Asymmetric Catalysis
FULL PAPER
(d, J = 14.8 Hz, 2H), 2.37–2.40 (m, 2H), 1.50–1.82 (br, 4H), 1.10–1.35
(br, 4H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d = 24.7, 31.5, 45.3,
60.7, 121.7, 125.5, 126.3 (2C), 129.7, 133.5, 145.7, 149.3; IR (Nujol): n˜ =
3286(w), 3104(w), 2926(s), 2849(s), 2351(w), 1604(w), 1515(m), 1493(m),
Experimental Section
General methods: All reactions were performed in a dry nitrogen atmos-
phere using standard Schlenk techniques. Anhydrous solvents and re-
agents were purchased from Fluka and Aldrich, and used as received. We
1465(s), 1327(s), 1249(m), 1094(s), 795(s) cmÀ1; UV/Vis (CH2Cl2): labs
=
271, 411 nm; elemental analysis calcd (%) for C24H24N4O4S4 (560.73): C
54.41, H 4.31, N 9.99; found: C 54.45, H 4.33, N 10.00.
recorded 1H NMR and 13C NMR spectra on
a Gemini Varian 200
(200 MHz) or Gemini Inova 300 (300 MHz) spectrometer. GC-MS spec-
tra were recorded with a Hewlett-Packard 5971 instrument. LC-electro-
spray ionization mass spectra were obtained with an Agilent Technolo-
gies MSD1100 mass spectrometer. IR analysis was performed with an
FT-IR Nicolet 205, and HPLC with a Hewlett-Packard HP1100 equipped
with a chiral column (Chiralcel OD/AD). Analytical GC was performed
on a Hewlett-Packard HP6890 gas chromatograph using a chiral Mega-
dex-5 (25 m) column. Melting points were determined with a Büchi 150
melting point unit and are not corrected. The UV/Vis spectrophotometer
was a Perkin-Elmer model 554.
Compound 3d–f: NaBH4 (5 mmol) was added in portions to a cooled so-
lution (08C) of diimine (1 mmol) in MeOH (5 mL), and the mixture was
stirred at RT until the diimine had disappeared completely (checked by
1H NMR). Then water (10 mL) was added, MeOH was evaporated, and
the product was extracted with CH2Cl2 (34 mL). Evaporation of the
volatiles afforded crude 3, which was purified by consecutive washings or
flash chromatography.
(R,R)-T2Me (3d): Purified by flash chromatography: pale yellow solid;
Rf = 0.30 (CH2Cl2/MeOH 99:1); yield 45% (two steps); m.p. 77–788C;
[a]D
=
+8.1 (c = 0.42 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C,
Synthesis of 2c–g
TMS): d = 6.90 (t, J = 3.6 Hz, 4H), 6.75 (d, J = 3.6 Hz, 2H), 6.61 (d, J
= 3.6 Hz, 2H), 4.08 (d, J = 14.2 Hz, 2H), 3.86 (d, J = 14.2 Hz, 2 Hz),
2.47 (s, 6H), 3.32–2.37 (m, 2H), 1.55–1.88 (m, 4H), 1.12–1.38 (m, 4H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d = 143.1, 138.6, 136.7, 135.4,
Compound 2c: Prepared by Suzuki coupling ([PdCl2(PPh3)2]/Na2CO3(aq)
/
dimethoxyethane/EtOH/508C, 95% yield) between commercially avail-
able 5-nitro-2-bromothiophene and 5-formyl-2-thiopheneboronic acid.
Purified by flash chromatography (c-hex/AcOEt7:3 !6:4): yellow-orange
solid; m.p. 139–1418C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d =
9.94 (s, 1H), 7.90 (d, J = 4.4 Hz, 1H), 7.75 (d, J = 4.0 Hz, 1H), 7.43 (d,
J = 4.0 Hz, 1H), 7.28 (d, J = 4.4 Hz, 1H); 13C NMR (50 MHz, CDCl3,
258C, TMS): d = 182.5, 151.9, 147.0, 146.1, 144.4, 136.8, 129.5, 126.8,
126.8, 125.2, 123.2, 122.4, 60.1, 45.4, 31.2, 24.9, 15.3; IR (Nujol): n˜
=
3280(w), 3000(w), 2921(s), 2853(s), 1695(w), 1462(m), 1376(m), 1262(w),
1097(m), 1022(m), 789(m) cmÀ1; UV/Vis (CH2Cl2): labs = 317 nm; ele-
mental analysis calcd (%) for C26H30N2S4 (498.79): C 62.61, H 6.06, N
5.62; found: C 62.58, H 6.01, N 5.60.
