RSS-Feed abonnieren
DOI: 10.1055/s-2008-1072789
Synthesis of Bispyrrolidines by Radical Cyclisation of Diallylamines Using Phosphorus Hydrides
Publikationsverlauf
Publikationsdatum:
07. Mai 2008 (online)
![](https://www.thieme-connect.de/media/synlett/200814/lookinside/thumbnails/10.1055-s-2008-1072789-1.jpg)
Abstract
Sequential radical addition-cyclisation reactions of diallylamines using either hypophosphorous acid or a bisphosphinothioate are shown to afford bispyrrolidines in good to excellent yields.
Key words
addition reactions - cyclisations - phosphorus - radical reactions
-
1a
Dochnahl M.Schulz SR.Blechert S. Synlett 2007, 2599 -
1b
Neukomm G.Roessler F.Johne S.Hesse M. Planta Med. 1983, 48: 246 - 2
Anderson FM.O’Hare CC.Hartley JA.Robins DJ. Anti-Cancer Drug Design 2000, 15: 119 -
3a
Stout DM.Black LA.Barcelon-Yang C.Matier WL.Brown BS.Quon CY.Stampfli HF. J. Med. Chem. 1989, 32: 1910 -
3b
Stout DM.Matier WL.Barcelon-Yang C.Reynolds RD.Brown BS. J. Med. Chem. 1985, 28: 295 -
4a
Williams MA.Rapoport H. J. Org. Chem. 1994, 59: 3616 -
4b
Bernauer K.Gretillat F. Helv. Chim. Acta 1989, 72: 477 -
5a
Denmark SE.Fu J.Lawler MJ. J. Org. Chem. 2006, 71: 1523 -
5b
Denmark SE.Fu J. J. Am. Chem. Soc. 2001, 123: 9488 -
5c
Periasamy M.Seenivasaperumal M.Dharma Rao V. Tetrahedron: Asymmetry 2004, 15: 3847 -
5d
Marshall WB.Brewbaker JL.Delaney MS. J. Appl. Polym. Sci. 1991, 42: 533 -
5e
Trost BM.Ito H.Silcoff ER. J. Am. Chem. Soc. 2001, 123: 3367 -
5f
Yang D.Chen Y.-C.Zhu N.-Y. Org. Lett. 2004, 6: 1577 - For recent work on addition reactions of phosphorus-centred radicals, see:
-
6a
Jessop CM.Parsons AF.Routledge A.Irvine DJ. Eur. J. Org. Chem. 2006, 1547 -
6b
Jessop CM.Parsons AF.Routledge A.Irvine D. Tetrahedron Lett. 2003, 44: 479 -
6c
Jessop CM.Parsons AF.Routledge A.Irvine DJ. Tetrahedron Lett. 2004, 45: 5095 -
6d
Cho DH.Jang DO. Synlett 2005, 59 -
6e
Hunt TA.Parsons AF.Pratt R. J. Org. Chem. 2006, 71: 3656 -
6f
Montchamp J.-L. J. Organomet. Chem. 2005, 690: 2388 -
6g
Leca D.Fensterbank L.Lacôte E.Malacria M. Chem. Soc. Rev. 2005, 34: 858 -
6h
Parsons AF.Sharpe DJ.Taylor P. Synlett 2005, 2981 -
6i
Hunt T.Parsons AF.Pratt R. Synlett 2005, 2978 -
6j
Healy MP.Parsons AF.Rawlinson JGT. Org. Lett. 2005, 7: 1597 -
6k
Carta P.Puljic N.Robert C.Dhimane A.-L.Fensterbank L.Lacôte E.Malacria M. Org. Lett. 2007, 9: 1061 -
6l
Montchamp J.-L.Antczak MI. Synthesis 2006, 3080 -
6m
Healy MP.Parsons AF.Rawlinson JGT. Synlett 2008, 329 -
6n
Beaufils F.Dénès F.Renaud P. Angew. Chem. Int. Ed. 2005, 44: 5273 -
9a
Williams RH.Hamilton LA. J. Am. Chem. Soc. 1955, 77: 3411 -
9b
Nifant’ev EE.Magdeeva RK.Shchepet’eva NP. J. Gen. Chem. USSR 1980, 50: 1416 -
