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Synlett 2009(6): 933-936  
DOI: 10.1055/s-0028-1087958
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Tripod l-Prolinamide Catalysts Based on Tribenzyl- and Triphenyl-phosphine Oxide for the Direct Aldol Reaction

Jun Hana, Hui Wua, Mingyu Tenga, Zhengyi Lia, Yangnian Wanga, Leyong Wang*a, Yi Pan*b
a Key Laboratory of Mesoscopic Chemistry of MOE and School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. of China
Fax: +86(25)83597090; e-Mail: lywang@nju.edu.cn;
b State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, P. R. of China
e-Mail: yipan@nju.edu.cn;
Further Information

Publication History

Received 8 December 2008
Publication Date:
16 March 2009 (online)

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Abstract

A series of C 3-symmetric triprolinamide catalysts based on triphenyl- and tribenzylphosphine oxide has been developed to catalyze the direct asymmetric aldol reaction of aromatic aldehydes and cyclohexanone. Under the optimal conditions, high isolated yield (up to 96%), diastereoselectivities (up to 88:12) and enantio-selectivities (up to 97% ee) were obtained.

Key words

asymmetric catalysis - triprolinamide - phosphine oxide - aldol reaction

12

Analytical data for compound 1: yield 78%; mp 182-186 ˚C. ¹H NMR (300 MHz, DMSO-d 6): δ = 10.23 (s, 3 H, CONH), 8.02-8.06 (d, 3 H, J = 13.1 Hz, ArH), 7.89-7.92 (d, 3 H, J = 7.9 Hz, ArH), 7.45-7.48 (m, 3 H, ArH), 7.20-7.26 (m,
3 H, ArH), 3.69-3.74 (m, 3 H, CH), 3.46 (m, 3 H, NH), 2.89 (m, 6 H, CH2), 1.47-2.03 (m, 12 H, CH2). ¹³C NMR (75 MHz, DMSO-d 6): δ = 26.09, 30.79, 47.10, 61.17, 122.30, 122.45, 123.09, 126.65, 126.77, 129.57, 129.74, 132.99, 134.35, 139.30, 139.49, 173.73. ³¹P NMR (202 MHz, DMSO-d 6): δ = 26.85 (s). IR (KBr disc): 1687 (CONH)
cm-¹. ESI-MS: m/z = 637.42 [M + Na+]. Anal. Calcd (%) for C33H39N6O4P: C, 64.48; H, 6.39; N, 13.67. Found: C, 64.46; H, 6.40; N, 13.66.

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Analytical data for compound 2: yield 99%; mp 212-218 ˚C. ¹H NMR (300 MHz, DMSO-d 6): δ = 10.17 (s, 3 H, CONH), 8.02-8.06 (d, 3 H, J = 13.1 Hz, ArH), 7.88-7.91 (d, 3 H, J = 8.0 Hz, ArH), 7.43-7.49 (m, 3 H, ArH), 7.19-7.25 (m,
3 H, ArH), 4.74 (br, 3 H, OH), 4.19 (s, 3 H, CH), 3.82-3.87 (t, 3 H, J = 8.2 Hz, CHOH), 3.42 (m, 3 H, NH), 2.73-2.88 (m, 6 H, CH2), 1.75-1.96 (m, 6 H, CH2). ¹³C NMR (75 MHz, DMSO-d 6): δ = 49.02, 55.56, 60.41, 71.86, 79.74, 122.34, 122.49, 123.12, 126.59, 126.72, 129.50, 129.68, 132.94, 134.30, 139.32, 139.51, 174.27. ³¹P NMR (202 MHz, DMSO-d 6): δ =  27.13 (s). IR (KBr disc): 1680 (OC=O, CONH) cm-¹. ESI-MS: m/z = 685.33 [M + Na+]. Anal. Calcd (%) for C33H39N6O7P: C, 59.81; H, 5.93; N, 12.68. Found: C, 59.78; H, 5.96; N, 12.66.

14

Analytical data for compound 3: yield 92%; mp 212-218 ˚C. ¹H NMR (300 MHz, DMSO-d 6): δ = 9.78 (s, 3 H, NH), 7.48 (s, 3 H, ArH), 7.27 (m, 3 H, ArH), 3.64-3.67 (m, 3 H, CH), 3.60-3.62 (m, 6 H, CH2), 3.06-3.10 (d, 6 H, J = 13.1 Hz, PCH2), 2.87 (t, 6 H, J = 6.4 Hz, CH2), 2.19 (s, 9 H, ArCH3), 1.69-2.07 (m, 6 H, CH2), 1.49-1.67 (m, 12 H, CH2), 1.27-1.39 (m, 27 H, CH2), 0.88 (t, 9 H, J = 7.3 Hz, CH3). ¹³C NMR (75 MHz, DMSO-d 6): δ = 14.20, 16.85, 19.20, 28.38, 28.42, 28.66, 28.76, 32.22, 55.34, 59.84, 68.40, 69.03, 72.74, 78.94, 79.05, 120.37, 121.00, 126.04, 131.18, 134.98, 135.07, 151.81, 153.80, 154.22, 171.08, 171.48. ³¹P NMR (202 MHz, DMSO-d 6): δ = 42.23 (s). ESI-MS: m/z = 937.75 [M + Na+]. Anal. Calcd (%) for C51H75N6O7P: C, 66.94; H, 8.26; N, 9.18. Found: C, 66.93; H, 8.29; N, 9.17.

