Harris et al.
JOCFeatured Article
NMR (125 MHz, CDCl3) δ 172.2, 155.6, 139.0, 136.3, 128.5,
128.5, 128.4, 128.0, 127.6, 126.7, 73.5, 70.6, 66.8, 56.4, 21.6,
21.3; HRMS (ESI) calcd for C20H23NO5Naþ 380.1468,
found 380.1469.
13a: mp 136-137 °C (DSC, sharp onset); FTIR (neat,
cm-1) 3392, 2978, 2943, 1713, 1685, 1517, 1473, 1578, 1422,
1389, 1355, 1327, 1313, 1293, 1234, 1218, 1170, 1146, 1116,
1100, 1055, 1039, 1022, 952, 917, 877, 848, 822, 790, 775, 755,
729, 703; 1H NMR (500 MHz, CDCl3) δ 7.41-7.26 (m, 5H),
5.38 (br d, J = 8.3 Hz, 1H), 5.23 (br d, J = 8.3 Hz, 1H), 5.12
(sept, J = 6.4 Hz, 1H), 4.43 (br s, 1H), 3.14 (br s, 1H), 1.40 (s,
9H), 1.33-1.28 (m, 6H); 13C NMR (125 MHz, CDCl3) δ
172.5, 155.0, 139.5, 128.5, 127.6, 126.7, 79.7, 73.6, 70.7, 55.8,
28.3, 21.7, 21.5; HRMS (ESI) calcd for C17H25NO5Naþ
346.1625, found 346.1634.
12b: mp 92-93 °C; FTIR (neat, cm-1) 3499, 3366, 3036,
2983, 2939, 1725, 1691, 1522, 1498, 1454, 1438, 1400, 1376,
1356, 1316, 1292, 1239, 1211, 1195, 1160, 1105, 1055, 1029,
1015, 1002, 980, 956, 916, 903, 863, 836, 795, 778, 737, 712,
703, 694, 669; 1H NMR (500 MHz, CDCl3) δ 7.35-7.19 (m,
10H), 5.66 (br d, J = 8.4 Hz, 1H), 5.17 (s, 1H), 5.05-4.93 (m,
3H), 4.54 (br d, J = 7.2 Hz, 1H), 3.13 (br s, 1H), 1.22 (d, J =
6.2 Hz, 3H), 1.14 (d, J = 6.2 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 170.1, 156.3, 139.7, 136.2, 128.4, 128.3, 128.3,
128.0, 127.8, 126.0, 73.8, 69.6, 66.9, 60.0, 21.6, 21.5; HRMS
(ESI) calcd for C20H23NO5Naþ 380.1468, found 380.1468.
Chiral Methods [Table 3, (þ)-12a, (-)-12a, (þ)-12b]. (þ)-
12a. Following the general AA procedure above, trans-
isopropyl cinnamate (150 mg, 0.79 mmol) was reacted with
osmium tetraoxide (8 mg, 32 μmol), (DHQ)2PHAL (31.0 mg,
39.5 μmol), and benzyl reagent 8 (338 mg, 1.11 mmol). (Note:
The solution changed from a yellow color to dark green very
quickly after addition of the trans-isopropyl cinnamate and
a colorless precipitate formed during the course of the reaction.)
Subsequent flash column chromatography (silica gel, petro-
leum spirit/ethyl acetate 4:1) afforded 270 mg (96%) of (þ)-12a
and 12b as a 12.7:1 mixture of regioisomers: (þ)-12a, 97% ee;
12b, 33% ee; (þ)-12a, [R]21D=þ15.1 (c 1.26, CHCl3); spectro-
scopic data was identical to (()-12a above.
13b: FTIR (neat, cm-1) 3432, 2981, 2935, 1695, 1498,
1454, 1392, 1367, 1334, 1267, 1162, 1106, 1054, 1027, 982,
936, 916, 861, 836, 823, 776, 736, 701; 1H NMR (500 MHz,
CDCl3) δ 7.42-7.20 (m, 5H), 5.34 (br s, 1H), 5.14 (br s, 1H),
5.02 (sept, J = 6.1 Hz, 1H), 4.46 (br s, 1H), 3.17 (br s, 1H),
1.42-1.26 (br m, 9H), 1.25 (d, J = 6.1 Hz, 3H), 1.17 (d, J =
6.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 170.3, 155.7,
140.0, 128.2, 127.8, 126.1, 79.9, 74.1, 69.4, 59.6, 28.1, 21.7,
21.5; HRMS (ESI) calcd for C17H25NO5Naþ 346.1625,
found 346.1625.
(()-(2S,3R)-Isopropyl 2-{[(9H-Fluoren-9-yl)methoxy]car-
bonylamino}-3-hydroxy-3-phenylpropanoate (14a) and (()-
(2S,3R)-Isopropyl 3-{[(9H-Fluoren-9-yl)methoxy]carbonylamino}-
2-hydroxy-3-phenylpropanoate (14b). Following the general
procedure above, trans-isopropyl cinnamate (150 mg, 0.79
mmol) was reacted with osmium tetraoxide (8 mg, 32 μmol)
and Fmoc reagent 10 (434 mg, 1.10 mmol). The crude
product was purified by flash column chromatography
(silica gel, ethyl acetate/petroleum spirit 1:4 and 3:7) to
afford 338 mg (96%) of a 1:1.9 mixture of regioisomers 14a
and 14b. Further column chromatography yielded analy-
tical samples of 14a and 14b as colorless solids.
