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DOI: 10.1055/s-0029-1217166
Asymmetric Synthesis of Substituted α-Amino Phosphonates with Chiral Crown Ethers as Catalysts
Publikationsverlauf
Publikationsdatum:
13. Mai 2009 (online)
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Abstract
A simple, phase-transfer catalytic synthesis of enantioenriched phosphonoglutaminic acid derivatives (ee up to 86%) has been developed by using ‘sugar-based’ crown ether catalysts.
Key words
Michael additions - asymmetric catalysis - chiral phase-transfer catalysis - chiral crown compounds - aminophosphonates
- 1
Oleksyszyn J. In Aminophosphonic and Aminophosphinic AcidsKukhar VP.Hudson HR. John Wiley and Sons; Chichester: 2000. Chap.15. p.537-558 - 2
Kafarski P.Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 63: 193 -
3a
Atherton FR.Hassall CH.Lambert RW. J. Med. Chem. 1986, 29: 29 -
3b
Lejczak B.Kafarski P.Zygmunt J. Biochemistry 1989, 28: 3549 -
4a
Allen MC.Fuhrer W.Tuck B.Wade R.Wood JM. J. Med. Chem. 1989, 32: 1652 -
4b
Rozenfeld R.Iturrioz X.Okada M.Maigret B.Llorens-Cortes C. Biochemistry 2003, 42: 14785 - 5
Abdel-Meguid SS.Zhao B.Murthy KHM.Winborne E.Choi JK.DesJarlais RL.Minnich MD.Culp JS.Debouck C. Biochemistry 1993, 32: 7972 -
6a
Smith AB.Taylor CM.Benkovic SJ.Hirschman R. Tetrahedron Lett. 1994, 35: 6853 -
6b
Tanaka F.Kinoshita K.Tanimura R.Fuji I. J. Am. Chem. Soc. 1996, 118: 2332 -
7a
Matczak-Jon E.Kurzak B.Sawka-Dobrowska W.Kafarski P.Lejczak B. J. Chem. Soc., Dalton Trans. 1996, 3455 -
7b
Kim WD.Kiefer GE.Huskens J.Sherry AD. Inorg. Chem. 1997, 36: 4128 - 8
Ordónez M.Rojas-Cabrera H.Cativiela C. Tetrahedron 2009, 65: 17 -
9a
Smith AB.Yager KM.Taylor CM. J. Am. Chem. Soc. 1995, 117: 10879 -
9b
Mikolajczyk M.Lyzwa P.Drabowicz J. Tetrahedron: Asymmetry 1997, 8: 3991 -
9c
Lefebvre IM.Evans SA. J. Org. Chem. 1997, 62: 7532 -
9d
Davis FA.Lee S.Yan H.Titus DD. Org. Lett. 2001, 3: 1757 -
10a
Schöllkopf U.Schütze R. Liebigs Ann. Chem. 1987, 45 -
10b
Groth U.Richter L.Schöllkopf U. Liebigs Ann. Chem. 1992, 903 - 11
Sasai H.Arai S.Tahara Y.Shibasaki M. J. Org. Chem. 1995, 60: 6656 - 12
Pettersen D.Marcolini M.Bernardi L.Fini F.Herrera RP.Sgarzani V.Ricci A. J. Org. Chem. 2006, 71: 6269 - 13
Joly GD.Jacobsen EN. J. Am. Chem. Soc. 2004, 126: 4102 - 14
Jászay ZM.Németh G.Truong SP.Petneházy I.Grûn A.Tõke L. Tetrahedron: Asymmetry 2005, 16: 3837 -
15a
Alonso-López M.Martin-Lomas M.Penades S. Tetrahedron Lett. 1986, 27: 3551 -
15b
Van Maarschalkerwaart DAH.Willard NP.Pandit UK. Tetrahedron 1992, 48: 8825 -
15c
Kanakamma PP.Mani NS.Maitra U.Nair V. J. Chem. Soc., Perkin Trans.1 1995, 2339 -
16a
Bakó P.Szöllõsy .Bombicz P.Tõke L. Synlett 1997, 291 -
16b
Bakó T.Bakó P.Szöllõsy .Czugler M.Keglevich G.Tõke L. Tetrahedron: Asymmetry 2002, 13: 203 -
