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0.80 mmol) dro0pwise. The solution was stirred for 45 min at
21088C. N,N -Dimethylpropyleneurea (0.13 mL) was
added dropwise and the mixture was stirred for 45 min at
21088C. Methyl iodide (0.14 mL, 2.2 mmol) was added in
one portion and the reaction was allowed to stir for 1 h. The
reaction was quenched with aqueous saturated ammonium
chloride (20 mL) and the mixture was allowed to warm to
room temperature. The layers were separated and the
aqueous layer was extracted with ethyl acetate (2£20 mL)
and CH2Cl2 (2£20 mL). The combined organic layers were
dried (MgSO4) and concentrated under reduced pressure.
The product was purified by column chromatography (SiO2,
25:1 CH2Cl2/diethyl ether) to give 25 (107 mg, 0.24 mmol,
33%) and starting material 24 (173 mg, 0.41 mmol, 56%).
3.1.7. 2-(Trimethylsilyl)ethoxymethyl (SEM) ether of 27.
To a solution of 8-phenylmenthyl ester 27 (0.95 g, 2 mmol)
in CH2Cl2 (2 mL) was added trimethylsilylethoxymethyl
chloride (0.53 mL, 3 mmol), tetrabutylammonium iodide
(1.11 g, 3 mmol), and diisopropylethyl amine (0.52 mL,
3 mmol) and the mixture was heated to 508C in a sealed
flask for 14 h. The mixture was cooled to room temperature
and quenched with saturated aqueous sodium bicarbonate
solution (10 mL) and the solvent was evaporated under
reduced pressure. The aqueous layer was extracted with
hexane (3£10 mL). The combined organic layers were dried
(MgSO4) and concentrated under reduced pressure. The
product was purified by column chromatography (SiO2,
24:1 hexane/diethyl ether) affording the SEM-protected
ester (1.2 g, 2 mmol, 100%) as a colorless oil. TLC:
Rf¼0.38 (SiO2, 9:1 hexane/diethyl ether); IR (film) 2947,
2918, 1720, 1016 cm21; 1H NMR (600 MHz, CDCl3) d 7.27
(m, 4H), 7.16 (m, 1H), 5.55 (m, 1H), 5.28 (app s, 1H), 4.87
(dt, J¼4.0, 10.5 Hz, 1H), 4.76 (d, J¼7.4 Hz, 1H), 4.67 (d,
J¼7.0 Hz, 1H), 3.77 (m, 1H), 3.63 (m, 1H), 2.47 (m, 2H),
2.26 (dt, J¼6.1, 12.7 Hz, 1H), 2.12–0.7 (band, 16H), 1.63
(s, 3H), 1.58 (s, 3H), 1.37 (s, 3H), 1.24 (s, 3H), 0.89 (d,
J¼7.0 Hz, 3H), 0.84 (d, J¼6.1 Hz, 3H), 0.02 (s, 9H); 13C
NMR (150 MHz, CDCl3) d 172.6, 150.6, 147.9, 132.9,
128.0, 126.5, 125.7, 125.3, 120.5, 91.1, 82.4, 76.8, 65.9,
51.7, 50.6, 41.5, 40.5, 39.4, 37.4, 34.5, 33.0, 31.3, 31.2,
28.1, 27.6, 25.7, 24.2, 23.5, 22.8, 21.8, 18.2, 16.8, 21.5.
1
TLC: Rf¼0.49 (SiO2, 3:1 ethyl acetate/hexane); H NMR
(500 MHz, CDCl3) d 7.37 (s, 5H), 6.06 (s, 1H), 5.35 (s, 1H),
4.91 (dd, J¼1.5, 9.2 Hz, 1H), 3.30 (m, 1H), 2.62 (d,
J¼11.4 Hz, 3H), 2.60 (m, 1H), 2.42 (m, 1H), 2.24 (m, 1H),
2.15 (m, 1H), 2.14 (s, 3H), 2.06 (m, 2H), 1.91 (m, 2H), 1.80
(dd, J¼3.3, 16.9 Hz, 1H), 1.72 (s, 3H), 1.16 (d, J¼6.2 Hz,
3H), 0.93 (d, J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 144.9 (d, JCP¼6.7 Hz), 136.1 (d, JCP¼7.4 Hz), 133.5,
131.0, 129.1, 128.6, 127.1, 119.7, 119.0 (d, JCP¼3.1 Hz),
85.8, 72.9 (d, JCP¼9.8 Hz), 61.7 (d, JCP¼11.5 Hz), 50.6 (d,
JCP¼2.6 Hz), 39.8, 37.4, 33.4, 28.2 (d, JCP¼3.1 Hz), 27.8,
27.7, 24.8, 23.5, 16.4, 15.2 (d, JCP¼10.5 Hz); HRMS
(MALDI-FTMS) C25H33N2O3P m/z calcd for [MþNa]þ
463.2126; found 463.2127.
