New and Convenient Synthesis of (R)-(+)-4,5-Dihydro-4-methyl-2(3H)-furanone and (R)-(-)-4-Bromo-3-methyl-1-O-tert-butyldimethylsilylbutan-1-ol

Article abstract of DOI:10.1002/(sici)1521-3897(199901)341:1<65::aid-prac65>3.0.co;2-u

A convenient partial synthesis of the lactone (+)-10 is reported starting from the readily available methyl (S)-(+)-3-hydroxy-2-methylpropanoate (+)-1. Furthermore, an efficient three step route to the optically active saturated isoprene unit (-)-13 in high yield starting from the lactone (+)-10 is reported for the first time.

Full text of DOI:10.1002/(sici)1521-3897(199901)341:1<65::aid-prac65>3.0.co;2-u

_________________________________________________________________PROCEDURES/DATA
New and Convenient Synthesis of (R)-(+)-4,5-Dihydro-4-methyl-2(3H)-furanone
and (R)-(–)-4-Bromo-3-methyl-1-O-tert-butyldimethylsilylbutan-1-ol
Alexander Pemp, and Karlheinz Seifert*
Bayreuth, Lehrstuhl für Organische Chemie I/2 der Universität
Received August 27th, 1998
Keywords: Lactones, Terpenoids, Synthetic methods, Labdanes, Isoprene side chain of labdanes
Abstract. A convenient partial synthesis of the lactone (+)-
10 is reported starting from the readily available methyl (S)-
(+)-3-hydroxy-2-methylpropanoate (+)-1. Furthermore, an
efficient three step route to the optically active saturated iso-
prene unit (–)-13 in high yield starting from the lactone (+)-
10 is reported for the first time.
During our investigations on the enantioselective total synthe-
sis of labdane diterpenes [1, 2] we required the optically active
saturated isoprene building block (–)-13. This compound can
readily be prepared starting from the (R)-enantiomer of the
β-substituted γ-butyrolactone (+)-10 adopting a convenient
three step sequence developed by Schmid and Barner [3, 4].
While the (S)-(–)-enantiomer of lactone 10 is commercially
available (Fluka Chemie AG, Buchs, Switzerland), no
effective method for the preparation of the corresponding (R)-
(+)-enantiomer has been reported, although (R)-(+)-10 is
known to be a useful chiral synthon for the synthesis of dif-
ferent natural products like mammalian dolichols [5] or
various labdane diterpenes [1, 2, 6, 7, 8]. There is only reported
the resolution of the racemic lactone (±)-10 with (R)-(+)-α-
phenylethylamine as the chiral auxiliary [1, 5] using the
method of Helmchen and Nill [9] and a multistep asymmetric
total synthesis starting from (E)-(2R,3S)-6-ethylidene-3,4-
dimethyl-2-phenylperhydro-1,4-oxazepine-5,7-dione for the
preparation of (R)-(+)-10 [10, 11]. (S)-(–)-10 was synthesized
by Mori [12] starting from methyl (R)-(–)-3-hydroxy-2-
methylpropanoate ((–)-1) in five steps with a total yield of
17%.
4
HO
OMe
1
3
2
(+)-1
O
CH2(OCH3)2
P4O10
TBDMSCl
imidazole
MOMO
OMe
TBDMSO
OMe
O
(+)-2 (84 %)
O
(+)-3 (97 %)
LiAlH4
LiAlH4
MOMO
OH
TBDMSO
OH
(+)-5 (76 %)
(+)-4 (79 %)
TsCl
pyridine
TsCl
pyridine
MOMO
OTs
TBDMSO
OTs
In this communication we report a convenient partial syn-
thesis of (+)-10 starting from commercial methyl (S)-(+)-3-
hydroxy-2-methylpropanoate ((+)-1), Fluka Chemie AG,
Buchs, Switzerland) with a total yield up to 49%. Furthermore,
an efficient three step route to the optically active saturated
isoprene unit (–)-13 in high yield starting from the lactone
(+)-10 is reported for the first time.
