^r.t. -26.1 (c = 1.42, CHCl₃). IR (neat): 2958, 2929, 1699, 1551, 1495, 1448, 1384, 1129, 697 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.21-1.58 (m, 1 H), 1.62-1.75 (m, 4 H), 2.04-2.10 (m, 1 H), 2.38-2.47 (m, 2 H), 2.68 (m, 1 H), 3.72-3.80 (dt, J = 4.5, 9.9 Hz, 1 H), 4.53-4.66 (dd, J = 10.0, 12.3 Hz, 1 H), 4.91-4.97 (dd, J = 4.5, 12.4 Hz, 1 H), 7.15-7.17 (d, J = 6.9 Hz, 2 H), 7.23-7.34 (m, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 25.0, 28.5, 33.1, 42.7, 43.9, 52.5, 78.8, 127.7, 128.1, 128.9, 137.7, 211.9. HPLC condition: Chiralpak AD-H, λ = 254 nm, flow rate: 0.5 mL/min, eluent: hexane-i-PrOH (90:10), t and the paragraph.