I. Hachiya et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 4 (2011)
421
to give propiophenone (2c) (17.0 mg, 85%) and the recovered
¡-tosyloxypropiophenone (1f) (5.6 mg, 12%), respectively.
Propiophenone (2c): Colorless oil; H NMR (500 MHz,
CDCl3): ¤ 1.22 (t, J = 7.3 Hz, 3H), 2.99 (q, J = 7.3 Hz, 2H),
7.42-7.46 (m, 2H), 7.52-7.55 (m, 1H), 7.95-7.96 (m, 2H);
13C NMR (126 MHz, CDCl3): ¤ 8.1, 31.6, 127.8, 128.4, 132.7,
136.8, 200.6; IR (neat): 2978, 2938, 1689, 1597, 1583, 1449,
1354, 1220, 952, 746, 690 cm¹1; HRMS (EI): Calculated for
C9H10O (M)+ 134.0732, found 134.0730.
References
1
1
2
3
A Typical Experimental Procedure for the Reductive
Aldol Reaction of ¡-Tosyloxy Ketone Derivatives is as
Follows (Table 2, Entry 1). To a solution of TiI4 (166.6 mg,
0.30 mmol) in ClCH2CN (1.0 mL) was added a solution of ¡-
tosyloxypropiophenone (1f) (45.7 mg, 0.15 mmol) in ClCH2CN
(1.0 mL) at room temperature under an argon atmosphere.
The mixture was stirred at room temperature for 2 h. To the
resulting solution was added a solution of benzaldehyde
(10.6 mg, 0.10 mmol) in chlorobenzene (1.0 mL) at room
temperature. The resulting mixture was stirred at room temper-
ature for 1 h. The reaction mixture was quenched with saturated
aqueous NaHCO3, and EtOAc and 10% aqueous NaHSO3 were
added successively. The mixture was filtered through a Celite
pad, and extracted with EtOAc. The combined organic extracts
were washed with brine, dried over Na2SO4 and concentrated in
vacuo. The residue was purified by preparative silica gel TLC
(hexane-EtOAc = 4:1 as an eluent) to give a mixture of
diastereomers. The diastereomers were separated by preparative
silica gel TLC (toluene-EtOAc = 15:1 as an eluent, developed
twice) to give syn-3a (18.6 mg) and anti-3a (3.4 mg), respec-
tively (92% yield, syn:anti = 85:15).
4
For examples of reduction of ¡-hydroxy or alkoxy ketones
using other metals or other methods, see: a) R. B. Turner, G. D.
Diana, G. E. Fodor, K. Gebert, D. L. Simmons, A. S. Rao, O.
McMurry, M. G. Silvestri, M. P. Fleming, T. Hoz, M. W. Grayston,
1992, 1895. For examples of reduction of acyloin ¡-acyl
derivatives under metal-free conditions, see: g) M. Ueki, A.
S. P. Y. Cutulic, N. J. Findlay, S.-Z. Zhou, E. J. T. Chrystal, J. A.
5
a) Y. Nakamura, S. Takeuchi, Y. Ohgo, M. Yamaoka, A.
Mikami, M. Yamaoka, A. Yoshida, Y. Nakamura, S. Takeuchi, Y.
(2S*,3S*)-3-Hydroxy-2-methyl-1,3-diphenylpropan-1-one
1
6
(syn-3a): Colorless oil; H NMR (500 MHz, CDCl3): ¤ 1.19
(d, J = 7.3 Hz, 3H), 3.66 (brs, 1H), 3.70 (dd, J = 3.1, 7.3 Hz,
1H), 5.23 (d, J = 3.1 Hz, 1H), 7.24-7.27 (m, 1H), 7.32-7.35
(m, 2H), 7.39-7.41 (m, 2H), 7.45-7.48 (m, 2H), 7.56-7.59 (m,
1H), 7.92-7.93 (m, 2H); 13C NMR (126 MHz, CDCl3): ¤ 11.2,
47.0, 73.1, 126.0, 127.3, 128.2, 128.4, 128.7, 133.5, 135.6,
141.8, 205.7; IR (neat): 3460 (OH), 1677 (C=O) cm¹1; HRMS
(EI): Calculated for C16H16O2 (M)+ 240.1150, found 240.1151.
(2R*,3S*)-3-Hydroxy-2-methyl-1,3-diphenylpropan-1-one
7
8
For examples of titanium tetraiodide-promoted reductive
aldol and Mannich-type reactions, see: a) R. Hayakawa, M.
1
(anti-3a): Colorless oil; H NMR (500 MHz, CDCl3): ¤ 1.07
(d, J = 7.3 Hz, 3H), 2.96 (d, J = 4.6 Hz, 1H), 3.80-3.86 (m,
1H), 5.00 (dd, J = 4.6, 7.9 Hz, 1H), 7.28-7.31 (m, 1H), 7.35-
7.38 (m, 2H), 7.41-7.43 (m, 2H), 7.45-7.49 (m, 2H), 7.56-7.59
(m, 1H), 7.97-7.98 (m, 2H); 13C NMR (126 MHz, CDCl3): ¤
15.7, 48.0, 76.8, 126.7, 127.9, 128.4, 128.5, 128.6, 133.3,
¹1
9
136.7, 142.2, 204.9; IR (neat): 3460 (OH), 1678 (C=O) cm
;
HRMS (EI): Calculated for C16H16O2 (M)+ 240.1150, found
365. Although the role of salicylic acid is not yet clear, we
presume that the titanium enolate species would be in situ
protonated with salicylic acid to generate the corresponding
ketone.
240.1151.
Supporting Information
1H NMR, 13C NMR, and IR spectra of 3b-3h are provided.
This material is available free of charge on the web at http://
10 S. Kobayashi, R. Matsubara, Y. Nakamura, H. Kitagawa,
12 Y. Yamamoto, Y. Kawano, P. H. Toy, H. Togo, Tetrahedron