Diastereoselective photodeconjugation of chiral α,β-unsaturated esters

Article abstract of DOI:10.1016/S0957-4166(01)00226-9

Chiral alcohols available in both enantiomeric forms have been tested for the diastereoselective photochemical deconjugation of 2,4-dimethylpentenoic acid esters. (R)-Pantolactone afforded selectively the (2R)-β,γ-unsaturated ester in good yield and high d.e. (89%), while analogous use of (S)-pantolactone gave the (2S)-stereoisomer with similar selectivity.

Full text of DOI:10.1016/S0957-4166(01)00226-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1389–1394
Diastereoselective photodeconjugation of chiral
a,b-unsaturated esters
Fre´de´ric Bargiggia and Olivier Piva*
Laboratoire de Chimie Organique, Photochimie et Synthe`se, UMR CNRS 5622, Universite´ Claude Bernard, Lyon I,
43, Bd du 11 novembre 1918, 69622 Villeurbanne, France
Received 10 May 2001; accepted 16 May 2001
Abstract—Chiral alcohols available in both enantiomeric forms have been tested for the diastereoselective photochemical
deconjugation of 2,4-dimethylpentenoic acid esters. (R)-Pantolactone afforded selectively the (2R)-b,g-unsaturated ester in good
yield and high d.e. (89%), while analogous use of (S)-pantolactone gave the (2S)-stereoisomer with similar selectivity. © 2001
Elsevier Science Ltd. All rights reserved.
1. Introduction
efficient chiral compound to answer to this purpose, we
tested the optically active and commercially available
alcohols 2a–2d. These compounds were esterified with
2,4-dimethyl-2-pentenoic acid 1 by the standard DCC
esterification procedure,4 which furnished substrates
3a–3d in moderate to good yields (Scheme 2).
Some years ago, we reported a useful and highly
diastereoselective procedure to prepare a-substituted
b,g-unsaturated esters from a,b-unsaturated isomers
under UV activation. We found that diacetone
D-glu-
cose (R*OH) was an effective chiral auxiliary for this
photochemical transformation1a and the reaction was,
therefore, applied to the synthesis of a number of
natural products.2
Irradiation of the conjugated esters was performed at
−40°C in the presence of (achiral) 2-(N,N-dimethyl-
amino)ethan-1-ol. The reaction was efficient with esters
3a–3c and furnished esters 4a–4c in yields of >80%
(Table 1). In contrast, compound 3d slowly degraded
after a long irradiation period, which could be con-
nected to the presence of the sulfonamide functionality
which is cleaved under photochemical activation.5
The success of this method was based on the stereose-
lective protonation of a prochiral photodienol interme-
diate. In the case of diacetone D-glucose derivatives, the
5,6-isopropylidene group shielded one face of the dienol
intermediate P and, therefore, protonation by an achi-
ral b-aminoalcohol took place at the less hindered face1
The diastereoselectivities were difficult to estimate
directly for esters 4a and 4b. In contrast, the d.e. for 4c
was easily measured from the 1H NMR spectrum of the
crude compound and determined as 88%. However, the
diastereoselectivities for 4a and 4b could be readily
(Scheme 1). Because diacetone L-glucose is not readily
available,3 this diastereoselective method was not to
date able to afford compounds with the opposite
configuration at C(2). In order to find a cheap and
O-R*
O
O
O-R*
R2
R1
R1
R1
OH
R2
N
OH
O
HO
O
OR*
hυ
*
R3
R2
CH2Cl2
-40°C
O
(1 equiv.)
R*OH =
O
O
R3
R3
P
d.e. >95%
Scheme 1.
* Corresponding author. E-mail: piva@univ-lyon1.fr
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00226-9

1390
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 12 (2001) 1389–1394
Scheme 2.
Table 1. Preparation and irradiation of esters 3
Alcohol 2
Ester 3
Yield (%) (E)/(Z)
Ester 4
Yield (%)
D.e. (%)
2a
2b
2c
2d
3a
3b
3c
3d
85 (55/45)
77 (65/35)
48 (72/28)
30 (7/3)
4a
4b
4c
4d
81
81
82
33
85a
83a
88
67
a D.e. measured on saturated ester 5.
determined after reduction of the isolated CꢀC bond by
hydrogenation over PtO2 and a d.e. of 85% for 5a and
83% for 5b were established. The absolute configuration
of the new stereogenic center was unambiguously deter-
compounds 5a–5c without significant levels of induc-
tion) (Table 2).
By using the three chiral alcohols 2a–2c, we obtained
the same (R)-configuration, already observed with the
diacetone D-glucose moiety. Fortunately, among these
three alcohols, the presence of a single stereogenic
center in 2c allows easy preparation of the enantiomeric
form (S)-2c. Recent published procedures7,8 based on a
Mitsunobu reaction9 can effectively furnish this
compound. Therefore, the (2S)-deconjugated ester
mined by
a
free racemization transesterification
process6 of esters 5a–5c with benzyl alcohol to the same
ester 6 (Scheme 3). By simple comparison of the specific
rotation of 6 with literature data,1a we were able
to establish the absolute configuration of the newly
created stereogenic center (it should be noted that
conjugated esters 3a–3c were also directly reduced to
H2, PtO2
ether
Ti(Oi-Pr)4
O-R*
OBn
O-R*
*
*
BnOH
O
O
O
∆
3a-3c
4a-4c
or
6
5a-5c
Scheme 3.