9c
Dubert O.Gautier A.Condamine E.Piettre SR. Org. Lett. 2002, 4: 359 - 10
Froestel W.Mickel SJ.Hall RG.von Sprecher G.Strub D.Baumann PA.Brugger F.Gentsch C.Jaekel J.Olpe H.-R.Rihs G.Vassout A.Waldmeier PC.Bittiger H. J. Med. Chem. 1995, 38: 3297 -
12a
Deprèle S.Montchamp J.-L. J. Organomet. Chem. 2002, 643-644: 154 -
12b
Montchamp J.-L. J. Organomet. Chem. 2005, 690: 2388 -
13a
Cristau H.-J.Coulombeau A.Genevois-Borella A.Sanchez F.Pirat J.-L. J. Organomet. Chem. 2002, 643-644: 381 -
13b
Deprèle S.Montchamp J.-L. J. Org. Chem. 2001, 66: 6745 -
14a
Gallagher MJ.Honegger H. Aust. J. Chem. 1980, 33: 287 -
14b
Kehler J.Ebert B.Dahl O.Krogsgaard-Larsen P. Tetrahedron 1999, 55: 771 - 17
Arndt H.-D.Welz R.Müller S.Ziemer B.Koert U. Chem. Eur. J. 2004, 10: 3945
References and Notes
All new compounds gave spectroscopic data and high-resolution mass spectrometric data consistent with their assigned structure.
8
Bis({4-methyl-1-[(4-methylphenyl)sulfonyl]-3-pyrrolidinyl}methyl)phosphinic
Acid
(8a)
A boiling solution
of N,N-diallyl-4-methylbenzenesulfon-
amide
(2a, 0.613 g, 2.439 mmol) and hypophosphorous
acid (0.070 g, 1.061 mmol), in anhyd THF (5 mL) was treated with
AIBN (4 × 0.087 g, 4 × 0.531
mmol) over 36 h. After cooling to r.t., brine (20 mL) was added
and the mixture extracted with CH2Cl2 (3 × 20
mL). The combined layers were dried (MgSO4), concentrated
(under reduced pressure), and column chromatography [SiO2,
PE-EtOAc (4:6) to EtOAc-MeOH (1:1)] gave
phosphinic acid 8a (0.495 g, 82%)
as an inseparable mixture of isomers, with a cis/trans ratio of 2.2:1 (from the ¹H
NMR spectrum); white solid; mp 118-127 ˚C.
IR (CH2Cl2): νmax = 3541,
3058, 2964, 2882, 1598, 1479, 1454, 1406, 1384, 1337, 1160, 1093,
1044, 955 cm-¹.
cis-Diastereomers: ¹H
NMR (400 MHz, CDCl3): δ = 7.72
(d, J = 8.0 Hz, 4 H, 4 × SCCH, arom), 7.43-7.38 (m, 4 H, 4 × CHCCH3, arom), 3.52 (dd, J = 9.5, 7.5 Hz, 2 H, 2 × CH
aHbCHCH2P),
3.36-3.26 (m, 2 H, 2 × CH3CHCH
aHb), 3.08-2.95
(m, 4 H, 2 × CHa
H
bNCHa
H
bCHCH2P), 2.50-2.30
(m, 2 H, 2 × CHCH2P),
2.43, 2.42 (2 × br s, 6 H, 2 × ArCH
3), 2.30-2.11 (m,
2 H, 2 × CH3CH),
1.47 (dq, J = 15.0, 4.5 Hz,
2 H, 2 × CH
aHbP),
1.37-1.10 (m, 2 H, 2 × CHa
H
bP), 0.68, 0.65 (d and dd, J = 7.0 Hz and 7.0, 2.5 Hz,
6 H, 2 × CH
3CH). ¹³C NMR
(100 MHz, CDCl3): δ = 145.0,
144.9 (2 × SCCH, arom),
135.2, 135.1 (2 × CHCCH3,
arom), 130.8 (4 × CHCCH3),
128.7, 128.6 (4 × SCCH,
arom), 55.6 (2 × CH3CHCH2), 53.0, 52.7 (br s and
d, ³
J
CP = 5.5
Hz, 2 × CH2CHCH2P),
37.9-37.4 (m, 2 × CHCH2P), 37.7, 37.2 (2 × d, ³
J
CP = 12.0, 10.5
Hz, 2 × CH3
CH),
30.3 (br d, ¹
J
CP = 89.5
Hz, 2 × CH2P),
21.5 (2 × ArCH3),
13.7, 13.6 (2 × CH3CH).