3.1.8. Alcohol 28. To a 2788C solution of the SEM ether of
8-phenylmenthyl ester 27 (0.50 g, 0.84 mmol) in toluene
(28 mL) was added diisobutylaluminum hydride (1 M in
toluene, 2.5 mL, 2.52 mmol). After 5 min, the mixture was
warmed to 08C and stirred for 10 min. The reaction was
quenched by the slow addition of methanol (1 mL) then
poured into 50 mL of saturated aqueous sodium potassium
tartrate and 30 mL of ethyl acetate. After stirring for 10 min,
the layers were separated. The aqueous layer was saturated
with sodium chloride and extracted with ethyl acetate
(3£50 mL). The combined organic layers were dried
(MgSO4) and concentrated under reduced pressure. The
product was purified by column chromatography (SiO2,
CH2Cl2) affording phenyl menthol (180 mg, 0.78 mmol,
93%) and alcohol 28 (285 mg, 0.78 mmol, 93%) as a
colorless oil. TLC: Rf¼0.18 (SiO2, CH2Cl2); IR (film) 3466,
2954, 1019 cm21; 1H NMR (600 MHz, CDCl3) d 5.60 (app
s, 1H), 5.28 (app s, 1H), 4.77 (d, J¼7.5 Hz, 1H), 4.65 (d,
J¼7.5 Hz, 1H), 3.72 (m, 2H), 3.58 (m, 2H), 2.99 (dd, J¼4.4,
9.2 Hz, 1H), 2.53 (dd, J¼4.9, 16.7 Hz, 1H), 2.13 (m, 2H),
2.02 (m, 2H), 1.87 (m, 1H), 1.78 (m, 2H), 1.68 (dd, J¼3.3,
16.2 Hz, 1H), 1.65 (s, 3H), 1.41 (s, 3H), 0.94 (m, 2H), 0.88
(d, J¼6.5 Hz, 3H), 0.01 (s, 9H); 13C NMR (150 MHz,
CDCl3) d 149.1, 133.5, 127.1, 120.2, 89.6, 81.0, 67.7, 65.6,
51.1, 39.2, 37.3, 33.5, 28.1, 26.1, 23.4, 21.9, 18.2, 16.8,
21.5; [a]2D5¼211.58 (c¼1.48, CHCl3); MS (ESI)
C21H38O3Si m/z calcd for [MþNa]þ 389; found 389.
3.1.6. 8-Phenylmenthyl ester 27. To a solution of trisyl
hydrazone 17 (2.30 g, 5 mmol) in diethyl ether/THF (5:1,
60 mL) at 2788C was added n-BuLi (1.5 M in hexane,
6.84 mL, 10.25 mmol) dropwise. The dark red solution was
stirred for 10 min. The cooling bath was removed and the
solution was allowed to warm to 2208C over 15 min during
which nitrogen gas evolved. The solution was cooled to
2788C and magnesium bromide diethyletherate (0.83 M,
6.3 mL, 5.25 mmol) was added dropwise. The mixture was
stirred for 10 min and then 8-phenylmenthyl pyruvate (26)
(1.59 g, 5.25 mmol) in 5 mL of THF was added in one
portion. After stirring at 2788C for 10 min, the reaction was
allowed to warm to room temperature. The reaction was
quenched with saturated aqueous NH4Cl (30 mL). The
layers were separated and the aqueous layer was extracted
with diethyl ether (3£50 mL). The combined organic layers
were dried (MgSO4) and concentrated under reduced
pressure. The product was purified by column chromato-
graphy (SiO2, 15:1 hexane/diethyl ether) affording
8-phenylmenthyl ester 27 (1.27 g, 2.73 mmol, 55%) as a
colorless oil. TLC: Rf¼0.57 (SiO2, 9:1 hexane/ethyl
acetate); IR (film) 3512, 2957, 2922, 1710 cm21 1H
;
NMR (600 MHz, CDCl3) d 7.29 (m, 4H), 7.17 (m, 1H),
5.62 (app t, J¼2.4 Hz, 1H), 5.28 (app s, 1H), 4.94 (dt,
J¼4.4, 11.0 Hz, 1H), 3.04 (s, 1H), 2.46 (ddd, J¼1.7, 6.5,
16.2 Hz, 1H), 2.25–0.75 (band, 16H), 1.65 (s, 3H), 1.39 (s,
3H), 1.34 (s, 3H), 1.24 (s, 3H), 0.90 (d, J¼6.5 Hz, 3H), 0.86
(d, J¼6.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 174.8,
150.5, 149.4, 133.6, 128.0, 126.2, 125.4, 125.3, 120.0, 77.5,
75.7, 51.4, 50.0, 41.4, 40.1, 39.9, 37.4, 34.3, 33.7, 31.5,
29.3, 28.0, 27.2, 26.4, 25.7, 25.2, 24.8, 23.4, 22.6, 21.7,
16.5; [a]2D5¼234.78 (c¼1.00, CHCl3); HRMS (MALDI-
FTMS) C31H44O2 m/z calcd for [MþNa]þ 487.3188; found
487.3195.
3.1.9. Aldehyde 29. To a solution of oxalyl chloride
(139 mL, 1.6 mmol) in CH2Cl2 (10 mL) at 2788C was
added dropwise DMSO (226 mL, 3.2 mmol) and the
resulting solution was stirred at 2788C for 30 min. Alcohol
28 (194 mg, 0.53 mmol) in CH2Cl2 (5 mL) was added and
the resulting solution was stirred for 10 min at 2788C, then
at 2408C for 20 min. Diisopropylethylamine (0.92 mL) was