16c
Bakó T.Bakó P.Keglevich G.Báthori N.Czugler M.Tatai J.Novák T.Parlagh G.Tõke L. Tetrahedron: Asymmetry 2003, 14: 1917
References and Notes
Preparation of
Compounds 2; General Procedure: The stirred mixture of the
Schiff base 1 (0.5 g, 1.5 mmol), crown ether 4 (0.15 mmol) and t-BuONa
(0.192 g, 2 mmol) in anhyd toluene (7 mL) was cooled to -78 ˚C
under an argon atmosphere. This was left stirring for 10 min after
which the toluene solution (3 mL) of the acrylic compound 3 (1.8 mmol) was added. After stirring
for the given time at -78 ˚C the reaction was
quenched with sat. NH4Cl and extracted with toluene.
The combined organic extracts were dried with MgSO4,
and toluene was evaporated. Product 2 was
isolated by column chromatography on silica gel using EtOAc-hexane
(7:3) as eluent. Crown ether 4 was also
recovered during the column chromatography.
Compound
2a: for physical and spectral data see ref. 14.
Compound 2b: colorless oil. HPLC conditions:
hexane-
i-PrOH (95:5),
flow rate: 1 mL/min, λ = 256 nm, 20 ˚C, major
diastereomer: t
R
(
major) = 6.8
min and t
R
(
minor) = 12.8 min;
minor diastereomer: t
R
(
major) = 9.1
min and t
R
(
minor) = 65.1
min. Major Diastereomer: ¹H
NMR (500 MHz, CDCl3, TMS): δ = 0.81
(d, J = 8.0 Hz, 3 H), 1.28-1.38
(m, 6 H), 1.36 (s, 9 H), 1.80-2.40 (m, 1 H), 2.22-2.40
(m, 1 H), 2.40-2.51 (m, 1 H), 3.90-4.01 (m, 1
H), 4.04-4.26 (m, 4 H), 7.30-7.83 (m, 10 H). ¹³C
NMR (60 MHz, CDCl3, TMS):
δ = 16.56
(OEt), 16.63 (OEt), 18.92 (CHMe), 28.04 (t-Bu), 34.73
(d, J
PC = 4.6 Hz,
CH2), 37.40 (d, J
PC = 15.0
Hz, CHMe), 59.52 (d, J
PC = 158.0
Hz, CHP), 62.37 (d, J
PC = 6.6 Hz,
POCH2Me), 62.60 (t-BuO), 62.71
(d, J
PC = 6.7 Hz, POCH2Me),
127.99 (Ph), 128.41 (Ph), 128.45 (Ph), 128.57 (Ph), 128.71 (Ph),
128.84 (Ph), 128.86 (Ph), 128.93 (Ph), 130.18 (Ph), 130.28 (Ph),
135.70 (Ph), 135.74 (Ph), 139.53 (Ph), 139.58 (Ph), 170.88 (CN),
175.56 (CO). ³¹P NMR (121 MHz, CDCl3,
H3PO4): δ = 24.4. Minor Diastereomer: ¹H NMR
(500 MHz, CDCl3, TMS): δ = 1.12 (δ, J = 6.8 Hz, 3 H), 1.28-1.38
(m, 6 H), 1.27 (s, 9 H), 1.80-2.40 (m, 1 H), 2.22-2.40
(m, 1 H), 2.40-2.51 (m, 1 H), 3.90-4.01 (m, 1
H), 4.04-4.26 (m, 4 H), 7.30-7.83 (m, 10 H). ¹³C
NMR (60 MHz, CDCl3, TMS): δ = 16.61
(OEt), 16.72 (OEt), 18.92 (CHMe), 27.97 (t-Bu),
35.16 (d, J
PC = 4.9
Hz, CH2), 37.74 (d, J
PC = 14.4
Hz, CHMe), 59.52 (d, J
PC = 158.0
Hz, CHP), 62.30 (d, J
PC = 6.6
Hz, POEt), 62.60 (t-BuO), 62.65 (d, J
PC = 6.6 Hz, POEt),
127.99 (Ph), 128.41 (Ph), 128.45 (Ph), 128.57 (Ph), 128.71 (Ph),
128.84 (Ph), 128.86 (Ph), 128.93 (Ph), 130.18 (Ph), 130.28 (Ph),
135.70 (Ph), 135.74 (Ph), 139.53 (Ph), 139.58 (Ph), 170.88 (CN),
175.56 (CO). ³¹P NMR (121 MHz, CDCl3,
H3PO4): δ = 24.3. MS (ESI):
m/z [M + H]+ calcd
for C26H37NO5P: 474.24039; found: 474.24005.
