Denmark and Heemstra
ration of (Z)-[1-(tert-Butyldimethylsilanyloxy)-1,3-butadienyl]-
dimethylamine (41). To a flame-dried, 200-mL, three-necked,
round-bottomed flask fitted with a magnetic stir bar, thermocouple,
gas inlet tube, and septum was added 1.13 g (10 mmol) of
2-butenoic acid dimethylamide and 50 mL of THF. The solution
was cooled to -72 °C, and then a solution of 2.19 g (1.1 mmol,
1.1 equiv) of potassium hexamethyldisilazide in 20 mL of THF
was added slowly dropwise over 5 min via syringe. The resulting
yellow solution was stirred for 30 min at -72 °C prior to addition
of a solution of 1.66 g (11 mmol, 1.1 equiv) of TBSCl in 10 of
THF via syringe. The dry ice bath was then removed, and the
solution was allowed to warm to 0 °C. The yellow solution was
then concentrated in vacuo, and the resulting residue was taken up
in 50 mL of pentane. The yellow precipitate was then filtered
through a pad of Celite, and the filtrate was concentrated in vacuo.
The residue was purified by bulb-to-bulb distillation (60 °C ABT
at 0.01 mmHg) to afford 1.738 g (77%) of 41 as a clear, colorless
1901 (w), 1817 (w), 1668 (m), 1652 (m), 1621 (m), 1598 (m), 1578
(w), 1494 (w), 1448 (m), 1418 (w), 1344 (m), 1285 (m), 1226 (m),
1180 (w), 1020 (m), 987 (m), 915 (w), 894 (w), 834 (w), 764 (m),
698 (m), 667 (m). MS (CI, CH4): 253 (M+ + H, 17), 236 (10),
235 (51), 175 (18), 148 (11), 147 (100), 146 (43), 145 (11), 107
(71), 105 (79), 79 (13). [R]24D: +14.40 (c ) 1.00, EtOH). TLC:
Rf 0.30 (hexanes/EtOAc, 3:2) [UV (254 nm)]. SFC: (R)-11, tR
3.04 min (99.0%); (S)-11, tR 4.06 min (1.0%) (Chiralpak AD,
175 psi, 40 °C, 20.0% MeOH in CO2, 3.0 mL/min, 220 nm). Anal.
Calcd for C17H16O2 (252.31): C, 80.93; H, 6.39. Found: C, 80.63;
H, 6.33.
Representative Procedure 5. Addition of Cyclic Ketone-
Derived Silyl Dienol Ether 10 to Aldehydes. Preparation of (+)-
(4R,7R)-4-(7-Hydroxy(phenyl)methyl)-2-cyclohexen-1-one (20)
(Table 2, entry 1). Diisopropylethylamine (18 µL, 0.1 mmol,
0.1 equiv) was added via syringe to a flame-dried, 5-mL, Schlenk
flask under N2 containing a solution of 42 mg (0.05 mmol,
0.05 equiv) of bisphosphoramide (R,R)-3 in CH2Cl2 (2 mL). To
this solution was added 102 µL (1.0 mmol) of benzaldehyde in
one portion. To the resulting solution was added 172 µL (1.5 mmol,
1.5 equiv) of SiCl4 in one portion, and the reaction mixture was
cooled to -72 °C over 15 min. Then, 224 µL (1.2 mmol, 1.2 equiv)
of 10 was added dropwise over 1 min. The resulting mixture was
stirred at -72 °C for 2 h, whereupon 3.0 mL of chilled CH2Cl2
was added before the cold reaction mixture was poured into a
rapidly stirring solution of 1:1 satd aq NaHCO3/satd aq KF
(25 mL) at 0 °C. This biphasic mixture was stirred vigorously for
1 h before being filtered through Celite on a glass frit. The phases
were then separated, and the aqueous layer was washed with CH2-
Cl2 (3 × 40 mL). The combined organic extracts were dried over
Na2SO4 and filtered, and the filtrate was concentrated in vacuo.