Table 2. Access to chiral esters 5
Substrate
Yield of 5 (%)
D.e. (%)
Benzyl ester 6
Config.
3a
4a
3b
4b
3c
4c
66
71
92
84
85
95
15
85
5
83
4
Not det.
(R)
Not det.
(R)
Not det.
(R)
40% ([h]D=−6.4 (c 0.2, CH2Cl2))
88% ([h]D=−6.6 (c 0.9, CH2Cl2))
75% ([h]D=−8.0 (c 0.7, CH2Cl2))
89

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 12 (2001) 1389–1394
1391
(S)-4c can be prepared by simple switching of one
(m, 1H), 4.20–4.05 (m, 2H), 3.95 (d, J=5.1 Hz, 1H),
3.80 (d, J=9.5 Hz, 1H), 2.64 (dh, J=9.5 Hz, J=6.6
Hz, 1H), 1.86 (d, J=1.5 Hz, 3H), 1.60 (s, 3H), 1.49 (s,
3H), 1.39 (s, 3H), 1.37 (s, 3H), 0.99 (d, J=6.6 Hz, 6H).
13C NMR (75.45 MHz, CDCl3): l 167.6 (C), 150.5
(CH), 124.7 (C), 111.9 (C), 109.5 (C), 75.1 (CH), 74.9
(CH), 73.7 (2CH), 71.6 (CH2), 69.9 (CH), 27.9 (CH3),
27.8 (CH), 26.0 (CH3), 22.6 (CH3), 21.8 (CH3), 20.6
(CH3), 12.2 (2CH3). (Z)-Isomer: l 5.78 (dq, J=10.3
Hz, J=1.5 Hz, 1H), 5.22 (d, J=8.1 Hz, 1H), 4.4–4.3
(m, 1H), 4.28–4.21 (m, 1H), 4.20–4.05 (m, 2H), 3.98 (d,
J=5.1 Hz, 1H), 3.84 (d, J=9.5 Hz, 1H), 3.30 (dh,
J=10.3 Hz, J=5.14 Hz, 1H), 1.91 (d, J=1.5 Hz, 3H),
1.57 (s, 3H), 1.49 (s, 3H), 1.38 (s, 3H), 1.36 (s, 3H), 1.02
(d, J=5.1 Hz, 6H). 13C NMR (75.45 MHz, CDCl3): l
167.1 (C), 151.4 (CH), 124.0 (C), 112.0 (C), 103.9 (C),
75.1 (CH), 74.9 (CH), 73.7 (2CH), 69.9 (CH), 60.3
(CH2), 28.8 (CH3), 27.7 (CH), 26.0 (CH3), 22.6 (CH3),
21.8 (CH3), 20.6 (CH3), 12.2 (2CH3). IR (E+Z): 2980,
2960, 2940, 2870, 1720, 1650, 1460, 1370 cm−1. (E)-Iso-
mer [h]2D1=−115 (c 1.0, CH2Cl2). (Z)-Isomer [h]2D1=−98
(c 0.1, CH2Cl2). MS: m/z: 371 (M+H+), 313, 111.
HRMS: [C19H30O7+H]+ requires: 371.20697. Found:
371.20705. UV (CH2Cl2): m238=2400.
pantolactone enantiomer for the other as detailed in
Scheme 4.
2. Conclusion
In summary, new chiral alkoxy groups have been suc-
cessfully tested for the diastereoselective photodeconju-
gation of 2,4-dimethyl-2-pentenoate esters. Of the
alcohols studied the pantolactonyl group is the most
suitable alcohol to obtain both (S)- and (R)-a-alkylated
acid derivatives with high selectivity.
3. Experimental
1H and 13C NMR spectra were recorded in CDCl3
using a Bruker AM 300 or DRX 500 instrument.
FT-IR were recorded on a Perkin–Elmer Spectrum
One. Optical rotations were measured on a Perkin–
Elmer 343 polarimeter. Mass spectra were obtained on
a Finigan-MAT 95 XL instrument. Flash chromatogra-
phy was performed on silica gel 60 (40–63 mesh).
3.1. General procedure for esterification reactions
To a solution of 2,4-dimethyl-2-pentenoic acid 1 (0.628
g, 3.3 mmol) in methylene chloride (10 mL) was added
DMAP (0.134 g, 1.1 mmol) followed by the chiral
alcohol 2a–2d (3.3 mmol). The reaction mixture was
cooled to 0°C and a solution of dicyclohexylcarbodi-
imide (0.678 g, 3.3 mmol) in CH2Cl2 (1.5 mL) was
added dropwise. After stirring the mixture for 5 min at
0°C, the cooling bath was removed and the mixture
stirred overnight at rt. Urea was filtered off and the
solvent removed by evaporation under reduced pres-
sure. Purification of the crude product by flash chro-
matography on silica (eluent: AcOEt/hexanes: 1/9)
afforded ester 3.
