From vinyl pyranoses to carbasugars by an iron-catalyzed reaction complementary to classical Ferrier carbocyclization

Article abstract of DOI:10.1039/b907632h

Starting from vinyl pyranoses an iron-catalyzed tandem isomerization- intramolecular aldolization reaction was developed to prepare cyclohexenone derivatives bearing substituents on the double bond, and it has been applied in a short synthesis of 4-epi-ga

Full text of DOI:10.1039/b907632h

Supplementary Material (ESI) for Chemical Communications
This journal is (c) The Royal Society of Chemistry 2009
Electronic Supplementary Information
From vinyl Pyranoses to Carbasugars by an iron-catalyzed Reaction
complementary to Classical Ferrier Carbocyclisation
Dinh Hung Mac,a Ramesh Samineni,a,b Julien Petrignet,a Pabbaraja Srihari,b
Srivari Chandrasekhar,b Jhillu Singh Yadav,*b René Grée.*a
a Université de Rennes 1, Laboratoire de Chimie et Photonique Moléculaires,
CNRS UMR 6510, Avenue du General Leclerc, 35042 Rennes Cedex, France.
b Indian Institute of Chemical Technology, 500607, Hyderabad, India.
Supporting Information
(11 pages)
I General methods
S 2
S 3
S 2
S 3
S 4
S 4
S 5
S 5
S 6
S 6
S 7
II Experimental procedures and characterizations
II.1 Tetrahydro-6-vinylpyran-2-one (4a)
II.2 Tetrahydro-6-((E)-prop-1-enyl)pyran-2-one(4b)
II.3 Tetrahydro-6-styrylpyran-2-one(4c)
II.4 Tetrahydro-6-vinyl-2H-pyran-2-ol (5a)
II.5 Tetrahydro-6-(prop-1-enyl)-2H-pyran-2-ol (5b)
II.6 Tetrahydro-6-styryl-2H-pyran-2-ol (5c)
II.7 2-Methylcyclohex-2-enone (6a)
II.8 2-Ethylcyclohex-2-enone (6b)
II.9 2-Benzylcyclohex-2-enone (6c)
II.10 (E)-Ethyl 3-(6-hydroxy-tetrahydro-2H-pyran-2-yl)acrylate (5d) S 7
II.11 Ethyl 2-(6-oxocyclohex-1-enyl)acetate (6d) S 8
II.12 (4S,5R,6S)-4,5,6-Tris(benzyloxy)-2-methylcyclohex-2-enone (9) S 9
II.13 (4S,5R,6S)-4,5,6-Trihydroxy-2-methylcyclohex-2-enone (10)
S 10
II.14 (2S,3R,4S,6R)-2,3,4-tris(benzyloxy)-6-methylcyclohexanone (11) S 10
II.15 (2S,3R,4S,6R)-2,3,4-Trihydroxy-6-methylcyclohexanone (12)
S 11
1

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I - General Methods
All reactions were carried out under argon or nitrogen atmosphere. TLC spots were examined
under UV light and revealed by sulfuric acid-anisaldehyde, KMnO4 solution or
phosphomolybdic acid. Dichloromethane was distilled from calcium hydride, tetrahydrofuran
and diethylether were distilled from sodium/benzophenone, methanol was distilled over
magnesium.
CAUTION: all reactions involving Fe(CO)5 have to be carried out under a well ventilated
hood. These iron carbonyl-mediated reactions have been performed in usual pyrex glassware
equipment. At the end of the reaction the residue of Fe(CO)5 can be destroyed by addition of
strong oxidizing agents such as Ce(NH4)2(NO3)6 or FeCl3.
NMR spectra were obtained at 300 MHz or 500 MHz for 1H and 75 MHz or 125MHz for 13C
with BRUCKER AVANCE 300 or 500 spectrometers. Chemical shifts are given in parts per
million (δ) relative to chloroform (7.26 ppm) or benzene (7.16 ppm) residual peaks.