(+)-6 (90 %)
(+)-7 (90 %)
NaCN
NaCN
DMSO
DMSO
5
1
CN
MOMO
TBDMSO
CN
4
2
3
To avoid by-products it was necessary to protect the
hydroxy group of the starting compound (+)-1 as its MOM-
or TBDMS-ether (+)-2 and (+)-3, respectively. (+)-2 and (+)-
3 can be transferred by means of LiAlH4 reduction to the cor-
responding alcohols (+)-4 and (+)-5. In order to receive a better
leaving group for the next step of the synthesis, alcohols (+)-
4 and (+)-5 were treated with p-tosyl chloride in pyridine
yielding the tosylates (+)-6 and (+)-7. Introduction of a cyano
group extended the carbon chain for one unit affording the
(+)-8 (90 %)
(+)-9 (91 %)
6
AcOH
H2SO4
H2O
AcOH
4
3
H2SO4
H2O
(60 %)
O
(93 %)
5
2
O
(+)-10
Scheme 1
J. Prakt. Chem. 1999, 341, No. 1
© WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 1436-9966/99/34101-65 $ 17.50 + .50/0
65

A. Pemp, K. Seifert
PROCEDURES/DATA _______________________________________________________________________
The mixture was stirred overnight at r.t. The solution was
decanted. 100 ml of CHCl3 and some crushed ice were added
to the residue, and the mixture was neutralized with 2N K2CO3-
solution. The organic phase was separated, and the aqueous
layer was extracted twice with 50 ml of CHCl3. The organic
phase was washed with NaHCO3 aq, water and brine, dried
(Na2SO4) and concentrated in vacuo to give 6.14 g (37.9 mmol,
84%) of (+)-2 as a colourless oil. Rf = 0.56 (cyclohexane/
EtOAc, 2:1). [α]D25 = + 11.9° (c=1.03, CHCl3). – IR: ν/cm–1
= 2950, 2880, 1730, 1460, 1440, 1390, 1140, 1110, 1040. –
1H NMR: δ/ppm = 2.65 (m, H-2), 3.55 (m, 2H-3), 1.08 (d, J
= 7.1, 3H-4), 3.59 (s, CH3O), 4.50 (s, CH3OCH2), 3.23 (s,
CH3OCH2). – 13C NMR: δ/ppm = 174.9 (C-1), 40.0 (C-2),
69.4 (C-3), 13.7 (C-4), 51.5 (CH3O), 96.3 (CH3OCH2), 55.0
(CH3OCH2). – MS: m/z (%) = 147 (10) [M+-15], 131 (7), 103
(11), 69 (100), 45 (10).
nitriles (+)-8 and (+)-9 in almost quantitative yield. Finally
cyclization of (+)-8 and (+)-9 under acidic conditions afforded
lactone (+)-10 in very good overall yield (up to 49%).
The synthesis of the optically active saturated isoprene
building block (–)-13 was achieved by transesterification of
lactone (+)-10 with 8M HBr in ethanol leading to the γ -
bromoester (+)-11. DIBAH-reduction of (+)-11 and protection
of the hydroxy group of the resulting alcohol (–)-12 as
TBDMS ether afforded the side chain building block (–)-13,
synthesized for the first time and in high overall yield.
5
O
8M HBr
2
DIBAH
4
Br
3
OEt
1
O
O
EtOH
(+)-10
(+)-11 (96 %)
TBDMS-triflate
Et3N
Br
Br
Methyl (S)-(+)-2-methyl-3-tert-butyldimethylsilyloxypro-
panoate (+)-3
OH
OTBDMS
(–)-13 (95%)
(–)-12 (96%)
5.36 g (45.1 mmol) methyl (S)-(+)-3-hydroxy-2-methylpro-
panoate ((+)-1) was added to a solution of 6.13 g (90 mmol)
imidazole and 10.2 g (67.7 mmol) of TBDMSCl in 100 ml of
N,N-dimethylformamide. The mixture was stirred overnight
at 60 °C. The solution was diluted with 100 ml of water and
100 ml of ether, and the organic layer was separated. The
aqueous layer was extracted three times with 30 ml of ether.
The organic layer was washed twice with 25 ml of water and
brine, dried (Na2SO4) and concentrated in vacuo. The crude
product was purified by MPLC (hexane/EtOAc, 2:1) to yield
10.17 g (43.7 mmol, 97%) of (+)-3 as a colourless liquid.
