Roy et al.
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Experimental Section
Na2SO4, and concentrated under reduced pressure. Celite (3.0 g)
was added to the residue followed by slow addition of Et2O
(10 mL, over 1 min) to induce the complete precipitation of the
TAP-supported mixture of sulfide 13 and sulfoxide 14. The
mixture was filtered on Celite and concentrated under reduced
pressure to afford pure aldehyde.
(40-{[4-(Methylthio)butoxy]carbonyl}-1,10-biphenyl-4-yl)(tri-
phenyl)phosphonium perchlorate (13). To a solution of acid 12
(9.0 g, 16.1 mmol, 1.0 equiv) in DCM (80 mL, 0.2 M) at 0 °C was
added (COCl)2 (1.69 mL, 19.32 mmol, 1.2 equiv) followed by
DMF (5-6 drops). The solution was stirred for 2 h, and the
excess of (COCl)2 was evaporated under reduced pressure. The
resultant foam was dissolved in DCM (80 mL, 0.2 M), and
pyridine (3.26 mL, 40.25 mmol, 2.5 equiv) was added followed
by a solution of 4-methyl(thio)butanol (2.35 mL, 19.32 mmol,
1.2 equiv) in THF (33 mL, 0.6 M). The mixture was heated to
reflux for 16 h and cooled to rt. The solution was diluted with
DCM (200 mL) and washed with aqueous 10% (w/w) HCl (3 ꢀ
20 mL), once with saturated aqueous NaHCO3 (20 mL) and
once with water (20 mL), dried over MgSO4, and concentrated
under reduced pressure. The crude product was dissolved with
DCM (5 mL) and was precipitated upon Et2O addition (50 mL,
over 5 min). The ether layer was decanted, and the above
isolation protocol was repeated twice to afford pure TAP-
supported sulfide 13 as a yellowish solid (9.6 g, 90%): mp
4-({[4-(Triphenylphosphonio)benzyl]oxy}carbonyl)oxy]-2,2,6,-
6-tetramethylpiperidin-1-oxyl perchlorate (16). To a solution of
triphosgene (356 mg, 1.2 mmol, 0.6 equiv) in DCM (4.0 mL) at
-20 °C was added pyridine (970 μL, 12.0 mmol, 6.0 equiv)
dropwise, followedby a solution of 4-hydroxy-TEMPO (690 mg,
4.0 mmol, 2.0 equiv) in DCM (4.0 mL). The mixture was stirred
for 15 min and warmed to rt and stirred for 30 min. Alcohol 15
(936 mg, 2.0 mmol, 1.0 equiv) was added, and the solution was
stirred for 2 h. The solution was diluted with DCM and washed
with water (2 ꢀ 10 mL), dried over anhydrous MgSO4, and
concentrated under reduced pressure. The crude product was
dissolved with DCM (2 mL) and was precipitated upon Et2O
addition (10 mL, over 1 min). The ether layer was decanted, and
the above isolation protocol was repeated twice to afford pure
TAP-supported TEMPO 16 as an orange solid (1.27 g, 95%): mp
80-85 °C; NMR characterization was achieved by in situ
reduction of the radical TAP-supported TEMPO 16 to the
hydroxylamine derivative with phenylhydrazine;26 1H NMR
(400 MHz, CDCl3) δ 7.91-7.87 (m, 3H), 7.79-7.74 (m, 8H),
7.68-7.60 (m, 8H), 5.31 (s, 2H), 4.95 (m, 1H), 3.90 (br, 1H), 2.08
(dd, J = 4.1 Hz, 12.8 Hz, 2H), 1.84 (t, J = 12.0 Hz, 2H), 1.34 (s,
6H), 1.27 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 154.4, 144.0 (d,
J = 3.0 Hz), 136.0 (d, J = 2.8 Hz), 135.0 (d, J = 10.7 Hz), 134.6
(d, J = 10.4 Hz), 131.0 (d, J = 12.9 Hz), 129.6 (d, J = 13.3 Hz),
116.9 (d, J = 89.6 Hz), 117.0 (d, J = 90.4 Hz), 71.0, 68.0, 60.8,
42.9, 30.8, 21.0; 31P NMR (162 MHz, CD2Cl2) δ 23.3; IR (solid)
2975, 2160, 1742, 1438, 1263, 1081, 689 cm-1; HRMS (ESþ)
calcd for C35H38N1O4P1 [M]þ 567. 2529, found 567.2538.
General Procedure for Alcohol Oxidation Using TAP-Sup-
ported TEMPO 16. To a solution of alcohol (1.00 mmol, 1.00
equiv) in DCM (2.5 mL, 0.4 M) at 0 °C were added TAP-
supported TEMPO 16 (6.7 mg, 0.01 mmol, 0.01 equiv), an
aqueous solution of NaOCl (3.57 mL, 1.25 mmol, 1.25 equiv)
buffered at pH 8.9 with NaHCO3, and an aqueous solution of
KBr (11.9 mg, 0.10 mmol, 0.10 equiv, 0.2 M). The reaction
mixture was vigorously stirred until TLC analysis indicated
complete consumption of the starting material. The solution
was diluted with DCM (10 mL); the layers were separated, and
the aqueous layer was extracted with DCM (3 mL). The
combined organic layers were washed with water (2 mL), dried
over anhydrous MgSO4, and concentrated under reduced pres-
sure to a minimum volume. Celite (30 mg) was added to the
residue followed by Et2O (4 mL, over 1 min) to induce the
complete precipitation of the TAP-supported TEMPO 16. The
mixture was filtered on Celite and concentrated under reduced
pressure to afford pure aldehyde or ketone.
