Syn-effect' in the diastereoselective alkylation of 3-[(E)-α,β-unsaturated-γ-substituted]-N-acyloxazolidinones

Article abstract of DOI:10.1016/j.tet.2015.05.037

Synthetic methods for the formation of alkenes usually produce the E-alkene because it is more stable. However, in isomerization reaction (double bond migration) that takes place in α, β-unsaturated carbonyl compounds, when these carbonyl compounds are exposed to strong bases, furnish Z-alkenes highly stereoselective depending on the γ-substituent in the α, β-unsaturated carbonyl. This stereoselectivity can be attributed to the known Syn-effect. The synthetic value of this methodology is the achievement of chiral alcohol bearing an electron rich Z-alkene, as well as substituted, which was accomplished via removal of the oxazolidinone moiety under treatment with NaBH₄, THF-H₂O.

Full text of DOI:10.1016/j.tet.2015.05.037

Tetrahedron 71 (2015) 4590e4597
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
‘Syn-effect’ in the diastereoselective alkylation of 3-[(E)-
a,
b-unsaturated-g-substituted]-N-acyloxazolidinones
a
a
b
a
ꢀ
ꢀ
ꢀ
Jacqueline Jimenez , JuanCarlos Ramírez , Gabriela Huelgas , Ruth Melendrez ,
Blanca M. Cabrera-Vivas a, Estibaliz Sansinenea a , Aurelio Ortiz
Facultad de Ciencias Químicas, Benemerita Universidad Autonoma de Puebla, Pue, 72570, Mexico
,
a,
*
*
a
ꢀ
ꢀ
b
ꢀ
ꢀ
ꢀ
Departamento de Ciencias Químico-Biologicas, Universidad de las Americas-Puebla, Sta Catarina Martir, 72820, Cholula, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthetic methods for the formation of alkenes usually produce the E-alkene because it is more stable.
Received 9 March 2015
Received in revised form 8 May 2015
Accepted 11 May 2015
However, in isomerization reaction (double bond migration) that takes place in
bonyl compounds, when these carbonyl compounds are exposed to strong bases, furnish Z-alkenes
highly stereoselective depending on the -substituent in the -unsaturated carbonyl. This stereo-
selectivity can be attributed to the known Syn-effect. The synthetic value of this methodology is the
achievement of chiral alcohol bearing an electron rich Z-alkene, as well as substituted, which was ac-
complished via removal of the oxazolidinone moiety under treatment with NaBH4, THF-H2O.
Ó 2015 Elsevier Ltd. All rights reserved.
a
,
b
ꢀunsaturated car-
g
a, b
Available online 16 May 2015
Keywords:
Syn effect
Diastereoselective
Alkylation
Oxazolidinones
Cis-Alkenes
1. Introduction
a pseudo p-orbital of
electrons in a p-orbital of a hetero atom at the
The stereochemistry in the conversion of (E)-
esters to the corresponding -unsaturated esters is well ratio-
d
-CH2. Alternatively, there is a lone pair of
-position (Fig. 1).
-unsaturated
d
Isomerization of conjugated
pounds to deconjugated
a
,
b
-unsaturated carbonyl com-
a,b
b
,g
-unsaturated carbonyl compounds has
b,g
been widely studied.1 An important feature of this reaction is that it
produces the thermodynamically less favorable and often difficult
to access Z-alkene with high stereoselectivity. The reaction of
dienolates derived from
electrophiles, such as proton or alkyl halide, often affords
substituted
-unsaturated carbonyl compounds.1 Chiral lithium
dienolates generated from chiral N-enoyl amides undergo allyla-
tion2 and methylation3 at the
-position to afford -substituted
a,b-unsaturated carbonyl compounds with
a
-
b,g
a
a
b,g-
olefinic amides with high diastereo- and Z-selectivity. The cause of
this unexpected stereoselectivity was rationalized by ‘conforma-
tional acidity’, which essentially implies syn-effect.4 In the transition
state for deprotonation of the g-H by strong base it is proposed that
hyperconjugation of developing anion is more effective in the
eclipsed conformations, wherein the developing anion is aligned
Fig. 1. a) Syn effect rationalized by ‘conformational acidity’;
s/p in two conforma-
tions. b) Syn effect rationalized by 6 -electron homoaromaticity.
p
with the
favored because it is stabilized by 6
which involves the developing charge at the
p
*C]C orbital. Furthermore, the syn-transition state is
-electron homoaromaticity,
-position and
p
g
nalized by syn-effect and the relative degree of this depends on the
-substituents, where it has seen that the fluorine atom at this
position favor the highest Z-selectivity, as shown in Fig. 2.
Kobayashi described an efficient method for the stereoselective
construction of chiral quaternary -carbon by regio- and stereo-
selective alkylation of chiral dienolate N-enoyl oxazolidinone.5
g
g-
* Corresponding authors. Tel.: þ52 222 2295500x7518; fax: þ52 222 2295584;
e-mail addresses: estisan@yahoo.com (E. Sansinenea), aurelioom@yahoo.com (A.
Ortiz).
a
http://dx.doi.org/10.1016/j.tet.2015.05.037
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4591
11 as a colorless liquid in 35 and 40% yield, respectively. Despite the
fact that chemical yields are moderate, both starting materials can
be easily recovered and once again subjected to the reaction, as
shown in Scheme 3.
