RSS-Feed abonnieren
DOI: 10.1055/s-0029-1218386
Utilization of Aminophosphonates in the Petasis Boronic Acid Mannich Reaction
Publikationsverlauf
Publikationsdatum:
27. November 2009 (online)
![](https://www.thieme-connect.de/media/synlett/201001/lookinside/thumbnails/10.1055-s-0029-1218386-1.jpg)
Abstract
Aminophosphonates were used as amine components in the Petasis boronic acid Mannich reaction. With the use of α-aminophosphonates, several N-phosphonomethylglycine derivatives were prepared in modest to good yields and high diastereoselectivities. The method affords the possibility of variation for the substituents in the position α to the phosphorus and nitrogen atoms. By using the same methodology, highly functionalized amino acids were prepared starting from (R)-β-amino-α,α-difluoromethylphosphonate.
Key words
boronic acids - aminophosphonates - multicomponent reaction - amino acids - stereoselective synthesis
- Supporting Information for this article is available online:
- Supporting Information
-
1a
Multicomponent Reactions
Zhu J.Bienaymé H. Wiley-VCH; Weinheim: 2005. -
1b
Yus M.Ramón DJ. Angew. Chem. Int. Ed. 2005, 44: 1602 -
1c
Dömling A. Chem. Rev. 2006, 106: 17 -
1d
Dömling A.Ugi I. Angew. Chem. Int. Ed. 2000, 39: 3168 -
1e
Simon C.Constantieux T.Rodriguez J. Eur. J. Org. Chem. 2004, 4957 -
2a
Petasis NA.Akritopoulou I. Tetrahedron Lett. 1993, 34: 583 -
2b
Petasis NA.Goodman A.Zavialov IA. Tetrahedron 1997, 53: 16463 -
2c
Petasis NA.Zavialov IA. J. Am. Chem. Soc. 1998, 120: 11798 -
2d
Petasis NA. Aust. J. Chem. 2007, 60: 795 - 3
Petasis NA. In Multicomponent ReactionsZhu J.Bienaymé H. Wiley-VCH; Weinheim: 2005. p.199-223 - 4
Southwood TJ.Curry MC.Hutton CA. Tetrahedron 2006, 62: 236 - 5
Petasis NA.Zavialov IA. J. Am. Chem. Soc. 1997, 119: 445 - 6
Petasis NA, andZavialov IA. inventors; US 6,232,467. - 7
Aminophosphonic
and Aminophosphinic Acids
Kukhar VP.Hudson HR. John Wiley and Sons; Chichester: 2000. -
8a
Kafarski P.Lejczak B. Curr. Med. Chem. 2001, 1: 301 -
8b
Ordóñez M.Rogas-Cabrera H.Cativiela C. Tetrahedron 2009, 65: 17 -
8c
Palacios F.Alonso C.de los Santos JM. Chem. Rev. 2005, 105: 899 -
8d
Romanenko VD.Kukhar VP. Chem. Rev. 2006, 106: 3868 -
8e
Moonen K.Laureyn I.Stevens CV. Chem. Rev. 2004, 104: 6177 -
8f
Mikolajczyk M.Balczewski P. Top. Curr. Chem. 2003, 223: 161 - 9
Candeias NR.Veiros LF.Afonso CAM.Gois PMP. Eur. J. Org. Chem. 2009, 1859 - 11
Röschenthaler G.-V.Kukhar VP.Belik MYu.Mazurenko KI.Sorochinsky AE. Tetrahedron 2006, 62: 9902
References and Notes