3.1.2. (1R,2S)-trans-2-Phenyl-1-cyclohexyl 2,4-dimethyl-
2-pentenoate 3b. Yield: 77%; (E)/(Z)=65/35. (E)-Iso-
mer: 1H NMR (300 MHz, CDCl3): l 7.30–7.10 (m, 5H),
6,24 (dq, J=9.5 Hz, J=1.5 Hz, 1H), 4.92 (dt, J=10.3
Hz, J=4.4 Hz, 1H), 2.74 (dt, J=10.8 Hz, J=3.7 Hz,
1H), 2.48 (dh, J=9.5 Hz, J=6.6 Hz, 1H), 1.60 (d,
J=1.5 Hz, 3H), 2.4–2.1 (m, 2H), 2.00–1.70 (m, 2H),
1.70–1.30 (m, 4H), 0.93 (d, J=6.6 Hz, 3H), 0.89 (d,
J=6.6 Hz, 3H). 13C NMR (75.45 MHz, CDCl3): l
167.9 (C), 148.3 (CH), 143.3 (C), 128.8 (C), 128.14
(2CH), 127.5 (2CH), 126.2 (CH), 76.6 (CH), 50.0 (CH),
33.5 (CH2), 32.3 (CH2), 27.6 (CH3), 25.9 (CH2), 24.8
(CH2), 21.8 (CH), 12.0 (2CH3). IR: 2930, 2860, 1710,
1650, 1450, 1250, 1160, 1090, 750, 700 cm−1. [h]D21=−66
(0.1, CHCl3). (Z)-Isomer: 1H NMR (300 MHz, CDCl3):
l 7.30–7.10 (m, 5H), 5.43 (dq, J=9.5 Hz, J=1.5 Hz,
1H), 5.07 (dt, J=10.3 Hz, J=4.4 Hz, 1H), 2.80–2.60
(m, 2H), 1.60 (d, J=1.5 Hz, 3H), 2.40–1.00 (m, 8H),
3.1.1. (1,2;4,5-Di-O-isopropyliden-a-D-fructopyranose-3-
O-yl) 2,4-dimethyl-2-pentenoate 3a. Yield: 85% (E)/
1
(Z)=55/45). Mp: 96°C. H NMR (CDCl3, 300 MHz):
(E)-Isomer: l 6.70 (dq, J=9.5 Hz, J=1.47 Hz, 1H),
5.21 (d, J=8.1 Hz, 1H), 4.40–4.30 (m, 1H), 4.28–4.21
O
(R)
hυ
CH2Cl2, -40 °C
O
*
O
R*OH = (R)-2c
O
(R)-4c
N
OH
[α]D21 = -74 (c 1.0, CH2Cl2)
O-R*
hυ
CH2Cl2, -40 °C
O
O
3c/ent-3c
(S)
O
R*OH = (S)-2c
*
O
N
OH
O
(S)-4c
[α]D21 = +78 (c 1.0, CH2Cl2)
Scheme 4.

1392
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 12 (2001) 1389–1394
0.81 (d, J=6.6 Hz, 3H), 0.77 (d, J=6.6 Hz, 3H). 13C
NMR (75.45 MHz, CDCl3): l 167.9 (C), 147.5 (CH),
143.3 (C), 128.8 (C), 128.7 (2CH), 127.9 (2CH), 125.5
(CH), 74.3 (CH), 53.2 (CH), 34.4 (CH2), 33.3 (CH2),
27.7 (CH3), 26.0 (CH2), 25.0 (CH2), 21.8 (CH), 12.0
(2CH3). IR: 2930, 2860, 1720, 1650, 1450, 1230, 1160,
700 cm−1. [h]D21=−22 (c 1.0, CH2Cl2). UV (CH2Cl2):
m236=2350. MS (E)+(Z): m/z: 288 (M+H+), 158, 111,
91, 83. HRMS: [C19H27O2]+ requires: 287.20110.
Found: 287.20125.
starting material (thin-layer chromatography control),
the solvent was removed by concentration. The decon-
jugated ester was purified by flash chromatography
(eluent: AcOEt/petrol ether: 5/95).
