Highly Enantioselective Alkynylation of Chloral
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1H), 4.12 (d, J¼13.3 Hz, 2H), 3.78 3.69 (m, 4H), 2.85 (m, 1H);
13C NMR (75 MHz, CDCl3): d¼150.4, 147.6, 138.8, 129.6,
128.9, 128.1, 127.8, 123.8, 70.0, 65.1, 58.7, 54.8; MS (EI): m/e
(rel. int.)¼361(Mþ ꢀ31, 0.5), 240 (48.6), 91 (100); anal. calcd.
for C23H24N2O4: C 70.41, H 6.12, N 7.14; found: C 70.38, H 6.23,
N 7.16.
Rt-bDEXcstTM (RESTEK), 1208C (20 min), 18C/min to
1508C (30 min), 8.0 psi N2]: tr ¼67.7 (major), 70.7 (minor);
[a]2D0: þ8.4o (c 1.0, EtOAc); FTIR (neat): n¼3392, 2246,
1045, 823 cmꢀ1; 1H NMR (300 MHz, CDCl3): d¼4.76 (s, 1H),
3.32 (s, 1H), 1.31 (m, 1H), 0.81 (m, 4H); 13C NMR (75 MHz,
CDCl3): d¼102.0, 93.2, 75.9, 70.1, 9.1, 9.0, 0.0; MS (CI): m/e
(rel. int.)¼233 (Mþ ꢀNH4þ, 100).
The above product (1.96 g, 5 mmol) in CH2Cl2 (50 mL) was
treatedwith imidazole (0.816 g, 12 mmol) andTBDMSCl
(0.825 g, 5.5 mmol) at 08C. The mixture was stirredovernight
at room temperature andwashedwith water (60 mL) and
brine. The organic layer was dried with Na2SO4 andconcentrat-
ed under vacuum. The crude product was purified by flash
chromatography on silica gel (hexane/EtOAc¼6:1) to afford
1g; yield: 2.3 g (91%); [a]2D0: þ140.1 (c 0.85, CHCl3); FTIR
1-Trichloromethyl-3-t-butyl-2-propyn-1-ol (3d): 60% yield
and93% ee as determinedby GC analysis [Chiralcel Rt-
bDEXcstTM (RESTEK),1208C (20 min), 18C/min to 1508C
(30 min), 8.0 psi N2]: tr ¼42.5(major), 45.5 (minor); [a]2D0:
þ1.7 (c 1.0, EtOAc); FTIR (neat): n¼3349, 2974, 2252, 1262,
1055, 824, 804 cmꢀ1; 1H NMR (300 MHz, CDCl3): d¼4.94 (s,
1H), 3.38 (s, 1H), 1.27 (s, 9H); 13C NMR (75 MHz, CDCl3): d¼
102.6, 98.1, 76.0, 74.0, 31.1, 28.2; MS (CI): m/e (rel. int.)¼229
(Mþ, 3), 175 (100).
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(KBr): n¼3403, 2931, 1525, 1344 cmꢀ1; H NMR (300 MHz,
CDCl3): d¼8.10 (d, J¼8.7 Hz, 2H), 7.40 7.26 (m, 12H), 5.06
(s, 1H), 4.76 (d, J¼9.9 Hz, 1H), 4.13 (d, J¼13.3 Hz, 2H),
3.76(dd, J¼11.4 and2.3 Hz, 1H), 3.64 (d, J¼12.8 Hz, 2H),
3.55 (dd, J¼11.4 and5.7 Hz, 1H), 2.74 (m, 1H), 0.92 (s, 9H),
0.04 (s, 6H); 13C NMR (75 MHz, CDCl3): d¼150.5, 147.6,
138.9, 129.5, 128.9, 128.2, 127.8, 123.6, 69.1, 65.2, 58.3, 54.9,
26.1, 18.3, ꢀ5.4; MS (ESI): m/e (rel. int.)¼507 (Mþ þ1);
anal. calcd. for C29H38N2O4Si: C 68.77, H 7.51, N 5.53; found:
C 68.63, H 7.35, N 5.41.