1
13
Assignments of H and C resonances for complex structures were confirmed by extensive
2D experiments (COSY, HMQC, HMBC). Mass spectral analyses were performed at the
Centre Régional de Mesures Physiques de l'Ouest (CRMPO) in Rennes (France). Rotation
data were recorded on a Perkin-Elmer 241 Polarimeter.
II Experimental procedures and characterizations
II.1 Tetrahydro-6-vinylpyran-2-one (4a)
O
O
To a solution 4-bromoorthobutyrate (764 µL, 4.40 mmol) in diethyl ether (12 mL) cooled at
−78°C was added dropwise a solution of t-butylithium (5.24 mL, 7.86 mmol, 1.5 M in
hexane). The cloudy mixture was stirred at −78°C for 1h and then at 0°C for 50 min. After
recooling to −78°C, a solution of acrolein (120 µL, 1.57 mmol) in Et2O (3 mL) was added and
2

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reaction mixture was stirred at −78°C for 30 min and then at 0°C for 40 min. The reaction
mixture was quenched with saturated solution of ammonium chloride (15 mL). Aqueous
phase was extracted with Et2O (2 x 20 mL) and the combined organic phases were dried over
MgSO4, filtered and concentrated under reduced pressure. The orthoester group was
hydrolyzed by stirring during 20 min the previous crude oil in a THF-H2O (15 mL – 5 mL)
solution in presence of 5 drops of HCl 6N. After extraction with diethyl ether, the residue was
purified by column chromatography on silica gel with Pentane/AcOEt (60/40) as eluent to
afford hydroxy ester 3a as a colorless oil.
This product (155 mg, 0.981 mmol) was dissolved in anhydrous acetonitrile (10 mL) in
presence of DBU (175 µL, 1.18 mmol) and the reaction mixture was stirred overnight at room
temperature. After concentration of the residue in vacuo, reaction mixture was resolubilized in
acetonitrile and stirred during 2h at room temperature. Solvent was evaporated and the residue
was purified by column chromatography on silica gel with CH2Cl2 as eluent to afford the
lactone 4a (100 mg, 81%) as a colorless oil [Rf 0.2; AcOEt/Pentane: 9/1].
1H NMR (300 MHz, CDCl3): δ = 1.56-2.00 (m, 4H), 2.39-2.61(m, 2H), 4.79 (m, 1H), 5.18-
5.34 (m, 2H), 5.84 (ddd,1H, J = 5.5, 10.6, 16.2Hz).
13C NMR (75 MHz, CDCl3): δ = 18.0, 27.8, 29.5, 30.9, 80.2, 116.8, 136.1, 171.1.
II.2 Tetrahydro-6-((E)-prop-1-enyl)pyran-2-one(4b)
O
O
This compound was obtained by the method employed for the preparation of 4a, and using 4-
bromoorthobutyrate (764 µL, 4.40 mmol), t-BuLi (5.24 mL, 7.86 mmol, 1.5 M in hexane),
crotonaldehyde (130 µL, 1.57 mmol), Et2O (15 mL), DBU (224 µL, 1.50 mmol) and CH3CN
(10 mL). Purification by column chromatography using CH2Cl2 as eluent afforded the lactone
4b as a colorless oil (120 mg, 54% overall yield) [Rf: 0.2; Et2O/Pentane 5/5].
1H NMR (300 MHz, CDCl3): δ = 1.54-1.96 (m, 7H), 2.36-2.60 (m, 2H), 4.72 (m, 1H), 5.44-
5.53 (m, 1H), 5.70-5.81 (m, 1H).
13C NMR (75 MHz, CDCl3): δ = 17.6, 18.2, 28.3, 29.5, 80.7, 129.3, 129.4, 171.4.
3

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II.3 Tetrahydro-6-styrylpyran-2-one(4c)
Ph
O
O
This compound was obtained by the method employed for the preparation of 4a, and using 4-
bromoorthobutyrate (764 µL, 4.40 mmol), t-BuLi (5.24 mL, 7.86 mmol, 1.5 M in hexane),
trans-cinnamaldehyde (205 µL, 1.57 mmol), Et2O (15 mL), DBU (224 µL, 1.50 mmol) and
CH3CN (10 mL). Purification by column chromatography using CH2Cl2 as eluent afforded the
lactone 4c as a colorless oil (205 mg, 59% overall yield) [Rf: 0.6; CH2Cl2/Et2O: 9/1].
