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N. Toselli et al. / Tetrahedron: Asymmetry 21 (2010) 1238–1245
stirred for 14 h at room temperature. The solvent and the excess of
trifluoroacetic acid were removed and the product was dissolved in
dichloromethane. The organic layer was successively washed with
a saturated solution of NaHCO3 (100 mL), water, (100 mL) and
brine (100 mL). Then, the organic layer was dried over Na2SO4, fil-
tered, and concentrated. Compound 11 was obtained as a white so-
lid and used without further purification. 97% yield. Mp: 162 °C.
54.7 (d, JPC = 7.3 Hz, CH2), 62.8 (d, JPC = 7.7 Hz, CH), 111.0 (d,
JPC = 11.1 Hz, CaroH), 115.2 (d, JPC = 12.9 Hz, CaroH), 120.0 (s, CaroH),
120.7 (s, CaroH), 121.9 (d, JPC = 4.5 Hz, CaroH), 123.7 (s, CaroH), 125.3
(s, CaroH), 127.8 (s, CaroH), 129.36 (s, CaroH), 129.38 (d, JPC = 6.8 Hz,
CaroH), 130.1 (d, JPC = 3.9 Hz, Caro), 144.9 (d, JPC = 13.9 Hz, Caro),
146.6 (d, JPC = 22.9 Hz, Caro), 153.0 (d, JPC = 5.7 Hz, Caro). HRMS
(ESI-MS) [M+Na]+: found 369.1123; calcd for C21H19N2NaOP:
369.1127.
½
a 2D0
ꢁ
¼ ꢀ74 (c 0.5, CH2Cl2). Rf 0.08 (petroleum ether/ethyl acetate:
70/30). 1H NMR (200 MHz, CDCl3) d 1.72 (broad s, 1H), 2.91 (dd,
J = 10.4, 16.4 Hz, 1H), 3.36 (dd, J = 5.3, 16.4 Hz, 1H), 3.69 (dd,
J = 5.3, 10.5 Hz, 1H), 4.01 (d, J = 17.0 Hz, 1H), 4.10 (d, J = 17.0 Hz,
1H), 7.07–7.23 (m, 5H), 7.30–7.38 (m, 2H), 7.60–7.64 (m, 2H),
9.35 (broad s, 1H); 13C {1H} NMR (50 MHz, DMSO) d 30.7 (s,
CH2), 46.7 (s, CH2), 56.6 (s, CH), 119.2 (s, CaroH), 123.2 (s, Caro H),
125.58 (s, Caro H), 125.64 (s, Caro H), 125.8 (s, Caro H), 128.6 (s, Caro
H), 128.8 (s, Caro H), 134.2 (s, Caro), 136.0 (s, Caro), 138.7 (s, Caro),
171.4 (s, NC(O)). HRMS (ESI-MS) [M+H]+: found 253.1335; calcd
for C16H17N2O: 253.1335.
Following the general procedure, 15b was obtained as a white
solid. 80% yield. ½a D20
ꢁ
¼ ꢀ187 (c 0.76, CH2Cl2). 31P {1H} NMR
(81 MHz, CDCl3) d 110.8 (s); 1H NMR (200 MHz, C6D6) d 2.18 (dd,
J = 6.7, 15.8 Hz, 1H), 2.46 (td, J = 3.1, 8.9 Hz, 1H), 2.59 (dd, J = 9.5,
15.9 Hz, 1H), 3.02 (tm, J = 9.0 Hz, 1H), 3.73–3.89 (m, 1H), 6.45–
7.52 (m, 18H). 13C {1H} NMR (50 MHz, CDCl3) d 35.1 (s, CH2),
54.6 (d, JPC = 7.5 Hz, CH2), 62.8 (d, JPC = 7.9 Hz, 1H), 110.8 (d,
JPC = 10.7 Hz, CaroH), 115.1 (d, JPC = 13.0 Hz, CaroH), 119.8 (s, CaroH),
120.3 (s, CaroH), 122.6 (d, JPC = 6.4 Hz, CaroH), 124.0 (s, CaroH), 124.8
(s, CaroH), 126.6 (s, CaroH), 127.5 (s, CaroH), 127.9 (s, CaroH), 128.3 (s,
CaroH), 129.1 (s, CaroH), 129.4 (s, CaroH), 129.6 (d, JPC = 4.3 Hz, Caro),
130.8 (s, CaroH), 135.4 (s, Caro), 138.5 (s, Caro), 144.6 (d, JPC = 18.8 Hz,
4.3.7. General procedure for the reduction of 10 and 11
At 0 °C, LiAlH4 (2.11 g; 55.65 mmol; 3 equiv) was carefully
added to a solution of amide (1 equiv) in THF (200 mL). The mix-
ture was stirred for 14 h at room temperature and after cooling
down to 0 °C, the reaction was quenched with a saturated solution
of Na2SO4. The mixture was stirred for 2 h. Salts were filtered off on
Büchner and washed with CH2Cl2 (3 ꢃ 100 mL). The two layers
were separated and the aqueous layer was extracted with CHCl3
(4 ꢃ 100 mL). The combined organic layers were dried over
Na2SO4, filtered, and concentrated. The products were purified by
column chromatography on silica gel.
C
aro), 146.1 (d, JPC = 22.6 Hz, Caro), 150.2 (d, JPC = 4.7 Hz, Caro).