trans-Diastereomers: ¹H
NMR (400 MHz, CDCl3): δ = 3.81-3.70
(m, 2 H, 2 × CH
aHbCHCH2P),
3.52-3.43 (m, 2 H, 2 × CH3CHCH
aHb), 3.08-2.90
(m, 2 H, 2 × CHa
H
bCHCH2P), 2.73
(br t, J = 9.5 Hz, 2 H, 2 × CH3CHCHa
H
b), 1.72-1.05 (m,
8 H, 2 × CHCHCH
2P), 0.91,
0.87 (d and dd, J = 6.5 Hz and
8.0, 6.5 Hz, 6 H, 2 × CH
3CH). ¹³C
NMR (100 MHz, CDCl3): δ = 55.7-55.2 (m,
2 × CH3CHCH2),
55.3-54.9 (2 × CH2CHCH2P),
41.9-41.3 (m, 2 × CH3
CHCH), 31.7
(br d, ¹
J
CP = 90.5
Hz, 2 × CH2P),
15.9, 15.8 (2 × CH3CH). ³¹P
NMR (162 MHz; CDCl3): δ = 39.6.
ESI-MS: m/z (%) = 316
(100), 567 (92) [M - H+].
ESI-HRMS: m/z calcd for C26H37N2O6PS2: 567.1758;
found: 567.1752.
In the absence of AIBN or Et3B, pyrrolidine products were formed in low yields after extended reaction times. For example, heating 2a (1 equiv) with H3PO2 (4.3 equiv) in degassed dioxane for 3 d, followed by esterification, gave a 4.7:1 mixture of 9 and 10, respectively, in a combined yield of only 34%.
15Bond-dissociation energies based on DFT calculations (B3LYP functional, 6-13G(d,p) basis set, calculations performed using Gaussian03) for PhP(S)(OEt)H and PhP(O)(OEt)H are around 316 and 345 kJ mol-¹, respectively. McGrady, J. E.; Pantazis, D. unpublished results.
16
O
-(3-{[({4-Methyl-1-[(4-methylphenyl)sulfonyl]-3-pyr-rolidinyl}methyl)(phenyl)phosphorothioyl]oxy}prop-yl){4-methyl-1-[(4-methylphenyl)sulfonyl]-3-pyrrolidinyl}methyl(phenyl)phosphinothioate
(16a)
A boiling solution of N,N-diallyl-4-methylbenzene sulfonamide
(2a, 0.372 g, 1.479 mmol) and O-(3-{[phen-
yl(thioxo)phosphoranyl]oxy}propyl)phenylphosphinothioate (14, 0.264 g, 0.741 mmol) in anhyd THF (15
mL) was treated portionwise with AIBN (4 × 0.024
g, 4 × 0.148 mmol) over 36 h. After cooling
to r.t., 1 M aq NaOH (20 mL) was added and the mixture extracted
with CH2Cl2 (3 × 15 mL).
The combined organic layers were dried (MgSO4), concentrated
(under reduced pressure), and column chromatography [SiO2,
CH2Cl2-EtOAc (97:3)] gave bispyrrolidine 16a (0.477 g, 75%) as an inseparable
mixture of isomers, with a cis/trans ratio of 2.5:1 (from the ¹H
NMR spectrum); white solid; mp 61-66 ˚C.