Fig. 2. Relative isomerization’s rate in terms of highest Z-selectivity to lowest Z-
selectivity.
Davies described the synthesis of
a-vinyl-b-hydroxyesters and a-
ethylidene- -hydroxyesters via the dienolate aldol reaction of (E)-
b
N-crotonyl oxazolidinone with high levels of syn-diaster-
eoselectivity.6 We previously described a high Z-selective and
diastereoselective alkylation reaction carried out on chiral N-enoyl
oxazolidinones.7 This highly stereoselective isomerization reaction
has been little exploited for the enantioselective production of
chiral molecules. Therefore, this work presents the obtaining of
chiral alcohols bearing an electron rich Z-alkene from the alkylation
in N-enoyl oxazolidinone followed by removal of oxazolidinone
moiety.
Scheme 3. N-acylation of oxazolidinones.
In contrast to traditional methods (LiHMDS, HMPA, ꢀ78 ꢁC),6
very low temperature (ꢀ78 ꢁC) did not favor the extraction of the
Hg from a,b-unsaturated carbonyl derivative in the compound 8;
however, when 8 was treated with NaHMDS in the presence of LiCl
at ꢀ60 ꢁC for 30 min and subsequent addition of a solution of NH4Cl
led to a migration of the double bond in 95% yield on the conju-
gated 8 to deconjugated 80 in a highly stereoselective manner (Z/
E>95:5). The cis-alkene geometry was established based on the
measurement of coupling constants of vinyl protons in the 1H NMR
spectrum (3J HeH¼6.3 Hz), as shown in Scheme 4.
2. Results and discussion
The (E)-a,b-unsaturated carboxylic acids 3aeb were prepared
according to a methodology described by Han and Ito.8 The ethyl
but-2-ynoate 1 was treated with the respective alcohol, triphenyl
phosphine and a catalytic amount of acetic acid to give the esters
2aeb in good yields. A subsequent basic hydrolysis with LiOH in
THF/H2O8 delivered the acids 3aeb in 90% and 96% yield re-
spectively, as shown in Scheme 1.
Scheme 4. Z-selective Double bond migration.
Scheme 1. Synthesis of (E)-a,b-unsaturated carboxylic acids.
Taking advantage of this high stereoselectivity (Z/E), the N-enoyl
oxazolidinones 8e10 were treated under the reaction conditions
above described to form the corresponding enolates, followed by
addition of iodomethane. The alkylation took place; when the re-
action mixture reached at temperature of ꢀ45 ꢁC, after stirring for
7 h at this temperature, the alkylated compounds 8ae10b were
achieved with high stereoselectivity (Z/E), moderate yields and
The g-(OTBS) substituted (E)-a,b-unsaturated carboxylic acid 7
was achieved via reduction reaction of the mono-ethyl fumarate 4
with BH3-THF 1M to give the compound 5 in good yield,9 followed
by protection of the hydroxyl group with tert-butyldimethylsilyl
chloride.10 A subsequent basic hydrolysis of 6 with NaOH in MeOH
and addition of a solution of 10% KHSO4 delivered the acid 7 in 95%
yield,11 as shown in Scheme 2.
moderate diastereoselectivity at the newly created
center. In all three cases, the like compounds 8ae10a (R,R) were
predominant. Despite the differences in bulkiness of the -sub-
a-stereogenic
g
stituents (OBn, OMe, OTBS) in the N-enoyl oxazolidinones 8e10,
the reaction always led to a high Z-selectivity in the alkylated
products 8ae10b, as shown in Table 1.
The use of other metals on the base (M0HMDS) (M0¼Na, Li) did
not lead to a significant change neither in yields of 8ae8b nor in
stereoselectivity of the reaction. However, the KHMDS provided
the best results. It is noteworthy to mention that the absence of
LiCl in the alkylation reaction led to a fast deacylation of the chiral
auxiliary even at ꢀ78 ꢁC. The presence of LiCl is necessary to
achieve the alkylated products. It is probably due to the formation
of a LiCl complex of the acyloxazolidinone, which produces con-
siderable stabilization. The dienolate was successfully alkylated
with allyl bromide and benzyl bromide to provide the like com-
pounds 12ae13a (R,R)13 in good yields and moderate di-
astereomeric ratios, as shown in Table 2.14 However, the treatment
of the dienolate with ethyl iodide did not produce its respective
alkylated compound, instead leading to isomerized compound 80
(Scheme 4).
Scheme 2. Synthesis of (E)-a,b-unsaturated carboxylic acid.
The g-substituted a,b-unsaturated carboxylic acids 3aeb and 7
were treated with triethylamine and pivaloyl chloride in THF, fol-
lowed by addition of the respective oxazolidinones11 (SuperQuat)12
at 0 ꢁC and after stirring for 18 h at room temperature afforded 8
and 9 as a white solid in 60 and 70% yield, respectively and 10 and

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4592
Table 1
Isomerization and alkylation
Reaction of N-enoyl oxazolidinone 8 with KHMDS and in the
presence of tert-butyldimethylsilyl chloride gave the respective
vinylketene silyl N,O-acetyl 17 in 95% yield. Only one product was
detected by 1H NMR.15 Alkylation reaction of 17 was carried out
with tetrabutyl ammonium fluoride and an excess of MeI in THF to
provide the
a-alkylated product 8a in 75% yield, high Z-selectivity
(Z:E) (>95:5) and with a diastereomeric ratio (80/20). The reaction
was also regioselective, the
as shown in Scheme 5.
g-alkylated product was not detected,
Entry
R
Yielda(%)
Z/Eb
d.r.b a/b
1
2
3
OBn
OMe
OTBS
80
80
60
>95:5
>95:5
>95:5
87/13
85/15
76/24
a
Yield corresponding to purified mixture of diastereomers.