Rf = 0.71 (cyclohexane/EtOAc, 2:1). [α]D25 = + 17.2° (c = 2.51,
CHCl3). – IR: ν/cm–1 = 2970, 2945, 2875, 1736, 1465, 1261,
1104, 841. – 1H NMR: δ/ppm = 2.60 (m, H-2), 3.66 (m, 2H-
3), 1.10 (d, J = 7.0, 3H-4), 3.62 (s, CH3O), –0.01(s, (CH3)2Si)),
0.83 (s, (CH3)3C). – 13C NMR: δ/ppm = 175.3 (C-1), 42.5 (C-
2), 65.2 (C-3), 13.4 (C-4), 51.4 (CH3O), –5.6 ((CH3)2Si), 25.7
((CH3)3C), 18.1 ((CH3)3C). – MS: m/z (%) = 201 (10) [M+–
31], 175 (24) [M+–57], 101 (100) [M+–131], 89 (18), 75 (16),
73 (16), 59 (14).
Scheme 2
Experimental
1H and 13C NMR spectra were taken on a Bruker AC 300
spectrometer. Chemical shifts are given in ppm (δ-scale),
coupling constants (J) in Hertz. 1H-chemical shifts (300 MHz)
were referenced to the residual CHCl3 signal (7.24).
13C-chemical shifts (75 MHz) were referenced to CDCl3
(77.0). MS were recorded at 70 eV on a Varian MAT-313
spectrometer. Optical rotations were measured on a Perkin
Elmer 241 polarimeter. IR-spectra were taken on a Perkin
Elmer 1420 ratio recording spectrometer, 1–2% solution in
CHCl3.
Thin layer chromatography was carried out on precoated
plates of Polygram® SILG/UV254 (layer thickness 0.25 mm,
Macherey-Nagel). Spots were visualized by UV (254 nm) and
spraying with phosphomolybdic acid reagent followed by
heating to about 200 °C. MPLC was performed on Merck
silica gel 60 (70–230 mesh ASTM).
(R)-(+)-2-Methyl-3-methoxymethyloxypropan-1-ol (+)-4
Methyl (S)-(+)-3-hydroxy-2-methylpropanoate was purch-
ased from Fluka Chemie AG (Buchs, Switzerland). All
reactions were carried out under nitrogen. Solvents were
distilled under nitrogen before use: CH2Cl2 and CHCl3 from
P2O5, ether from Na/benzophenone.
Preparation of 8M HBr in EtOH: Bromine was slowly added
to a stirred mixture of tetrahydronaphthalene (dried over
Na2SO4 and distilled) and some Fe-shavings (as catalyst) at
r.t. The resulting HBr gas was bubbled through tetrahydro-
naphthalene and a gas trap (cooled to –60 °C) to remove rests
of bromine and tetrahydronaphthalene. The purified HBr gas
was bubbled through anhydrous ethanol (100 g), until the mass
increased about 65 g. The resulting solution can be stored at
–20 °C for several weeks under exclusion of moisture.
A solution of 4.90 g (30.2 mmol) (+)-2 in anhydrous ether
(25 ml) was added dropwise to a stirred suspension of LiAlH4
(750 mg) in anhydrous ether (25 ml) at 0–5 °C. The stirring
was continued for 4 h at r.t. The excess of LiAlH4 was
destroyed by successive careful addition of water (10 ml) and
10% KOH aq (2ml) to the stirred mixture. After stirring for
2 h the suspension was filtered, and the solid was washed
three times with 25 ml of ether. The combined filtrates and
washings were washed with brine, dried (Na2SO4) and
concentrated in vacuo to give 3.20 g (23.9 mmol, 79%) of
(+)-4. Rf = 0.26 (cyclohexane/EtOAc, 2:1). [α]D25 = + 10.9° (c
= 1.65, CHCl3). – IR: ν/cm–1 = 3490, 2995, 2930, 2875, 1460,
1
1410, 1140, 1040, 1005. – H NMR (DMSO-D6): δ/ppm =
3.24 (m, 2H-1), 1.75 (m, H-2), 3.36 (m, 2H-3), 0.84 (d, J =
6.8, 3H-4), 4.52 (s, CH3OCH2), 3.22 (s, CH3OCH2), 4.41 (t, J
= 5.3, OH). – 13C NMR (DMSO-D6): δ/ppm = 69.6 (C-1),
36.1 (C-2), 63.3 (C-3), 14.1 (C-4), 95.8 (CH3OCH2), 54.4
(CH3OCH2). – MS: m/z (%) = 133 (2) [M+–1], 115 (24) [M+–
1–18], 89 (17), 73 (10), 63 (35), 55 (19), 45 (100), 43 (20).