Compound 2c: colorless oil. HPLC conditions:
hexane-
i-PrOH (90:10),
flow rate: 1 mL/min, λ = 220 nm, 10 ˚C, major
diastereomer: t
R
(
major) = 14.1
min and t
R
(
minor) = 17.7 min;
minor diastereomer: t
R
(
major) = 60.3
min and t
R
(
minor) = 75.3
min. Major Diastereomer: ¹H
NMR (500 MHz, CDCl3, TMS): δ = 1.058
(t, J = 7.1 Hz, 3 H), 1.063
(t, J = 7.0 Hz, 3 H), 3.11 (s,
3 H), 3.45-3.55 (m, 2 H), 3.82-4.12 (m, 6 H),
6.95-7.41 (m, 15 H). ¹³C NMR
(60 MHz, CDCl3, TMS): δ = 16.42, 16.46
(OEt), 35.41 (CH2CO2Me), 43.55 (d, J
PC = 3.3 Hz, CHPh),
51.58 (OMe), 60.11 (d, J
PC = 132.0
Hz, CHP), 62.51 (d, J
PC = 6.4
Hz, POEt), 62.55 (d, J
PC = 7.1
Hz, POEt), 127.11 (Ph), 127.26 (Ph), 127.46 (Ph), 127.55 (Ph), 127.86
(Ph), 128.43 (Ph), 128.45 (Ph), 128.62 (Ph), 128.87 (Ph), 139.46
(Ph), 145.25 (Ph), 145.55 (Ph), 172.20 (CN), 172.97 (CO). ³¹P
NMR (121 MHz, CDCl3, H3PO4): δ = 25.1. Minor Diastereomer: ¹H
NMR (500 MHz, CDCl3, TMS):
δ = 1.12
(t, J = 7.0 Hz, 3 H), 1.19 (t, J = 7.0 Hz, 3 H), 3.35 (dd, J = 16.1, 4.0 Hz, 2 H), 3.41
(s, 3 H), 3.82-4.12 (m, 6 H), 6.95-7.41 (m, 15
H). ¹³C NMR (60 MHz, CDCl3,
TMS): δ = 16.61, 16.72 (OEt), 35.68 (CH2CO2Me),
43.55 (d, J
PC = 3.3 Hz,
CHPh), 51.68 (OMe), 64.65 (d, J
PC = 14.1
Hz, POEt), 66.51 (d, J
PC = 126.0
Hz, CHP), 127.11 (Ph), 127.26 (Ph), 127.46 (Ph), 127.55 (Ph), 127.86
(Ph), 128.43 (Ph), 128.45 (Ph), 128.62 (Ph), 128.87 (Ph), 139.46
(Ph), 145.25 (Ph), 145.55 (Ph), 172.20 (CN), 172.97 (CO). ³¹P
NMR (121 MHz, CDCl3, H3PO4): δ = 22.7.