1H NMR (300 MHz, CDCl3): δ = 1.71-2.13 (m, 4H), 2.48-2.71 (m, 2H), 4.98-5.04 (m, 1H),
6.22 (dd, 1H, J = 15.9, 6.0Hz), 6.69 (dd, J = 16.0, 0.9Hz), 7.35 (m, 5H).
13C NMR (75 MHz, CDCl3): δ = 18.3, 28.5, 29.6, 80.4, 126.7, 127.1, 128.2, 128.7, 132.1,
136.6, 171.2.
HRMS m/z M+ Calculated for C13H14O2: 202.0994, found 202.1001.
II.4 Tetrahydro-6-vinyl-2H-pyran-2-ol (5a)
O
OH
To a solution of lactone 4a (73 mg, 0.58 mmol) in CH2Cl2 (4 mL) cooled at −78°C was added
dropwise a solution of DIBAl-H (1.1 mL, 1.1 mmol, 1.0 M solution in toluene). The reaction
mixture was stirred at −78°C for 2h and then was quenched with a saturated solution of
sodium and potassium tartrate (5 mL). After stirring during 1h and decantation, aqueous phase
was extracted with CH2Cl2 (2 x 5 mL). The combined organic phases were dried over MgSO4,
filtered and concentrated under reduced pressure to afford pure lactol 5a as a colorless oil (59
mg, 80% yield, mixture of diastereoisomers: 50/50 by 1H NMR) [Rf: 0.25; CH2Cl2/Et2O: 9/1]
1H NMR (300 MHz, CDCl3): δ = 1.33-1.92 (m, 12H), 3.19 (s, 1H), 3.69 (d, 1H, J = 5.5 Hz,),
3.93-4.02 (m, 1H), 4.46-4.51 (m, 1H), 4.76-4.81 (m, 1H), 5.09-5.30 (m, 4H), 5.34-5.38 (m,
1H), 5.79-5.95 (m, 2H).
13C NMR (75 MHz, CDCl3): δ = 17.2, 21.9, 29.5, 30.4, 31.2, 32.4, 69.7, 91.9, 96.5, 115.0,
115.2, 138.2, 139.2.
HRMS m/z [M-H2O ]+ Calculated for C7H10O: 110.0732, found 110.0728.
4

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II.5 Tetrahydro-6-(prop-1-enyl)-2H-pyran-2-ol (5b):
O
OH
This compound was obtained by the method used for the preparation of 5a, starting with 135
mg of lactone 4b, 1.45 mL of DIBAL-H (as a 1M solution in toluene). Purification by column
chromatography using Et2O/Pentane 1/1 as eluent afforded the lactol 5b as a colorless oil (105
mg, 77%, mixture of diastereoisomers: 45/55 by 1H NMR) [Rf: 0.3; Et2O/Pentane 1/1].
1H NMR (300 MHz, CDCl3): δ = 1.23-1.91 (m, 6H), 1.68 (d, J = 6.4Hz, 3H), 3.20 (broad s,
1H), 3.70 (br, 1H), 3.89 (dd, J = 6.9, 10.4Hz, 1H), 4.39 (t, J = 9.3Hz, 1H), 4.72 (d, J = 8.9Hz,
1H), 5.29 (broad s, 1H), 5.48 (dd, J = 6.3, 17.1Hz, 1H), 5.68 (dq, J = 6.3, 15.3Hz, 1H).
13C NMR (75 MHz, CDCl3): δ = 17.7, 17.8, 21.9, 29.5, 30.7, 31.5, 32.4, 69.7, 70.0, 91.9,
96.4, 127.2, 127.4, 131.3, 132.1.
HRMS m/z M+ Calculated for C8H14O2: 142.0994, found 142.0996.