124.7; IR (Nujol): n˜
= 2926(s), 2853(m), 1732(s), 1660(m), 1461(s),
1335(w), 1209(m) cmÀ1; UV/Vis (MeOH): labs = 340 nm; MS (70 eV):
m/z (%): 239 (100), 209 (10), 149 (50), 121 (20).[32]
(R,R)-T2MeO (3e): Used without further purification; pale beige solid;
yield 49% (two steps); m.p. 76–778C; [a]D
= +15.0 (c = 1.22 in
CHCl3); 1H NMR (200 MHz, CDCl3, 258C, TMS): d = 6.78–6.83 (m,
4H), 6.72 (d, J = 3.6 Hz, 2H), 6.07 (d, J = 4.2 Hz, 2H), 4.09 (d, J =
14.2 Hz, 2H), 3.90 (s, 6H), 3.85 (d, J = 14.2 Hz, 2H), 2.33–2.39 (m, 2H),
1.65–1.88 (br, 4H), 1.20–1.56 (br, 4H); 13C NMR (50 MHz, CDCl3, 258C,
TMS): d = 165.1, 142.4, 136.7, 124.8, 124.2, 121.6, 120.8, 104.3, 60.3, 60.2,
Compound 2d: Prepared by Suzuki coupling ([Pd(PPh3)4]/K2CO3/tolu-
ene/MeOH/reflux) of commercially available 5-methyl-2-thiophenebor-
onic acid and 5-bromothiophenecarboxaldehyde.[32]
Compound 2e: Prepared by Stille coupling ([Pd(PPh3)4]/THF/reflux,
85% yield) of 5-methoxy-2-tributyltinthiophene[33] and 5-bromothiophe-
necarboxaldehyde.[34]
45.7, 31.5, 24.9; IR (Nujol): n˜
= 3291(w), 2921(s), 2846(s), 2362(w),
1572(w), 1540(m), 1508(m), 1456(s), 1386(m), 1196(w), 1062(w),
793(w) cmÀ1; UV/Vis (CH2Cl2): labs = 326 nm; elemental analysis calcd
(%) for C26H30N2O2S4 (530.79): C 58.83, H 5.70, N 5.28; found: C 58.79,
H 5.65, N 5.26.
Compound 2 f: Prepared by Stille coupling ([Pd(PPh3)4]/toluene/reflux,
70% yield) of 5-pyrrolidine-2-tributyltinthiophene and 5-bromothiophe-
necarboxaldehyde.
Compound 2g: Prepared by Suzuki coupling ([PdCl2(PPh3)2]/Na2CO3/
DME/EtOH/508C, 70% yield). Purified by flash chromatography: white
Compound 3 f, 3g: The imine precursors were synthesized as described
in the typical procedure by reaction in toluene at 808C (24 h).
solid; Rf
=
0.33 (c-hex/AcOEt8:2); m.p. 135–137 8C; 1H NMR
(R,R)-T2NR (3 f): Purified by flash chromatography: pale brown solid;
Rf = 0.31 (CH2Cl2/MeOH 98.5:1.5); yield 31% (two steps); m.p. 80–
(200 MHz, CDCl3, 258C, TMS) d = 9.92 (s, 1H), 7.44–7.46 (m, 1H), 7.39
(d, J = 1.6 Hz, 1H), 7.09 (t, J = 4.2 Hz, 1H), 4.44 (s, 4H); 13C NMR
828C; [a]D
258C, TMS): d = 6.83 (dd, J = 2.4, 4.2 Hz, 2H), 6.72–6.84 (m, 4H), 5.61
(dd, J 2.1, 4.2 Hz, 2H), 4.09 (d, J 14.1 Hz, 2H), 3.84 (d, J =
=
+56.6 (c = 0.5 in CHCl3); 1H NMR (300 MHz, CDCl3,
(50 MHz, CDCl3, 258C, TMS): d
= 179.3, 148.6, 136.8, 133.3, 127.5,
126.8, 125.8, 114.7, 97.1, 65.2, 64.7; IR (Nujol): n˜ = 3002(m), 1648(s),
1.520(m), 1488(m), 1463(s), 1373(m), 1271(m) cmÀ1; UV/Vis (MeOH):
labs = 370 nm; MS (70 eV): m/z (%): 252 (68), 156 (18), 127 (100), 111
(33), 69 (55).
