Synthesis of 2-Methyl-D-erythritol
d, J ) 11.9 Hz), 4.54 (1H, d, J ) 11.9 Hz), 3.86 (1H, dd, J )
10.5, 4.2 Hz), 3.74 (1H, dd, J ) 10.5, 6.4 Hz), 3.46 (1H, d, J )
12.0 Hz), 3.31 (1H, d, J ) 11.9 Hz), 3.11 (1H, br s), 2.83 (1H,
br s), 2.12 (3H, s), 1.09 (3H, s). 13C NMR (75 MHz): 171.5 (s),
137.3 (s), 128.5 (d), 127.9 (d), 127.7 (d), 73.9 (d), 73.5 (t), 73.1
(s), 68.5 (t), 67.1 (t), 21.0 (q), 19.3 (q).
4-Ben zyl-2-C-m et h yl-D-er yt h r it ol 1,3-Dia cet a t e (10).
Treatment of 8 (28.4 mg) with 22 mg of acetic anhydride in
0.8 mL of pyridine gave, after silica gel chromatography, 29.2
mg (89%). TLC Rf 0.21 (hexane/ethyl acetate 2:1). [R]22D -5.81
(c 0.91, CH2Cl2). 1H NMR (600 MHz): 7.38-7.32 (2H, Ph),
7.32-7.27 (3H, Ph), 5.10 (1H, t, J ) 4.9 Hz, C-3), 4.55 (1H, d,
J ) 11.9 Hz, PhCH2), 4.53 (1H, d, J ) 11.9 Hz, PhCH2), 4.13
(1H, d, J ) 11.6 Hz, C-1), 3.93 (1H, d, J ) 11.6 Hz, C-1), 3.74
(2H, d, J ) 4.9 Hz, C-4), 3.28 (1H, br s, OH), 2.08 (3H, s, Ac),
2.07 (3H, s, Ac), 1.20 (3H, s, Me). 13C NMR (150 MHz): 170.9
(Ac), 170.1 (Ac), 137.1 (Ph), 128.5 (Ph), 128.0 (Ph), 127.7 (Ph),
73.6 (PhCH2), 72.9 (C-2), 72.4 (C-3), 68.6 (C-4), 68.3 (C-1), 20.9
(Ac Me), 20.8 (Ac Me), 20.7 (2-Me). Anal. Calcd for C16H22O6:
C, 61.92; H, 7.14. Found: C, 61.99; H, 7.15.
4-Ben zyl-2-C-m eth yl-D-er yth r itol (14). A mixture of 8
and 9 (6.3 mg) in 1 mL of MeOH was treated with 10 mg of
K2CO3 at rt for 16 h. Evaporation, followed by extraction with
ether, filtration, and evaporation of the solvent, gave 5.3 mg
of 14 (quantitative). TLC Rf 0.25 (hexane/ethyl acetate 1:2).
[R]21 +8.04 (c 0.98, CHCl3). Lit. (enantiomer): [R]D -8.2 (c
D
1.5, CHCl3).11 NMR data matched those reported for the
enantiomer.11
2-C-Meth yl-D-er yth r itol (4). Hydrogenation of 14 (18.5
mg) in 1 mL of methanol with 3 mg of 10% Pd/C for 3 h,
followed by filtration and evaporation of the solvent, gave 11.1
mg (quantitative) of a clear, colorless oil. [R]22 +11.2 (c 0.57,
D
CH3OH). 1H NMR (600 MHz, D2O): 3.78 (1H, dd, J ) 11.5,
2.7 Hz), 3.62 (1H, dd, J ) 8.5, 2.7 Hz), 3.55 (1H, dd, J ) 11.5,
8.5 Hz), 3.54 (1H, d, J ) 11.8 Hz), 3.43 (1H, d, J ) 11.8 Hz),
1.08 (3H, s). 13C NMR (151 MHz, D2O): 75.4, 74.5, 66.7, 62.4,
18.8.
4-Ben zyl-2-C-m eth yl-D-er yth r itol 1-(R)-O-Acetylm a n -
d ela te. This was produced in quantitative yield by esterifi-
cation of 14 with 1 equiv of (R)-O-acetylmandelic acid in DCM
using EDC with DMAP catalysis (67% yield).10 TLC Rf 0.66
(hexane/ethyl acetate 1:1). 1H NMR (600 MHz): 7.48-7.44
(2H), 7.41-7.33 (5H), 7.33-7.28 (3H), 5.92 (1H, s), 4.50 (2H,
s), 4.23 (1H, d, J ) 11.3 Hz), 4.08 (1H, d, J ) 11.3 Hz,), 3.63-
3.53 (3H, m), 2.81 (1H, br s), 2.61 (1H, br d, J ) 5.1 Hz), 2.20
(3H, s), 1.08 (3H, s). 13C NMR (150 MHz): 170.4, 168.8, 137.4,
133.5, 129.4, 128.9, 128.5, 128.0, 127.8, 127.6, 74.6, 73.7, 73.1,
72.8, 70.6, 69.4, 20.7, 20.3.