The ratios Z/E and diastereomeric ratios to the new stereogenic centers at C
b
a
were determined by 1H NMR of the crude reaction mixture. E-isomers were not
observed by 1H NMR.
Table 2
Z-selective migration of the double bond and alkylation with different alkyl halides
Scheme 5. Alkylation reaction via vinylketene silyl N,O-acetal.
The stereochemistry at the newly formed chiral center of 8a was
established as R by comparison to the known compounds 19e20.16
Compounds 19e20 were prepared via a sequence of reactions as
described below: hydrogenation of 8a with PdeC in EtOH provided
the compound 18 in quantitative yield, removal of the chiral aux-
iliary with LiOH, H2O2 in THF/H2O17 delivered the carboxylic acid 19
in 80% yield. The alcohol 20 was achieved as a colorless liquid in
83% yield by reduction of 18 with NaBH4 in THF/H2O,18 as shown in
Scheme 6.
Entry
Base
R-X
Yielda(%)
Z/Eb
d.r.b a/b
1
2
3
4
5
NaHMDS
LiHMDS
KHMDS
KHMDS
KHMDS
CH3I
CH3I
AllylBr
BnBr
EtI
74
50
85
85
0
>95:5
>95:5
>95:5
>95:5
0
85/15
83/17
72/28
76/24
0
a
Yield corresponding to purified mixture of diastereomers.
The ratios Z/E and diastereomeric ratios to the new stereogenic center at C
b
a
were determined by 1H NMR of the crude reaction mixture. E-isomers were not
observed by 1H NMR.
The dienolate of the N-enoyl oxazolidinone 11 was treated with
alkyl halides to furnish the like compounds 14ae16a (S,S) as the
major products in moderate yields (50e60%), high diaster-
eoselectivity (98:2) and with high Z-selectivity (Z/E) (>95:5). From
these results, it can be argued that the chiral auxiliary bearing an
isopropyl group provided higher levels of stereocontrol than chiral
auxiliary with phenyl group as substituent in the respective alkyl-
ation reaction of the dienolates, as shown in Table 3.
Scheme 6. Chiral auxiliary removal. Reagent and conditions i) H2, Pd/C, EtOH, 16 h,
25 ꢁC; ii) LiOH, H2O2, THF/H2O 0e25 ꢁC, 90 min, aq. Na2SO3, 1M HCl soln.; iii) NaBH4
THF/H2O 25 ꢁC 3 h.
Table 3
Removal of the chiral auxiliary under Evans’ experimental
conditions in the compound 8a led to a diastereomeric mixture of
liquid
Z-Selective migration of double bond and highly diastereoselective alkylation
g
-lactones19 21aeb in 80% yield and with d.r. 70:30. The
carboxylic acid 22 was achieved in 80% yield under Evans’ experi-
mental conditions if the aqueous solution 1M HCl was replaced
with an aqueous solution of KHSO4. However, the carboxylic acid
can be transformed to the corresponding g-lactones 21aeb after
storage by several days, as shown in Scheme 7.
Removal of the oxazolidinone moiety from alkylated adduct 8a
with Sm(OTf)3 or Sn(OTf)2 as Lewis acids in MeOH20 did not afford
the corresponding carboxylic ester. Apparently, under this reaction
condition the double bond of 8a was not stable in the presence of
these Lewis acids. The reaction mixture led to a decomposition of
the starting material. On the other hand, treatment of alkylated
adducts 8ae13b with sodium borohydride in a mixture of THF-H2O
gave rise to chiral alcohol 23ae25b bearing a cis-alkene in 80e84%
Entry
R-X
Yielda (%)
Z/Eb
d.r.b a/b
1
2
3
CH3I
AllylBr
BnBr
60
52
50
>95:5
>95:5
>95:5
98/2
98/2
98/2
a
Yield corresponding to purified diastereomer.
The ratios Z/E and diastereomeric ratios to the new stereogenic center at C
b
a
were determined by 1H NMR of the crude reaction mixture. E-isomers were not
observed by 1H NMR.

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J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4593
77.0 ppm (CDCl3) as internal reference. High resolution mass
spectra were performed with QQHQ mass analyzer type. HPLC,
were performed with Photodiode Array Detector using chiral col-
umns OD and AS-H.
