Y. Xie et al. / Tetrahedron: Asymmetry 20 (2009) 1425–1432
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4.2.6.1. (R)-7-O-((S)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
(DMSO-d6) d 148.2; HRMS (APCI) calcd for C28H20ClNO3P [M+1]:
2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine 4a.
White
484.0869, found: 484.0888.
solid, 65.0% yield, mp: 117 °C (dec). ½a D20
ꢃ
¼ þ78:1 (c 0.19, CHCl3).
1H NMR (400 MHz, CD3COCD3) d 2.13–2.18 (m, 1H), 2.53–2.57 (m,
1H), 2.80–2.91 (m, 1H), 3.01–3.04 (m, 1H), 5.84–5.87 (m, 1H), 7.02
(d, J = 8.8 Hz, 1H), 7.24–7.31 (m, 4H), 7.37–7.43 (m, 2H), 7.46–7.52
(m, 3H), 7.62 (d, J = 8.8 Hz, 1H), 7.72–7.82 (m, 2H), 7.88–7.92 (m,
2H); 8.01–8.05 (m, 1H), 8.12–8.15 (m, 1H), 8.30 (d, J = 8.4 Hz, 2H);
13C NMR (100 MHz, CD3COCD3) d 162.4, 156.9, 149.1, 149.0, 148.7,
140.0, 136.5, 134.9, 133.6, 133.2, 132.5, 132.0, 131.4, 130.3, 129.7,
129.6, 129.4, 129.3, 127.6, 127.3, 127.2, 127.1, 127.0, 126.0, 125.7,
125.0, 124.9, 123.6, 123.1, 122.7, 120.8, 79.9, 32.9, 23.3; 31P NMR
(DMSO-d6) d 153.4; HRMS (APCI) calcd for C34H25NO3P [M+1]:
526.1572, found: 526.1584.
4.2.6.5. (R)-8-O-((S)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
2-phenyl-5,6,7,8-tetrahydroquinoine 6a.
White solid, 90.1%
yield, mp: 109 °C (dec). ½a D20
ꢃ
¼ þ72:9 (c 0.20, CHCl3), 1H NMR
(400 MHz, CD3COCD3) d 1.74–1.97 (m, 2H), 2.09–2.14 (m, 2H),
2.76–2.85 (m, 2H), 5.55–5.59 (m, 1H), 6.56 (d, J = 8.8 Hz, 1H),
7.22–7.30 (m, 4H), 7.35–7.39 (m, 2H), 7.40–7.47 (m, 3H), 7.61–
7.72 (m, 3H), 7.86 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H); 8.02
(d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 8.31 (d, J = 8.4 Hz, 2H);
13C NMR (100 MHz, CD3COCD3) d 155.3, 154.6, 149.1, 149.0,
139.8, 139.2, 133.6, 133.3, 132.7, 132.4, 131.9, 131.3, 130.0,
129.7, 129.5, 129.4, 129.2, 127.6, 127.3, 127.2, 127.1, 126.9,
125.9, 125.6, 125.1, 125.0, 123.8, 123.0, 122.8, 120.5, 74.6, 31.9,
23.3, 14.3; 31P NMR (DMSO-d6) d 154.4; HRMS (APCI) calcd for
C35H27NO3P [M+1]: 540.1728, found: 540.1698.
4.2.6.2. (R)-7-O-((R)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine 4b.
White
solid, 55.1% yield.
½
a 2D0
ꢃ
¼ ꢁ221:5 (c 0.42, CHCl3). 1H NMR
(400 MHz, CD3COCD3) d 2.15–2.21 (m, 1H), 2.48–2.54 (m, 1H),
2.74–2.81 (m, 1H), 2.95–3.01 (m, 1H), 5.70–5.75 (m, 1H), 7.22–
7.34 (m, 4H), 7.38–7.48 (m, 3H), 7.54 (d, J = 8.0 Hz, 2H), 7.61 (d,
J = 8.8 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.75 (t, J = 8.8 Hz, 2H), 7.95
(d, J = 8.4 Hz, 1H), 8.04 (t, J = 8.8 Hz, 2H), 8.11 (d, J = 8.4 Hz, 1H),
8.23 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CD3COCD3) d 162.3,
156.9, 149.5, 148.6, 140.1, 136.4, 134.8, 133.6, 133.3, 132.5,
132.0, 131.5, 130.8, 129.7, 129.6, 129.5, 129.4, 127.8, 127.6,
127.4, 127.3, 127.2, 127.1, 126.1, 125.8, 125.1, 125.0, 123.4,
123.3, 122.7, 120.8, 79.6, 33.3, 27.9; 31P NMR (DMSO-d6) d 145.4;
HRMS (APCI) calcd for C34H25NO3P [M+1]: 526.1572, found:
526.1547.
4.2.6.6. (R)-8-O-((R)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
2-phenyl-5,6,7,8-tetrahydroquinoine 6b.
White solid, 29.3%
yield, mp: 104 °C (dec). ½a D20
ꢃ
¼ ꢁ290:7 (c 0.35, CHCl3). 1H NMR
(400 MHz, CD3COCD3) d 1.81–1.90 (m, 2H), 2.13–2.29 (m, 1H),
2.26–2.30 (m, 1H), 2.72–2.88 (m, 2H), 5.54–5.58 (m, 1H), 7.25–
7.35 (m, 4H), 7.37–7.54 (m, 5H), 7.58–7.61 (m, 3H), 7.75 (d,
J = 8.0 Hz, 1H), 7.89–8.08 (m, 4H), 8.30 (d, J = 8.0 Hz, 2H); 13C
NMR (100 MHz, CD3COCD3) d 155.1, 154.8, 149.5, 149.4, 148.9,
139.9, 139.0, 133.6, 133.3, 133.1, 132.4, 132.3, 132.0, 131.2,
130.4, 129.8, 129.5, 129.4, 129.3, 127.7, 127.3, 127.2, 127.1,
127.0, 125.9, 125.6, 125.2, 125.1, 123.6, 123.5, 122.7, 120.2, 73.9,
31.9, 28.5, 19.6; 31P NMR (CD3COCD3) d 153.4; HRMS (APCI) calcd
for C35H27NO3P [M+1]: 540.1728, found: 540.1759.
