398
N. Ljungdahl et al.
LETTER
(19) (a) Duursma, A.; Lefort, L.; Boogers, J. A. F.; de Vries, A.
H. M.; de Vries, J. G.; Minnaard, A. J.; Feringa, B. L. Org.
Biomol. Chem. 2004, 2, 1682. (b) de Vries, J. G.; Lefort, L.
Chem. Eur. J. 2006, 12, 4722.
(20) Konya, D.; Robert, F.; Gimbert, Y.; Greene, A. E.
Tetrahedron Lett. 2004, 45, 6975.
(21) Achard, M.; Tenaglia, A.; Buono, G. Org. Lett. 2005, 7,
2353.
(22) Bernsmann, H.; van den Berg, M.; Hoen, R.; Minnaard, A.
J.; Mehler, G.; Reetz, M. T.; de Vries, J. G.; Feringa, B. L.
J. Org. Chem. 2005, 70, 943.
(23) (a) For ligand 2a, see ref. 19a. (b) For ligand 2d, see:
Lefort, L.; Boogers, J. A. F.; de Vries, A. H. M.; de Vries, J.
G. Org. Lett. 2004, 6, 1733. (c) For ligand 2e, see: Panella,
L.; Aleixandre, A. M.; Kruidhof, G. J.; Robertus, J.; Feringa,
B. L.; de Vries, J. G.; Minnaard, A. J. J. Org. Chem. 2006,
71, 2026. (d) For ligand 2f, see: Boiteau, J.-G.; Imbos, R.;
Minnaard, A. J.; Feringa, B. L. Org. Lett. 2003, 5, 681.
(e) For ligand 2g, see ref. 19b. (f) For ligands 2h and 2i, see
ref. 21. (g) For ligands 2j and 2k, see ref. 16a. (h) For
ligands 2l and 2m, see: Peña, D.; Minnaard, A. J.; de Vries,
A. H. M.; de Vries, J.; Feringa, B. L. Org. Lett. 2003, 5, 475.
(i) For ligand 2n, see: Imbos, R.; Brilman, M. H. G.;
Pineschi, M.; Feringa, B. L. Org. Lett. 1999, 1, 623.
(24) General Procedure for the Parallel Synthesis of the
Ligands:21 The amine (0.25 mmol) was added to a carousel
tube, followed by Et3N (0.25 mmol). The tube was sealed,
flushed with argon and cooled to –40 °C. A 0.25 M stock
solution of BINOL-chlorophosphite (1 mL) in toluene was
added, and the reaction was left to warm overnight. The
reaction mixture was rapidly filtered through a small plug of
silica gel into a new sealed and degassed carousel tube. The
filtrate was washed with toluene (1 mL), and the combined
toluene solutions of the ligand were used directly in the next
step.
phosphoramidite–cobalt–alkyne complex thus formed was
used directly in the Nicholas reaction in the same reaction
tube.
(27) (a) General Procedure for the Asymmetric Nicholas
Reaction: The phosphoromidite–cobalt–alkyne complex
(0.25 mmol) was dissolved in CH2Cl2 (1 mL) and cooled to
–30 °C. BF3·OEt2 (47.5 mL, 0.375 mmol,) was added,
followed by the dropwise addition of the nucleophile (0.5
mmol). After 16 h, the reaction was quenched with Et3N
(69.7 mL, 0.5 mmol), and the solvent was removed in vacuo.
Decomplexation was effected by dissolving the residue in
THF–H2O (9:1), cooling to –10 °C, followed by the
portionwise addition of a 0.18 M solution of cerium
ammonium nitrate in THF–H2O (9:1) until the dark red
solution turned orange-yellow (the amount of CAN solution
used corresponded to approximately 5 equiv in most cases,
and up to 10 equiv in a few cases). The reaction mixture was
diluted with brine (1 mL) and extracted with Et2O (3 × 2
mL). The combined organic phases were dried over MgSO4
and concentrated. The crude product was purified by flash
chromatography, eluting with 5–10% EtOAc in PE. The
enantioselectivity was measured by HPLC on both the crude
and the pure product, using a Daicel Chiralpak AD-H
column (hexane–i-PrOH, 95:5). (b) For compound 5, see:
Asao, N.; Ohishi, T.; Sato, K.; Yamamoto, Y. Tetrahedron
2002, 58, 8195. (c) For compounds 7, 9, 10 and 11, see ref.
4b.
(28) Yang, D.; Chen, F.; Dong, Z.-M.; Zhang, D.-W. J. Org.
Chem. 2004, 69, 2221.
(29) Hoffman, R. V.; Kim, H.-O. J. Org. Chem. 1995, 60, 5107.
