RSS-Feed abonnieren
DOI: 10.1055/s-0028-1087958
Novel Tripod l-Prolinamide Catalysts Based on Tribenzyl- and Triphenyl-phosphine Oxide for the Direct Aldol Reaction
Publikationsverlauf
Publikationsdatum:
16. März 2009 (online)
![](https://www.thieme-connect.de/media/synlett/200906/lookinside/thumbnails/10.1055-s-0028-1087958-1.jpg)
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
- Supporting Information for this article is available online:
- Supporting Information
- 1
List B.Lerner RA.Barbas III CF. J. Am. Chem. Soc. 2000, 122: 2395 -
2a
Dalko PI.Moisan L. Angew. Chem. Int. Ed. 2001, 40: 3726 -
2b
Dalko PI.Moisan L. Angew. Chem. Int. Ed. 2004, 43: 5138 -
2c
Xiong Y.Wen YH.Wang F.Gao B.Liu XH.Huang X.Feng XM. Adv. Synth. Catal. 2007, 349: 2156 -
2d
Yang ZG.Liu J.Liu XH.Wang Z.Feng XM.Su ZS.Hu CW. Adv. Synth. Catal. 2008, 350: 2001 -
2e
Liu J.Yang ZG.Wang Z.Wang F.Chen XH.Liu XH.Feng XM.Su ZS.Hu CW. J. Am. Chem. Soc. 2008, 130: 5654 -
2f
Wang F.Xiong Y.Liu XH.Feng XM. Adv. Synth. Catal. 2007, 349: 2665 -
2g
Chen XH.Wang J.Zhu Y.Shang DJ.Gao B.Liu XH.Feng XM.Su ZS.Hu CW. Chem. Eur. J. 2008, 14: 10896 -
3a
Marigo M.Fielenbach D.Braunton A.Kjærsgaard A.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 3703 -
3b
Marigo M.Wabnitz TC.Fielenbach D.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 794 -
4a
Ouellet SG.Tuttle JB.MacMillan DWC. J. Am. Chem. Soc. 2005, 127: 32 -
4b
Northrup AB.Mangion IK.Hettche F.MacMillan DWC. Angew. Chem. Int. Ed. 2004, 43: 2152 -
5a
Torii H.Nakadai M.Ishihara K.Saito S.Yamamoto H. Angew. Chem. Int. Ed. 2004, 43: 1983 -
5b
Saito S.Yamamoto H. Acc. Chem. Res. 2004, 37: 570 -
6a
Tang Z.Jiang F.Yu L.-T.Cui X.Gong L.-Z.Mi A.-Q.Jiang Y.-Z.Wu Y.-D. J. Am. Chem. Soc. 2003, 125: 5262 -
6b
Tang Z.Jiang F.Cui X.Gong L.-Z.Mi A.-Q.Jiang Y.-Z.Wu Y.-D. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 5755 - 7
Chen J.-R.Lu H.-H.Li X.-Y.Cheng L.Wan J.Xiao W.-J. Org. Lett. 2005, 7: 4543 - 8
Wu Y.-Y.Zhang Y.-Z.Yu M.-L.Zhao G.Wang S.-W. Org. Lett. 2006, 8: 4417 - 9
Dinér P.Amedjkouh M. Org. Biomol. Chem. 2006, 4: 2091 - 10
Liu X.-W.Le TN.Lu Y.-P.Xiao Y.-J.Ma J.-M.Li X.-W. Org. Biomol. Chem. 2008, 6: 3997 - 11
Xin J.-G.Chang L.Hou Z.-R.Shang D.-J.Liu X.-H.Feng X.-M. Chem. Eur. J. 2008, 14: 3177 - 16
Zheng J.-F.Li Y.-X.Zhang S.-Q.Yang S.-T.Wang X.-M.Wang Y.-Z.Bai J.Liu F.-A. Tetrahedron Lett. 2006, 47: 7793 - 18
Xiong Y.Wang F.Dong S.-X.Liu X.-H.Feng X.-M. Synlett 2008, 73
References and Notes
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.
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.
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.
15Analytical 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.
17Compound 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.