3.2.1. (1,2;4,5-Di-O-isopropyliden-a-D-fructopyranose-3-
O-yl) 2,4-dimethyl-3-pentenoate 4a. Yield: 81%. 1H
NMR (300 MHz, CDCl3): l 5.20 (d, J=8.8 Hz, 1H),
5.10 (d, J=7.3 Hz, 1H), 4.30–4.18 (m, 2H), 4.13–4.07
(m, 2H), 3.93 (d, J=9.5 Hz, 1H), 3.76 (d, J=8.8 Hz,
1H), 3.38 (dq, J=8.8 Hz and 6.6 Hz, 1H), 1.70 (s, 3H),
1.65 (s, 3H), 1.54 (s, 3H), 1.48 (s, 3H), 1.41 (s, 3H), 1.35
(s, 3H), 1.26 (d, J=6.6 Hz, 3H). 13C NMR (75.45
MHz, CDCl3): l 174.8 (C), 134.4 (C), 123.3 (CH), 111.8
(C), 109.5 (C), 103.7 (C) 74.8 (CH), 73.6 (CH), 71.6
(CH2), 71.6 (CH2), 69.9 (CH), 39.1 (CH), 27.7 (CH3),
26.3 (CH3), 26.3 (CH3), 26.0 (CH3), 25.6 (CH3), 18.2
3.1.3. (3R)-(−)-(4,4−Dimethyl-2-oxotetrahydrofuran-3-
yl) 2,4-dimethyl-2-pentenoate 3c. Yield: 48%; (Z)/(E)=
1
28/72. (E)-Isomer: H NMR (300 MHz, CDCl3): l 6.71
(dq, J=9.5 Hz, J=1.5 Hz, 1H), 5.44 (s, 1H), 4.08 (d,
J=8.8 Hz, 1H), 4.05 (d, J=8.8 Hz, 1H), 2.68 (dh,
J=9.6 Hz, J=1.5 Hz, 1H), 1.89 (d, J=1.5 Hz, 3H),
1.23 (s, 3H), 1.15 (s, 3H), 1.05 (d, J=1.5 Hz, 3H), 1.03
(J=1.5 Hz, 3H). 13C NMR (75.45 MHz, CDCl3): l
173.9 (C), 172.1 (C), 134.7 (C), 122.8 (CH), 76.0 (CH2),
74.6 (CH), 40.0 (C), 38.6 (CH3), 25.4 (CH), 22.8 (CH3),
19.6 (CH3), 18.0 (CH3), 17.9 (CH3). (Z)-Isomer: 1H
NMR (300 MHz, CDCl3): l 5.86 (dq, J=10.0 Hz,
J=1.5 Hz, 1H), 5.46 (s, 1H), 4.07 (s, 1H), 4.06 (s, 1H),
3.30 (dh, J=10.0 Hz, J=1.5 Hz, 1H), 1.94 (d, J=1.5
Hz, 3H), 1.23 (s, 3H), 1.15 (s, 3H), 1.02 (d, J=1.5 Hz,
3H), 1.00 (J=1.5 Hz, 3H). IR: 2970, 2930, 2870, 1790,
1720, 1650, 1470, 1370, 1240, 1150, 1100 cm−1. UV
(CH2Cl2): m238=2460. (E)-Isomer [h]2D1=+6 (c 1.0,
CH2Cl2). (Z)-Isomer [h]2D1=+7 (c 0.1, CH2Cl2). MS:
+
21
’
(CH3), 18.0 (CH3). MS m/z: 371 (M +1), 313. [h]D =
−17 (c 1.0, CH2Cl2). UV (CH2Cl2): m232=1690. HRMS:
[C19H30O7+H]+ requires: 371.20697. Found: 371.20696.
3.2.2.
(1R,2S)-trans-2-Phenyl-1-cyclohexyl
4b. Yield: 81%.
2,4-
Major
dimethylpent-3-enoate
1
diastereoisomer: H NMR (300 MHz, CDCl3): l 7.30–
7.10 (m, 5H), 4.97 (dt, J=11.0 Hz, J=4.4 Hz, 1H),
4.74 (dh, J=8.8 Hz, J=1.5 Hz, 1H), 3.02 (dq, J=8.8
Hz, J=6.6 Hz, 1H), 2.67 (dt, J=11.0 Hz, J=3.7 Hz,
1H), 1.53 (s, 3H), 1.37 (d, J=1.5 Hz, 3H), 2.2–1.7 (m,
4H), 1.7–1.3 (m, 4H), 0.92 (d, J=6.6 Hz, 3H). 13C
NMR (75.45 MHz, CDCl3): l 174.4 (C), 143.0 (C),
133.3 (C), 128.0 (CH), 127.3 (2CH), 126.0 (2CH), 123.6
(CH), 75.2 (CH), 49.7 (CH), 38.8 (CH), 34.1 (CH2),
32.1 (CH2), 25.7 (CH2), 25.4 (CH3), 24.6 (CH2), 17.5
+
+
’
m/z: 240 (M +1), 128, 111, 83. HRMS [C13H20O4]
requires: 240.13615. Found: 240.13618.