The ratio of γ:R addition products was determined to be >99:1 by
1H NMR (500 MHz) analysis of the crude reaction mixture. The
residue was purified by column chromatography (SiO2 (25 g),
3 cm diameter, pentane/Et2O, 1:1) to yield 182 mg (90%) of (+)-
20 as a thick, colorless oil that solidified upon standing. The
diastereomeric ratio was determined to be anti:syn, 97.5:2.5 by SFC
analysis. The spectroscopic data for 20 matched those in the
literature.21 1H NMR (500 MHz, CDCl3): 7.43-7.32 (m, 5H, HC-
(9,10,11)), 7.25 (dt, J ) 10.3, 1.7, 1 H, HC(3)), 6.09 (dd, J ) 10.3,
2.4, 1 H, HC(2)), 4.59 (dd, J ) 7.8, 3.2, 1 H, HC(7)), 2.78-2.73
(m, 1 H, HC(4)), 2.49-2.21 (m, 1 H, HC(6)), 2.35-2.28 (m, 1 H,
HC(6)), 2.03 (br s, 1H, OH), 1.75-1.68 (m, 2 H, H2C(5)). 13C
NMR (125 MHz, CDCl3): 200.0 (C(1)), 151.6 (C(3)), 142.2 (C(8)),
129.9 (C(2)), 128.6 (C(10)), 128.1 (C(11)), 126.2 (C(9)), 76.5
(C(7)), 43.6 (C(4)), 36.7 (C(6)), 25.8 (C(5)). [R]24D +114.38 (c )
1.00, EtOH). TLC: Rf 0.10 (pentane/Et2O, 1:1) [UV (254 nm)].
SFC: (4S,7S)-20, tR 6.52 min (2.5%); (4R,7R)-20, tR 9.65 min
(97.5%) (Chiralpak OJ, 150 psi, 40 °C, 6.0% MeOH in CO2,
2.75 mL/min, 220 nm).
Representative Procedure 6. Addition of Bissilyl Dienol
Ethers to Conjugated Aldehydes. Preparation of (-)-(2R)-2,3-
Dihydro-6-methyl-2-phenylpyran-4-one (34) (Table 3, Entry 3).
Diisopropylamine (18 µL, 0.1 mmol, 0.1 equiv) was added via
syringe to a flame-dried, 20-mL, two-necked, round-bottomed flask
fitted with a magnetic stir bar, thermocouple, gas inlet tube, and
septum under N2 containing a solution of 9 mg (0.01 mmol,
0.01 equiv) of bisphosphoramide (R,R)-3 in CH2Cl2 (2 mL). To
this solution was added 102 µL (1.0 mmol) of benzaldehyde in
one portion. The resulting solution was cooled to -90 °C over
15 min, and to the reaction mixture was added 172 µL (1.5 mmol,
1.5 equiv) of SiCl4 in one portion. Then, 394 mg (1.2 mmol, 1.2
equiv) of 32b was added dropwise over 5 min. The resulting mixture
was stirred at -90 °C for 2 h, whereupon 3.0 mL of chilled CH2-
Cl2 was added before the cold reaction mixture was poured into a
rapidly stirring solution of 1:1 satd aq NaHCO3/satd aq KF
(25 mL) at 0 °C. This biphasic mixture was stirred vigorously for
3 h after which the aqueous layer was washed with CH2Cl2 (3 ×
50 mL). The combined organic extracts were dried over Na2SO4
1
oil. H NMR (500 MHz, CDCl3): 6.54 (dt, J ) 17.1, 10.5, 1 H,
HC(3)), 4.79 (dd, J ) 17.1, 2.2, 1 H, HC(4)), 4.61 (d, J ) 10.7, 1
H, HC(2)), 4.53 (dd, J ) 10.5, 2.3, 1 H, HC(4)), 2.58 (s, 6 H,
1
H3C(5)), 1.00 (s, 9 H, H3C(8)), 0.16 (s, 6 H, H3C(6)). NOE H
NMR (500 MHz, CDCl3): irradiation at 3.58 ppm (H3C(5))
enhanced signal at 4.61 ppm (HC(2)). 13C NMR (126 MHz,
CDCl3): 155.5 (C(1)), 133.4 (C(3)), 105.6 (C(4)), 89.2 (C(2)), 39.5
(C(5)), 25.7 (C(8)), 18.3 (C(7)), -4.7 (C(6)). IR (neat): 3083 (m),
3060 (m), 3013 (m), 2955 (s), 2932 (s), 2886 (m), 2859 (s), 2793
(m), 1631 (s), 1474 (s), 1461 (s), 1438 (m), 1419 (s), 1390 (m),
1346 (s), 1298 (m), 1281 (m), 1254 (s), 1195 (s), 1145 (s), 1125
(s), 1102 (m), 1055 (m), 1023 (s), 1005 (m), 996 (m), 944 (m),
881 (s), 839 (s), 825 (s), 810 (s), 782 (s), 739 (m), 679 (m), 655
(m), 642 (m). MS (EI, 70 eV): 228 (18), 227 (M+, 85), 212 (51),
171 (32), 170 (71), 157 (15), 156 (100), 147 (12), 130 (14), 96
(19), 81 (13), 75 (13), 73 (52), 59 (12), 57 (19). HRMS: calcd for
C12H25NOSi 227.170543, found 227.1694.
