The Journal of Organic Chemistry
NOTE
corresponding sugar aldehyde 1 affords the corresponding 2-chloro-
3-oxy ester or amide 7. Metalation of 7 with two additional
equivalents of chromium dichloride gives access to enolate
intermediate 8ꢀ80, which would undergo a spontaneous elim-
ination reaction rendering, after workup, the corresponding
R,β-unsaturated esters 3 or amides 5.
We assume that the elimination process takes place through a
cyclic six-membered ring transition state 80, guided by coordina-
tion of the CrIII center with the oxygen atom of the alcoholate
function. Two conformations, I and II, are feasible for inter-
mediate 80. Conformer I is presumably more stable than II, as the
sugar moiety adopts a pseudo-equatorial orientation, thus avoid-
ing unfavorable interactions with the chromium coordination
sphere. Elimination from I renders (E)-R,β-unsaturated esters
3 or amides 5.
In conclusion, we have described a novel and efficient
chromium-mediated olefination protocol of aldehydes readily
prepared from sugars directed toward the synthesis of carbohy-
drate-derived di- and trisubstituted (E)-R,β-unsaturated esters or
amides. This process took place with total E-stereoselectivity and
in high yields under mild conditions maintaining the stereo-
chemical integrity of the sugar backbone.
[Mþ þ Na]þ 413.1940. Found 413.1934. Rf = 0.40 (hexane/EtOAc
5:1).
Ethyl (E)-3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-
C-phenylmethyl-R-D-xylo-hept-5-enofuranuronate (3e). Yel-
low oil; [R]20D = ꢀ52.7 (c = 1 in CHCl3). 1H NMR (300 MHz, CDCl3):
δ 7.41ꢀ7.12 (m, 10 H), 7.07 (d, J = 8.2 Hz, 1 H), 6.03 (d, J = 3.8 Hz,
1 H), 5.05 (dd, J = 8.2, 3.2 Hz, 1 H), 4.67 (d, J = 3.2 Hz, 1 H), 4.55 (d, J =
12.0 Hz, 1 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.23 (c, J = 7.0 Hz, 2 H), 3.84
(d, J = 15.2 Hz, 1 H), 3.76 (d, J = 3.2 Hz, 1 H), 3.65 (d, J = 15.2 Hz, 1 H),
1.52 (s, 3 H), 1.33 (s, 3 H), 1.29 (t, J = 7.0 Hz, 3 H). 13C NMR (75 MHz,
CDCl3): δ 166.9 (C), 139.1 (C), 137.2 (C), 136.7 (CH), 134.2 (C),
128.4 (2 ꢁ CH), 128.3 (2 ꢁ CH), 128.2 (2 ꢁ CH), 127.9 (CH), 127.6
(2 ꢁ CH), 126.1 (CH), 111.7 (C), 105.1 (CH), 83.5 (CH), 82.9 (CH),
76.9 (CH), 72.2 (CH2), 60.9 (CH2), 33.1 (CH2), 26.8 (CH3), 26.2
(CH3), 14.1 (CH3). MS (ESIþ-TOF) m/z (%): 439 [Mþ þ H]þ (100),
351 (10), 273 (13). IR (neat): 3058, 1712, 1076, 737 cmꢀ1. HRMS
(ESIþ) calcd for [C26H31O6]þ [Mþ þ H]þ 439.2121. Found 439.2115.
Rf = 0.30 (hexane/EtOAc 5:1).
Isopropyl (E)-3-O-Benzyl-5,6-dideoxy-1,2-O-isopropyli-
dene-6-C-methyl-R-D-xylo-hept-5-enofuranuronate (3f). Yel-
low oil; [R]20D = ꢀ54.3 (c = 1 in CHCl3). 1H NMR (300 MHz, CDCl3):
δ 7.24ꢀ7.19 (m, 5 H), 6.81 (dd, J = 7.5, 1.2 Hz, 1 H), 5.94 (d, J = 3.7 Hz,
1 H), 5.08ꢀ4.96 (m, J = 6.3 Hz, 1 H), 4.85 (dd, J = 7.5, 3.2 Hz, 1 H), 4.59
(s, 1 H), 4.58 (d, J = 12.2 Hz, 1 H), 4.39 (d, J = 12.2 Hz, 1 H), 3.87 (d, J =
2.5 Hz, 1 H), 1.73 (s, 3 H), 1.44 (s, 3 H), 1.27 (s, 3 H), 1.21 (d, J = 6.3 Hz,
6 H). 13C NMR (75 MHz, CDCl3): δ 168.7 (C), 137.1 (CH), 134.9
(C), 131.2 (C), 128.4 (2 x CH), 127.9 (CH), 127.7 (2 x CH), 111.7 (C),
105.5 (CH), 83.0 (CH), 82.9 (CH), 77.2 (CH), 72.2 (CH2), 68.0 (CH),
26.8 (CH3), 26.1 (CH3), 21.8 (2 ꢁ CH3), 13.2 (CH3). MS (ESIþ-TOF)
m/z (%): 399 [Mþ þ Na]þ (100), 377 (23), 317 (17), 289 (29). IR
(neat): 3414, 1710, 1254, 738 cmꢀ1. HRMS (ESIþ) calcd for [C21H29O6]þ
[Mþ þ H]þ 377.1964. Found 377.1958. Rf = 0.19 (hexane/EtOAc 1:1).