Methyl (S)-(+)-2-methyl-3-methoxymethyloxypropanoate
(+)-2
7.10 g (50 mmol) P2O5 was added to a mixture of 5.33 g
(45.1 mmol) of methyl (S)-(+)-3-hydroxy-2-methylpropanoate
((+)-1) and 34.25 g (450 mmol) methylal in 100 ml of CHCl3.
6 6
J. Prakt. Chem. 1999, 341, No. 1

Synthesis of (R)-(+)-4,5-Dihydro-4-methyl-2(3H)-furanone
__________________________________________________________________________________PROCEDURES/DATA
overnight at 50 °C, diluted with 100 ml of water and extracted
three times with 25 ml of pentane. The organic extract was
washed with water and brine, dried (Na2SO4), and the pentane
was evaporated in vacuo to give 2.18 g (15.2 mmol, 90%)
(+)-8 as a slightly yellow oil. Rf = 0.37 (cyclohexane/EtOAc,
2:1). [α]D25 = + 27.8° (c = 0.64, CHCl3). – IR: ν/cm–1 = 2925,
2880, 2250, 1455, 1420, 1390, 1140, 1105, 1040, 970, 920. –
1H NMR: δ/ppm = 3.39 (m, 2H-2), 2.09 (m, H-3), 3.38 (m,
2H-4), 1.03 (d, J = 6.9, 3H-5), 4.55 (s, CH3OCH2), 3.31 (s,
CH3OCH2). – 13C NMR: δ/ppm = 118.4 (C-1), 21.2 (C-2),
30.9 (C-3), 70.4 (C-4), 16.1 (C-5), 96.4 (CH3OCH2), 55.1
(CH3OCH2). – MS: m/z (%) = 142 (2) [M+-1], 113 (5), 98 (2),
82 (15), 61 (7), 55 (13), 45 (100).
(R)-(+)-2-Methyl-3-tert-butyldimethylsilyloxypropan-1-ol
(+)-5
Compound (+)-5 was synthesized as described for compound
(+)-4 starting from 9.78 g (42.0 mmol) (+)-3 in 50 ml of ether.
After work up the reaction yielded 6.95 g (34.0 mmol) of
crude (+)-5. Purification by MPLC (hexane/EtOAc, 2:1 – 1:1)
finally yielded 6.52 g (31.9 mmol, 76%) of (+)-5 as a
colourless liquid. Rf = 0.39 (cyclohexane/EtOAc, 5:1). [α]D25=
+ 5.9° (c = 1.13, CHCl3). – IR: ν/cm–1 = 3475, 3000, 2950,
2925, 2852, 1462, 1255, 1082, 1060, 1022, 835. – 1H NMR:
δ/ppm = 3.54 (m, 2H-1), 1.83 (m, H-2), 3.52 (m, 2H-3), 0.76
(d, J = 6.9, 3H-4) ), –0.01(s, (CH3)2Si)), 0.82 (s, (CH3)3C),
3.08 (br s, OH). – 13C NMR: δ/ppm = 68.0 (C-1), 37.2 (C-2),
67.4 (C-3), 13.0 (C-4), ), –5.7 ((CH3)2Si), 25.7 ((CH3)3C),
18.1 ((CH3)3C). – MS: m/z (%) = 203 (2) [M+–1], 189 (5)
[M+–15], 147 (30), 115 (5), 105 (67), 75 (100), 73 (47), 59
(14), 55 (25), 45 (13).
