8914 J . Org. Chem., Vol. 64, No. 24, 1999
Doyle et al.
) 8.9 Hz, 1 H), 7.90-7.84 (comp, 2 H), 7.58-7.47 (comp, 2 H),
7.53 (d, J ) 8.9 Hz, 1 H), 6.19 (s, 1 H), 4.68 (ddd, J ) 4.2, 3.6,
2.2 Hz, 1 H), 4.36 (dddd, J ) 4.7, 2.4, 2.1, 2.0 Hz, 1 H), 4.28
(dd, J ) 12.9, 4.2 Hz, 1 H), 4.12 (dd, J ) 12.9, 3.6 Hz, 1 H),
2.82 (dd, J ) 17.8, 2.0 Hz, 1 H), 2.75 (dd, J ) 17.8, 4.7 Hz, 1
H); 13C NMR (75 MHz, CDCl3) δ 174.9, 133.5, 133.4, 133.2,
128.9, 128.2, 127.7, 126.7, 126.5, 126.1, 123.9, 95.8, 66.2, 60.4,
36.5, 29.7; HRMS calcd for [C16H14O4 + H]+ 271.2927, found
271.0970. This 2-naphthylidene-protected 2-deoxy-1,4-xylono-
lactone was hydrogenolyzed to 2-deoxy-1,4-xylonolactone as
previously described for 18.
1,3-Dia lk oxy-2-p r op a n ol. The preparation of 1,3-diethoxy-
2-propanol is representative. To a continually stirred solution
of sodium ethoxide in 75 mL of ethanol, prepared by reacting
freshly cut sodium (5.98 g, 0.260 mol) with absolute ethanol,
at 0 °C was added 1,3-dichloro-2-propanol (12.89 g, 0.100 mol)
dropwise over 30 min through an additional funnel. The
reaction mixture was then heated at reflux for 90 min, after
which the cooled mixture was diluted with 100 mL of ether to
precipitate NaCl and then filtered. Solvents were removed
under reduced pressure, and the residual yellow oil was
distilled, bp 93-96.5 °C at 13 Torr, to yield 13.77 g (0.093 mol,
93% yield) of a colorless oil. 1,3-Dimethoxy-2-propanol, bp °C
at Torr, was obtained in % yield; 1,3-dibenzyloxy-2-propanol,
bp 175-180 °C at 0.05 Torr (lit.27 bp 195-210 °C at 3 Torr),
was obtained in 81% yield.
1,3-Dia lk oxy-2-p r op yl Dia zoa ceta tes (21). The prepara-
tion of 1,3-diethoxy-2-propyl diazoacetate is representative. A
solution of 1,3-diethoxy-2-propanol (10.0 g, 67.5 mmol) and
freshly distilled 2,2,6-trimethyl-4H-1,3-dioxin-4-one (9.50 g,
67.5 mmol) in xylene (67 mL) was heated with rapid stirring
in a preheated oil bath at 150 °C for 30 min until acetone had
evaporated.28 Xylene was removed by distillation, and the
residue was purified by bulb-to-bulb distillation (bp 100-195
°C at 0.1 Torr) to yield 12.5 g (54.0 mmol, 80% yield) of 1,3-
diethoxy-2-propyl acetoacetate as a colorless oil: 1H NMR δ
5.18 (quin, J ) 5.1 Hz, 1 H), 3.59 (d, J ) 5.1 Hz, 4 H), 3.60-
3.42 (m, 4 H), 3.48 (s, 2 H), 2.28 (s, 3 H), 1.18 (t, J ) 7.0 Hz,
6 H); enol form at δ 5.04 and 1.96.
Methanesulfonyl azide (6.76 g, 55.9 mmol) in 50 mL of
acetonitrile was added dropwise over 45 min to a solution of
1,3-diethoxy-2-propyl acetoacetate (10.00 g, 43.0 mmol) and
Et3N (5.06 g, 51.6 mmol) in 50 mL of anhydrous acetonitrile.
The resulting yellow solution was maintained at room tem-
perature for an additional 18 h, whereupon LiOH‚H2O (5.92
g, 0.149 mol) in 57 mL of water was added, and stirring was
continued for 8 h. The resulting aqueous reaction solution was
diluted with 100 mL of 1:1 ether in ethyl acetate. The combined
organic layer was washed with saturated aqueous NaCl (50
mL) and dried (MgSO4), and the solvent was removed under
reduced pressure. The resulting dark yellow oil was purified
by column chromatography on silica gel eluting with 19:1
hexanes:ethyl acetate to give 1,3-diethoxy-2-propyl diazo-
acetate (4.35 g, 47% yield) as a yellow oil.
(CdN2), 1693 (CdO) cm-1. Anal. Calcd for C19H20O4N2: C,
67.05; H, 5.92; N, 8.23. Found: C, 67.01; H, 5.98; N, 8.17.