1
72-75 °C; H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.0
Hz, 2H), 7.99 (dd, J = 2.1 Hz, 8.0 Hz, 2H), 7.86 (t, J = 7.2 Hz,
3H), 7.78-7.71 (m, 10H), 7.67-7.62 (m, 6H), 4.33 (t, J = 6.2
Hz, 2H), 2.55 (t, J = 7.0 Hz, 2H), 2.07 (s, 3H), 1.91-184 (m,
2H), 1.78-1.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 166.1,
147.0 (d, J = 3.0 Hz), 142.7, 135.8 (d, J = 2.9 Hz), 135.2 (d, J =
10.7 Hz), 134.5 (d, J = 10.4 Hz), 130.9 (d, J = 12.9 Hz), 130.8,
130.4, 129.4 (d, J = 13.3 Hz), 127.7, 117.5 (d, J = 89.7 Hz),
116.7 (d, J = 90.8 Hz), 64.8, 33.8, 27.8, 25.6, 15.5; 31P NMR (162
MHz, CDCl3) δ 23.3; IR (solid) 2915, 2160, 1709, 1437, 1273,
1080, 996, 724, 688 cm-1; HRMS (API-ES, Pos) calcd for
C36H34O2PS [M]þ 561.2009, found 561.2012.
(40-{[4-(Methylsulfinyl)butoxy]carbonyl}-1,10-biphenyl-4-yl)-
(triphenyl)phosphonium perchlorate (14). To a solution of sulfide
13 (5.0 g, 7.56 mmol, 1.0 equiv) in a mixture of DCM/MeOH
(2:1, 27 mL, 0.3 M) at 0 °C was added H2O2 (35% (w/w) aq
solution) (3.0 mL, 37.0 mmol, 5.0 equiv). The solution was
vigorously stirred at rt for 3 h and diluted with DCM (100 mL).
The organic layer was washed with brine (15 mL) and water (15
mL), dried over anhydrous MgSO4, and concentrated under
reduced pressure. The crude product was dissolved with DCM
(3 mL) and was precipitated upon Et2O addition (30 mL, over
3 min). The ether layer was decanted, and the above isolation
protocol was repeated twice to afford pure TAP-supported
sulfoxide 14 as a yellowish solid (5.15 g, 99%): mp 75-80 °C;
1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.4 Hz, 2H), 7.99
(dd, J = 3.1 Hz, 8.4 Hz, 2H), 7.86 (m, 3H), 7.79-7.70 (m, 10H),
7.67-7.62 (m, 6H), 4.35 (m, 2H), 2.79 (m, 2H), 2.58 (s, 3H),
1.91-184 (m, 2H), 1.97-1.95 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 166.1, 147.0 (d, J = 3.1 Hz), 142.7, 135.9 (d, J = 3.0
Hz), 135.2 (d, J = 10.7 Hz), 134.5 (d, J = 10.4 Hz), 130.9 (d, J =
12.9 Hz), 130.7 130.6, 129.5 (d, J = 13.3 Hz), 127.7, 117.6 (d,
J = 89.6 Hz), 116.7 (d, J = 90.9 Hz), 64.5, 54.0, 38.8, 27.9, 19.7;
31P NMR (162 MHz, CDCl3) δ 23.3; IR (solid) 2915, 2160, 1709,
1437, 1273, 1082, 996, 724, 688 cm-1; HRMS (API-ES, Pos)
calcd for C36H34O2PS [M]þ 577.1961, found 577.1960.
General Procedure for the Swern Oxidation Using TAP-
Supported DMSO 14. To a solution of oxalyl chloride (131
μL, 1.5 mmol, 1.5 equiv) in DCM (1.5 mL, 1 M) at -40 °C was
slowly added a solution of TAP-DMSO 14 (1.49 g, 2.2 mmol,
2.2 equiv) in DCM (6.0 mL, 0.37 M). After 10 min, a solution of
alcohol (1.0 mmol, 1.0 equiv) in DCM (2.5 mL, 0.4 M) was
added and the solution was stirred at -30 °C for 1-2 h. After
1-2 h, DIPEA (871 μL, 5.0 mmol, 5.0 equiv) was added and the
solution was stirred at -30 °C for 10 min and at rt for 30 min.
The solution was diluted with DCM (40 mL), washed with aq
10% (w/w) HCl (2 ꢀ 5 mL) and water (5 mL), dried over
[4-({[(4-Iodophenoxy)carbonyl]oxy}methyl)phenyl](triphenyl)-
phosphonium perchlorate (17). To a solution of triphosgene (1.27
g, 4.60 mmol, 0.43 equiv) in (75 mL) at -30 °C was added
pyridine (2.25 mL, 27.8 mmol, 2.6 equiv) dropwise. The resulting
mixture was warmed to rt and stirred for 30 min (it became a
clear yellowish homogeneous solution) and then cooled to
-78 °C (heterogeneous solution). A solution of alcohol 15
(5.0 g, 10.7 mmol, 1.0 equiv) in DCM (75 mL) at -78 °C was
slowly added in a way to keep the internal reaction temperature
below -70 °C. After 1 h, a solution of sodium 4-iodophenolate
(5.18 g, 21.4 mmol, 2.0 equiv) in THF (30 mL) was added at
-78 °C. The resulting yellow solution was left to warm to rt
overnight. The solution was diluted with DCM (300 mL),
washed with brine (2 ꢀ 40 mL), dried over Na2SO4, and
(26) Lee, T. D.; Keana, J. F. W. J. Org. Chem. 1975, 40, 3145.
8514 J. Org. Chem. Vol. 74, No. 22, 2009