1-Trichloromethyl-2-heptyn-1-ol (3e): 79% yieldand98%
ee as determined by GC analysis [Chiralcel Rt-bDEXcstTM
(RESTEK), 1208C (20 min), 18C/min to 1508C (30 min), 8.0
psi N2]: tr ¼69.9 (major), 72.3 (minor); [a]2D0: þ12.7 (c 1.0,
EtOAc); FTIR (neat): n¼3390, 2961, 2243, 1059, 825 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d¼4.80 (d, J¼7.4 Hz, 1H), 3.19
(d, J¼7.9 Hz, 1H), 2.29 (dt, J¼6.9 Hz and1.9 Hz, 2H), 1.49
(m, 4H), 0.93 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d¼102.1, 90.3, 75.9, 75.2, 30.6, 22.4, 18.9, 14.1; MS (CI): m/e
(rel. int.)¼229 (Mþ, 3), 93 (100).
General Procedure for the Asymmetric Alkynylation
of Choral
1-Trichloromethyl-3-trimethylsilyl-2-propyn-1-ol (3f): 70%
yieldand92% ee as determinedby GC analysis [Chiralcel
Rt-bDEXcstTM (RESTEK), 1008C (30 min), 18C/min to
1808C (20 min), 8.0 psi N2]: tr ¼60.7(major), 61.2 (minor);
[a]2D0: þ12.6 (c 1.2, EtOAc); FTIR (KBr): n¼3272, 2962,
To a solution of Zn(OTf)2 (181 mg, 0.50 mmol) andchiral li-
gand(0.55 mmol), triethylamine (104 mL, 0.75 mmol) in dried
toluene (1 mL) was added the terminal acetylene
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2192, 1253, 1090, 846 cmꢀ1; H NMR (300 MHz, CDCl3): d¼
(1.1 mmol) under an argon atmosphere over 2 h at 258C.
Then chloral (98 mL, 1 mmol) was introduced by a syringe.
The mixture was stirredovernight at room temperature and
pouredinto saturatedNH 4Cl (10 mL). The mixture was ex-
tractedwith EtOAc (15 mL ꢁ3) anddriedwith Na 2SO4. After
removal of the solvent, the crude product was purified by flash
chromatography on silica gel (hexane: EtOAc¼15:1) to af-
forded the trichloromethyl propargylic alcohol.
4.78 (d, J¼8.8 Hz, 1H), 3.03 (d, J¼8.6 Hz, 1H), 0.21 (s, 9H);
13C NMR (75 MHz, CDCl3): d¼100.9, 98.8, 94.5, 75.6, ꢀ0.3;
MS (CI): m/e (rel. int.)¼244 (Mþ, 2), 93 (100).
1-Trichloromethyl-4-t-butyldimethylsilyoxy-2-butyn-1-ol
(3g): 71% yieldand98% ee as determinedby GC analysis
[Chiralcel Rt-bDEXcstTM (RESTEK), 1508C (10 min), 18C/
min to 1808C (40 min), 8.3 psi N2]: tr ¼67.3(major), 68.6 (mi-
nor); [a]2D0: þ10.4 (c 1.0, EtOAc); FTIR (neat): n¼3381,
(S)-1-Trichloromethyl-3-phenyl-2-propyn-1-ol (3a): 93%
yieldand96% ee as determinedby HPLC analysis (Chiralcel
OJ, i-PrOH/hexane¼5/95, 0.7 mL/min, 254 nm): tr ¼26.9 (mi-
nor), 33.2 (major); [a]2D0: þ19.2 (c 1.0, EtOAc); FTIR (neat):
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2957, 2931, 2860, 1258, 1095, 836 cmꢀ1; H NMR (300 MHz,
CDCl3): d¼4.84 (d, J¼9.2 Hz, 1H), 4.39 (d, J¼1.5 Hz, 2H),
3.11 (d, J¼8.9 Hz, 1H), 0.90 (s, 9H), 0.12 (s, 6H); 13C NMR
(75 MHz, CDCl3): d¼100.8, 86.9, 78.8, 75.2, 51.6, 29.7, 25.7,
18.3, 1.0, ꢀ5.2; MS (CI): m/e (rel. int.)¼223 [Mþ ꢀ35(Cl)
57(t-Bu), 3], 93 (100), 75 (77), 57 (48); anal. calcd. for C11H19
Cl3SiO2: C 41.77, H 6.01; found: C 41.95, H, 6.12.