1
(CH3), 17.4 (CH3). Minor diastereoisomer: H NMR
(300 MHz, CDCl3): l 7.30–7.10 (m, 5H), 4.97 (dt,
J=11.0 Hz, J=4.4 Hz, 1H), 4.74 (dh, J=8.8 Hz,
J=1.5 Hz, 1H), 3.02 (dq, J=11.0 Hz, J=6.6 Hz, 1H),
2.67 (dt, J=11.0 Hz, J=3.7 Hz, 1H), 1.53 (s, 3H), 1.37
(d, J=1.5 Hz, 3H), 2.2–1.7 (m, 4H), 1.7–1.3 (m, 4H),
0.89 (d, J=6.6 Hz, 3H). IR: 2930, 2860, 1730, 1450,
1170, 700 cm . MS: m/z: 286 (M ), 175, 158, 111, 91,
83. [h]2D1=−11 (c 1.0, CH2Cl2). HRMS: [C19H26O2+H]+
requires: 287.20115. Found: 287.20111.
3.1.4. (−)-1-[(Dicyclohexylsulfonamoyl)-methyl]-7,7-di-
methyl-bicyclo[2.2.1]hept-2-yl 2,4-dimethyl-2-pentenoate
3d. Yield: 30%; (E)/(Z)=7/3. (E)-Isomer: 1H NMR
(300 MHz, CDCl3): l 6.71 (d, J=9.5 Hz, 1H), 4.09 (dd,
J=7.3 Hz, J=4.4 Hz, 1H), 3.40–3.20 (m, 3H), 2.69 (s,
1H), 2.64 (s, 1H), 2.00–1.50 (m, 27H), 1.50–1.20 (m,
−1
+
’
1
4H), 1.20–1.00 (m, 8H), 0.80 (s, 3H). (Z)-Isomer: H
NMR (300 MHz, CDCl3): l 5.10 (d, J=9.5 Hz, 1H),
4.09 (dd, J=7.3 Hz, J=4.4 Hz, 1H), 2.69 (s, 1H), 2.64
(s, 1H), 2.8–2.5 (m, 1H), 2.00–1.50 (m, 27H), 1.50–1.20
(m, 4H), 1.20–1.00 (m, 8H), 0.80 (s, 3H). UV (CH2Cl2):
m238=2320. MS: m/z: 507, 464, 397, 380, 327, 245, 181,
138, 111. (E)-Isomer [h]2D1=−25 (c 1.0, CH2Cl2). (Z)-
Isomer [h]2D1=−0.4 (c 1.0, CH2Cl2). HRMS
[C29H49NO4S]+ requires: 507.33823. Found: 507.33869.
3.2.3. (3R)-(−)-(4,4-Dimethyl-2-oxotetrahydrofuran-3-yl)
2,4-dimethyl-3-pentenoate 4c. Yield: 82% (d.e.=87.5%
1
according to H NMR). Major diastereoisomer (2R):
1H NMR (300 MHz, CDCl3): l 5.33 (s, 1H), 5.19 (dtt,
J=9.5 Hz, J=1.5 Hz and 1.5 Hz, 1H), 4.04 (d, J=8.8
Hz, 1H), 4.01 (d, J=8.8 Hz, 1H), 3.46 (dq, J=9.6 Hz,
J=6.6 Hz, 1H), 1.73 (d, J=1.5 Hz, 3H), 1.67 (d, J=1.5
Hz, 3H), 1.29 (d, J=6.6 Hz, 3H), 1.19 (s, 3H), 1.10 (s,
3H). 13C NMR (75.45 MHz, CDCl3): l 174.0 (C), 172.2
(C), 134.8 (C), 122.8 (CH), 76.0 (CH2), 74.6 (CH), 40.1
(C), 38.6 (CH), 25.5 (CH3), 22.9 (CH3), 19.7 (CH3),
18.1 (CH3), 18.0 (CH3). 13C NMR (75.45 MHz,
CDCl3): l 174.0 (C), 172.2 (C), 134.8 (C), 122.8 (CH),
76.0 (CH2), 74.6 (CH), 40.1 (C), 38.6 (CH), 25.5 (CH3),
22.9 (CH3), 19.7 (CH3), 18.1 (CH3), 18.0 (CH3). Minor
3.2. General procedure for irradiation of a,b-
unsaturated esters
To a solution of the ester 3 (10 mmol) in methylene
chloride
(100
mL)
was
added
N,N-
dimethylethanolamine. The resulting solution first
deoxygenated by a stream of nitrogen for 10 min was
poured into 12 mm diameter quartz tubes which were
fitted with septa and placed around a transparent
quartz Dewar equipped with a short wavelength
OSRAM lamp (u=254 nm). The irradiation was car-
ried out at −40°C. After total disappearance of the
1
diastereoisomer (2S): H NMR (300 MHz, CDCl3): l
5.35 (s, 1H), 5.19 (dtt, J=9.5 Hz, J=1.5 Hz and 1.5
Hz, 1H), 4.04 (d, J=8.8 Hz, 1H), 4.01 (d, J=8.8 Hz,
1H), 3.46 (dq, J=9.6 Hz, J=6.6 Hz, 1H), 1.73 (d,

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 12 (2001) 1389–1394
1393
J=1.5 Hz, 3H), 1.70 (d, J=1.5 Hz, 3H), 1.29 (d, J=6.6
Hz, 3H), 1.19 (s, 3H), 1.10 (s, 3H). 13C NMR (75.45
MHz, CDCl3): l 174.0 (C), 172.2 (C), 134.8 (C), 123.2
(CH), 76.0 (CH2), 74.6 (CH), 40.1 (C), 38.5 (CH), 25.5
(CH3), 22.8 (CH3), 19.5 (CH3), 18.1 (CH3), 17.4 (CH3).
