2420
C. Anaya de Parrodi, P. J. Walsh
CLUSTER
General Procedure for Ethylation of Ketones. The bis(sulfona-
mide) diol 4 (2–10 mol%, 4.5–22.5 mg) was weighed into the reac-
tion vessel, and diethylzinc (1.0 M toluene, 1.6 equiv, 1.6 mL) and
titanium(IV) isopropoxide (1.0 M toluene, 1.2 equiv, 1.2 mL) were
added at r.t. After 10 min, the substrate ketone (1.0 equiv, 0.42
mmol) was added neat or as a solution in toluene (1 mL). The ho-
mogeneous reaction mixture was stirred at r.t. After 12–48 h the re-
action was quenched with H2O (5 mL), diluted with EtOAc, filtered
through Celite, and the layers separated. The aqueous layer was ex-
tracted with EtOAc (2 × 40 mL) and the combined organic layers
washed with brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by flash chromatography on deactivated
silica gel (Et3N–SiO2 = 2.5% v/v, hexanes–EtOAc 95:5) to afford
the ethyl addition products, which were fully characterized and
compared with the data reported in the literature.7
Schlenk flask containing the vinylzirconocene and dimethylzinc at
–78 °C. After the addition, the solution was warmed to 0 °C and ac-
etophenone (59 mL, 0.50 mmol, 1 equiv) was added. The reaction
mixture was warmed to r.t. and stirred during 48 h. The reaction was
quenched with sat. aq NaHCO3 (5 mL), diluted with EtOAc, filtered
through Celite, and the layers were separated. The aqueous layer
was extracted with EtOAc (2 × 40 mL) and the combined organic
layers were washed with brine, dried over MgSO4, and concentrated
in vacuo. The residue was purified by flash chromatography on de-
activated silica gel (Et3N–SiO2 = 2.5% v/v, hexanes–EtOAc 95:5)
to afford the product, which was fully characterized and compared
with the data reported in the literature.9
Acknowledgment
Procedure for Phenylation of 3¢-Chloropropiophenone. The
bis(sulfonamide) diol 4 (11.7 mg, 15 mol%), was weighed into a
dried Schlenk flask. Diphenylzinc was added (20% toluene solu-
tion, 0.32 mmol, 2.3 equiv, 0.39 mL) followed by titanium(IV) iso-
propoxide (1.0 M toluene solution, 1.2 mmol, 0.8 equiv, 0.12 mL).
The homogenous reaction mixture was stirred at r.t. for 15 min. 3¢-
Chloropropiophenone (24.1 mg, 0.14 mmol, 1.0 equiv) was added
dissolved in toluene (1.0 mL). The reaction mixture was stirred at
r.t. for 48 h. The reaction was quenched with H2O (5 mL), diluted
with EtOAc, filtered through Celite, and the layers were separated.
The aqueous layer was extracted with EtOAc (2 × 40 mL) and the
combined organic layers were washed with brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified by
flash chromatography on deactivated silica gel (Et3N–SiO2 = 2.5%
v/v, hexanes–EtOAc 95:5) to afford the product, which was fully
characterized and compared with the data reported in the literature.8
This work was supported by the NIH National Institute of General
Medical Sciences (GM58101) and CONACYT, Consejo Nacional
de Ciencia y Tecnología (Project No. 39500-Q). We thank Azko
Nobel for dialkylzinc reagents.
References
(1) Corey, E. J.; Guzmán-Pérez, A. Angew. Chem. Int. Ed. 1998,
37, 388.
(2) Pu, L. Tetrahedron 2003, 59, 9873.
(3) Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2004, 43, 284.
(4) Betancort, J. M.; García, C.; Walsh, P. J. Synlett 2004, 749.
(5) Dosa, P. I.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 445.
(6) Jeon, S.-J.; Walsh, P. J. J. Am. Chem. Soc. 2003, 125, 9544.
(7) García, C.; LaRochelle, L. K.; Walsh, P. J. J. Am. Chem. Soc.
2002, 124, 10970.
Procedure for Vinylation of Acetophenone. To a solution of
Cp2ZrHCl (155 mg, 0.60 mmol, 1.2 equiv) in CH2Cl2 (2.0 mL) un-
der N2 was added 1-hexyne (70 mL, 0.60 mmol, 1.2 equiv). The re-
action mixture was stirred for 10 min at r.t., after which it was a
homogeneous yellow solution. The solvent was removed in vacuo
and the residue was dissolved in dry toluene (2.0 mL), cooled to
–78 °C, and treated with Me2Zn (0.30 mL, 2.0 M in toluene, 0.60
mmol, 1.2 equiv) for 10 min. In another Schlenk flask were mixed
ligand 4 (27.2 mg, 0.05 mmol, 10 mol%) in 1.0 mL toluene, and ti-
tanium(IV) isopropoxide (0.29 mL, 0.3 mmol, 1.0 M toluene solu-
tion, 1.2 equiv), Me2Zn (0.10 mL, 2.0 M in toluene, 0.20 mmol) at
r.t. and stirred for 15 min. The resulting solution was added to the
(8) García, C.; Walsh, P. J. Org. Lett. 2003, 5, 3641.
(9) Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2004, 126, 6538.
(10) DiMauro, E. F.; Kozlowski, M. C. J. Am. Chem. Soc. 2002,
124, 12668.
(11) Funabashi, K.; Jachmann, M.; Kanai, M.; Shibasaki, M.
Angew. Chem. Int. Ed. 2003, 42, 5489.
(12) Waltz, K. M.; Gavenovis, J.; Walsh, P. J. Angew. Chem. Int.
Ed. 2002, 41, 3697.
(13) Mastranzo, V. M.; Quintero, L.; Anaya de Parrodi, C.;
Juaristi, E.; Walsh, P. J. Tetrahedron 2004, 60, 1781.
(14) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compounds; Wiley and Sons: New York, 1994.
Synlett 2004, No. 13, 2417–2420 © Thieme Stuttgart · New York