II.6 Tetrahydro-6-styryl-2H-pyran-2-ol (5c):
Ph
O
OH
This compound was obtained by the method used for the preparation of 5a, starting with 95
mg of lactone 4c, 0.52 mL of DIBAL-H (as a 1M solution in toluene). Purification by column
chromatography using CH2Cl2/Et2O:9/1 as eluent afforded the lactol 5c as a colorless oil
(70mg, 73%, mixture of diastereoisomers: 50/50 by 1H NMR) [Rf: 0.3; CH2Cl2/Et2O: 9/1].
1H NMR (300 MHz, CDCl3): δ = 1.36-2.04 (m, 12H), 3.41-3.59 (m, 1H), 3.91-4.09 (m, 1H),
4.12-4.18 (m, 1H), 4.66-4.72 (m, 1H), 4.82-4.87 (m, 1H), 5.40-5.44 (m, 1H), 6.22 (dd, 1H, J
= 16.0, 6.2 Hz), 6.27 (dd, 1H, J = 16.0, 6.2 Hz), 6.61 (d, 1H, J = 16.0 Hz), 6.64 (d, 1H, J =
16.0 Hz), 7.24-7.42 (m, 12H).
13C NMR (75 MHz, CDCl3): δ = 17.3, 22.0, 29.6, 30.9, 31.6, 32.4, 69.6, 76.8, 92.0, 96.5,
126.46, 126.50, 127.56, 127.63, 128.5, 129.6, 130.3, 130.4, 130.5, 136.8, 136.9.
HRMS m/z M+ Calculated for C13H16O2: 204.1150, found 204.1158.
5

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II.7 2-Methylcyclohex-2-enone (6a)
O
A solution of lactol 5a (50mg, 0.39 mmol) and Fe(CO)5 (5µL) in dry THF (2 mL), under
magnetic stirring in a pyrex round bottomed flask, was irradiated with a Philip HPK125 W
during 1 hour. After being cooled to room temperature and concentrated, the residue was
diluted in diethylether, filtered on a short pad of silica gel and concentrated under vacuum to
afford a mixture of aldol products (45 mg).
To an ice–cold solution of previous aldol products and Et3N (10 equiv) in CH2Cl2, was added
MsCl (3equiv) at 0°C. After being stirred at RT during 24 hours the mixture was diluted with
CH2Cl2 and H2O. Then the organic phase was separated and the aqueous phase was extracted
with CH2Cl2. The combined organic phases were dried over MgSO4, filtered and concentrated
under vacuum to afford a residue, which was purified by chromatography on silica gel with
Pentane/Et 2O (80/20) as eluent to afford cyclohexenone 6a as a colorless liquid 18 mg, (42%
over 2 steps) [Rf: 0.7; Pentane/Et2O: 1/1].
1H NMR (300 MHz, CDCl3): δ = 1.70 (q, 3H, J = 1.8Hz), 1.9 (quin, 2H, J = 6.4Hz), 2.30-
2.20 (m, 2H), 2.40 (t, 2H, J = 6.7Hz), 6.70-6.64 (m, 1H).
13C NMR (75 MHz, CDCl3): δ =16.0, 23.3, 26.0, 38.3, 135.7, 145.6, 200.0.
II.8 2-Ethylcyclohex-2-enone (6b)
O
This compound was obtained by the method used for the preparation of 6a, starting with 100
mg of lactol 5b (0.7 mmol). Purification by column chromatography using Et2O/Pentane 1/1
as eluent (Rf: 0.7) afforded the cyclohexenone 6b as a colorless oil (43 mg, 50% over 2 steps)
[Rf: 0.7; Pentane/Et2O: 1/1].
1H NMR (300 MHz, CDCl3): δ = 1.01 (t, 3H, J = 1.0Hz), 1.98 (q, 2H, J = 6.3Hz), 1.98 (q,
2H, J = 7.4Hz), 2.33-2.38 (m, 2H) 2.43 (t, 2H, J = 6.7Hz), 6.71 (broad s, 1H).
13C NMR (75 MHz, CDCl3): δ = 12.8, 22.5, 23.2, 26.0, 38.6, 141.2, 143.9, 199.6.
