2346
J. E. Hein, P. G. Hultin / Tetrahedron: Asymmetry 16 (2005) 2341–2347
4.3.2. (30S,4S,40R,5R,50S)-4-Benzyl-3-((50-methyl-20,30-
diphenylisoxazolidin-40-yl)carbonyl)-5-(10H,10H,20H,-20H-
perfluorooctyl)-2-oxazolidinone, 4. Isolated as a yellow
(0.02 g, 0.025 mmol) in toluene (2 mL). The reaction
was then heated to reflux and left to stir for 5 h, after
which the reaction was cooled and the reaction evapo-
rated to dryness. The crude mixture was adsorbed onto
FluoroFlashTM fluorous-modified silica gel (ꢀ0.1 g) and
applied to an FPSE cartridge charged with 5.5 g of
dry FluoroFlashTM. The solid phase was washed
with 70% methanol in water (150 mL), allowing 7
(0.0076 g, 0.023 mmol, 92% yield) to be isolated as a
colourless oil. Washing the solid phase with methanol
gave (4S,5R)-4-benzyl-5-(10H,10H,20H,20H-perfluoro-
octyl)-2-oxazolidinone 1b (0.011 g, 0.021 mmol, 83%
yield) as a crystalline solid. 1H NMR values for 7
matched those reported in the literature. The absolute
configuration was determined by chemical correlation
to literature results; [a]D = +43.7 (c 0.65, CHCl3); lit.
[a]D = +35.19c
1
oil; H NMR (300 MHz, CDCl3) d 7.46–6.91 (m, 15H),
5.09 (d, 3J = 7.2 Hz, 1H), 4.93–4.85 (m, 1H), 4.68
(dd, 3J1 = 7.5 Hz, 3J2 = 7.4 Hz, 1H), 4.49–4.41 (m,
1H), 4.31 (dq, 3J1 = 7.4 Hz, 3J2 = 6.3 Hz, 1H), 3.02
(dd, 3J1 = 14.4 Hz, 3J1 = 4.6 Hz, 1H), 2.94 (dd,
3J1 = 14.4 Hz, 3J2 = 8.6 Hz, 1H), 2.37–2.23 (m, 1H),
2.22–2.05 (m, 2H), 2.00–1.88 (m, 1H), 1.53 (d,
3J = 6.3 Hz, 3H); 13C (75 MHz, CDCl3) d 18.2, 21.3,
27.7, 33.0, 58.9, 63.1, 72.1, 74.3, 79.1, 114.7, 121.7,
126.5, 127.3, 128.0, 128.6, 128.8, 128.9, 129.0, 135.5,
140.6, 151.4, 152.1, 170.1; 19F (282 MHz, CDCl3)
d
À81.20, À114.89, À122.34, À123.29, À123.90,
À126.55; [a]D = +32.8 (c 0.5, Et2O). Anal. Calcd for
formula C35H29F13N2O4: C, 53.31; H, 3.71; N, 3.55.
Found: C, 53.68; H, 3.98; N, 3.12.
4.5. Reductive cleavage applied in recyclability study
4.3.3. (30S,4S,40S,5R,50R)-4-Benzyl-3-((50-methyl-20,30-
diphenylisoxazolidin-40-yl)carbonyl)-5-(10H,10H,20H,-20H-
perfluorooctyl)-2-oxazolidinone, 5. Isolated as a yellow
Sodium borohydride (0.179 mL, 5.07 mmol) was dis-
solved in water (2 mL) and added to a solution ofcyclo-
addition products 3, 4, 5 and 6 (1 g, 1.268 mmol) in
THF (20 mL). The reaction was left to stir at rt for
5 h, after which the reaction was quenched with 1 M
HCl (5 mL) and evaporated to dryness. The crude
mixture was adsorbed onto FluoroFlashTM fluorous-
modified silica gel (ꢀ0.5 g) and applied to an FPSE
cartridge charged with 5.5 g ofdry FluoroFlash TM. The
solid phase was washed with 70% methanol in water
(250 mL), allowing 8 to be isolated (0.2 g, 0.743 mmol,
58.6% yield). Washing the solid phase with methanol
gave (4S,5R)-4-benzyl-5-(10H,10H,20H,20H-perfluoro-
octyl)-2-oxazolidinone 1b (0.59 g, 1.127 mmol, 89%
yield) as a crystalline solid.