Dia zo Decom p osition of 1,3-Dia lk oxy-2-p r op yl Dia zo-
a ceta tes. To the dirhodium(II) catalyst (0.1 mol %) in 50 mL
of refluxing dichloromethane was added by syringe pump the
diazoester (1.0 mmol) in 10 mL of anhydrous dichloromethane
during 10 h (1.0 mL/h). The initial color of the solution
containing Rh2(5S-MEPY)4 or Rh2(5R-MEPY)4 was blue, which
generally changed to an olive color by the end of the addition;
with Rh2(4S-MEOX)4 the initial color was light red, which
became light yellow at the end of the addition. After addition
was complete, CH2Cl2 was evaporated under reduced pressure,
and the lactone product(s) was isolated by column chroma-
tography on silica (7:3 hexane:ethyl acetate). This product
mixture, which was chromatographically pure, was analyzed
spectroscopically, and enantiomeric excess was obtained on a
Chiraldex G-TA column with baseline resolution for diethoxy
derivatives.
3O,5O-Dim eth yl-2-d eoxy-1,4-xylon ola cton e: 1H NMR
(300 MHz, CDCl3) δ 4.64 (ddd, J ) 5.8, 4.8, 4.6 Hz, 1 H), 4.19
(ddd, J ) 4.9, 4.8, 3.5 Hz, 1 H), 3.78 (dd, J ) 11.0, 4.6 Hz, 1
H), 3.73 (dd, J ) 11.0, 5.8 Hz, 1 H), 3.45 (s, 3 H), 3.38 (s, 3 H),
2.70 (dd, J ) 17.6, 3.5 Hz, 1 H), 2.68 (dd, J ) 17.6, 4.9 Hz, 1
H); mass spectrum, m/z (relative abundance) 160 (M, 1), 132
(1), 115 (15), 101 (93), 85 (25), 83 (35), 73 (83), 71 (92), 59 (73),
58 (100); IR (film) 1786 cm-1. Anal. Calcd for C7H12O4: C,
52.49; H, 7.55. Found: C, 52.51; H, 7.52.
3O,5O-Dim eth yl-2-d eoxy-1,4-r ibon ola cton e: 1H NMR
(300 MHz, CDCl3) δ 4.53 (ddd, J ) 6.7, 4.9, 4.8 Hz, 1 H), 4.05
(ddd, J ) 4.9, 2.1, 1.9 Hz, 1 H), 3.59 (dd, J ) 11.0, 4.8 Hz, 1
H), 3.54 (dd, J ) 11.0, 1.9 Hz, 1 H), 3.36 (s, 3 H), 3.34 (s, 3 H),
2.82 (dd, J ) 18.0, 6.7 Hz, 1 H), 2.50 (dd, J ) 18.0, 2.1 Hz, 1
H); mass spectrum, m/z (relative abundance) 160 (M, 1), 132
(17), 115 (11), 101 (14), 85 (10), 83 (19), 73 (41), 71 (48), 59
(40), 59 (100). Spectral data are consistent with those of
2-deoxy-1,4-lactone.23
3O,5O-Dieth yl-2-d eoxy-1,4-xylon ola cton e: 1H NMR (300
MHz, CDCl3) δ 4.60 (ddd, J ) 5.9, 4.9, 4.8 Hz, 1 H), 4.22 (ddd,
J ) 4.8, 4.4, 3.8 Hz, 1 H), 3.78 (dd, J ) 10.9, 4.9 Hz, 1 H), 3.74
(dd, J ) 10.9, 5.9 Hz, 1 H), 3.66-3.37 (m, 4 H), 2.68 (dd, J )
17.4, 3.8 Hz, 1 H), 2.66 (dd, J ) 17.4, 4.4 Hz, 1 H), 1.22 (t, J
) 6.5 Hz, 3 H), 1.19 (t, J ) 6.7 Hz, 3 H); mass spectrum, m/z
(relative abundance) 188 (M, 1), 159 (18), 129 (79), 115 (16),
114 (4), 101 (62), 87 (37), 85 (52), 73 (37), 72 (86), 71 (43), 59
(100), 57 (45); IR (film) 1786 cm-1. Anal. Calcd for C9H16O4:
C, 57.43; H, 8.57. Found: C, 57.38; H, 8.55.