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II.9 2-Benzylcyclohex-2-enone (6c)
O
This compound was obtained by the method used for the preparation of 6a starting with 70mg
of lactol 5c (0.34 mmol). Purification by column chromatography using Et2O/Pentane 1/1 as
eluent afforded the cyclohexenone 6c as a colorless oil (35 mg, 55% over 2 steps) [Rf: 0.5;
Et2O/Pentane 1/1].
1H NMR (300 MHz, CDCl3): δ = 2.0 (q, 2H, J = 6.7 Hz), 2.32-2.37 (m, 2H) 2.47 (t, 3H, J=
6.7Hz), 3.54 (d, 2H, J = 1.1Hz), 6.57 (t, 1H, J = 4.2Hz), 7.18-7.32 (m, 5H).
13C NMR (75 MHz, CDCl3): δ = 23.1, 26.1, 35.4, 38.5, 126.1, 128.4, 129.2, 139.5, 139.8,
146.4, 199.0.
II.10 (E)-Ethyl 3-(6-hydroxy-tetrahydro-2H-pyran-2-yl)acrylate (5d)
O
OH
EtOOC
Step 1: synthesis of lactol 5a by route 2
The commercially available glutaraldehyde, as a 50% aqueous solution, was saturated with
sodium chloride an extracted 5 times with ether. The ether extract was dried over anhydrous
magnesium sulfate, filtered, and concentrated under reduced pressure to give crude
glutaraldehyde. To the solution of previous glutaraldehyde (1 g, 10 mmol) in THF (20 mL) at
0°C was added vinylmagnesium bromide (12 mL, 1M in THF). After 2 h, the reaction was
quenched by 10% NH4Cl (20 mL). The aqueous phase was extracted by Et2O (3x20 mL). The
combined organic phases were dried over Mg2SO4, filtered and concentrated under reduced
pressure to afford a residue, which was purified by chromatography on silica gel with
Pentane/AcOEt (9/1) as eluent to give pure lactol 5a as a colorless oil (820 mg, 64%).
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Step 2: synthesis of lactol 5d by metathesis reaction
A solution of lactol 5a (128 mg, 1 mmol), ethyl acrylate (660 μl, 6 mmol) and second-
generation Grubbs catalyst (16 mg, 3% mol) was heated at 40°C in CH2Cl2 (10 mL) during 16
h. The solvent was removed under vacuum and the residue was purified by column
chromatography on silica gel using as eluent mixtures of pentane and Et2O (95:5 then 60:40).
The lactol 5d was obtained as a viscous oil (112 mg, 56% ) [Rf: 0.1; CH2Cl2/Et2O: 9/1].
1H NMR (300 MHz, CDCl3): δ = 1.22 (t, J = 7.1Hz, 3H), 1.29-1.93 (m, 6H), 3.87 (broad s,
1H), 4.14 (q, J = 7.3Hz, 1H), 4.35 (d, J = 6.1Hz, 1H), 4.61 (m, 1H), 4.73 (m, 1H), 5.30 (s,
1H), 5.94 (dd, J = 1.8Hz, 1H), 6.85 (dd, J = 4.6, 15.7Hz)
13C NMR (75 MHz, CDCl3): δ = 14.1, 17.3, 22.0, 29.5, 30.0, 30.7, 32.1, 60.4, 60.42, 67.5,
67.9, 74.6, 91.7, 96.4, 119.7, 120.1, 146.9, 148.4, 166.7, 166.8.
HRMS m/z Calculated for [M-H2O ]+.:C10 H14 O3 182.0943 found 182.0941.
II.11 Ethyl 2-(6-oxocyclohex-1-enyl)acetate (6d)
O
CO2Et
This compound was obtained by the method used for the preparation of 6a starting with
100mg of lactol 5d (0.5 mmol). Purification by column chromatography using Et2O/Pentane
1/1 as eluent afforded the cyclohexenone 6d as a colorless oil (50 mg, 55% over 2 steps) [Rf:
0.5; Et2O/Pentane: 1/1].
