A R T I C L E S
Kim et al.
using standard Schlenk techniques. All NMR spectra were obtained
on either a Bru¨ker 500 or 300 MHz Fourier transform spectrometer at
the University of Pennsylvania NMR facility. H NMR spectra were
mmol) was weighed into a Schlenk flask and purged with nitrogen.
Dichloromethane (0.8 mL) and titanium(IV) isopropoxide (35.4 µL,
0.12 mmol) were added, giving a red homogeneous solution. 2-Propanol
(612 µL, 8 mmol) and tetraallylstannane (144.4 µL, 0.6 mmol) were
added successively. The substrate, 2-pentyl-2-cyclopenten-1-one (66
µL, 0.4 mmol), was added and the reaction was stirred at room
temperature until it turned pale yellow (48 h). After the allylation
reaction was complete (TLC), TBHP (80 µL, 5-6 M solution in decane,
>0.4 mmol) was added. After 18 h, the reaction was quenched with
saturated aqueous NH4Cl and extracted with dichloromethane (3 × 20
mL). The remainder of the workup is identical to that in General
Procedure A. The residue was purified by column chromatography on
1
referenced to tetramethylsilane in CDCl3 or residual protiated solvent
in C6D6; 13C{1H} NMR spectra were referenced to residual solvent.
The infrared spectra were obtained using a Perkin-Elmer 1600 series
spectrometer. Thin-layer chromatography was performed on Whatman
precoated silica gel 60 F-254 plates and visualized by ultraviolet light
or by staining with ceric ammonium molybdate stain or phosphomo-
lybdic acid hydrate stain. Silica gel (230-400 mesh, Silicycle) was
used for air-flashed chromatography. All reagents were purchased from
Aldrich, Acros, or Gelest chemical companies. Titanium(IV) isopro-
poxide, tetraallylstannane, 2-propanol, and all liquid ketone substrates
were distilled prior to use and stored under an inert atmosphere. All
glassware was flame- or oven-dried (150 °C). Full characterization of
some of the products listed in Table 1 has been previously reported.20
Only representative procedures and characterization of the products are
described here. Full details can be found in the Supporting Information.
Procedures for the Enantioselective Allylation of Ketones.
Preparation of 1-Allyl-2-pentyl-cyclopent-2-enol (General Procedure
A). (R)-BINOL (42.9 mg, 0.15 mmol) was weighed into a Schlenk
flask and purged with nitrogen. Dichloromethane (1 mL) and tita-
nium(IV) isopropoxide (44.3 µL, 0.15 mmol) were then added, giving
a red homogeneous solution. 2-Propanol (766 µL, 10 mmol) and
tetraallylstannane (180 µL, 0.75 mmol) were added successively. The
substrate, 2-pentyl-2-cyclopenten-1-one (82.6 µL, 0.5 mmol), was added
and the reaction was stirred at room temperature until the solution turned
pale yellow. After completion (48 h, TLC), the reaction was quenched
with saturated aqueous NH4Cl and extracted with dichloromethane (3
× 20 mL). The organic layer was dried over MgSO4, and the solvent
was removed under reduced pressure. Hexanes were added, and the
solution was filtered through Celite and concentrated under reduced
pressure. The residue was purified by column chromatography on silica
silica gel (hexanes:EtOAc, 95:5) to give the product (59.8 mg, 72%
1
yield, 94% ee) as an oil. [R]20 ) 11.57 (c ) 0.47, CHCl3); H NMR
D
(CDCl3, 300 MHz) 0.90 (t, J ) 6.8 Hz, 3H), 1.20-1.75 (m, 9H), 1.81-
1.90 (m, 2H), 1.95-2.06 (m, 2H), 2.24 (dd, J ) 13.9, 7.5 Hz, 1H),
2.45 (ddd, J ) 13.9, 7.0, 1.0 Hz, 1H), 3.38 (s, 1H), 5.10-5.22 (m,
2H), 5.84 (m, 1H) ppm; 13C{1H} NMR (CDCl3, 75 MHz) 14.4, 22.9,
24.3, 25.9 (2C), 32.6, 33.5, 41.2, 62.1, 70.0, 81.3, 119.0, 133.4 ppm;
IR (neat) 3472, 2930, 2859, 1641, 1462, 1379, 1174, 1113, 1055, 1000,
912, 887 cm-1; HRMS calcd for C13H22O2(MH)+ 211.1718, found
211.1709.
