S. Eröksüz et al. / Tetrahedron: Asymmetry 21 (2010) 2535–2541
2539
1H), 2.39 (s, 3H), 2.31 (s, 1H), 1.85 (m, 1H), 1.71 (d, J = 6.5, 1H),
1.69–1.50 (m, 2H), 0.99 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 199.20, 144.71, 132.73, 129.83, 127.94, 78.70, 72.70,
70.86, 69.80, 69.23, 68.62, 40.52, 33.74, 24.90, 21.60, 10.44; IR
(neat) cmꢀ1 3120, 2969, 1645, 1455, 1357, 1182, 1261, 1150,
869, 790, 822. MS–ESI+: m/z 482.1 [M+H]+. HRMS–EI (m/z): calcd
for C24H28FeNO4S [M+H]+: 482.1088; found: 482.1081.
(br, 1H), 2.15–2.02 (m, 2H), 1.81 (d, J = 3.3 Hz, 1H), 1.72–1.48 (m,
3H), 1.36–1.26 (m, 1H), 1.23 (d, J = 6.4 Hz, 1H), 0.89 (t, J = 7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 132.89 (JC,P = 8 Hz), 132.70
(JC,P = 8 Hz), 128.70, 128.60, 128.46, 128.40, 89.80, 68.50, 68.09,
67.91, 67.24, 67.02, 66.07, 42.11, 34.18 (JC,P = 14 Hz), 30.63, 28.59
(JC,P = 8 Hz), 10.16; 31P NMR (161.97 MHz, CDCl3) d ꢀ23.5; IR (neat)
cmꢀ1 3396, 3071, 2964, 1480, 1260, 815, 742, 697. MS–ESI+:
m/z 498.1 [M+H]+. HRMS–EI (m/z): calcd for C29H33FeNOP [M+H]+:
498.1649; found: 498.1649. POFAM3: Rf = 0.15, hexane/EtOAc
4.1.3. Synthesis of phosphorus aziridines PFAM1 and POFAM1
Compound 5 (450 mg, 0.936 mmol) was dissolved in THF (3 mL,
dried and degassed) in a reaction flask. The flask was cooled to
ꢀ78 °C and potassium diphenylphosphide (2.10 mL used from a
0.5 M solution in THF) was added slowly over 30 min. After stirring
for about 1 h, TLC analysis showed no starting material. The crude
reaction mixture was filtered through a short plug of basic alumina
using hexanes/EtOAc 5:1 as the eluent under N2. After evaporation
of the solvent, pure PFAM1 was isolated in 75% yield (348 mg, an
orange oil that oxidizes slowly upon standing in air) along with
POFAM1 isolated in 20% yield (102 mg) as a red oily product.
1:1 + 2% Et3N; ½a 2D8
ꢁ
¼ ꢀ20:9 (c 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.61–7.51 (m, 4H), 7.43–7.37 (m, 6H), 4.23 (s, 1H), 4.18 (s,
1H), 4.14 (s, 5H), 4.11 (s, 2H), 3.97 (d, J = 5.5 Hz, 1H), 2.32–2.13 (m,
2H), 1.81 (s, 1H), 1.73–1.43 (m, 4H), 1.33 (d, J = 6.3 Hz, 1H), 1.19
(m, 1H), 0,84 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
132.90 (JC,P = 50 Hz), 131.92 (JC,P = 50 Hz), 130.41, 130.00, 129.45,
129.32, 127.44, 127.33, 127.26, 89.51, 68.58, 67.66, 66.79, 66.72,
66.43, 63.93, 63.99, 62.85, 41.14, 33.67 (JC,P = 58 Hz), 31.40, 27.72,
24.16, 8.71; 31P NMR (161.97 MHz, CDCl3) d 28.27. MS–ESI+: m/z
514.1 [M+H]+. HRMS–EI (m/z): calcd for C29H32FeNO2PNa [M+Na]+:
536.1418; found: 536.1429.