MS (ESI): m/z [M + H]+ calcd
for C28H33NO5P: 494.20909; found:
494.20838.
Compound 2d: for physical
and spectral data see ref. 14.
Compound
2e: colorless oil. [α]D
²0 14.2
(c = 0.6, CHCl3). HPLC
conditions: hexane-i-PrOH (95:5),
flow rate: 1 mL/min, λ = 256 nm, 5 ˚C,
major diastereomer: t
R
(
major) = 36.5 min
and t
R
(
minor) = 22.5
min; minor diastereomer: t
R
(
major) = 51.7
min and t
R
(
minor) = 18.5
min. Major Diastereomer:
¹H
NMR (500 MHz, CDCl3, TMS): δ = 1.02
(d, J = 7.0 Hz, 3 H), 1.24 (t, J = 7.0 Hz, 3 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.98-2.10
(m, 1 H), 2.22-2.70 (m, 2 H), 3.88-4.00 (m, 1
H), 4.00-4.20 (m, 4 H), 7.19-7.62 (m, 10 H). ¹³C
NMR (60 MHz, CDCl3, TMS): δ = 16.53
(OEt), 16.60 (OEt), 18.63 (Me), 23.02 (d, J
PC = 16.2
Hz, CHMe), 36.34 (d, J
PC = 4.3
Hz, CH2), 59.14 (d, J
PC = 157.3
Hz, CHP), 62.78 (d, J
PC = 7.9
Hz, POEt), 65.40 (d, J
PC = 6.5
Hz, POEt), 122.68 (CHCN), 128.13 (Ph), 128.32 (Ph), 128.46 (Ph),
128.48 (Ph), 128.48 (Ph), 128.56 (Ph), 128.68 (Ph), 128.90 (Ph),
128.91 (Ph), 129.0 (Ph), 129.08 (Ph), 130.1 (Ph), 130.65 (Ph), 132.46 (Ph),
135.06 (Ph), 135.32 (Ph), 139.12 (Ph), 139.25 (Ph), 171.90 (CN). ³¹P
NMR (121 MHz, CDCl3, H3PO4): δ = 22.8. Minor Diastereomer: ¹H
NMR (500 MHz, CDCl3, TMS):
δ = 1.18
(d, J = 7.1 Hz, 3 H), 1.23 (t, J = 7.1 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H), 1.98-2.10
(m, 1 H), 2.22-2.70 (m, 2 H), 3.88-4.00 (m, 1
H), 4.00-4.20 (m, 4 H), 7.19-7.62 (m, 10 H). ¹³C
NMR (60 MHz, CDCl3, TMS): δ = 16.53
(OEt), 16.60 (OEt), 17.70 (Me), 22.69 (d, J
PC = 15.2
Hz, CHMe), 35.94 (d, J
PC = 4.8
Hz, CH2), 59.20 (d, J
PC = 159.1
Hz, CHP), 62.87 (d, J
PC = 4.4
Hz, POEt), 62.97 (d, J
PC = 4.0
Hz, POEt), 122.04 (CHCN), 128.13 (Ph), 128.32 (Ph), 128.46 (Ph), 128.48
(Ph), 128.48 (Ph), 128.56 (Ph), 128.68 (Ph), 128.90 (Ph), 128.91
(Ph), 129.0 (Ph), 129.08 (Ph), 130.1 (Ph), 130.65 (Ph), 132.46 (Ph),
135.06 (Ph), 135.32 (Ph), 139.12 (Ph), 139.25 (Ph), 172.61 (CN). ³¹P
NMR (121 MHz, CDCl3, H3PO4): δ = 22.8.
MS (ESI): m/z [M + H]+ calcd
for C22H28N2O3P: 399.18321;
found: 399.18296.