To a stirred suspension of glyoxylic acid monohydrate (92 mg, 1.00 mmol) in EtOAc (5 mL) tetraethyl pyrrolidine-2,2-diyldiphosphonate (3, 343 mg, 1.00 mmol) was added dropwise, after 5 min 2-thiopheneboronic acid (128 mg, 1.00 mmol) was added in one portion, and the reaction mixture was refluxed over 4 h while monitored by TLC (5% MeOH in CHCl3). After the completion of the reaction the solvent was evaporated yielding the crude product as yellow oil. Flash chromatography using 5% of MeOH in CH2Cl2 afforded 390 mg (80%) of compound 4d as colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 1.05 (t, 3 H, OCH2CH 3),1.15 (t, 3 H, OCH2CH 3), 1.30 (t, 3 H, OCH2CH 3), 1.31 (t, 3 H, OCH2CH 3), 1.77-1.84 (m, 2 H, CH2), 2.19 (m, 2 H, CH2), 3.01-3.07 (m, 1 H, CH2), 3.17-3.23 (m, 1 H, CH2), 3.78-3.88 (m, 1 H, OCH 2CH3), 3.90-4.10 (m, 3 H, OCH 2CH3), 4.14-4.26 (m, 4 H, OCH 2CH3), 5.83 (s, 1 H, CHCOOH), 6.87 (dd, J HH = 3.7 Hz, J HH = 5.1 Hz, 1 H, Hthiophene), 7.08 (dd, J HH = 1.0 Hz, J HH = 3.7 Hz, 1 H, Hthiophene), 7.20 (dd, J HH = 1.0 Hz, J HH = 5.1 Hz, 1 H, Hthiophene). ¹³C NMR (100 MHz, CDCl3): δ = 16.2 (d, J CP = 6.0 Hz, OCH2 CH3), 16.5 (d, J CP = 6.0 Hz, OCH2 CH3), 16.5 (d, J CP = 6.0 Hz, OCH2 CH3), 16.6 (d, J CP = 6.0 Hz, OCH2 CH3), 24.0 (t, J CP = 3.0 Hz, CH2), 32.3 (t, J CP = 4.0 Hz, CH2), 48.1 (d, J CP = 4.0 Hz, CH2), 59.8 (s, CHCOOH), 62.3 (d, J CP = 7.0 Hz, OCH2CH3), 63.2 (d, J CP = 7.0 Hz, OCH2CH3), 63.5 (d, J CP = 7.0 Hz, OCH2CH3), 63.5 (dd, J CP = 150.0 Hz, J CP = 155.0 Hz, PCP), 64.6 (d, J CP = 7.0 Hz, OCH2CH3), 125.9, 125.9, 128.7, 138.3, 172.5 (s, COOH). ³¹P NMR (162 MHz, CDCl3): δ = 20.8 (d, J PP = 92.3 Hz, 1 P), 23.3 (d, J PP = 92.3 Hz, 1 P). CI MS (CI, pos.): m/z (%) = 346 (100), 206 (15); MS (CI, neg.): m/z (%) = 482 (100) [M - H]-, 438 (10), 328 (10), 233 (40), 138 (10), 103 (30), 85 (45). Anal. Calcd for C18H31NO8P2S: C, 44.72; H, 6.46, N, 2.90, S, 6.63. Found: C, 44.61; H, 6.41; N, 2.87; S, 6.68.
12To a stirred solution of pyruvic acid
(44 mg, 0.50 mmol) in CH2Cl2 (3 mL) aminophosphonate 6 (147 mg, 0.50 mmol) was added dropwise,
after 5 min (E)-2-phenylethenyl boronic
acid (74 mg, 0.50 mmol) was added in one portion, and the reaction
mixture was stirred for 24 h while monitored by TLC (5% MeOH
in CHCl3). The solvent was evaporated, and the residual
oil was chromatographed using a gradient of i-PrOH
(7 → 13%) in CH2Cl2 to yield
75 mg (34%) as a mixture of diastereomers 7b,
and 35 mg (15%) as pure major diastereomer. Summary yield
110 mg (49%).
Major diastereomer: ¹H
NMR (400 MHz, CDCl3): δ = 1.26 (t,
3 H, OCH2CH
3),1.33
(t, 3 H, OCH2CH
3),
1.50 (s, 3 H, CH
3), 4.09-4.33
(m, 4 H, OCH
2CH3),
4.38 (dd, J
HF = 23.0 Hz, J
HF = 8.0
Hz, 1 H, CF2CH), 5.94 (d, J
HH = 16.0
Hz, 1 H, PhCH=CH), 6.48 (d, J
HH = 16.0
Hz, 1 H, PhCH=CH), 6.40 (br
s, NH), 7.07 (d, J
HH = 7.0
Hz, 2 H, H
Ph), 7.18-7.39
(m, 8 H, HPh). ¹³C NMR (100
MHz, CDCl3): δ = 16.4
(m, OCH2CH3), 22.2
(s, CH3), 63.5 (s, CHCOOH),
64.7 (d, J
CP = 7.0
Hz, OCH2CH3), 65.2
(d, J
CP = 7.0
Hz, OCH2CH3), 126.7,
128.07, 128.5, 128.6, 128.6, 129.1, 130.9, 131.5, 136.1. ¹9F
NMR (376 MHz, CDCl3): δ = -121.6
(ddd, J
FF = 304.0
Hz, J
FP = 108.0
Hz, J
FH = 23.0
Hz, 1 F), -110.6 (ddd, J
FF = 304.0
Hz, J
FP = 104.0
Hz, J
FH = 8.0
Hz, 1 F).
¹9P NMR (162 MHz, CDCl3): δ = 6.7
(dd, J
PF = 108.0
Hz, J
PF = 104.0
Hz). Anal. Calcd for C23H28F2NO5P:
C, 59.10; H, 6.04. Found: C, 59.06; H, 6.14.