New chiral dihydroxycyclopropane block from L-tartaric acid

Full text of DOI:10.1134/S1070428011090326

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1439–1440. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © G.M. Khalikova, F.A. Gimalova, V.A. Egorov, M.S. Miftakhov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 9, pp. 1412–1413.
SHORT
COMMUNICATIONS
New Chiral Dihydroxycyclopropane Block from L-Tartaric Acid
G. M. Khalikova, F. A. Gimalova, V. A. Egorov, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received January 15, 2011
DOI: 10.1134/S1070428011090326
Functionalized hydroxycyclopropane derivatives at-
tract interest as binding units and building blocks in
organic synthesis [1, 2]. In this connection, widely
used Kulinkovich reaction (transformation of RCO2Me
into R-cyclopropanol) should be noted [3]. The present
communication reports on the synthesis of a new chiral
dihydroxycyclopropane derivative I with the use of
accessible L-tartaric acid as source of chirality. The
scheme of synthesis of compound I includes the fol-
lowing steps. Reduction of known L-tartaric acid di-
methyl ester acetonide II [4] with sodium tetrahydrido-
borate gave alcohol III in a moderate yield [5]. Com-
pound III was converted first into p-toluenesulfonate
IV and then into bromide V. The latter underwent
intramolecular cyclization to produce target product I
by the action of hexamethyldisilazane sodium salt in
THF (yield ~60%).
trans-junction of the three and five-membered rings is
exceptionally unfavorable.
Methyl (1S,5R)-3,3-dimethyl-2,4-dioxabicyclo-
[3.1.0]hexane-1-carboxylate (I). A solution of 0.2 g
(0.79 mmol) of compound V in 2 ml of tetrahydrofuran
was cooled to –78°C, 0.6 ml (1.2 mmol) of a 2 M so-
lution of hexamethyldisilazane sodium salt in THF was
added dropwise, and the mixture was stirred for 1.5 h
at that temperature, allowed to warm up to room tem-
perature, and treated with a saturated solution of am-
monium chloride. Tetrahydrofuran was evaporated,
and the residue was extracted with chloroform. The
combined extracts were dried over MgSO4 and evap-
orated, and the residue was purified by column chro-
matography on silica gel using petroleum ether–ethyl
acetate (2 :1) as eluent. Yield 0.09 g (~61%), light
yellow oily substance, [α]D20 = +94.6° (c = 2.44,
CHCl3). IR spectrum, ν, cm–1: 2992, 2955, 2937, 1749,
1730, 1441, 1375, 1358, 1306, 1267, 1240, 1211,
1196, 1159, 1136, 1107, 1014, 978, 868, 833, 795, 741,
The configuration of the new chiral center in com-
pound I is determined by configuration of C5 in bro-
mide V, which is not involved in ring closure, for the
formation of dioxabicyclo[3.1.0]hexane structure with
1
548. H NMR spectrum (CDCl3), δ, ppm: 1.39 s (3H),
O
(1) TsCl, pyridine
(2) LiBr, Me2CO
5
O
O
O
O
O
Me
Me
Me
Me
Me
Me
NaBH4, MeOH, 0°C
OMe
OMe
OH
X
1
2
3
OMe
OMe
O
O
O
O
II
III
IV, V
Ac
O
(Me3Si)2NNa (1.1 equiv)
THF, –78 to 20°C
Me
Me
2
1
5
3
O
60%
OMe
O
I
IV, X = OTs; V, X = Br.
1439