1H NMR (300 MHz, CDCl3): δ = 1.18 (t, J = 7.1Hz, 3H), 1.97 (quin, J = 6.4Hz, 2H), 2.34
(m, 2H), 2.41 (t, J = 6.8Hz, 4H), 3.11 (d, J = 1.1Hz, 2H), 4.06 (q, J = 7.1Hz, 2H), 6.81 (t, J =
4.2Hz, 1H)
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.9, 26.0, 35.4, 37.9, 60.8, 133.6, 148.3, 171.4,
198.3.
8

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II.12 (4S,5R,6S)-4,5,6-Tris(benzyloxy)-2-methylcyclohex-2-enone (9)
O
BnO
OBn
OBn
A solution of lactol 7 (890 mg, 2 mmol) and Fe(CO)5 (26 μl, 10%mol) in dry THF (20 mL)
was irradiated with a Philip HPK125 W during 1 hour. After being cooled to room
temperature and concentrated, the residue was diluted in ether, filtered on a short pad of silica
gel and concentrated under vacuum to afford a mixture of aldol products. The crude product
was purified by column chromatography on silica gel with Pentane/AcOEt: 7/3 as eluent to
afford 845 mg of product 8 (95%, a 45/50/5 mixture of isomers by 1H NMR).
To an ice–cold solution of previous aldol products (700 mg, 1.57 mmol) and Et3N (660µl, 3
equiv) in dry CH2Cl2 (15 mL), was added MsCl (243 µl, 2equiv) at 0°C. After being stirred at
RT for 24 hours, the mixture was diluted with CH2Cl2 and H2O. The organic phase was
separated and the aqueous phase was extracted with CH2Cl2 (3x20 mL). The combined
organic phases were dried over MgSO4, filtered and concentrated under vacuum to afford a
residue, which was purified by chromatography on silica gel with Pentane/AcOEt (9/1) as
eluent to afford cyclohexenone 9 as a white solid (464 mg, 69%) [Rf: 0.3; Pentane/AcOEt:
9/1].
Mp:64-66°C
1H NMR (300 MHz, CDCl3): δ = 1.75 (dd, J = 2.1, 1.6Hz, 3H), 3.87 (dd, J = 10.7, 7.8Hz,
1H), 3.95 (d, J = 10.7Hz, 1H), 4.24 (ddq, J = 7.8, 3.3, 2.1Hz, 1H), 4.67 (d, J = 11.5Hz, 2H),
4.73 (d, J = 10.9Hz, 1H), 4.76 (d, J = 11.6Hz, 1H), 4.89 (d, J = 10.9Hz, 1H), 5.03 (d, J =
10.3Hz, 1H), 6.52 (dq, J = 3.3, 1.6Hz, 1H), 7.23-7.39 (m, 15H).
13C NMR (75 MHz, CDCl3): δ = 15.3, 73.5, 74.6, 75.6, 78.5, 83.9, 84.7, 127.78, 127.8,
127.91, 127.98, 128.2, 128.3, 128.38, 128.41, 128.6, 135.0, 137.8, 137.9, 138.3, 143.0, 197.6.
HRMS m/z Calculated for [M +Na]+.C28H28O4Na: 451.1885 found 451.1876.
[α]20D -3.6 (c 0.19, MeOH).
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II.13 (4S,5R,6S)-4,5,6-Trihydroxy-2-methylcyclohex-2-enone (10)
O
HO
OH
OH
The cyclohexenone 9 (142 mg, 0.33 mmol) was dissolved in anhydrous CH2Cl2 under argon
and anhydrous FeCl3 (162 mg, 3 equiv) was added at 0°C. After 15 min the reaction was
complete as indicated by TLC analysis and quenched with H2O (5mL). It was stirred for 1
min and then extracted with AcOEt (3x30mL). The organic layers were dried over Na2SO4,
filtered, and the solvent was removed under pressure. This crude reaction mixture was
purified by flash silica gel column chromatography (AcOEt as eluent) to afford 4-epiGabosine
A as a white solid 28 mg (55% yield) [Rf: 0.2; AcOEt/MeOH: 8/2].