PFAM1: Rf = 0.73, hexane/EtOAc 1:1 + 2% Et3N; ½a D22
¼ þ13 (c 0.5,
ꢁ
DCM); 1H NMR (400 MHz, CDCl3) d 7.34 (m, 4H), 7.23 (m, 6H),
4.77 (s, 2H), 4.43 (s, 2H), 4.08 (s, 5H), 2.32 (t, J = 7.5 Hz, 2H), 2.27
(d, J = 7.1 Hz, 1H), 1.74 (m, 2H), 1.65 (d, J = 6.6 Hz, 1H), 1.38 (m,
1H), 0.94 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 200.20,
132.92 (JC,P = 18 Hz),, 132.61 (JC,P = 18 Hz),, 128.82, 128.59,
128.51, 128.23, 78.53, 72.33, 70.29, 69.83, 69.13, 68.88, 40.80,
37.00, 34.55 (JC,P = 13.9 Hz), 28.73, 10.53; 31P NMR (161.97 MHz,
CDCl3) d ꢀ21.5; IR (neat) cmꢀ1 3051, 2967, 1665, 1457, 1255,
913, 745, 697, 823. MS–ESI+: m/z 496.1 [M+H]+. HRMS–EI (m/z):
calcd for C29H31FeNOP [M+H]+: 496.1493; found: 496.1496. PO-
4.1.5. Synthesis of PFAM4 and POFAM4 ligands
PFAM1 (163 mg, 0.329 mmol) was dissolved in THF (2.5 mL,
dried and degassed) in a reaction flask. The flask was cooled to
ꢀ78 °C and L-Selectride (0.5 mL, from a 1 M THF solution) was
added slowly over 30 min. After stirring for eight hours TLC analy-
sis showed no starting material. The reaction mixture was parti-
tioned between 10% NaOH (10 mL) and EtOAc (15 mL ꢂ 2). The
combined organic layers were dried over Na2SO4, concentrated,
and purified by flash chromatography through a short plug of basic
alumina using hexane/EtOAc 3:1 as an eluent under N2. After evap-
oration of the solvent, pure PFAM4 was obtained in 40% yield
(65 mg) as a pale yellow oil together with its oxidized form PO-
FAM4 in 55% yield (93 mg) as a yellow oily product. It should be
noted that PFAM4 is highly sensitive to oxidation. When exposed
to air overnight it was completely converted to POFAM4. PFAM4:
Rf = 0.64, hexane/EtOAc 1:1 + 2% Et3N. This compound was highly
susceptible to oxidation; full characterization was performed on
its phosphine oxide. POFAM4: Rf = 0.17, hexanes/EtOAc 1:1 + 2%
FAM1: Rf = 0.12, hexane/EtOAc 1:1 + 2% Et3N; ½a D22
¼ þ21:4 (c
ꢁ
0.35, DCM); 1H NMR (400 MHz, CDCl3) d 7.65 (m, 4H), 7.39 (m,
4H), 7.28 (m, 2H), 5.00 (s, 1H), 4.77 (s, 1H), 4.41 (s, 2H), 4.05 (s,
5H), 2.96 (dd, J = 2.9 and 3.2 Hz, 1H), 2.52 (m, 2H), 2.32 (s, 1H),
2.05 (m, 1H), 1.82 (d, J = 6.2, 1H), 1.62 (m, 1H), 1.54 (m, 1H), 0.81
(t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 200.3, 131.80,
130.60, 128.80, 128.70, 128.59, 78.67, 72.51, 71.02, 69.79, 68.70,
64.78, 40.06, 37.93, 35.01, 29.64, 10.40; 31P NMR (161.97 MHz,
CDCl3) d 29.07. MS–ESI+: (m/z) 512.1 [M+H]+. HRMS–EI (m/z): calcd
for C29H31FeNO2P [M+H]+: 512.1442; found: 512.1438.
Et3N; ½a 2D2
ꢁ
¼ þ32:8 (c 1.5, DCM); 1H NMR (400 MHz, CDCl3) d
When crude PFAM1 was purified by flash column chromatogra-
phy on silica gel, pure PFAM1 was isolated in 96% yield and there
was no oxidized product POFAM1. We believe that neutral alu-
mina catalyzes the oxidation. A sample of PFAM1 was stirred in
ethyl acetate in open air and no oxidation was observed after
6 days. However when PFAM1 was stirred under the same condi-
tions with a small amount of neutral alumina, it was oxidized com-
pletely to POFAM1 in approximately 10 h.