IR (CHCl3): νmax = 3022,
2967, 2892, 2433, 2401, 2255, 1965, 1919, 1822, 1598, 1479, 1437,
1400, 1385, 1342, 1305, 1289, 1216, 1160, 1109, 1095, 1041, 1017,
968 cm-¹.
cis-Diastereomers: ¹H
NMR (400 MHz, CDCl3): δ = 7.89-7.75
(m, 4 H, 4 × PCCH,
arom), 7.72-7.66 and 7.62-7.56 (2 × m,
4 H, 4 × SCCH,
arom), 7.59-7.51 (m, 2 H, 2 × PCCHCHCH, arom), 7.55-7.41 (m, 4 H,
2 × PCCHCH, arom),
7.35-7.26 (m, 4 H, 4 × SCCHCH, arom), 4.20-4.04 and 3.75-3.58
(2 × m, 4 H, POCH
2CH2CH
2), 3.25 (dd, J = 9.5, 6.5 Hz, 2 H, 2 × CH3CHCH
aHbN), 3.17 (br
t, J = 9.0 Hz, 2 H, 2 × NCH
aHbCHCH2P),
3.04-2.94 (m, 2 H, 2 × CH3CHCHa
H
bN), 2.80-2.67 (m,
2 H, NCHa
H
bCHCH2P),
2.56-2.35 (m, 2 H, 2 × CHCH2P), 2.44, 2.42 (2 × s,
6 H, 2 × ArCH
3),
2.30-1.96 (m, 2 H, 2 × CH3CH), 2.05-1.65 (m, 4 H, 2 × CH
2P), 1.97-1.78 (m,
2 H, POCH2CH
2),
0.74, 0.70 (2 × d, J = 7.0,
7.0 Hz) and 0.65-0.59 (m, 6 H, 2 × CH
3CH). ¹³C
NMR (100 MHz, CDCl3): δ = 143.2
(2 × SCCH,
arom), 133.8-131.6 (m, 2 × PCCH, 2 × SCCHCHCCH3, arom), 132.5-132.2
(m, 2 × PCCHCHCH,
arom), 131.3-129.0 (m, 4 × PCCH, arom), 129.6, 129.5 (4 × SCCHCH, arom), 128.8-128.4 (4 × PCCHCH, arom), 127.3, 127.2 (4 × SCCH, arom), 60.9-60.2 (m, 2 × POCH2),
54.1, 53.9 (2 × CH3CHCH2N), 51.2, 50.9 (2 × d, ³
J
CP = 5.5, 8.5 Hz,
2 × CH2CHCH2P),
36.3 (s) and 36.0-35.8 (m) (2 × CHCH2P), 35.7, 35.6 (2 × d,
³
J
CP = 10.5, 10.5
Hz, 2 × CH3
CH),
34.5, 34.3 (2 × d, ¹
J
CP = 79.5, 80.0
Hz, 2 × CH2P),
31.1-30.7 (m, POCH2
CH2),
21.4, 21.4 (2 × ArCH3),
13.2, 13.1 (2 × CH3CH).
trans-Diastereomers: ¹H
NMR (400 MHz; CDCl3): δ = 3.82-3.68
(m, 2 H, 2 × NCH
aHbCHCH2P),
3.56-3.35 (m, 4 H, 2 × CH3CH
aHbNCHa
H
bCHCH2P), 0.91-0.85
and 0.81-0.76 (2 × m, 6 H, 2 × CH3CH). ¹³C
NMR (100 MHz; CDCl3): δ = 53.6-53.3
(m, 2 × CH3CHCH2),
53.4-53.0 (m, 2 × CH2CHCH2P), 40.3-40.1
and 40.0-39.8 (2 × m, 2 × CHCH2P), 40.0-39.6
(m, 2 × CH3
CH),
38.9-37.5 (m, 2 × CH2P), 15.6, 15.3 (2 × CH3CH). HRMS-FAB: m/z calcd for C41H52N2O6P2S4:
859.2256; found: 859.2264.