HRMS (ESI-MS) [M+H]+: found 423.1625; calcd for C27H24N2OP:
423.1621.
4.5. General procedure for the enantioselective Co(I)-catalyzed
[6+2] cycloaddition
Under a nitrogen atmosphere, the ligand (0.10 equiv) was
added to a solution of CoI2 (13 mg; 0.042 mmol; 0.05 equiv) in
1,2-dichloroethane (1 mL). The mixture was stirred for 10 min.
and powdered zinc (8.3 mg; 0.127 mmol; 0.15 equiv) was added.
4.3.7.1. (S)-2-(Anilinomethyl)indoline 1217
. Brown solid. 1.41 g;
Then,
a solution of 1,3,5-cycloheptatriene (93 mg; 1 mmol;
83% yield. Mp: 75 °C. ½a D20
¼ þ84 (c 1.0, CHCl3). Rf 0.61 (Petroleum
ꢁ
1.20 equiv) in 1,2-dichloroethane (1 mL) and a solution of alkyne
(1 equiv) in 1,2-dichloroethane (1 mL) and zinc iodide (27 mg;
0.085 mol; 0.10 equiv) were added successively. The resulting mix-
ture was heated at 40 °C for 20 h. After cooling to room tempera-
ture, the reaction was quenched with petroleum ether (5 mL).
The reaction mixture was filtered through CeliteÒ and removal of
solvent followed by column chromatography on silica gel (petro-
leum ether) gave compounds 3a–c. Analytic data, in particular
the NMR spectra, are in agreement with those of known com-
ether/AcOEt: 70/30). 1H NMR (200 MHz, CDCl3) d 2.89 (dd, J = 7.4,
15.6 Hz, 1H), 3.19 (dd, J = 9.0, 15.6 Hz, 1H), 3.28 (d, J = 5.7 Hz,
2H), 4.02 (br s, 2H), 4.10–4.24 (m, 1H), 6.62–6.76 (m, 5H), 7.00–
7.22 (m, 4H); 13C {1H} NMR (50 MHz, CDCl3) d 33.5 (s, CH2), 48.5
(s, CH2), 58.4 (s, CH), 109.6 (s, CaroH), 112.9 (s, CaroH), 117.6 (s, Car-
oH), 118.9 (s, CaroH), 124.8 (s, CaroH), 127.4 (s, CaroH), 128.4 (s, Caro),
129.2 (s, CaroH), 148.1 (s, Caro), 150.4 (s, Caro).
13b
pounds.
4.3.7.2. (S)-3-(Anilinomethyl)-1,2,3,4-tetrahydroisoquinoline 13.
Pale yellow solid. 4.05 g; 92% yield. Mp: 87 °C. ½a D20
¼ ꢀ76:3 (c
ꢁ
Acknowledgments
1.0, CH2Cl2). Rf 0.20 (AcOEt). 1H NMR (200 MHz, CDCl3) d 1.60 (br
s, 1H), 2.65 (dd, J = 9.9, 16.2 Hz, 1H), 2.86 (dd, J = 3.9, 16.3 Hz, 1H),
3.04–3.40 (m, 3H), 4.07 (s, 2H), 4.24 (br s, 1H), 6.67–6.76 (m, 3H),
7.02–7.24 (m, 6H); 13C {1H} NMR (50 MHz, CDCl3) d 33.0 (s, CH2),
48.0 (s, CH2), 49.1 (s, CH2), 53.0 (s, CH), 112.9 (s, CaroH), 117.4 (s, Car-
oH), 125.9 (s, CaroH), 126.0 (s, CaroH), 126.1 (s, CaroH), 129.2 (s, 2 Car-
oH), 134.0 (s, Caro), 135.6 (s, Caro), 148.4 (s, Caro). HRMS (ESI-MS)
[M+H]+: found 239.1541; calcd for C16H19N2: 239.1543.
We thank Dr. Nicolas Vanthuyne for chiral HPLC analyses, and
the ‘Centre Informatique National de l’Enseignement Supérieur’
(CINES) and the ‘Centre Régional de Compétences en Modélisation
Moléculaire’ (CRCMM) for the allocation of computational re-
sources. N.T. acknowledges MENRT for fundings.
References
4.4. General procedure for the synthesis of diazaphospholidines
15a–b
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A solution of diazaphospholidine
6 (1 mmol) and alcohol
(1 mmol) in toluene (4 mL) was refluxed until no starting material
was detected by means of 31P NMR. After removal of the solvent,
the ligand was obtained as a white solid after filtration on a neutral
alumina column (toluene).
Following the general procedure, 15a was obtained as a white
solid. 81% yield. ½a D20
ꢁ
¼ ꢀ176 (c 1.0, CH2Cl2). 31P {1H} NMR
(81 MHz, C6D6) d 108.3 (s); 1H NMR (200 MHz, C6D6) d 2.17 (dd,
J = 6.5, 16.0 Hz, 1H), 2.47 (td, J = 3.0, 9.0 Hz, 1H), 2.58 (dd, J = 9.6,
16.0 Hz, 1H), 2.97 (tm, J = 7.7 Hz, 1H), 3.72–3.88 (m, 1H), 6.73–
7.24 (m, 14H); 13C {1H} NMR (50 MHz, CDCl3) d 35.0 (s, CH2),