KHALIKOVA et al.
1440
1.41 s (3H, CH3), 1.47 d.d (1H, CH2, J = 3.2, 6.5 Hz),
1.70 d (J = 4.6 Hz), 1.74 d (1H, CH2, J = 5.6 Hz),
3.76 s (3H, OMe), 4.30 d.d (1H, 5-H, J = 3.4, 5.2 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 24.82 and 25.96
(CH3), 33.12 (CH2), 52.44 (OMe), 63.09 (C5), 63.63
(C1), 123.02 (C3), 171.23 (CO2Me). Found, %: C 55.01;
H 6.87. C8H12O4. Calculated, %: C 55.81; H 7.02.
for 5–6 h under reflux. The mixture was cooled, the
precipitate was filtered off, and the filtrate was evap-
orated. The residue was dissolved in 10 ml of methyl-
ene chloride, the solution was washed with a saturated
solution of sodium chloride, dried over MgSO4, and
evaporated, and the residue was subjected to column
chromatography on silica gel using petroleum ether–
ethyl acetate (2:1) as eluent. Yield 0.31 g (83%),
[α]D20 = –11.75° (c = 4.56, CHCl3). IR spectrum, ν,
cm–1: 2989, 2939, 1763, 1734, 1437, 1380, 1288, 1211,
Methyl (4R,5S)-5-hydroxymethyl-2,2-dimethyl-
1,3-dioxolane-4-carboxylate (III) was synthesized
according to the procedure described in [5]. Its specific
optical rotation and other spectral parameters were
consistent with the data given in [5].
1
1157, 1103, 1015, 889, 831, 765. H NMR spectrum
(CDCl3), δ, ppm: 1.44 s and 1.50 s (6H, CH3), 3.54 d.t
(J = 1.4, 1.6 Hz), 3.58 d.d (1H, CH2, J = 3.8, 0.5 Hz),
3.65 q (1H, CH2, J = 1.4 Hz), 3.79 s (3H, CO2Me),
4.41–4.42 m (2H, 4-H, 5-H). 13C NMR spectrum
(CDCl3), δC, ppm: 25.87 and 26.86 (CH3), 32.40
(CH2), 52.51 (OMe), 77.45 (C5), 77.60 (C4), 111.99
(C2), 170.40 (CO2Me). Found, %: C 37.30; H 4.79;
Br 32.17. C8H13BrO4. Calculated, %: C 37.96; H 5.18;
Br 31.57.
Methyl (4R,5S)-2,2-dimethyl-5-(4-methylphenyl-
sulfonyloxymethyl)-1,3-dioxolane-4-carboxylate
(IV). A solution of 0.9 g (4.72 mmol) of compound III
in 5 ml of anhydrous pyridine was cooled to 0°C,
1.08 g (7.0 mmol) of p-toluenesulfonyl chloride was
added under stirring, and the mixture was stirred for
4–5 h at room temperature, poured into ice water, and
extracted with chloroform (3×20 ml). The extracts
were combined, washed with cold water and a saturat-
ed solution of sodium chloride, dried over MgSO4,
filtered, and evaporated. The residue was subjected to
column chromatography on silica gel using petroleum
ether–ethyl acetate (2:1) as eluent. Yield 1.26 g (70%),
colorless crystals, mp 40–43°C, [α]D20 = –20.0° (c =
2.71, CHCl3). IR spectrum, ν, cm–1: 2989, 2954, 1761,
1738, 1597, 1438, 1367, 1292, 1251, 1211, 1176, 1107,
985, 928, 852, 831, 818, 791, 665, 555. 1H NMR spec-
trum (CDCl3), δ, ppm: 1.40 s (6H, 2-CH3), 2.46 s (3H,
4′-CH3), 3.78 s (3H, OMe), 4.19 d.d (1H, OCH2, J =
5.0 Hz), 4.30–4.36 m (3H, OCH2, 4-H, 5-H), 7.37 d
(2H, Harom, J = 8.0 Hz), 7.82 d (2H, Harom, J = 8.3 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 21.55 (CH3),
25.69 and 26.55 (2-CH3), 52.53 (OMe), 68.32 (OCH2),
74.94 (C5), 76.23 (C4), 112.08 (C2), 127.94, 129.82,
132.57, 145.04 (C6H4), 170.14 (CO2Me). Found, %:
C 51.79; H 5.56; S 8.91. C15H20O7S. Calculated, %:
C 52.31; H 5.85; S 9.31.
The IR spectra were recorded on a Shimadzu IR
Prestige-21 spectrometer from samples prepared as
1
thin films. The H and 13C NMR spectra were meas-
ured on a Bruker AM-300 instrument at 300.13 and
75.47 MHz, respectively, using tetramethylsilane as
internal reference. The optical rotations were measured
on a Perkin–Elmer-341 instrument. The progress of
reactions was monitored by TLC on Sorbfil plates
(Russia); spots were developed by treatment with a so-
lution of 4-methoxybenzaldehyde in ethanol contain-
ing sulfuric acid, followed by heating at 120–150°C.
L-Tartaric acid (99%) was commercial product (from
Aldrich).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011