Isopropyl (E)-6,7-Dideoxy-1,2:3,4-di-O-isopropylidene-7-
C-phenylmethyl-β-D-galacto-oct-6-enopyranuronate (3g).
’ EXPERIMENTAL SECTION
Synthesis of Compounds 3 and 5. To a stirred suspension of
anhydrous CrCl2 (6 mmol) in THF (10 mL) were added a solution of a
2,2-dichloroester or 2,2-dichloroamide (1 mmol) and the corresponding
aldehyde (1 mmol) at room temperature and under an inert atmosphere.
After stirring at 75 °C for three hours, the reaction mixture was
quenched with HCl (0.1 M) and extracted with diethyl ether (3 ꢁ
10 mL). The combined extracts were dried over Na2SO4 and concen-
trated under vacuum. The organic layer was then filtered through a pad
of Celite, and the solvents were removed in vacuo. Purification by
column chromatography on silica gel (Hexane/EtOAc 5:1) afforded the
corresponding R,β-unsaturated compound 3 or 5.
1
Yellow oil; [R]20 = ꢀ96.6 (c = 1 in CHCl3). H NMR (300 MHz,
CDCl3): δ 7.24ꢀD7.06 (m, 5 H), 6.88 (d, J = 8.0 Hz, 1 H), 5.51 (d, J = 4.4
Hz, 1 H), 4.95ꢀ4.87 (sx, J = 6.0 Hz, 1 H), 4.61 (d, J = 8.0 Hz, 1 H), 4.51
(d, J = 7.6 Hz, 1 H), 4.25 (dd, J = 4.8, 2.4 Hz, 1 H), 4.04 (d, J = 8.0 Hz, 1
H), 3.74 (d, J = 15.3 Hz, 1 H), 3.63 (d, J = 15.3 Hz, 1 H), 1.43 (s, 3 H),
1.32 (s, 3 H), 1.25 (s, 3 H), 1.24 (s, 3 H), 1.11 (d, J = 6.2 Hz, 3 H), 1.09
(d, J = 6.2 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ 166.4 (C), 138.8
(C), 136.9 (CH), 134.4 (C), 128.3 (2 ꢁ CH), 128.2 (2 ꢁ CH), 126.0
(CH), 109.5 (C), 108.5 (C), 96.3 (CH), 72.7 (CH), 70.7 (CH), 70.1
(CH), 68.3 (CH), 65.1 (CH), 33.1 (CH2), 25.9 (2 ꢁ CH3), 24.7 (CH3),
24.2 (CH3), 21.6 (2 ꢁ CH3). MS (ESIþ-TOF) m/z (%): 433 [Mþ þ
H]þ (100), 375 (28), 315 (19), 257(15). IR (neat): 3433, 1713, 1066,
749 cmꢀ1. HRMS (ESIþ) calcd for [C24H33O7]þ [Mþ þ H]þ 433.2226.
Found 433.222. Rf = 0.32 (hexane/EtOAc 5:1).
Spectroscopic data for compounds 3a23 and 3c24 were previously
reported in the literature.
Ethyl (E)-2,3-Dideoxy-4,5:6,7-di-O-isopropylidene-L-xylo-
hept-2-enonate (3b). Colorless oil; [R]20D = ꢀ2.3 (c = 1 in CHCl3).