4.2. Procedure for the N-acylation of oxazolidinones
4.2.1. (4R,E)-3-(40-Benzyloxy-but-20-enoyl)-4,5,5-triphenyl-ox-
azolidinone 8. To an oven-dried 100 mL round-bottom equipped
with a magnetic stir bar, anhydrous LiCl (0.42 g, 10.0 mmol) was
added followed of THF (10 mL), dry triethylamine (2.43 g,
24.0 mmol) and pivaloyl chloride (1.45 g, 12.0 mmol). To reaction
mixture a solution of the corresponding carboxylic acid (2.30 g,
12.0 mmol) in THF (5 mL) under an argon atmosphere at 0 ꢁC was
added. The reaction mixture was stirred for 1 h at the same tem-
perature and oxazolidinone (3.15 g, 10.0 mmol) in 5 mL THF was
added. Then, the reaction mixture was warmed up to room tem-
perature and continued being stirred for 18 h. Then, the reaction
was quenched by the addition of a saturated solution of NH4Cl
(3 mL), and THF was removed under reduced pressure. The organic
layer was extracted with CH2Cl2 (3ꢂ30 mL), and washed with
a solution of NaHCO3, dried over Na2SO4, filtered and concentrated
under reduced pressure. The residue was purified by flash column
chromatography eluting with hexaneeethyl acetate (90:10) to give
the respective N-enoyl oxazolidinone 8 (2.94 g, 60%) as a white
Scheme 7. Chiral auxiliary removal. Reagent and conditions i) LiOH, H2O2, THF/H2O
0e25 ꢁC, 90 min, aq. Na2SO3, 1M HCl soln.; ii) LiOH, H2O2, THF/H2O 0e25 ꢁC, 90 min,
aq. Na2SO3, aq. KHSO4 soln.; iii) three day at room temperature.
yields. The enantiomeric purities of the alcohols were determined
by HPLC (equipped with chiral OD and AS-H columns) analysis and
comparison with racemic samples. The achieved results are shown
in Fig. 3.
solid, mp 115.6 ꢁC, ½a D25
ꢃ
þ156.6 (c 1.60, CHCl3); 1H NMR (400 MHz,
CDCl3)
d
7.65 (2H, dt, J¼8.0, 1.6 Hz, Ph), 7.55 (1H, dt, J¼15.3, 2.0 Hz,
CH¼), 7.45e7.00 (19H, m, Ph, CH¼), 6.28 (1H, s, CH), 4.56 (2H, s,
CH2Ph), 4.19 (2H, dd, J¼4.4, 2.0 Hz, CH2O); 13C NMR (100 MHz,
CDCl3) d: 163.8, 152.6, 146.8, 141.6, 137.9, 135.6, 134.0, 129.0128.8,
128.7, 128.6, 128.4, 128.3, 128.2, 128.0, 127.8, 127.7, 127.5, 127.4,
127.0, 126.4, 126.2, 126.0, 120.1, 89.0, 72.8, 69.0, 66.0; IRymax: 2844.1,
1786, 1688.4, 1640.2, 1587.0, 1496.0, 1450.1, 1364.0, 1022.6, 1000.1,
753.8, 693.4 cmꢀ1; EI-HRMS: calculated for (C32H27NO4), 489.1940;
found, 489.1942.
Fig. 3. Chiral alcohols bearing cis-alkene.
3. Conclusion
4.2.2. (4R,E)-3-(40-Methoxybut-20-enoyl)-4,5,5-triphenyl-ox-
azolidinone 9. Purified by flash chromatography with hex-
aneeethyl acetate (95:5) to afford the desired product as a white
In conclusion we described a diastereomeric alkylation reaction
carried out in 3-[(E)-
azolidinones with strong bases to provide 3-[(Z)-
unsaturated]-N-acyloxazolidinones in moderate yields. The re-
a
,b
-unsaturated-
g
-substituted]-N-acylox-
solid, (18.3 mg, 70%), mp 143e144 ꢁC, ½a D25
ꢃ
þ109.7 (c 0.9, CHCl3); 1H
a
-substituted-b,g-
NMR (500 MHz, CDCl3) 7.64 (2H, dt, J¼7.5, 1.6 Hz, Ph), 7.48e7.34
(4H, m, Ph, CH¼), 7.11e7.00 (11H, m, Ph, CH¼), 6.27 (1H, s, CH), 4.10
(2H, dd, J¼4.5, 2.0 Hz, CH2), 3.38 (3H, s, OCH3); 13C NMR (125 MHz,
action was highly regioselective giving only product of alkylation at
a
-position. Depending on the chiral auxiliary (oxazolidinone moi-
ety) the diastereoselectivity can be moderate to high. A high Z-se-
lectivity was observed (Z/E) (>95:5) in the formation of a cis-alkene
in the alkylated product. This Z-selectivity was attributed to the
important Syn-effect. The synthetic relevance of this methodology
is that chiral molecules can be achieved bearing an electron rich cis-
alkenes as substituent, which may be useful in organic synthesis.
CDCl3) d: 163.8, 152.6, 146.8, 141.6, 137.9, 135.6, 134.0, 129.0128.9,
128.3, 128.2, 128.4, 127.7, 127.5, 127.4, 126.2, 126.0, 120.0, 89.1, 71.4,
66.1, 58.7; IRymax: 3061.6, 1775.4, 1691.5, 1334.1, 1208.2, 991.8, 751.9,
689.54 cmꢀ1; FAB-HRMS: calculated for (C26H24NO4), 414.1705;
found, 414.1888.