Results and Discussion
Catalyst Development. At the time we initiated our inves-
tigations into the catalytic asymmetric allylation of ketones, the
only reported example of this reaction was from Tagliavini and
was based on titanium(IV) and BINOL.38 Our interest in
studying this reaction was to gain sufficient insight into the
nature of the catalyst to expedite development of catalysts that
exhibited increased levels of enantioselectivity. As shown in
Scheme 4, the Tagliavini protocol involved precatalyst genera-
tion by reaction of Cl2Ti(OiPr)2 and BINOL with allyltributyl-
stannane. After mixing for 1 h, tetraallylstannane and the ketone
substrate were added. Homoallylic alcohols were isolated in
good yields and moderate enantioselectivities.
gel (hexanes:EtOAc, 95:5) to give the product (89.0 mg, 92% yield,
1
94% ee) as an oil: [R]20 ) -7.62 (c ) 0.315, MeOH); H NMR
D
(C6D6, 500 MHz) 0.90 (t, J ) 6.9 Hz, 3H), 1.30 (m, 4H), 1.4-2.2 (m,
9H), 2.24 (dd, J ) 13.6, 6.9 Hz, 1H), 2.42 (dd, J ) 13.6, 7.6 Hz, 1H),
4.9-5.1 (m, 2H), 5.35 (t, J ) 1.8 Hz, 1H), 5.79 (m, 1H) ppm; 13C{1H}
NMR (C6D6, 125 MHz) 14.3, 23.1, 26.3, 28.2, 29.2, 32.4, 38.3, 43.8,
85.5, 117.6, 125.5, 134.9, 148.6 ppm; IR (neat) 3362, 3075, 2927, 2856,
1640, 1458, 1378, 1164 cm-1; HRMS calcd for C13H22O (M - H2O)+
176.1565, found 176.1560.
Scheme 4. Catalyst Preparation and Ketone Allylation Using the
Tagliavini Protocol38
Preparation of 1-Allyl-2-methyl-cyclopent-2-enol (General Pro-
cedure B). (R)-BINOL (25.7 mg, 0.09 mmol) was weighed into a
Schlenk flask and purged with nitrogen. Dichloromethane (0.6 mL)
and titanium(IV) isopropoxide (26.6 µL, 0.09 mmol) were added, giving
a red homogeneous solution. 2-Propanol (459 µL, 6 mmol) and
tetraallylstanne (108 µL, 0.45 mmol) were added successively. This
mixture was maintained at room temperature under a static nitrogen
atmosphere with stirring for 24 h. The substrate, 2-methyl-2-cyclo-
penten-1-one (29.5 µL, 0.3 mmol), was added, and the reaction was
stirred at room temperature until the solution turned pale yellow (48
h). The reaction was worked up as outlined in general procedure A.
The residue was purified by column chromatography on silica gel
In our initial experiments, we repeated the precatalyst
synthesis introduced by Tagliavini38 to investigate the structure
of the resulting titanium complex. The procedure above was
conducted in CDCl3, and the resulting (BINOLate)Ti species
was examined by NMR spectroscopy. Like Tagliavini38 and co-
workers, we observed production of tributyltin chloride. We
were surprised to find, however, that the main (BINOLate)Ti-
containing product was (BINOLate)Ti(OiPr)2, which is dimeric
in solution and trimeric in the solid state.56,57 We were able to
identify this compound, because we had previously prepared it
for use in a mechanistic study,58 and we reported a high-quality
crystal structure of this complex.57 It can be prepared on a
multigram scale by mixing titanium tetraisopropoxide and
(pentane:Et2O, 95:5) to give the product (31.2 mg, 75% yield, 87%
1
ee) as an oil: [R]20 ) -9.10 (c ) 1.165, CHCl3); H NMR (C6D6,
D
500 MHz) 1.11 (s, 1H),1.61 (dd, J ) 3.8, 2.0 Hz, 3H), 1.67 (m, 1H),
1.9-2.15 (m, 3H), 2.18 (dd, J ) 13.6, 7.0 Hz, 1H), 2.36 (dd, J )
13.6, 7.5 Hz, 1H), 4.9-5.1 (m, 2H), 5.28 (m, 1H), 5.76 (m, 1H) ppm;
13C{1H} NMR (C6D6, 125 MHz): 11.7, 29.0, 38.0, 43.5, 85.0, 117.6,
127.2, 134.8, 143.91 ppm; IR (neat): 3364, 3076, 2925, 2854, 1640,
1438, 1376, 1164 cm-1; HRMS calcd for C9H14O(M - H2O)+:
120.0939; found: 120.0937.
(56) Martin, C. Design and Application of Chiral Ligands for the Improvement
of Metal-Catalyzed Asymmetric Transformations. Ph.D. Thesis, MIT, 1989.
(57) Davis, T. J.; Balsells, J.; Carroll, P. J.; Walsh, P. J. Org. Lett. 2001, 3,
699-702.
(58) Balsells, J.; Davis, T. J.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc.
2002, 124, 10336-10348.
One-Pot Synthesis of Epoxy Alcohols. Preparation of 2-Allyl-1-
pentyl-6-oxa-bicyclo[3.1.0]hexan-2-ol. (R)-BINOL (34.4 mg, 0.12
(55) Bonini, C.; Righib, G. Tetrahedron 2002, 58, 4981-5021.
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12582 J. AM. CHEM. SOC. VOL. 126, NO. 39, 2004