1H NMR (300 MHz, CDCl3): δ 6.99 (dd, J = 15.8, 5.0 Hz, 1 H), 6.18 (d,
J = 15.8 Hz, 1 H), 4.63 (t, J = 5.7 Hz, 1 H), 4.22 (q, J = 6.9 Hz, 2
H), 3.88ꢀ3.79 (m, 3 H), 3.74ꢀ3.70 (m, 1 H), 1.46 (s, 6 H), 1.43 (s, 6
H), 1.31 (t, J = 6.9 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ 163.3 (C),
145.2 (CH), 135.8 (C), 122.0 (CH), 110.0 (C), 80.6 (CH), 77.7 (CH),
72.3 (CH), 63.4 (CH2), 60.6 (CH2), 26.9 (2 ꢁ CH3), 26.6 (2 ꢁ CH3),
14.1 (CH3). MS (ESIþ-TOF) m/z (%): 283 (100), 261 (17), 203 (16).
HRMS (ESIþ) calcd for [C15H25O6]þ [Mþ þ H]þ 301.1651. Found
301.1645. IR (neat): 3414, 1714, 1266, 740 cmꢀ1. Rf = 0.19 (hexane/
EtOAc 1:1).
Isopropyl (E)-6-O-Benzyl-2,3-dideoxy-4,5-O-isopropyli-
dene-2-C-phenylmethyl-D-erythro-hex-2-enonate (3h). Yel-
1
low oil; [R]20 = þ48.8 (c = 1 in CHCl3). H NMR (300 MHz,
D
CDCl3): δ 7.28ꢀ7.04 (m, 10 H), 6.75 (d, J = 9.5 Hz, 1 H), 5.12ꢀ4.84
(m, 1 H), 4.53ꢀ4.48 (m, 1 H), 4.29ꢀ4.21 (m, 1 H), 3.71 (d, J = 15.2
Hz, 1 H), 3.56 (d, J = 15.2 Hz, 1 H), 3.47ꢀ3.25 (m, 4 H), 1.45 (s, 3
H), 1.31 (s, 3 H), 1.10 (t, J = 6.2 Hz, 3 H), 1.07 (t, J = 6.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ 166.3 (C), 139.0 (C), 137.7 (C),
136.6 (CH), 134.7 (C), 128.4 (2 ꢁ CH), 128.3 (2 ꢁ CH), 128.2 (2 ꢁ
CH), 127.6 (2 ꢁ CH), 127.5 (CH), 126.1 (CH), 109.5 (C), 77.3
(CH), 73.7 (CH), 73.4 (CH2), 69.0 (CH2), 68.3 (CH), 32.7 (CH2),
27.8 (CH3), 25.3 (CH3), 21.6 (2 ꢁ CH3). MS (ESIþ-TOF) m/z (%):
447 [Mþ þ Na]þ (100), 442 (47), 367 (30), 307 (12). IR (neat):
Ethyl (E)-2,3-Dideoxy-4,5:6,7-di-O-isopropylidene-2-C-
phenylmethyl-L-xylo-hept-2-enonate (3d). Yellow oil; [R]20
=
D
ꢀ19.6 (c = 1 in CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.26ꢀ7.08 (m,
5 H), 6.73 (d, J = 8.8 Hz, 1 H), 4.70 (apparent t, J = 7.2 Hz, 1 H), 4.05
(apparent q, J = 7.0 Hz, 2 H), 4.11ꢀ3.61 (m, 4 H), 3.77 (d, J = 15.1 Hz, 1
H), 3.68 (d, J = 15.1 Hz, 1 H), 1.38 (s, 3 H), 1.33 (s, 3 H), 1.28 (s, 3 H),
1.23 (s, 3 H), 1.11 (t, J = 7.0 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ
167.0 (C), 138.0 (C), 138.0 (CH), 135.0 (C), 128.4 (2 ꢁ CH), 128.2
(2 ꢁ CH), 126.0 (CH), 110.3 (C), 109.6 (C), 81.5 (CH), 76.5 (CH),
76.1 (CH), 67.2 (CH2), 60.8 (CH2), 32.7 (CH2), 27.1 (CH3), 27.0
(CH3), 26.6 (CH3), 25.1 (CH3), 14.0 (CH3). MS (ESIþ-TOF) m/z
(%): 413 [Mþ þ Na]þ (100), 233 (28), 211 (5), 187 (10). IR (neat):
3437, 1720, 1063, 750 cmꢀ1. HRMS (ESIþ) calcd for [C22H30O6Na]þ
3414, 1710, 1110, 738 cmꢀ1. HRMS (ESIþ) calcd for [C26H32
-
O5Na]þ [Mþ þ Na]þ 447.2147. Found 447.2141. Rf = 0.42 (hexane/
EtOAc 5:1).
5463
dx.doi.org/10.1021/jo200548g |J. Org. Chem. 2011, 76, 5461–5465