4.2.3. (4R,E)-3-[(40-tert-Butyldimethylsilyloxy)but-20-enoyl]-4,5,5-
triphenyloxazolidinone 10. Purified by flash chromatography with
hexaneeethyl acetate (97:3) to afford the desired product as a liq-
4. Experimental section
4.1. General information
uid, (1.80 g, 35%); ½a D25
ꢃ
þ145.0 (c 1.3, CHCl3); 1H NMR (400 MHz,
CDCl3) 7.65 (2H, dt, J¼7.2, 1.2 Hz, Ph), 7.58 (1H, dt, J¼14.8, 2.4 Hz,
¼CH), 7.44e7.34 (3H, m, Ph), 7.13e7.00 (11H, m, ¼CH, Ph), 6.28 (1H,
s, CHN), 4.35 (2H, dd, J¼3.6, 2.4 Hz, CH2), 0.93 (9H, s, t-Bu-), 0.08
(3H, s, CH3), 0.07 (3H, s, CH3); 13C NMR (100 MHz, CDCl3) 164.1,
152.5, 150.2, 141.7, 138.0, 135.7, 129.0, 128.8, 128.2, 128.0, 127.6,
127.4, 127.3, 126.12, 126.0, 118.4, 88.8, 66.0, 62.5, 25.7, 18.2, 5.5; FAB-
HRMS: calculated for C31H36NO4Si: 514.2414; found, 514.2379.
All moisture-sensitive reactions were carried out in oven-dried
glassware under argon atmosphere. Dichloromethane was distilled
from CaH2 under argon. THF was distilled from Na/benzophenone
under argon. Optical rotations were measured in a polarimeter with
sodium D-line (589 nm) and are reported on a concentration (c) of
grams/100 mL of solvent. 1H and 13C NMR spectra and 1He1H COSY,
DEPT and HMQC, experiments were measured with a 400 MHz
FTNMR spectrometer. 1H NMR chemical shifts (
d) are reported in
4.2.4. (4S,E)-3-(40-Benzyloxy-but-20-enoyl)-4-isopropyl-5,5-
dimethyl-oxazolidinone 11. Purified by flash chromatography with
hexaneeethyl acetate (95:5) to afford the desired product as a liq-
parts per million (ppm) relative to Me4Si (
d
¼0.0 ppm) with cou-
pling constants (J) reported in Hertz (Hz). Multiplicities are re-
ported as singlet (s), doublet (d), triplet (t), quartet (q), multiplet
(m), broad singlet (br s). 13C NMR spectra are reported using
uid, (1.33 g, 40%); ½a D25
ꢃ
þ23.0 (c 1.7, CHCl3); 1H NMR (400 MHz,
CDCl3) 7.60 (1H, dt, J¼15.2, 2.0 Hz, CH¼), 7.40e7.30 (5H, m, Ph), 7.14

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J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4594
(1H, dt, J¼15.6, 4.6 Hz, CH¼), 4.60 (2H, s, CH2Ph), 4.24 (2H, dd,
J¼4.8, 2.0 Hz, CH2O), 4.22 (1H, d, J¼3.2 Hz, CHN), 2.16 (1H, m,
CH(CH3)2), 1.52 (3H, s, CH3), 1.39 (3H, s, CH3), 1.04 (3H, d, J¼6.8 Hz,
CH3), 0.96 (3H, d, J¼7.2 Hz, CH3); 13C NMR (100 MHz, CDCl3) 165.3,
153.4, 146.0, 137.6, 128.4, 127.7, 120.6, 82.8, 72.8, 69.0, 66.3, 26.6,
28.7, 21.4, 21.3, 17.0; IRymax: 2966.8, 2912.6, 1766.2, 1685.0, 1636.8,
1453.3, 1363.0, 959.8, 740.2, 695.1 cmꢀ1; FAB-HRMS: calculated for
(C19H26NO4), 332.1862; found, 332.1820.
CDCl3) 174.7, 152.2, 145.1, 141.8, 138.1, 137.3, 136.0, 128.7, 128.6,
128.3, 128.2, 128.0, 127.7, 127.6, 127.3, 127.1, 126.2, 126.0, 105.7, 88.6,
73.4, 66.2, 34.5, 17.8; IRymax: 2922.1, 1782.0, 1703.7, 1450.7, 1329.8,
; FAB-HRMS: calculated for (C33H30NO4),
504.2175; found, 504.2154.
989.6, 696.7. cmꢀ1
4.4.2. (20S,4R,Z)-3-(40-Benzyloxyl-20-methylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 8b. Liquid, (20.5 mg, 10%); ½a D25
þ138.7 (c
ꢃ
0.75, CHCl3); 1H NMR (400 MHz, CDCl3) 7.63 (2H, dt, J¼7.2, 1.6 Hz,
Ph), 7.44e7.28 (8H, m, Ph), 7.08e7.00 (10H, m, Ph), 6.21 (1H, s,
CHN), 6.02 (1H, dd, J¼6.4, 1.2 Hz, CH¼), 4.77 (1H, dq, J¼8.4, 7.0 Hz,
CHCH3), 4.75 (1H, d, J¼12.4 Hz, CHaHbPh), 4.71 (1H, d, J¼12.4 Hz,
CHbHaPh), 4.47 (1H, dd, J¼8.4, 6.0 Hz, CH¼), 1.11 (3H, d, J¼7.2 Hz,
CH3); 13C NMR (100 MHz, CDCl3) 174.7, 152.2, 145.6, 141.8, 138.0,
137.3,135.6,128.8,128.4,128.3,128.1,128.0,127.8,127.6,127.5,127.4,
127.3, 126.3, 126.1, 105.4, 88.7, 73.7, 66.0, 34.6, 17.9; IRymax: 2922.1,
1782.0, 1703.7, 1450.7, 1329.8, 989.6, 696.7. cmꢀ1; EI-HRMS: calcu-
lated for (C33H29NO4), 503.2097; found, 503.2085.