(R)-(+)-3-Methyl-4-tert-butyldimethylsilyloxybutanenitrile
(+)-9
735 mg (15 mmol) NaCN was added to a solution of 3.55 g
(9.9 mmol) (+)-7 in 10 ml DMSO. The mixture was stirred
overnight at 50 °C, diluted with 100 ml of water and extracted
three times with 25 ml of pentane. The organic extract was
washed with water and brine, dried (Na2SO4), and the pentane
was evaporated in vacuo to give 1.92 g (8.99 mmol, 91%) of
(+)-9 as a slightly yellow oil. Rf = 0.67 (cyclohexane/EtOAc,
1:1). [α]D25 = + 11.7° (c = 1.75, CHCl3). – IR: ν/cm–1 = 2950,
(S)-(+)- 2-Methyl-3-methoxymethyloxypropan-1-yl-tosylate
(+)-6
4.50 g (23.6 mmol) p-TsCl was added to a stirred solution of
3.10 g (23.0 mmol) (+)-4 in 25 ml anhydrous pyridine at 0–
5 °C. The mixture was left to stand overnight in a refrigerator,
then poured in ice-water and extracted three times with 25 ml
of ether. The ether solution was washed with water, CuSO4
solution, water and brine, dried (Na2SO4) and concentrated
in vacuo to afford 5.95 g (20.6 mmol, 90%) (+)-6 as a
colourless oil. Rf = 0.42 (cyclohexane/EtOAc, 2:1). [α]D25 = +
3.5° (c = 1.04, CHCl3). – IR: ν/cm–1 = 3015, 2975,1645, 1610,
1500, 1472, 1365, 1180, 1130, 1045, 985, 955, 820. – 1H NMR:
δ/ppm = 3.97 (m, 2H-1), 2.03 (m, H-2), 3.35 (m, 2H-3), 0.87
(d, J = 6.9, 3H-4), 4.45 (s, CH3OCH2), 3.25 (s, CH3OCH2),
7.75 (d, J = 8.0, H-2', H-6'), 7.30 (d, J = 8.0, H-3', H-5'), 2.41
(s, 3H-7'). – 13C NMR: δ/ppm = 71.9 (C-1), 33.3 (C-2), 68.3
(C-3), 13.3 (C-4), 96.2 (CH3OCH2), 54.9 (CH3OCH2), 132.7
(C-1'), 129.6 (C-2', C-6'), 127.6 (C-3', C-5'), 144.6 (C-4'), 21.3
(C-7'). – MS: m/z (%) = 288 (2) [M+], 243 (8) [M+–15], 227
(16), 155 (98), 105 (7), 91(100), 45 (100).
1
2925, 2855, 2250, 1465, 1390, 1255, 1100, 1030, 840. – H
NMR: δ/ppm = 3.32 (m, 2H-2), 1.98 (m, H-3), 3.47 (m, 2H-
4), 1.00 (d, J = 6.8, 3H-5), –2 (s, (CH3)2Si), 0.86 (s, (CH3)3C).
–
13C NMR: δ/ppm = 18.8 (C-1), 20.8 (C-2), 33.2 (C-3), 65.9
(C-4), 13.0 (C-5), –5.6 ((CH3)2Si), 25.7 ((CH3)3C), 18.1
((CH3)3C). – MS: m/z (%) = 212 (2) [M+–1], 198 (11) [M+–
15], 156 (100), 131 (3), 129 (19), 115 (25), 98 (22), 89 (10),
75 (62), 73 (26), 59 (9), 45 (4).
(R)-(+)-4,5-Dihydro-4-methyl-2(3H)-furanone (+)-10
A: Cyclization of (+)-8
1.90 g (13.3 mmol) of (+) 8 was added to a mixture of 15 ml
of conc. H2SO4/conc. AcOH/water (1:1:1). The mixture was
stirred and heated under reflux for 1.5 h. After pouring onto
ice the mixture was neutralized with 10% NaOH aq, extracted
three times with ether (25 ml) and then with CH2Cl2 (25 ml).
The combined organic phases were washed with 5% KHCO3-
solution and brine, dried (Na2SO4) and concentrated in vacuo
to yield 1.24 g (12.4 mmol, 93%) of (+)-10 as a colourless
liquid.