IR: 2970, 2930, 2880, 1790, 1750, 1460, 1380, 1150,
1090 cm . MS (m/z): 240 (M ), 110, 83. UV (CH2Cl2):
m229=890. [h]2D1=−74 (c 1.0, CH2Cl2). HRMS:
[C12H20O3]+ requires: 241.14398. Found: 241.14359.
MHz, CDCl3): l 5.12 (d, J=7.4 Hz, 1H), 4.30–4.24 (m,
1H), 4.23–4.18 (m, 1H), 4.13–4.07 (m, 2H), 3.93 (d,
J=9.5 Hz, 1H), 3.80 (d, J=9.5 Hz, 1H), 2.59 (tq,
J=7.4 Hz, J=6.6 Hz, 1H), 1.70–1.55 (m, 2H), 1.53 (s,
3H), 1.47 (s, 3H), 1.41 (s, 3H), 1.35 (s, 3H), 1.30–1.10
(m, 1H), 1.18 (d, J=6.6 Hz, 3H), 0.90 (d, J=6.6 Hz,
3H), 0.88 (d, J=5.9 Hz, 3H). 13C NMR (75.45 MHz,
CDCl3): l 176.5 (C), 111.8 (C), 109.5 (C), 103.8 (C)
74.8 (CH), 73.8 (CH), 71.8 (CH2), 69.8 (CH), 60.5
(CH2), 42.7 (CH2), 37.6 (CH), 27.7 (CH3), 26.4 (CH3),
26.2 (CH3), 26.2 (CH3), 25.7 (CH3), 22.5 (CH3), 22.3
(CH3), 17.3 (CH3). IR: 2980, 2960, 2940, 2900, 1730,
1460, 1460, 1380, 1220, 1080 cm−1. MS: m/z: 373
−1
+
’
3.2.4. (−)-1-[(Dicyclohexylsulfonamoyl)-methyl]-7,7-di-
methyl-bicyclo[2.2.1]hept-2-yl,2,4-dimethylpent-3-enoate
4d.
+
’
21
(M +1), 315. [h]D =−13 (c 1.0, CH2Cl2). HRMS:
[C19H32O7+H]+ requires: 373.22262. Found: 373.22297.
Yield: 33% (d.e.=67%).
1
3.3.2.
(1R,2S)-trans-2-Phenyl-1-cyclohexyl
2,4-
Major diastereoisomer: H NMR (300 MHz, CDCl3): l
dimethylpentanoate 5b.
5.20 (d, J=8.8 Hz, 1H), 4.89 (dd, J=8.1 Hz, J=3.7
Hz, 1H), 3.40–3.10 (m, 3H), 2.67 (d, J=5.9 Hz, 1H),
2.63 (d, J=5.9 Hz, 1H), 1.71 (s, 3H), 1.62 (s, 3H),
2.00–1.50 (m, 21H), 1.50–1.00 (m, 9H), 0.98 (s, 3H),
0.88 (s, 3H). Minor diastereoisomer: 1H NMR (300
MHz, CDCl3): l 5.09 (d, J=8.8 Hz, 1H), 4.89 (dd,
J=8.1 Hz, J=3.7 Hz, 1H), 4.20–4.00 (m, 1H), 3.40–
3.10 (m, 2H), 2.67 (d, J=5.9 Hz, 1H), 2.63 (d, J=5.9
Hz, 1H), 1.71 (s, 3H), 1.62 (s, 3H), 2.00–1.50 (m, 21H),
1.50–1.00 (m, 9H), 0.98 (s, 3H), 0.88 s, 3H). IR: 3520,
2930, 2860, 1730, 1650, 1450, 1330, 1170, 1140, 1050
From 3b: Yield: 92% (d.e.=5%)
From 4b: Yield: 84% (d.e.=83%)
1
Major diastereoisomer: H NMR (300 MHz, CDCl3): l
7.30–7.10 (m, 5H), 4.99 (dt, J=10.3 Hz, J=4.4 Hz,
1H), 2.68 (dd, J=11.8 Hz, J=3.7 Hz, 1H), 2.64 (dd,
J=10.3 Hz, J=3.7 Hz, 1H), 2.20 (tq, J=6.6 Hz, J=2.2
Hz, 1H), 2.20–2.10 (m, 1H), 2.00–1.70 (m, 3H), 1.70–
1.00 (m, 6H), 0.86 (d, J=7.3 Hz, 3H), 0.65 (d, J=6.6
Hz, 3H), 0.60 (d, J=6.6 Hz, 3H). 13C NMR (75.45
MHz, CDCl3): l 176.2 (C), 143.1 (C), 128.1 (2CH),
127.5 (2CH), 126.2 (CH), 75.2 (CH), 49.9 (CH), 42.8
(CH2), 37.5 (CH), 34.1 (CH2), 32.2 (CH2), 25.7 (CH2),
25.4 (CH3), 24.6 (CH2), 22.4 (CH), 22.0 (CH3), 17.2
(CH3). Minor diastereoisomer: 1H NMR (300 MHz,
CDCl3): l 7.30–7.10 (m, 5H), 4.98 (dt, J=10.3 Hz,
J=4.4 Hz, 1H), 2.68 (dd, J=11.8 Hz, J=3.7 Hz, 1H),
2.64 (dd, J=10.3 Hz, J=3.7 Hz, 1H), 2.20 (dq, J=6.6
Hz, J=2.2 Hz, 1H), 2.20–2.10 (m, 1H), 2.01–1.70 (m,