Representative Procedure 4. Addition of Acyclic R,â-
Unsaturated Ketone-Derived Silyl Dienol Ethers to Aldehydes.
Preparation of (+)-(5R,2E)-5-Hydroxy-1,5-diphenyl-2-penten-
1-one (11) (Table 1, Entry 1). Diisopropylethylamine (35 µL,
0.2 mmol, 0.2 equiv) was added via syringe to a flame-dried, 5-mL,
Schlenk flask under Ar containing a solution of 42 mg (0.05 mmol,
0.05 equiv) of bisphosphoramide (R,R)-3 CH2Cl2 (2 mL). To this
solution was added 102 µL (1.0 mmol, 1.0 equiv) of benzaldehyde
in one portion, and the reaction mixture was cooled to -50 °C
over 15 min. To the resulting solution was added 172 µL (1.1 mmol,
1.1 equiv) of SiCl4 in one portion. Then, 284 µL (1.2 mmol,
1.2 equiv) of 6 was added dropwise over 1 min via syringe. The
resulting mixture was stirred at -50 °C for 24 h whereupon
3.0 mL of chilled CH2Cl2 was added before the cold reaction
mixture was poured into a rapidly stirring solution of 1:1 satd aq
NaHCO3/satd aq KF (25 mL) at 0 °C. This biphasic mixture was
stirred vigorously for 1 h before being filtered through Celite on a
glass frit. The phases were then separated, and the aqueous layer
was washed with CH2Cl2 (3 × 40 mL). The combined organic
extracts were dried over Na2SO4 (5 g) and filtered, and the filtrate
was concentrated in vacuo. The ratio of γ:R addition products was
1
determined to be >99:1 by H NMR (500 MHz) analysis of the
crude reaction mixture. The residue was purified by column
chromatography (SiO2 (25 g), 3 cm diameter, hexanes/EtOAc, 4:1)
to yield 201 mg (80%) of (+)-11 as a thick, colorless oil. 1H NMR
(500 MHz, CDCl3): 7.88 (d, J ) 7.1, 2 H, HC(11)), (dt, J ) 7.5,
1.5, 1 H, HC(13)), 7.43 (t, J ) 7.6 2 H, HC(12)), 7.39-7.35 (m,
4 H, HC(7,8)), 7.32-7.28 (m, 1 H, HC(9)), 7.06-7.00 (m, 1 H,
HC(3)), 6.91 (dt, J ) 15.4, 1.3, 1 H, HC(2)), 4.90 (dd, J ) 7.7,
5.1, 1 H, HC(5)), 2.83-2.71 (m, 2 H, HC(4)), 2.31 (br s, 1 H,
OH). 13C NMR (125 MHz, CDCl3): 190.7 (C(1)), 145.0 (C(3)),
143.5 (C(6)), 137.6 (C(10)), 132.8 (C(13)), 128.6 (C(11)), 128.6
(C(8)), 128.6 (C(2) or C(12)), 128.5 (C(2) or C(12)), 127.9 (C(9)),
125.8 (C(7)), 73.2 (C(5)), 42.5 (C(4)). IR (neat): 4057 (w), 3430
(m), 3061 (w), 3030 (w), 2894 (w), 2360 (w), 2340 (w), 1964 (w),
5686 J. Org. Chem., Vol. 72, No. 15, 2007