n¼3377, 2242, 1491, 1073, 823 cmꢀ1
;
1H NMR (300 MHz,
CDCl3): d¼7.50 (m, 2H), 7.37 (m, 3H), 5.06 (s, 1H), 3.38 (s,
1H); 13C NMR (75 MHz, CDCl3): d¼132.2, 129.6, 128.7,
121.4, 101.3, 88.3, 83.2, 76.0; MS (EI) m/e 248 (Mþ, 1.5),
131(100).
1-Trichloromethyl-4-cyclopentyl-2-butyn-1-ol (3h): 95%
yieldand95% ee as determinedby GC analysis [Chiralcel
Rt-bDEXcstTM (RESTEK), 1508C (20 min), 18C/min to 1808
(30 min), 10.0 psi N2]: tr ¼59.4(major), 60.3 (minor); [a]2D0:
þ25.0 (c 1.0, EtOAc); FTIR (neat): n¼3393, 2955, 2869,
1-Trichloromethyl-5-phenyl-2-pentyn-1-ol (3b): 76% yield
and98% ee as determinedby HPLC analysis (Chiralcel AD,
i-PrOH/hexane¼5/95, 0.7 mL/min, 254 nm): tr ¼21.9 (minor),
24.0 (major); [a]2D0: þ10.4 (c 1.0, EtOAc); FTIR (neat): n¼
3378, 2242, 1497, 1059 cmꢀ1; 1H NMR (300 MHz, CDCl3): d¼
7.30 (m, 5H), 4.80 (s, 1H), 3.08 (s, 1H), 2.90 (t, J¼7.5 Hz, 2H),
2.61 (dt, J¼1.7 Hz and8.8 Hz, 2H); 13C NMR (75 MHz,
CDCl3): d¼140.65, 129.1, 129.0, 127.1, 89.4, 87.1, 76.0, 75.9,
34.9, 21.5; MS (CI): m/e (rel. int.)¼277 (Mþ, 2), 169 (100);
anal. calcd. for C12H11Cl3O: C 52.17, H 3.99; found: C 52.54,
H 3.97.
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2242, 1057, 823 cmꢀ1; H NMR (300 MHz, CDCl3): d¼4.78
(dt, J¼2.2 and8.6 Hz, 1H), 2.94 (d, J¼9.3 Hz, 1H), 2.28 (dd,
J¼2.2 and6.7 Hz, 2H), 2.06(m, 1H), 1.83 1.74(m, 2H), 1.66
1.47(m, 4H), 1.32 1.21(m, 2H); 13C NMR (75 MHz, CDCl3):
d¼89.5, 75.6, 74.8, 38.8, 32.2, 25.5, 24.6; MS (CI): m/e (rel.
int.)¼220 [Mþ ꢀ35(Cl), 1], 137 (100), 91 (31), 69 (77), 41
(76); anal. calcd. for C10H13Cl3O: C 47.24, H 5.12; found: C
47.36, H 5.15.
1-Trichloromethyl-3-cyclopropyl-2-propyn-1-ol (3c): 90%
yieldand96% ee as determinedby GC analysis [Chiralcel
Adv. Synth. Catal. 2004, 346, 669 674
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¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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