15

Analytical data for compound 4: yield 65%; mp 212-218 ˚C. ¹H NMR (300 MHz, DMSO-d 6): δ = 9.77 (s, 3 H, NH), 7.46 (s, 3 H, ArH), 7.25 (s, 3 H, ArH), 4.77 (s, 3 H, OH), 4.17 (s, 3 H, CH), 3.80 (t, 3 H, J = 8.1 Hz, CH), 3.60 (t, 6 H, J = 6.3 Hz, CH2), 3.03-3.07 (d, 6 H, J = 13.2 Hz, PCH2), 2.74-2.88 (m, 6 H, CH2), 2.17 (s, 9 H, ArCH3), 1.67-2.00 (m, 6 H, CH2), 1.47-1.56 (m, 6 H, CH2), 1.27-1.35 (m, 6 H, CH2), 0.87 (t, 9 H, J = 7.2 Hz,CH3). ¹³C NMR (75 MHz, DMSO-d 6): δ = 14.29, 16.76, 19.22, 29.45, 30.24, 32.25, 55.53, 60.34, 71.89, 72.81, 120.17, 120.97, 126.09, 126.19, 131.25, 134.30, 151.75, 151.82, 173.28. ³¹P NMR (202 MHz, DMSO-d 6): δ = 42.56 (s). ESI-MS: m/z = 985.67 [M + Na+]. Anal. Calcd (%) for C51H75N6O10P: C, 63.60; H, 7.85; N, 8.73. Found: C, 63.61; H, 7.88; N, 8.75.

17

Compound 5a: reaction time: 72 h; yield: 89%;
anti/syn = 85:15; HPLC (Chiralcel AD-H, hexane-i-PrOH = 95:5, flow rate: 1.0 mL/min, 25 ˚C, UV: λ = 
254 nm): t R(minor) = 43.6 min, tR(major) = 59.2 min.
Compound 5b: reaction time: 72 h; yield: 88%; anti/syn = 82:18; HPLC (Chiralcel AD-H, hexane-i-PrOH = 95:5, flow rate: 1.0 mL/min, 20 ˚C, UV: λ = 
254 nm): t R(major) = 37.8 min, t R(minor) = 46.5 min.
Compound 5c: reaction time: 72 h; yield: 78%;
anti/syn = 88:12; HPLC (Chiralcel OD-H, hexane-i-PrOH = 95:5, flow rate: 1.0 mL/min, 20 ˚C, UV: λ = 
254 nm ): t R(major) = 13.8 min, tR(minor) = 16.0 min.
Compound 5d: reaction time: 120 h; yield: 81%;
anti/syn = 79:21; HPLC (Chiralcel AD-H, hexane-i-PrOH = 90:10, flow rate: 0.5 mL/min, 17 ˚C, UV: λ = 
254 nm): tR(major) = 26.5 min, tR(minor) = 20.7 min.
Compound 5e: reaction time: 120 h; yield: 81%;
anti/syn = 80:20; HPLC (Chiralcel AD-H, hexane-i-PrOH = 90:10, flow rate: 0.5 mL/min, 21 ˚C, UV: λ = 220nm): t R(major) = 27.7 min, tR(minor) = 31.2 min.
Compound 5f: reaction time: 120 h; yield: 87%; anti/syn = 67:33; HPLC (Chiralcel AD-H, hexane-i-PrOH = 90:10, flow rate: 0.5 mL/min, 17 ˚C, UV: λ = 
254 nm): tR(minor) = 40.1 min, tR(major) = 60.7 min.
Compound 5g: reaction time: 120 h; yield: 92%; anti/syn = 85:15; HPLC (Chiralcel AD-H, hexane-i-PrOH = 95:5, flow rate: 0.5 mL/min, 21 ˚C, UV: λ = 
220 nm): t R(major) = 31.1 min, t R(minor) = 36.9 min.
Compound 5h: reaction time: 120 h; yield: 68%;
anti/syn = 78:22; HPLC (Chiralcel OD-H, hexane-i-PrOH = 90:10, flow rate: 1.0 mL/min, 20 ˚C, UV: λ = 
220 nm): t R(major) = 9.6 min, t R(minor) = 14.3 min.
Compound 5i: reaction time: 120 h; yield: 43%; anti/syn = 83:17; HPLC (Chiralcel AD-H, hexane-i-PrOH = 90:10, flow rate: 1.0 mL/min, 21 ˚C, UV: λ = 
254 nm): t R(major) = 18.5 min, t R(minor) = 10.2 min.