(30) General Procedure for the Preparation of the Precursor
Propargylic Alcohols, Exemplified by 6: 4-Iodoaceto-
phenone (500 mg, 2.03 mmol), Pd(PPh3)4 (23.5 mg, 0.020
mmol) and CuI (7.7 mg, 0.040 mmol) were added to a 5-mL
microwave reaction tube flushed with argon. Freshly
distilled Et3N (2 mL) and anhyd DMF (1 mL) were added,
followed by 1-octyn-3-ol (355 mL, 2.43 mmol). The reaction
was heated at 100 ºC for 10 min using a Biotage Initiator
microwave reactor. The reaction mixture was then filtered
through a pad of Celite, diluted with Et2O and washed with
brine. Drying over MgSO4 followed by rotary evaporation
afforded 6 (390 mg) as an amber-yellow oil. For larger-scale
reactions, the reaction was run with conventional heating at
40 ºC for 16 h. Data for 6: 1H NMR (400 MHz, CDCl3): d =
7.87 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 2 H), 4.56–4.64
(m, 1 H), 2.59 (s, 3 H), 1.74–1.84 (m, 2 H), 1.30–1.60 (m, 6
H), 0.89 (t, J = 7.0 Hz, 3 H). 13C NMR (100 MHz, CDCl3):
d = 197.5, 136.4, 131.9, 128.3, 127.8, 93.8, 84.1, 63.1, 37.8,
31.6, 26.7, 25.0, 22.7, 14.1. IR: 3421, 2931, 2365, 2250,
1684, 1602, 1266, 909, 733 cm–1. Anal. Calcd for C16H20O2:
C, 78.65; H, 8.25. Found: C, 78.53; H, 8.65. Compound 8
was prepared from 1-octyn-3-ol and 3,5-dimethyl-1-
iodobenzene in the same manner. Data for 8: 1H NMR (400
MHz, CDCl3): d = 7.07 (s, 2 H), 6.96 (s, 1 H), 4.72–4.80 (m,
1 H), 2.92 (s, 6 H), 1.94 (d, J = 5.2 Hz, 1 H), 1.55 (d, J = 6.8
Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 138.00, 130.44,
129.56, 122.47, 90.63, 84.43, 58.95, 24.63, 21.29. Anal.
Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.65; H,
8.03.
Spectral Data for Crude 2b: 1H NMR (400 MHz, CDCl3):
d = 7.80–8.10 (m, 4 H), 7.20–7.60 (m, 12 H). 13C NMR (100
MHz, CDCl3): d = 145.7, 144.9, 132.0, 131.6, 131.5, 128.7,
128.6, 127.3, 127.2, 127.0 (J = 2.3 Hz), 126.2, 126.1, 121.0,
120.2 (J = 38 Hz). IR: 1298, 1224, 966, 929, 881, 816, 752
cm–1.
Spectral Data for Crude 2c: 1H NMR (400 MHz, CDCl3):
d = 7.85–8.00 (m, 4 H), 7.25–7.60 (m, 14 H). 13C NMR (100
MHz, CDCl3): d = 147.4, 147.1, 132.9, 132.6, 131.8, 131.4,
130.6, 130.0, 128.6 (d, J = 7.6 Hz), 127.1 (d, J = 9.9 Hz),
126.5, 126.4, 125.4, 125.1, 124.5, 123.2, 122.0, 121.8. IR:
1225, 1198, 884, 820 cm–1.
(25) Nicholas, K. M.; Pettit, R. J. Organomet. Chem. 1972, 44,
C21.
(26) General Procedure for the Formation of the
Intermediate Cobalt Complexes: The propargylic alcohol
(1-butyn-3-ol, 6 or 8) was dissolved in CH2Cl2 in a two-
necked flask under argon. An equimolar amount of dicobalt
octacarbonyl, dissolved in CH2Cl2, was added. The reaction
was protected from light by wrapping the flask in foil, and
the solution was stirred at r.t. for 3 h. The mixture was
filtered through a short plug of silica, eluting with CH2Cl2,
and concentrated, affording the complex as a dark red oil.
The ligand (0.25 mmol) was added to a Radleys carousel
tube and dissolved in toluene (1 mL). The tube was sealed
and flushed with argon. A 0.125 M stock solution of the
alkyne–cobalt complex (1 mL) in toluene was added to the
tube. The reaction mixture was heated at 50 °C overnight.
The solvent was removed in vacuo, and the crude
(31) Carousel 12 Reaction Station was obtained from Radleys
Discovery Technologies.
(32) Castro, J.; Moyano, A.; Pericás, M. A.; Riera, A.; Maestro,
M. A.; Mahía, J. Organometallics 2000, 19, 1704.
Synlett 2008, No. 3, 394–398 © Thieme Stuttgart · New York