(S)-(+)- 2-Methyl-3-tert-butyldimethylsilyloxypropan-1-yl-
tosylate (+)-7
Compound 7 was synthesized as described for compound (+)-
6 starting from 4.70 g ( 23.0 mmol) of (+)-5 in 25 ml of
pyridine. After work up the reaction yielded 5.95 g (20.6
mmol, 90%) of (+)-7 as a colourless oil. Rf = 0.49 (cyclo-
hexane/EtOAc, 5:1). [α]D25 = + 2.6° (c = 0.99, CHCl3). – IR:
ν/cm–1 = 3041, 2965, 2949, 2865, 1605, 1475, 1366, 1261,
B: Cyclization of (+)-9
Compound (+)-10 was synthesized as described under A
starting from 1.82 g (8.53 mmol) (+)-9. After work up the
reaction yielded 512 mg (5.12 mmol, 60%) of (+)-10 as a
1
1182, 1105,1051, 980, 945, 843. – H NMR: δ/ppm = 3.93
colourless oil. Rf = 0.59 (cyclohexane/EtOAc, 1:1). [α]D25
=
(m, 2H-1), 1.90 (m, H-2), 3.41 (m, 2H-3), 0.84 (d, J = 6.9,
3H-4), 7.75 (d, J = 8.0, H-2', H-6'), 7.29 (d, J = 8.0, H-3', H-
5'), 2.40 (s, 3H-7'), –0.06 (s, (CH3)2Si), 0.78 (s, (CH3)3C). –
13C NMR: δ/ppm = 72.1 (C-1), 35.6 (C-2), 63.7 (C-3), 13.1
(C-4), 133.1 (C-1'), 129.7 (C-2', C-6'), 127.8 (C-3', C-5'), 144.5
(C-4'), 21.5 (C-7'), –5.7 ((CH3)2Si), 25.7 ((CH3)3C), 18.1
((CH3)3C). – MS: m/z (%) = 301 (3) [M+–57], 271 (4), 229
(100), 203 (2), 149 (9), 131 (3), 115 (4), 91 (11).
+ 23° (c = 4.00, MeOH) [5] [α]D26= + 25.7° (c = 4.0, MeOH).
1
– IR: ν/cm–1 = 2996, 2990, 1779, 1365, 1170, 1020. – H
NMR: δ/ppm = 2.01 (m, H-3), 2.46 (m, H-3), 2.52 (m, H-4),
3.71 (m, H-5), 4.25 (m, H-5), 1.11 (d, J = 5.9, 3H-6). –
13C NMR: δ/ppm = 177.0 (C-2), 35.7 (C-3), 30.0 (C-4), 74.4
(C-5), 17.5 (C-6). – MS: m/z (%) = 100 (21) [M+], 56 (69), 42
(100), 41 (87).
Ethyl (R)-(+)-4-Bromo-3-methylbutanoate (+)-11
(R)-(+)- 3-Methyl-4-methoxymethyloxybutanenitrile (+)-8
1.06 g (10.6 mmol) (+)-10 was added dropwise to a solution
1.34 g (27.3 mmol) NaCN was added to a solution of 5.00 g
of 8M HBr in anhydrous ethanol (15 ml) at r.t. After the
(17.3 mmol) (+)-6 in 15 ml of DMSO. The mixture was stirred
J. Prakt. Chem. 1999, 341, No. 1
67

A. Pemp, K. Seifert
PROCEDURES/DATA _______________________________________________________________________
addition was complete, the mixture was stirred for 16 h at r.t.
The reaction mixture was poured onto ice, and, after addition
of water (50 ml), extracted with ether (3 × 25 ml). The com-
bined organic layers were washed successively with NaHCO3
solution and brine, dried (Na2SO4), and the solvent was
evaporated in vacuo at r.t. to afford 2.13 g (10.2 mmol, 96%)
of (+)-11 as a colourless liquid. Rf = 0.55 (cyclohexane/EtOAc,
8:1). [α]D25 = +2.8° (c = 4.34, CHCl3) [3] (–)-11 [α]D26 = –2.3°
(c = 4.0, CHCl3). – IR: ν/cm–1 = 2960, 2925, 2875, 1715,
ether solution was washed successively with 5% NaHCO3
aq. solution (25 ml), water (20 ml) and brine (20 ml), dried
(Na2SO4), and the solvent was evaporated in vacuo to yield
3.10 g (11.0 mmol, 95%) of (–)-13 as a colourless oil. Rf =
0.77 (cyclohexane/EtOAc, 2:1). [α]D25 = –2.5° (c = 1.62,
CHCl3). – IR: ν/cm–1 = 2957, 2931, 2858, 1472, 1388, 1256,
1100, 837. – 1H NMR: δ/ppm = 3.63 (m, 2H-1), 1.43 (m, H-
2), 1.64 (m, H-2), 1.98 (m, H-3), 3.38 (m, 2H-4), 1.01 (d, J =
6.7, 3H-5), –0.03 (s, (CH3)2Si), 0.87 (s, (CH3)3C). – 13C NMR:
δ/ppm = 60.7 (C-1), 37.6 (C-2), 31.9 (C-3), 41.6 (C-4), 18.7
(C-5), –5.4 ((CH3)2Si), 25.9 ((CH3)3C), 18.2 ((CH3)3C). –
MS: m/z (%) = 225/223(9/10), 169/167 (69/70), 139/137 (53/
55), 73 (32), 69 (100), 59 (16), 41 (62).