3H), 1.70–1.00 (m, 6H), 0.76 (d, J=6.6 Hz, 3H), 0.72
(d, J=6.6 Hz, 3H), 0.69 (d, J=5.9 Hz, 3H). 13C NMR
(75.45 MHz, CDCl3): l 176.0 (C), 143.1 (C), 128.0
(2CH), 127.4 (2CH), 126.2 (CH), 75.1 (CH), 49.9 (CH),
42.5 (CH2), 37.7 (CH), 34.0 (CH2), 32.2 (CH2), 25.7
(CH2), 25.4 (CH3), 24.6 (CH2), 22.6 (CH), 22.0 (CH3),
17.4 (CH3). IR: 2930, 2860, 1730, 1450, 1180, 730 cm−1.
−1
+
’
cm . MS: m/z: 507 (M +1), 380, 327, 246, 181, 135,
83. HRMS: [C29H49NO4S+H]+ requires: 508.34605.
Found: 508.34628.
3.3. General procedure for hydrogenation of a,b-unsatu-
rated esters 3a–3c and deconjugated isomers 4a–4c
A solution of ester 3 or 4 (3 mmol) in ether (15 mL)
was reduced over PtO2 with hydrogen under 1 atm
within 3 hours. After filtration over Celite and washing
with ether, compound 5 (0.40 g, 0.92 mmol) was iso-
lated as an oil and purified by flash chromatography
(eluent: AcOEt/hexanes: 1/19).
3.3.1. (1,2;4,5-Di-O-isopropyliden-a-
O-yl) 2,4-dimethylpentanoate 5a.
D-fructopyranose-3-
21
+
’
[h]D =−28 (c 1.0, CHCl3). MS: m/z: 289 (M +1), 159.
HRMS: [C19H28O2+H]+ requires: 289.21675. Found:
289.21639.
From 3a: Yield: 66% (d.e.=15% according to 13C
NMR).
From 4a: Yield: 71% (d.e.=85% according to 13C
NMR).
3.3.3. (3R)-(−)-(4,4-Dimethyl-2-oxotetrahydrofuran-3-yl)
2,4-dimethylpentanoate 5c.
Major diastereoisomer (2R): 1H NMR (300 MHz,
CDCl3): l 5.12 (d, J=8.1 Hz, 1H), 4.30–4.24 (m, 1H),
4.23–4.18 (m, 1H), 4.13–4.07 (m, 2H), 3.93 (d, J=9.5
Hz, 1H), 3.80 (d, J=9.5 Hz, 1H), 2.59 (tq, J=7.4 Hz,
J=6.6 Hz, 1H), 1.70–1.55 (m, 2H), 1.53 (s, 3H), 1.47 (s,
3H), 1.41 (s, 3H), 1.35 (s, 3H), 1.30–1.10 (m, 1H), 1.18
(d, J=6.6 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H), 0.87 (d,
J=5.9 Hz, 3H). 13C NMR (75.45 MHz, CDCl3): l
176.5 (C), 111.8 (C), 109.5 (C), 103.8 (C) 74.8 (CH),
73.8 (CH), 71.8 (CH2), 69.8 (CH), 60.5 (CH2), 42.6
(CH2), 37.6 (CH), 27.7 (CH3), 26.4 (CH3), 26.2 (CH3),
26.2 (CH3), 25.7 (CH3), 22.5 (CH3), 22.3 (CH3), 17.5
(CH3). Minor diastereoisomer (2S): 1H NMR (300
From 3c: Yield: 85% (d.e.=4%)
From 4c: Yield: 95% (d.e.=89%)
Major diastereoisomer (2R): 1H NMR (300 MHz,
CDCl3): l 5.36 (s, 1H), 4.05 (J=8.8 Hz, 1H), 4.02 (d,
J=8.8 Hz, 1H), 2.68 (tq, J=6.6 Hz, J=6.6 Hz, 1H),
2.80–2.60 (m, 2H), 1.22 (d, J=6.6 Hz, 3H), 1.20 (s,
3H), 1.12 (s, 3H), 1.40–1.20 (m, 1H), 0.93 (d, J=5.9
Hz, 3H), 0.90 (d, J=5.9 Hz, 3H). 13C NMR (75.45
MHz, CDCl3): l 175.6 (C), 172.2 (C), 75.9 (CH2), 74.4
(CH), 42.6 (CH2), 40.0 (C), 37.3 (CH), 25.6 (CH), 22.8
(CH3), 22.2 (2CH3), 19.7 (CH3), 17.4 (CH3). Minor

1394
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 12 (2001) 1389–1394
1
diastereoisomer (2S): H NMR (300 MHz, CDCl3): l
5.37 (s, 1H), 4.05 (J=8.86 Hz, 1H), 4.02 (d, J=8.8 Hz,
1H), 2.55 (tq, J=6.6 Hz, J=6.6 Hz, 1H), 2.80–2.60 (m,