(-)-12a. Following the general AA procedure above,
trans-isopropyl cinnamate (150 mg, 0.79 mmol) was reacted
with osmium tetraoxide (8 mg, 32 μmol), (DHQD)2PHAL
(31.0 mg, 39.5 μmol), and benzyl reagent 8 (338 mg, 1.11
mmol). (Note: The solution changed from a yellow color to
dark green very quickly after addition of the trans-isopropyl
cinnamate and a colorless precipitate formed during the
course of the reaction.) Subsequent flash column chroma-
tography (silica gel, petroleum spirit/ethyl acetate 4:1) af-
forded 269 mg (96%) of the products (-)-12a and 12b in a
13.4:1 ratio of regioisomers: (-)-12a, 97% ee; 12b, 28% ee.
14a: mp 118 °C (DSC, sharp onset); FTIR (neat, cm-1
)
3384, 2976, 1721, 1695, 1519, 1449, 1355, 1324, 1287, 1250,
1217, 1182, 1112, 1026, 978, 914, 823, 776, 757, 732, 740, 700;
1H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 7.7 Hz, 2H),
7.59-7.50 (m, 2H), 7.42-7.25 (m, 9H), 5.70 (d, J = 9.4 Hz,
1H), 5.29 (d, J = 9.4 Hz, 1H), 5.11 (sept, J = 6.2 Hz, 1H),
4.46 (s, 1H), 4.41-4.29 (2H, m), 4.19 (t, J = 6.3 Hz, 1H), 3.23
(br s, 1H), 1.29 (d, J = 6.2 Hz, 3H), 1.24 (d, J = 6.2 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 172.2, 155.6, 143.8, 141.3,
139.0, 128.7, 127.8, 127.7, 127.1, 126.7, 125.0, 120.0, 73.4,
70.9, 67.0, 56.3, 47.2, 21.7, 21.5; HRMS (ESI) calcd for
C27H27NO5Naþ 468.1781, found 468.1782.
(-)-12a: [R]21 -14.7 (c 1.07, CHCl3); spectroscopic data
D
were identical to (()-12a above.
(þ)-12b. Following the general AA procedure above,
trans-isopropyl cinnamate (150 mg, 0.79 mmol) was treated
with osmium tetraoxide (8 mg, 32 μmol), (DHQ)2AQN (31.0
mg, 39.5 μmol), and benzyl reagent 8 (338 mg, 1.11 mmol).
(Note: The solution changed from a yellow color to dark
green within a minute after addition of the trans-isopropyl
cinnamate and no precipitate formed during the course of the
reaction.) Subsequent flash column chromatography (silica
gel, petroleum spirit/ethyl acetate 4:1) afforded 253 mg
(90%) of 12a and 12b in a 1:1.6 ratio of regioisomers: 12a,
71% ee; 12b, 71% ee.
14b: mp 133 °C (DSC, slow onset); FTIR (neat, cm-1
)
3502, 3385, 2981, 1720, 1691, 1524, 1449, 1374, 1315, 1288,
1247, 1232, 1163, 1105, 1088, 1065, 1039, 992, 960, 836, 759,
1
742, 728, 713, 702; H NMR (500 MHz, CDCl3) δ 7.74 (d,
J = 7.5 Hz, 2H), 7.55-7.47 (m, 2H), 7.41-7.25 (m, 9H), 5.60
(br d, J = 8.4 Hz, 1H), 5.24 (br s, 1H), 5.07 (sept, J = 6.5 Hz,
1H), 4.58 (br d, J = 6.7 Hz, 1H), 4.32-4.18 (m, 2H), 4.15-
4.08 (m, 1H), 2.68 (br s, 1H), 1.26 (d, J = 6.5 Hz, 3H), 1.19 (d,
J = 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 170.0,
156.2, 143.8, 141.3, 139.6, 128.5, 128.2, 127.7, 127.0, 126.1,
125.1, 119.9, 74.0, 69.7, 67.2, 59.9, 47.1, 21.7, 21.6; HRMS
(ESI) calcd for C27H27NO5Naþ 468.1781, found 468.1781.
(()-Benzyl 2-Hydroxy-2-phenylethylcarbamate (15a)32
and (()-Benzyl 2-Hydroxy-1-phenylethylcarbamate (15b).32
Following the general procedure above, styrene (250 μL, 2.18
mmol) was reacted with osmium tetraoxide (22.1 mg, 87.1
μmol) and benzyl reagent 8 (933 mg, 3.05 mmol). The crude
(()-(2S,3R)-Isopropyl 3-(tert-Butoxycarbonylamino)-2-
hydroxy-3-phenylpropanoate (13a) and (()-(2S,3R)-Isopropyl
2-(tert-Butoxycarbonylamino)-3-hydroxy-3-phenylpropanoate
(13b). Following the general procedure above, trans-isopropyl
cinnamate (150 mg, 0.79 mmol) was reacted with osmium
tetraoxide (8 mg, 32 μmol) and Boc reagent 9 (300 mg, 1.10
mmol). Subsequent flash column chromatography (silica gel,
ethyl acetate/petroleum spirit 15:85) gave 238 mg (93%) of
13a and 13b in a 1:1.8 ratio of regioisomers. Further column
chromatography yielded analytical samples of 13a and 13b.
J. Org. Chem. Vol. 76, No. 2, 2011 367