=
=
14.1 Hz, 2H), 3.26–3.29 (m, 8H), 2.32–2.35 (m, 2H), 2.18–2.20 (m, 4H),
2.02–2.12 (m, 8H), 1.72–1.75 (2H), 1.21–1.25 (m, 2H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d = 154.9, 141.2, 138.3, 125.3 (2C), 123.9,
(1R,2R)-N,N’-Bis(thienylmethyl)cyclohexane-1,2-diamines (3)
120.7, 120.0, 100.5, 66.1, 60.4, 51.0, 45.8, 26.0, 25.2; IR (neat): n˜
3283(w), 3058(w), 2936(m), 2851(m), 1558(w), 1535(s), 1505(s), 1481(s),
1456(m), 1352(m), 1054(m), 739(m) cmÀ1
UV/Vis (CH2Cl2): labs
371 nm; elemental analysis calcd (%) for C32H40N4S4 (608.21): C 63.12, H
6.62, N 9.20; found: C 63.17, H 6.57, N, 9.19.
=
Typical procedure: The desired aldehyde 2 (2 mmol) and (1R,2R)-diami-
nocyclohexane 1 (1 mmol) were dissolved in dry CH2Cl2 (10 mL) under
an N2 atmosphere in a two-necked flask (50 mL). MgSO4 (5 mmol) was
added and the mixture was stirred at RT for 24–48 h (checked by
1H NMR). The solution was filtered on Celite and the solvent was re-
moved under vacuum. The crude diimine was diluted with cyclohexane
and stirred overnight. The purified insoluble product was collected by fil-
tration.
;
=
(R,R)-EDOT-T (3g): Purified by flash chromatography: white solid; Rf
= 0.32 (CH2Cl2/MeOH 9:1); yield 45% (two steps); m.p. 50–528C; [a]D
1
= +40.0 (c = 0.38 in CHCl3); H NMR (300 MHz, CDCl3, 258C, TMS):
d = 7.13–7.16 (m, 2H), 6.95–6.98 (m, 2H), 4.27–4.29 (m, 4H), 4.19–4.22
(m, 4H), 3.95 (d, J = 15.2 Hz, 2H), 3.73 (d, J = 15.2 Hz, 2H), 2.28–2.31
(m, 2H), 2.15 (pseudod, J = 12.9 Hz, 2H), 2.00 (br, 4H), 1.72–1.75 (m,
2H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d = 138.2, 137.1, 135.0,
127.0, 123.2, 122.4, 114.5, 109.7, 65.0, 64.6, 60.2, 41.2, 31.3, 24.9; IR
(R,R)-T2NO2 (3c): HCl (2 mmol, 1m in Et2O) was added to a cooled so-
lution (08C) of diimine (1 mmol) in THF (5 mL). The resulting orange
slurry was stirred for 10 min, then NaBH3CN (3 mmol) was added. The
clear solution was allowed to warm at RT and stirred overnight. Then
water (10 mL) was added, MeOH was evaporated, and the product was
extracted with CH2Cl2 (34 mL). Evaporation of the volatiles afforded
crude 3c, which was purified by flash chromatography: deep brown solid;
Rf = 0.33 (CH2Cl2/MeOH 99:1); yield 55% (two steps); m.p. 119–1218C;
[a]D = À9.3 (c = 0.95 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C,
TMS): d = 7.78 (d, J = 5.6 Hz, 2H), 7.21 (d, J = 3.6 Hz, 2H), 7.00 (d, J
= 3.6 Hz, 2H), 6.35 (d, J = 3.4 Hz, 2H), 4.15 (d, J = 14.8 Hz, 2H), 3.94
(neat):
n = 3424(s), 2924(s), 2846(m), 1643(m), 1534(m), 1436(s),
1362(m), 1088(s) cmÀ1; LC-ESI-MS: m/z: 587 [M+H]+; elemental analy-
sis calcd (%) for C28H30N2O4S4 (586.11): C 57.31, H 5.15, N 4.77; found:
C 57.28, H 5.12, N 4.76.
Pd-catalyzed AAA (4c/5a): A two-necked flask (25 mL) was charged,
under
a
nitrogen atmosphere, with [Pd(allyl)Cl]2 (2.7 mg, 7.5
10À3 mmol), diamine 3g (8.8 mg, 0.015 mmol), and anhydrous THF
Chem. Eur. J. 2006, 12, 667 – 675
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
673