4-Ben zyl-2-C-m eth yl-D-er yth r itol 1-(S)-O-Acetylm a n -
d ela te. This was made as above using (S)-O-acetylmandelic
acid. TLC Rf 0.66 (hexane/ethyl acetate 1:1). 1H NMR (600
MHz): 7.48-7.43 (2H), 7.42-7.33 (5H), 7.33-7.27 (3H), 5.92
(1H, s), 4.48 (2H, s), 4.24 (1H, d, J ) 11.2 Hz), 4.03 (1H, d, J
) 11.2 Hz), 3.59-3.44 (3H, m), 2.86 (1H, br s), 2.75 (1H, br d,
J ) 5.4 Hz), 2.20 (3H, s), 1.13 (3H, s). 13C NMR (150 MHz):
170.5, 168.9, 137.3, 133.5, 129.4, 128.9, 128.5, 128.0, 127.8,
127.6, 74.6, 73.7, 73.2, 72.3, 70.7, 69.5, 20.7, 20.4.
2-C-Meth yl-D-er yth r itol 1,3-Dia ceta te (11). Hydrogena-
tion of 10 (2.51 g) in 100 mL of ethyl acetate with 0.63 g of
10% Pd/C for 1.5 h, followed by filtration and evaporation of
the solvent, gave 1.74 g (98%). TLC Rf 0.21 (hexane/ethyl
acetate 1:1). [R]23 -2.26 (c 0.88, CH2Cl2). 1H NMR (300
D
MHz): 4.92 (1H, dd, J ) 5.7, 4.6 Hz), 4.15 (1H, d, J ) 11.6
Hz), 3.96 (1H, d, J ) 11.6 Hz), 3.95 (1H, dd, J ) 11.8, 4.5 Hz),
3.81 (1H, dd, J ) 12.0, 5.5 Hz), 3.16 (1H, br s), 2.69 (1H, br s),
2.11 (3H, s), 2.10 (3H, s), 1.23 (3H, s). 13C NMR (75 MHz):
171.0 (s), 170.8 (s), 75.0 (d), 73.2 (s), 68.5 (t), 61.8 (t), 20.9 (q),
20.7 (q), 20.2 (q). Anal. Calcd for C9H16O6: C, 49.09; H, 7.32.
Found: C, 48.94; H, 7.28.
4-Ben zyl-2-C-m eth yl-D-er yth r itol 1,2,3-Tr ia ceta te (12).
Acetylation of 10 (190 mg) with 2 mL of acetic anhydride/
pyridine 1:1 and 40 mg of DMAP (overnight at rt) gave 12
(quantitative). TLC Rf 0.36 (hexane/ethyl acetate 4:1). 1H NMR
(600 MHz): 7.37-7.27 (5H), 5.58 (1H, dd, J ) 7.1, 3.1 Hz),
4.59 (1H, d, J ) 12.1 Hz), 4.51 (1H, d, J ) 12.1 Hz), 4.48 (1H,
d, J ) 12.1 Hz), 4.35 (1H, d, J ) 12.1 Hz), 3.73 (1H, dd, J )
11.0, 3.0 Hz), 3.64 (1H, dd, J ) 11.0, 7.1 Hz), 2.09 (3H, s),
2.05 (3H, s), 1.98 (3H, s), 1.52 (3H, s). 13C NMR (75 MHz):
170.5, 169.8, 169.7, 137.9, 128.4, 127.7, 127.6, 81.6, 73.0, 71.3,
68.3, 64.1, 22.0, 21.0, 20.7, 17.7. Anal. Calcd for C18H24O7: C,
61.35; H, 6.86. Found: C, 61.51; H, 6.79.
Hyd r olysis of 6: Treatment of 6 (51.0 mg) with 0.5 M H2-
SO4 in 5 mL of 9:1 THF/H2O (rt, 4 h) gave, after silica gel
chromatography, 28.0 mg of 8 (51%), 5.3 mg of 9 (10%), and
9.3 mg of 14 (20%).
Hyd r olysis of 5: Treatment of 5 (50 mg) with 0.5 M H2-
SO4 in 2.5 mL of 9:1 THF/H2O (rt, overnight) gave, after silica
gel chromatography, 39.4 mg of 14 (73%).
2-C-Meth yl-D-er yth r itol 1,2,3-Tr ia ceta te (13). Hydrogen-
ation of 12 (48 mg) in 20 mL of ethyl acetate with 16 mg of
10% Pd/C for 30 min, followed by filtration and evaporation
of the solvent, gave 13 (quantitative). NMR showed this
material to be only 85% pure. The contaminant appears to be
formed by transesterification and could not be removed by
chromatography. TLC Rf 0.31 (hexane/ethyl acetate 1:1). 1H
NMR (600 MHz): 5.30 (1H, dd, J ) 7.1, 2.8 Hz), 4.54 (1H, d,
J ) 12.1 Hz), 4.35 (1H, d, J ) 12.1 Hz), 3.95 (1H, br m), 3.74
(1H, br m), 2.12 (3H, s), 2.06 (3H, s), 2.02 (3H, s), 1.52 (3H, s).
13C NMR (150 MHz): 170.9, 170.4, 169.7, 81.5, 74.6, 63.8, 61.9,
22.0, 20.9, 20.7, 17.4.
Ack n ow led gm en t. We thank the Petroleum Re-
search Fund, administered by the American Chemical
Society, for financial support.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 4 and 7, and 2D NMR spectra for 4 and 10. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O020168Y
J . Org. Chem, Vol. 67, No. 14, 2002 4859