4.3. Procedure for the isomerization (double bond migration)
4 . 3 .1. ( 4 R , Z ) - 3 - ( 4 0- B e n z y l o x y - b u t - 3 0- e n o y l ) - 4 , 5 , 5 -
triphenyloxazolidinone 80. To an oven-dried 100 mL round-bottom
equipped with a magnetic stir bar was added anhydrous LiCl
(15.3 mg, 0.36 mmol) under an argon atmosphere followed of N-
enoyl oxazolidinone 8 (150 mg, 0.30 mmol). Both solids were
dissolved in anhydrous THF (25 mL) and the reaction mixture was
stirred for 15 min at e60 ꢁC and then was added 1.0 M NaHMDS
(0.54 mL, 0.54 mmol) and the resulting solution was stirred vig-
orously. After 30 min the temperature was increased ate45 ꢁC and
the reaction was stirred for 7 h. After the reaction was quenched
by the addition of a saturated solution of NH4Cl (3 mL), THF was
removed under reduced pressure. The organic layer was extracted
with CH2Cl2 (3ꢂ30 mL), dried over Na2SO4, filtered and concen-
trated under reduced pressure. The oily residue was purified by
flash column chromatography eluting with hexaneeethyl acetate
4.4.3. (20R, 4R, Z)-3-(40-Methoxy-20-methylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 9a. Waxy, purified by flash chromatogra-
phy with hexaneeethyl acetate (95:5) to afford the desired product
as a liquid, (70.7 mg, 80%); ½a D25
ꢃ
þ86.7 (c 1.1, CHCl3); r.d. 96:4; 1H
NMR (500 MHz, CDCl3) 7.63 (2H, d, J¼7.5, Hz, Ph), 7.42e7.34 (3H, m,
Ph), 7.10e7.00 (10H, m, Ph), 6.20 (1H, s, CHN), 5.77 (1H, dd, J¼6.0,
1.0 Hz, CH¼), 4.63 (1H, dq, J¼8.0, 7.0 Hz, CHCH3), 4.47 (1H, dd, J¼8.0,
6.0 Hz, CH¼), 3.36 (3H, s, OMe), 1.20 (3H, d, J¼7.0 Hz, CH3); 13C NMR
(125 MHz, CDCl3) 174.8, 152.3, 147.0, 142.0, 138.2, 136.0, 136.0, 128.8,
128.7, 128.2, 128.1, 127.6, 127.4, 126.3, 126.2, 105.0, 88.7, 66.2, 60.0,
34.4, 17.9; IRymax: 2930.0, 1784.0, 1704.0, 1451.0, 1215.0, 1105.0,
(95:5) to give the compound 80 as a liquid (140 mg, 95%); ½a 2D5
ꢃ
þ136.9 (c 2.0, CHCl3); 1H NMR (400 MHz, CDCl3) 7.63 (2H, dt,
J¼7.0, 1.5 Hz, Ph), 7.44e7.25 (8H, m, Ph), 7.10e6.98 (10H, m, Ph),
6.21 (1H, s, CHN), 6.12 (1H, dt, J¼6.4, 1.5 Hz, CH¼), 4.74 (2H, s,
CH2Ph), 4.58 (1H, dt, J¼6.4, 6.8 Hz, CH¼), 3.80 (1H, ddd, J¼19.2,
6.8, 1.5 Hz, CHa), 3.75 (1H, ddd, J¼19.2, 6.8, 1.5 Hz, CHb); 13C NMR
756.0, 699.0. cmꢀ1
; FAB-HRMS: calculated for (C27H26NO4),
428.1862; found, 428.1884.
(100 MHz, CDCl3)
d: 170.6, 152.6, 146.8, 141.7, 138.0, 137.2,
135.7, 128.8, 128.7, 128.4, 128.3, 128.1, 128.0, 127.8, 127.6,
127.4, 127.3, 127.2, 126.1, 125.9, 97.5, 89.0, 73.6, 66.0, 31.5; IRy
2923.4, 1788.7, 1712.8, 1496.1, 1450.5, 1364.2, 1347.4, 997.0, 845.0,
759.7 cmꢀ1; EI-HRMS: calculated for (C32H27NO4), 489.1940;
found, 489.1942.