1
oil; H NMR (300 MHz, CDCl3) d 7.58–6.90 (m, 15H),
5.12 (dq, 3J1 = 9.7 Hz, 3J2 = 6.0 Hz, 1H), 5.10 (d,
3J = 10.9 Hz, 1H), 4.60–4.53 (m, 1H), 4.43–4.37 (m,
1H), 4.25 (dd, 3J1 = 10.7 Hz, 3J2 = 9.7 Hz, 1H), 2.88
(dd, 3J1 = 13.9 Hz, 3J1 = 5.2 Hz, 1H), 2.78 (dd,
3J1 = 13.9 Hz, 3J2 = 8.4 Hz), 2.29–2.09 (m, 1H), 1.94–
3
1.71 (m, 4H), 1.61–1.52 (m, 1H), 1.48 (d, J = 6.0 Hz,
3H); 13C (75 MHz, CDCl3) d 17.1, 20.7, 27.7, 32.0,
58.2, 60.3, 71.9, 74.8, 77.7, 115.9, 122.3, 127.0, 128.4,
128.5, 128.6, 128.8, 128.9, 136.3, 138.6, 149.8, 151.9,
168.7; 19F (282 MHz, CDCl3) d À81.19, À114.97,
À122.36, À123.30, À123.94, À126.54; [a]D = +88.5 (c
0.5, Et2O). Anal. Calcd for formula C35H29F13N2O4:
C, 53.31; H, 3.71; N, 3.55. Found: C, 53.64; H, 3.60;
N, 3.38.
4.5.1. 5-Methyl-2,3-diphenyl-isoxazolidine-4-methanol,
8. Obtained as a mixture ofstereoisomers, 1H and
13C NMR values matched those reported in the
literature.19b
4.3.4. (30R,4S,40R,5R,50S)-4-Benzyl-3-((50-methyl-20,30-
diphenylisoxazolidin-40-yl)carbonyl)-5-(10H,10H,20H,-20H-
perfluorooctyl)-2-oxazolidinone, 6. Isolated as a yellow
1
oil; H NMR (300 MHz, CDCl3) d 7.39–7.17 (m, 15H),
4.5.2. 10-((50-Methyl-20,30-diphenylisoxazolidin-40-yl)car-
bonylamino)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-11-phen-
yl-undecan-9-ol, 9. 1H NMR (300 MHz, CDCl3) 7.54–
6.89 (m, 15H), 5.90 (d, 3J = 7.3 Hz, 1H), 4.90 (d,
5.01 (dq, 3J1 = 9.3 Hz, 3J2 = 6.1 Hz, 1H), 4.81 (d,
3J = 10.7 Hz,
1H),
4.35
(dd,
3J1 = 10.7 Hz,
3J2 = 9.3 Hz, 1H), 4.08–4.02 (m, 1H), 3.51–3.43 (m,
1H), 2.88 (dd, 3J1 = 13.9 Hz, 3J1 = 5.2 Hz, 1H), 2.78
(dd, 3J1 = 13.9 Hz, 3J2 = 8.4 Hz, 1H), 2.29–2.09 (m,
1H), 2.04–1.81 (m, 2H), 1.64–1.55 (m, 1H), 1.39 (d,
3J = 6.1 Hz, 3H); 13C (75 MHz, CDCl3) d 17.8, 21.2,
26.8, 34.8, 58.3, 60.3, 71.8, 74.6, 78.6, 116.6, 122.8,
127.2, 128.4, 128.5, 128.6, 128.8, 129.1, 135.7, 138.5,
149.6, 152.1, 168.5; 19F (282 MHz, CDCl3) d À81.17,
À114.79, À122.32, À123.27, À123.86, À126.53;
[a]D = +27.4 (c 0.32, Et2O). Anal. Calcd for formula
C35H29F13N2O4: C, 53.31; H, 3.71; N, 3.55. Found: C,
53.54; H, 3.56; N, 3.41.
3
3
3J = 8.7 Hz), 4.15 (dq, J1 = 8.7 Hz, J2 = 6.7 Hz, 1H),
3
3
3.93–3.87 (m, 1H), 3.34 (dd, J1 = 8.7 Hz, J2 = 4.1 Hz,
1H), 3.15–3.09 (m, 1H), 2.81 (dd, 3J1 = 14.1 Hz,
3J2 = 4.8 Hz, 1H), 2.53 (dd, 3J1 = 14.1 Hz, 3J2 =
3
11.1 Hz, 1H), 2.34 (d, J = 6.5 Hz, 1H), 3.32–2.14 (m,
1H), 2.01–1.79 (m, 1H), 1.41–1.23 (m, 2H), 1.11 (d,
3J = 6.5 Hz, 3H).
Acknowledgements
The authors thank Dr. Jim Britton and Dr. Laura Har-
rington at the McMaster Analytical X-ray diffraction
facility for structural analysis, and Dr. Frank Schweizer
for providing access to HPLC–MS. We also acknow-
ledge the support ofFluorous Technologies Inc., and
an operating grant from the Natural Sciences and Engi-
neering Research Council ofCanada.
4.4. (3R,4S,5R)-4-Isoxazolidinecarboxylic acid,
5-methyl-2,3-diphenyl-, isopropyl ester, 7
Following the procedure described in the literature,19c
Ti(iPrO)4 (0.074 mL, 0.254 mmol) and iPrOH
(0.039 mL, 0.507 mmol) were added to a solution of 3