2H), 1.22 (d, J=6.6 Hz, 3H), 1.20 (s, 3H), 1.12 (s, 3H),
1.40–1.20 (m, 1H), 0.92 (d, J=5.9 Hz, 3H), 0.89 (d,
J=5.9 Hz, 3H). 13C NMR (75.45 MHz, CDCl3): l
175.6 (C), 172.2 (C), 75.9 (CH2), 74.4 (CH), 42.7 (CH2),
40.0 (C), 37.3 (CH), 25.8 (CH), 22.8 (CH3), 22.3
(2CH3), 19.8 (CH3), 17.4 (CH3). IR: 2960, 2940, 2880,
References
1. (a) Piva, O.; Pete, J.-P. Tetrahedron: Asymmetry 1992, 3,
759–768; (b) Mortezaei, R.; Awandi, D.; Henin, F.;
Muzart, J.; Pete, J.-P. J. Am. Chem. Soc. 1988, 110,
4824–4826.
2. (a) Piva, O.; Caramelle, D. Tetrahedron: Asymmetry 1995,
6, 831–832; (b) Piva, O. J. Org. Chem. 1995, 60, 7879–
7883; (c) Comesse, S.; Piva, O. Tetrahedron: Asymmetry
1999, 10, 1061–1067; (d) Faure, S.; Connolly, J. D.;
Fakunle, C. O.; Piva, O. Tetrahedron 2000, 56, 9647–9653.
3. (a) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Chirality
2000, 12, 338–341; (b) Hajko, J.; Liptak, A.; Pozsgay, V.
Carbohydr. Res. 1999, 321, 116–120.
1800, 1750, 1470, 1380, 1150, 1100 cm−1. MS: m/z: 243
(M +1), 113. HRMS: [C12H22O3+H]+ requires:
+
’
243.15963. Found: 243.16024. [h]2D1=−11 (c 1.0,
CH2Cl2).
3.4. Transesterification6 of esters 5 to compound 6
4. Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978,
17, 522–524.
3.4.1. Benzyl 2,4-dimethylpentanoate1a 6. To a solution
of ester 5 (0.60 mmol) in toluene (3 mL) was added
benzyl alcohol (0.63 mL, 6.0 mmol) and titanium(IV)
iso-propoxide (0.18 mL, 0.60 mmol). The resulting
mixture was heated at 120°C until the starting material
completed disappeared. After cooling to rt, the crude
product was directly purified by flash chromatography
(AcOEt/hexanes: 5/95), affording ester 6.
5. Pincock, J. A. In Handbook of Organic Photochemistry and
Photobiology; Horspool, W. M.; Song, P.-S., Eds.; CRC
Press: Boca Raton, 1995; pp. 757–765.
6. (a) Seebach, D.; Hungerbu¨hler, E.; Naef, R.; Schnurren-
berger, P.; Weidmann, B.; Zu¨ger, M. Synthesis 1982, 138–
141; (b) Imwinkelried, R.; Schiess, M.; Seebach, D. In
Organic Synthesis; Vedejs, E., Ed.; Wiley: New York,
1987; pp. 230–235; (c) Fe´re´zou, J. P.; Julia, M.; Liu, L. W.;
Pancrazi, A. Synlett 1991, 614–617.
7. Moriarty, R. M.; Zhuang, H.; Penmasta, P.; Liu, K.;
Awasthi, A. K.; Tuladhar, S. M.; Rao, M. S. C.; Singh, V.
K. Tetrahedron Lett. 1993, 34, 8029–8032.
Acknowledgements
8. Calmes, M.; Daunis, J.; Jacquier, R.; Natt, F. Org. Prep.
F.B. thanks M.R.S. for financial support. O.P.
acknowledges CNRS and Re´gion Rhoˆne-Alpes for sub-
stantial funding, respectively ‘AIP Jeune Equipe 1999–
2001’ and ‘Programme Emergence’.
Proced. Int. 1995, 27, 107–108.
9. (a) Mitsunobu, O. Synthesis 1981, 1–28; (b) Hughes, D. L.
In Organic Reactions; Paquette, L. A., Ed.; Wiley: New
York, 1992; Vol. 42, pp. 335–656.
.