4.4.4. (20R,4R,Z)-3-[(40-tert-Butyldimethylsilyloxy)-20-methylbut-30-
enoyl]-4,5,5-triphenyloxazolidinone 10a. Purified by flash column
chromatography eluting with hexaneeethyl acetate (97:3) to give
a diastereomeric mixture of the compounds 10a and 10b. Their
isolation was carried out by preparative thin layer chromatogra-
phy eluting with hexane-CH2Cl2 7:3, to give the compound 10a as
:
max
4.4. General procedure for the alkylation reaction
a white solid (120 mg, 44%); m.p. 80.2 ꢁC. ½a D25
þ85.8 (c 1.9, CHCl3);
ꢃ
1H NMR (400 MHz, CDCl3) 7.64 (2H, dt J¼7.6, 1.2 Hz, Ph), 7.44e7.34
(3H, m, Ph), 7.13e7.00 (10H, m, Ph), 6.21 (1H, s, CHN), 6.13 (dd,
J¼5.7 Hz, ¼CH), 4.84 (1H, dq, J¼8.8, 7.2 Hz, CH), 4.61 (1H, dd, J¼8.8,
5.7 Hz, ¼CH), 1.22 (3H, d, J¼7.2 Hz, CH3), 0.83 (9H, s, t-Bu), 0.05
4.4.1. (20R,4R,Z)-3-(40-Benzyloxyl-20-methylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 8a. To an oven-dried 100 mL round-bottom
equipped with a magnetic stir bar was added anhydrous LiCl
(0.24 mmol, 10.3 mg) under an argon atmosphere followed of N-
enoyl oxazolidinone 8 (0.2 mmol, 0.10 g). Both solids were dis-
solved in anhydrous THF (25 mL) and the reaction mixture was
stirred for 15 min ate60 ꢁC and then was added NaHMDS
(0.41 mmol, 0.41 mL) and the resulting solution was stirred vigor-
ously during 30 min. After, was added CH3I (1.2 mmol, 0.17 g), the
temperature was increased ate45 ꢁC and the reaction mixture was
stirred for 7 h. After the reaction was quenched by the addition of
a saturated solution of NH4Cl (3 mL), THF was removed under re-
duced pressure. The organic layer was extracted with CH2Cl2
(3ꢂ30 mL), dried over Na2SO4, filtered and concentrated under
reduced pressure. The oily residue was purified by flash column
chromatography eluting with hexaneeethyl acetate (95:5) to give
a diastereomeric mixture of the compounds 8a and 8b. Their iso-
lation was carried out by preparative thin layer chromatography
eluting twice with hexane-CH2Cl2 9:1, to give the compound 8a as
(3H, s, CH3), 0.01 (3H, s, CH3). 13C NMR (100 MHz, CDCl3)
d:
175.0, 152.0, 141.8, 139.5, 138.2, 136.0, 128.8, 128.6, 128.2, 128.0,
127.6, 127.3, 126.2126.0, 108.5, 88.5, 66.1, 33.8, 25.4, 18.0, ꢀ5.6;
FAB-HRMS: calculated for (C32H38NO4Si): 528.2570; found:
528.2574.
4.4.5. (20R,4R,Z)-3-(40-Benzyloxyl-20-allylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 12a. Purified by flash column chromatog-
raphy eluting with hexaneeethyl acetate (95:5) to give a di-
astereomeric mixture of the compounds 12a and 12b. Their
isolation was carried out by preparative thin layer chromatography
eluting with hexane-CH2Cl2 9:1, to give the compound 12a as
a liquid (160 mg, 61%); ½a D25
ꢃ
þ69.5 (c 1.34, CHCl3); 1H NMR
(400 MHz, CDCl3) 7.60 (2H, dt, J¼6.4, 1.6 Hz, Ph), 7.36e7.20 (8H, m,
Ph), 7.10e7.00 (10H, m, Ph), 6.20 (1H, s, CHN), 5.94 (1H, dd, J¼6.0,
0.8 Hz, CH¼), 5.63 (1H, m, CH¼), 4.88 (1H, m, CH), 4.84 (2H, s,
CH2¼), 4.56 (1H, d, J¼12.8 Hz, CHaHbPh), 4.52 (1H, d, J¼12.8 Hz,
CHbHaPh), 4.46 (1H, dd, J¼8.4, 6.0 Hz, CH¼), 2.49 (1H, m, CHaHb),
a liquid (144.0 mg, 70%); ½a D25
ꢃ
þ82.9 (c 2.0, CHCl3); 1H NMR
(400 MHz, CDCl3) 7.60 (2H, dd, J¼7.0, 1.6 Hz, Ph), 7.38e7.22 (8H, m,
Ph), 7.12e7.00 (10H, m, Ph), 6.20 (1H, s, CHN), 5.90 (1H, dd, J¼6.0,
1.2 Hz, CH¼), 4.73 (1H, dq, J¼8.4, 7.0 Hz, CHCH3), 4.60 (1H, d,
J¼12.8 Hz, CHaHbPh), 4.56 (1H, d, J¼12.8 Hz, CHbHaPh), 4.53 (1H, dd,
J¼8.4, 6.0 Hz, CH¼), 1.21 (3H, d, J¼7.0 Hz, CH3); 13C NMR (100 MHz,
2.23 (1H, m, CHbHa); 13C NMR (100 MHz, CDCl3)
d: 173.6, 152.2,
146.0, 142.0, 138.1, 137.2, 136.0, 134.7, 128.7, 128.6, 128.3, 128.1,
128.0, 127.7, 127.6, 127.5, 127.3, 127.0, 126.2, 126.0, 117.0, 103.7, 88.6,
73.4, 66.2, 39.1, 36.7; IRymax: 3065.9, 2917.3, 1789.4, 1704.6, 1496.0,

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J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4595
1450.5, 1209.0, 994.0, 916.0, 759.8, 751.9 cmꢀ1; EI-HRMS: calcu-
lated for (C35H31NO4), 529.2253; found, 529.2259.
16.9; IRymax: 2970.8, 2929.2, 1770.2, 1701.9, 1452.3, 1369.1, 1066.0,
730.2, 697.0 cmꢀ1; EI-HRMS: calculated for (C20H27NO4), 345.1940;
found, 345.1932.