4.2.6.3. (R)-7-O-((S)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridine 5a.
White
4.3. General procedure for asymmetric 1,4-conjugate addition
solid, 78.4% yield, mp: 123 °C (dec). ½a D20
ꢃ
¼ þ231:0 (c 0.16, CHCl3).
1H NMR (400 MHz, CD3COCD3) d 2.13–2.18 (m, 1H), 2.51–2.57 (m,
1H), 2.81–2.89 (m, 1H), 2.97–3.03 (m, 1H), 5.74–5.79 (m, 1H),
7.29–7.35 (m, 4H), 7.39–7.52 (m, 4H), 7.61 (d, J = 8.8 Hz, 1H),
7.65 (d, J = 8.0 Hz, 1H), 7.97–8.00 (m, 2H), 8.05 (d, J = 8.0 Hz, 1H),
8.13 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CD3COCD3) d 162.9,
150.7, 148.9, 148.5, 137.4, 137.2, 133.6, 133.2, 132.6, 132.1,
131.5, 130.5, 129.5, 129.3, 127.4, 127.3, 127.2, 127.0, 126.1,
125.8, 124.9, 124.8, 123.5, 123.4, 122.6, 78.7, 33.3, 27.5; 31P NMR
(DMSO-d6) d 150.3; HRMS (APCI) calcd for C28H20ClNO3P [M+1]:
484.0869, found: 484.0880. Crystal data for 5a. Mw = 483.86,
T = 293(2) K, k = 0.71073 Å, monoclinic, P2(1), a = 9.0228(19) Å,
4.3.1. Preparation of catalyst
To a 25 mL air-free Schlenk tube, were added 53.9 mg of 6a
(0.10 mmol), 8.8 mg of CuBr2 (0.04 mmol), and 8 mL of CH2Cl2 un-
der nitrogen atmosphere. After the mixture was stirred at 40 °C for
45 min, the catalyst solution was used for eight separated conju-
gate addition reactions.
4.3.2. Asymmetric 1,4-conjugate addition
Chalcone substrate (0.5 mmol) and 1 mL of the above pre-
pared catalyst solution were added to a flame-dried Schlenk tube
under an argon atmosphere. After the solvent had been removed,
2 mL of diethyl ether was added. The slurry was stirred at room
temperature for 10 min and then cooled to the desired tempera-
ture. After the slurry had been stirred for 15 min at the desired
temperature, 0.7 mL of Et2Zn (1.1 M in toluene, 1.5 mol equiv)
was added slowly. The resulting mixture was stirred at this tem-
perature for the time indicated. Dilute hydrochloric acid (4 mL,
5%) was added to quench the reaction. The mixture was allowed
to warm to room temperature, and then 15 mL of diethyl ether
was added. The organic layer was washed with 5 mL of saturated
NaHCO3 and 5 mL of brine and then dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure, and
the residue was purified by column chromatography on silica
gel and eluted with EtOAc/hexanes (1/40–1/20) to afford the
addition product.
b = 12.6596 (13) Å, c = 10.0940(10) Å,
a
= 90° (3), b = 94.861° (2),
c
l
= 90°
(2),
V = 1148.8(2) Å3,
Z = 2,
Dcalcd = 1.399 mg/m3,
= 0.268 mmꢁ1
,
F(0 0 0) = 500. Crystal size 0.202 ꢂ 0.147 ꢂ
0.086 mm, independent reflections 4549 [Rint = 0.0451], reflections
collected 6834, refinement method, full-matrix least-squares on F2,
goodness-of-fit on F2 0.917, final R indices [I > 2
r(I)] R1 = 0.0491,
wR2 = 0.0975, R indices (all data) R1 = 0.0726, wR2 = 0.1052, abso-
lute structure parameter was ꢁ0.13 (9), largest diff. peak and hole
0.269 and ꢁ0.235 e Å-3
.
4.2.6.4. (R)-7-O-((R)-2,20-O,O-(1,10-Binaphthyl)-dioxo-phosphite)-
2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridine 5b.
White
solid, 79.7% yield, mp: 121 °C (dec). ½a D20
ꢃ
¼ ꢁ206:1 (c 0.16, CHCl3),
1H NMR (400 MHz, CD3COCD3) d 2.21–2.26 (m, 1H), 2.57–2.63 (m,
1H), 2.83–2.87 (m, 1H), 2.99–3.05 (m, 1H), 5.64–5.69 (m, 1H),
7.30–7.36 (m, 5H), 7.44–7.53 (m, 2H), 7.63 (d, J = 8.8 Hz, 1H),
7.71–7.42 (m, 2H), 8.00 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.8 Hz, 2H),
8.15 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CD3COCD3) d 161.4,
149.1, 147.4, 146.8, 136.8, 136.3, 132.0, 131.7, 131.2, 130.8,
130.6, 130.1, 128.6, 128.5, 126.7, 126.5, 125.9, 125.8, 125.3,
125.1, 124.0, 123.4, 123.3, 121.9, 121.6, 78.4, 32.1, 26.5; 31P NMR
Acknowledgments
This work was financially supported by the National Natural
Science Foundation of China (NSFC, 20876149), the Natural Science
Foundation of Zhejiang Province (Y406419), and the Chinese Acad-
emy of Sciences.