Mp:100-102°C
1H NMR (300 MHz, MeOD): δ = 1.82 (t, J = 1.8Hz, 3H), 3.32 (broad s, 3HOH), 3.54 (dd, J =
10.9, 8.2Hz, 1H), 4.00 (d, J = 10.9Hz, 1H), 4.30 (ddq, J = 8.2, 3.1Hz, 1H), 6.67 (dq, J =
3.2Hz, 1.6Hz, 1H).
13C NMR (75 MHz, MeOD): δ= 15.2, 72.6, 78.0, 80.0, 134.8, 147.9, 200.1.
HRMS m/z Calculated for [M +Na]+.C7H10O4Na: 181.0471 found 181.0474.
[α]20D + 47.3 (c 0.3, MeOH).
II.14 (2S,3R,4S,6R)-2,3,4-tris(benzyloxy)-6-methylcyclohexanone (11)
O
BnO
OBn
OBn
To a solution of 9 (100 mg, 0.232 mmol) in absolute ethanol (2.5 mL) was added palladium
on activated carbon (7 mg). The flask was flushed with hydrogen three times. The reaction
mixture was then stirred vigorously under an atmosphere of hydrogen for 3 h. The reaction
mixture was filtered through a pad of silica gel and concentrated under vacuum to afford
cyclohexanone 11 as a white solid (95 mg, 95%).
Mp:74-76°C
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1H NMR (500 MHz, CDCl3): δ = 1.10 (d, J = 6.5Hz, 3H), 1.34 (dt, J = 11.6, 13.5Hz, 1H),
2.23 (dt, J = 13.1, 5.0Hz, 1H), 2.39 (ddq, J = 5.5, 12.3, 6.5Hz, 1H), 3.67 (dd, J = 9.6, 9.1Hz,
1H), 3.85 (ddd, J = 4.8, 8.9, 11.5Hz, 1H), 4.08 (dd, J = 9.8, 1.3Hz, 1H), 4.55 (d, J = 11.4Hz,
1H), 4.72 (d, J = 11.6Hz, 1H), 4.76 (d, J = 11.6Hz, 1H), 4.84 (d, J = 10.7Hz, 1H), 4.91 (d, J =
11.0Hz, 2H), 7.28-7.42 (m, 15H).
13C NMR (125 MHz, CDCl3): δ= 13.4, 35.2, 39.1, 72.9, 73.5, 75.9, 78.8, 85.8, 86.2, 127.67,
127.7, 127.8, 128.1, 128.2, 128.35, 128.4, 128.5, 137.8, 138.4, 138.5, 206.8.
[α]20D -39.8 (c 0.46, CHCl3).
HRMS m/z Calculated for [M+Na]+. C28H30O4Na: 453.2042 found 453.2038.
II.15 (2S,3R,4S,6R)-2,3,4-Trihydroxy-6-methylcyclohexanone (12)
O
HO
OH
OH
To a solution of 9 (200 mg, 0.467 mmol) in absolute ethanol (2.5 mL) was added palladium
on activated carbon (7 mg). The flask was flushed with hydrogen three times and the reaction
mixture was kept under hydrogen for 3 days at RT. When analytical TLC showed the absence
of starting material 9 and reduced cyclohexanone 11, the reaction mixture was filtered
through a pad of silica gel. The filtrate was concentrated to afford pure target molecule 12 as a
white solid (67mg, 90%).
Mp: 108-110°C
1H NMR (300 MHz, MeOD): δ = 0.96 (d, J = 6.5Hz, 3H), 1.18 (dt, J = 13.2, 11.5, Hz, 1H),
2.07 (dt, J =13.0, 5.0Hz, 1H), 2.56 (ddq, J = 5.5, 10.3, 6.5Hz, 1H), 3.15 (dd, J = 9.3, 9.7Hz,
1H), 3.79 (ddd, J = 4.7, 9.0, 11.5Hz, 1H), 3.98 (dd, 10.0, 1.4Hz).
13C NMR (75 MHz, MeOD): δ= 13.9, 39.0, 40.2, 71.8, 79.4, 81.4, 210.3.
[α]20D -107.8 (c 0.4, CHCl3).
HRMS m/z Calculated for [M]+. C7H12O4: 160.0735 found 160.0743.
11