1
1450, 1370, 1290, 1135, 1020. – H NMR: δ/ppm = 2.16–
2.51 (m, 2H-2), 2.28 (m, H-3), 3.39 (m, 2H-4), 1.03 (d, J =
6.6, 3H-5), 4.09 (q, J = 7.1, (OCH2CH3), 1.21 (t, J = 7.1,
OCH2CH3). – 13C NMR: δ/ppm = 171.9 (C-1), 39.2 (C-2),
32.0 (C-3), 40.0 (C-4), 18.6 (C-5), 60.3 (OCH2CH3), 14.0
(OCH2CH3). – MS: m/z (%) = 165/163 (16/15), 137/135 (6/
5), 129 (8), 88 (100), 60 (30), 55 (46), 41 (35).
This work was supported by the Deutsche Forschungs-
gemeinschaft (Grant Se 595/5-1 and 5-2). We thank the DFG.
R-(–)-4-Bromo-3-methyl-1-butanol (–)-12
References
To 25 ml of a solution of 1M DIBAH in hexane was added
dropwise (+)-11 (2.43 g, 11.6 mmol) in hexane (10 ml) at
0 °C. After the addition was complete, the mixture was allowed
to stand at –20 °C for 12 h. Excessive DIBAH was destroyed
by adding MeOH at 0 °C, and then the mixture was poured
onto ice. The mixture was treated with 2N H2SO4 until pH 3 –
4 was reached, and extracted with ether (3 × 25 ml). The com-
bined organic layers were washed successively with 5%
aqueous NaHCO3 solution (20 ml) and brine (20 ml), dried
(Na2SO4), and the solvent was evaporated in vacuo at r.t. to
give 1.87 g (11.3 mmol, 96%) of (–)-12 as a pale yellow liquid.
Rf = 0.42 (cyclohexane/EtOAc, 1:1). [α]D25 = –2.5° (c = 2.75,
CHCl3). – IR: ν/cm–1 = 3400, 2960, 2940, 2855, 1465, 1380,
1275, 1235, 1093, 725. – 1H NMR: δ/ppm = 3.70 (m, 2H-1),
1.45 (m, H-2), 1.69 (m, H-2), 1.99 (m, H-3), 3.36 (J = 5.1,
1.1, 2H-4), 1.01 (d, J = 6.7, 3H-5), 2.44 (br.s, OH). –
13C NMR: δ/ppm = 58.9 (C-1), 37.1 (C-2), 31.6 (C-3), 41.2
(C-4), 18.5 (C-5). – MS: m/z (%) = 150/148 (9/8), 122/120
(30/31), 69 (91), 56 (52), 41 (100).
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R-(–)-4-Bromo-3-methyl-1-O-tert.-butyldimethylsilylbutan-
1-ol (-)-13
Address for correspondence:
Prof. Dr. K. Seifert
Universität Bayreuth
Lehrstuhl Organische Chemie I/2
D-95440 Bayreuth
Fax: Internat. code (0)921 55 5358
e-Mail: karlheinz.seifert@uni-bayreuth.de
To a solution of (–)-12 (1.95 g, 11.6 mmol) and triethylamine
(3.54 g, 34.5 mmol) in CH2Cl2 (50 ml) was added dropwise
TBDMS-triflate (5.85 g, 23 mmol) at 0 °C. After the addition
was complete, the mixture was stirred for 1 h at 0 °C and was
then allowed to stand at –20 °C for 12 h. The solvent was
evaporated, and ether (100 ml) was added to the residue. The
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J. Prakt. Chem. 1999, 341, No. 1