7.64 (m, 4H), 7.41 (m, 6H), 4.24 (s, 1H), 4.17 (s, 5H), 4.13 (s, 1H),
4.07 (s, 2H), 3.91 (d, J = 6.0 Hz, 1H), 2.56 (m, 1H), 2.38 (m, 1H),
1.71 (m, 2H), 1.62–1.48 (m, 3H), 1.30 (d, J = 7.1 Hz, 1H), 1.19 (br,
1H), 0.80 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 133.60
(JC,P = 80 Hz), 132.62 (JC,P = 80 Hz), 131.33, 130.93, 130.84, 130.72,
128.61, 128.54, 91.86, 70.82, 68.59, 67.38, 67.20, 66.09, 65.63,
64.71, 44.54, 35.23, 34.53, 32.08, 29,20, 14.24. 31P NMR
(161.97 MHz, CDCl3) d 30.50. MS–ESI+: m/z 514.1 [M+H]+. HRMS–
EI (m/z): calcd for C29H32FeNO2PNa [M+Na]+: 536.1418; found:
536.1417.
4.1.4. Synthesis of PFAM3 and POFAM3 ligands
PFAM1 (155 mg, 0.313 mmol) was dissolved in MeOH (3 mL,
degassed) and cooled to ꢀ78 °C. Next, ZnCl2 (64 mg, 0.47 mmol)
was added to this stirred solution. After 1 h, NaBH4 (23.7 mg,
0.626 mmol) was added and stirring was continued at ꢀ78 °C for 4
hours. At that time TLC analysis showed that the reaction was
complete. The reaction mixture was partitioned between DCM
(2 ꢂ 10 mL) and water (10 mL). The combined organic layers were
dried over Na2SO4, filtered, and concentrated to give crude PFAM3.
Purification by flash column chromatography under N2 through a
short plug of basic alumina eluting with hexane/EtOAc 5:1 gave pure
PFAM3 in 60% yield (93 mg) as a pale yellow oil and its oxidized form
POFAM3 in 35% yield (56 mg) as a yellow oily product. When pure
PFAM3 was exposed to air, oxidation takes place slowly. PFAM3:
4.1.6. Synthesis of tosylate 6
Starting from aziridine 4 (920 mg, 2.81 mmol) and following the
same procedure used for the synthesis of 5, pure compound 6 (or-
ange oily product) was obtained in 96% yield (1.30 g) after flash
column chromatography (silica gel, hexane/EtOAc 1:1). Rf = 0.68,
hexanes/EtOAc 1:2;
½
a 2D2
ꢁ
¼ þ95:7 (c 0.98, DCM); 1H NMR
(400 MHz, CDCl3) d 7.80 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H),
4.86 (s, 2H), 4.51 (s, 2H), 4.17 (s, 5H), 4.11 (d, J = 5.7 Hz, 2H), 2.51
(m, 1H), 2.45 (s, 3H), 2.22 (br, 1H), 1.91 (d, J = 6.6 Hz, 1H), 1.83
(m, 1H), 1.66–155 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 199.4, 144.7, 133.1, 129.9, 128.3, 78.2, 72.5,
71.9, 69.8, 69.4, 68.7, 40.2, 35.6, 24.9, 21.6, 10.0; IR (neat) cmꢀ1
2925, 1657, 1460, 1360, 1177, 1259, 1100, 840, 820. MS–ESI+: m/
z 482.1 [M+H]+. HRMS–EI (m/z): calcd for C24H28FeNO4S [M+H]+:
482.1088; found: 482.1071.
Rf = 0.52, hexane/EtOAc 1:1 + 2% Et3N; ½a D22
= ꢀ24.6 (c 1.0, DCM);
ꢁ
1H NMR (400 MHz, CDCl3) d 7.34–7.23 (m, 10H), 4.29 (d, J = 4.3 Hz,
1H), 4.19 (s, 1H), 4.16 (s, 1H), 4.11 (s, 5H), 4.08 (s, 2H), 2.46