3O,5O-Dieth yl-2-d eoxy-1,4-r ibon ola cton e: 1H NMR (300
MHz, CDCl3) δ 4.53 (ddd, J ) 4.9, 3.0, 2.1 Hz, 1 H), 4.15 (ddd,
J ) 6.8, 2.1, 1.9 Hz, 1 H), 3.66-3.37 (m, 6 H), 2.84 (dd, J )
18.0, 6.8 Hz, 1 H), 2.48 (dd, J ) 18.0, 2.1 Hz, 1 H), 1.21 (t, J
) 6.4 Hz, 3 H), 1.18 (t, J ) 6.7 Hz, 3 H); mass spectrum, m/z
(relative abundance) 189 (M + 1, 1), 188 (M, 6), 159 (14), 129
(11), 115 (7), 114 (25), 101 (53), 87 (29), 85 (15), 73 (26), 72
(76), 71 (11), 59 (100), 57 (23). Spectral data are consistent
with those of 2-deoxy-1,4-lactone.23
1,3-Dim et h oxy-2-p r op yl Dia zoa cet a t e (21a ): 1H NMR
(300 MHz, CDCl3) δ 5.18 (quin, J ) 5.0 Hz, 1 H), 4.81 (br s, 1
H), 3.52 (d, J ) 5.0 Hz, 4 H), 3.34 (s, 6 H); IR (film) 2108
(CdN2), 1696 (CdO) cm-1. Anal. Calcd for C7H12O4N2: C,
44.68; H, 6.43; N, 14.87. Found: C, 44.63; H, 6.48; N, 14.92.
1,3-Dieth oxy-2-p r op yl Dia zoa ceta te (21b): 1H NMR (300
MHz, CDCl3) δ 5.17 (quin, J ) 5.1 Hz, 1 H), 4.82 (br s, 1 H),
3.58 (d, J ) 5.1 Hz, 4 H), 3.59-3.44 (m, 4 H), 1.18 (t, J ) 7.0
Hz, 6 H); IR (film) 2112 (CdN2), 1692 (CdO) cm-1. Anal. Calcd
for C9H16O4N2: C, 49.99; H, 7.46; N, 12.96. Found: C, 50.03;
H, 7.53; N, 12.93.
3O,5O-Diben zyl-2-d eoxy-1,4-xylon ola cton e: bp 220-230
1
°C (0.2 Torr); [R]23 ) -5.40 (c 0.537, MeOH); H NMR (300
D
MHz, CDCl3) δ 7.37-7.22 (m, 10 H), 4.63-4.51 (m, 5 H), 4.44
(d, J ) 11.9 Hz, 1 H), 3.86 (d, J ) 5.3 Hz, 2 H), 2.72 (dd, J )
17.6, 3.1 Hz, 1 H), 2.62 (dd, J ) 17.6, 5.8 Hz, 1 H); 13C NMR
(75 MHz, CDCl3) δ 174.7, 137.8, 137.1, 128.6, 128.5, 128.1,
127.9, 127.8, 127.7, 82.0, 74.5, 73.7, 71.8, 67.7, 35.6; mass
spectrum, m/z (relative abundance) 312 (M, 0.2), 222 (33), 221
(100), 115 (75), 108 (19), 107 (99), 105 (18), 97 (51), 92 (71), 91
(100), 89 (22), 79 (47), 77 (51), 71 (23), 65 (97); IR (film) 1784
cm-1. Anal. Calcd for C19H20O4: C, 73.05; H, 6.45. Found: C,
73.14; H, 6.54.
1,3-Diben zyloxy-2-p r op yl Dia zoa ceta te (21c): 1H NMR
(300 MHz, CDCl3) δ 7.38-7.23 (m, 10 H), 5.28 (quin, J ) 5.1
Hz, 1 H), 4.79 (br s, 1 H), 4.56 (d, J ) 12.0 Hz, 2 H), 4.50 (d,
J ) 12.0 Hz, 2 H), 3.65 (d, J ) 5.1 Hz, 4 H); IR (film) 2112
3O,5O-Diben zyl-2-deoxy-1,4-r ibon olacton e: 1H NMR (300
MHz, CDCl3) δ 7.38-7.24 (m, 10 H), 4.62 (ddd, J ) 3.3, 3.0,
2.2 Hz, 1 H), 4.54 (d, J ) 12.0 Hz, 1 H), 4.53 (d, J ) 11.4 Hz,
1 H), 4.48 (d, J ) 11.4 Hz, 1 H), 4.47 (d, J ) 12.0 Hz, 1 H),
4.27 (dt, J ) 6.9, 2.2 Hz, 1 H), 3.66 (dd, J ) 10.8, 3.3 Hz, 1 H),
3.61 (dd, J ) 10.8, 3.0 Hz, 1 H), 2.86 (dd, J ) 18.1, 6.9 Hz, 1
H), 2.57 (dd, J ) 18.1, 2.2 Hz, 1 H); 13C NMR (75 MHz, CDCl3)
δ 175.6, 137.4, 137.1, 128.7, 128.6, 128.1, 128.0, 127.8, 127.7,
(27) Olgivie, K. K.; Ngugen, N. B.; Gillan, M. F.; Radatus, B. K.;
Cheriyean, V. U.; Hanna, H. R.; Smith, K. S. Can. J . Chem. 1984, 62,
24.
(28) Clemens, R. J .; Hyatt, J . A. J . Org. Chem. 1985, 50, 2431.