4.4.6. (20S,4R,Z)-3-(40-Benzyloxyl-20-allylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 12b. Its isolation was carried out by pre-
parative thin layer chromatography eluting with hexane-CH2Cl2
4.4.10. (20S, 4S, Z)-3-(40-Benzyloxyl-20-allylbut-30-enoyl)-4-
isopropyl-5,5-dimethyloxazolidinone 15a. Purified by flash column
chromatography eluting with hexaneeethyl acetate (95:5) to give
9:1, to give the compound 12b as a liquid (63 mg, 24%); ½a D25
þ159.5
ꢃ
(c 1.71, CHCl3); 1H NMR (400 MHz, CDCl3) 7.63 (2H, dt, J¼6.8, 1.6 Hz,
Ph), 7.44e7.28 (8H, m, Ph), 7.00 (10H, br s, Ph), 6.20 (1H, s, CHN),
6.04 (1H, dd, J¼6.0, 1.2 Hz, CH¼), 5.55 (1H, m, CH¼), 4.97 (1H, m,
CH), 4.74 (1H, dd, J¼15.6, 1.6 Hz, CHaHb¼), 4.73 (2H, s, CH2Ph), 4.66
(1H, dd, J¼10.2, 1.6 Hz, CHbHa¼), 4.43 (1H, dd, J¼8.7, 6.0 Hz, CH¼),
2.32 (1H, m, CHaHb), 2.21 (1H, m, CHbHa); 13C NMR (100 MHz,
CDCl3) 173.5, 152.3, 146.1, 141.8, 138.0, 137.3, 135.6, 134.6, 128.8,
128.4, 128.0, 127.9, 127.7, 127.6, 127.4, 127.3, 127.2, 126.2, 126.1, 116.7,
103.6, 88.6, 73.7, 66.1, 39.4, 37.2; IRymax: 3065.9, 2917.3, 1789.4,
1704.6, 1496.0, 1450.5, 994.0, 916.0, 759.8, 751.9 cmꢀ1; FAB-HRMS:
calculated for (C35H32NO4), 530.2331; found, 530.2355.
the compound 15a as a liquid (96.6 mg, 52%); ½a D25
þ52.2 (c 2.71,
ꢃ
CHCl3); 1H NMR (400 MHz, CDCl3) 7.36e7.26 (5H, m, Ph), 6.10 (1H,
dd, J¼6.0, 1.2 Hz, CH¼), 5.85 (1H, ddt, J¼17.2, 10.4, 6.8 Hz, CH¼), 5.10
(1H, dd, J¼17.2, 2.0 Hz, CH¼), 5.03 (1H, dd, J¼10.4, 2.0 Hz, CH¼),
4.97 (1H, m, CH), 4.78 (1H, d, J¼2.4 Hz, CH2Ph), 4.57 (1H, dd, J¼8.2,
6.0 Hz, CH¼), 4.11 (1H, d, J¼3.2 Hz, CHN), 2.62 (1H, ddd, J¼14.0, 7.0,
6.8 Hz, CHaHb), 2.38 (1H, ddd, J¼14.0, 7.0, 6.8 Hz, CHbHa), 2.11 (1H,
m, CH(CH3)2), 1.47 (3H, s, CH3), 1.23 (3H, s, CH3), 1.00 (3H, d,
J¼7.2 Hz, CH3), 0.94 (3H, d, J¼7.2 Hz, CH3); 13C NMR (100 MHz,
CDCl3) 175.0, 153.2, 146.0, 137.2, 135.3, 128.4, 127.8, 127.3, 117.0,
104.5, 82.5, 73.8, 66.5, 38.7, 37.5, 29.5, 28.3, 21.4, 21.3, 16.8; IRy
:
max
2972.1, 2917.7, 1773.8, 1690.9, 1459.2, 1364.9, 913.0, 732.9,
695.0 cmꢀ1; EI-HRMS: calculated for (C22H29NO4), 371.2097; found,
371.2096.
4.4.7. (20R,4R,Z)-3-(40-Benzyloxyl-20-benzylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 13a. Purified by flash column chromatog-
raphy eluting with hexaneeethyl acetate (95:5) to give a di-
astereomeric mixture of the compounds 13a and 13b. Their
isolation was carried out by preparative thin layer chromatography
eluting with hexane-CH2Cl2 9:1, to give the compound 13a as
4.4.11. (20S, 4S, Z)-3-(40-Benzyloxyl-20-benzylbut-30-enoyl)-4-
isopropyl-5,5-dimethyloxazolidinone 16a. Purified by flash column
chromatography eluting with hexaneeethyl acetate (95:5) to give
a Liquid (190 mg, 65%); ½a D25
ꢃ
þ67.2 (c 1.43, CHCl3); 1H NMR
the compound 16a as a liquid (110 mg, 50%); ½a D25
þ50.6 (c 1.73,
ꢃ
(400 MHz, CDCl3) 7.61 (2H, dt, J¼6.8, 1.6 Hz, Ph), 7.38e7.23 (6H, m,
Ph), 7.17e6.90 (17H, m, Ph), 6.20 (1H, s, CHN), 5.86 (1H, dd, J¼6.0,
1.0 Hz, CH¼), 5.18 (1H, m, CH), 4.44 (1H, dd, J¼8.4, 6.0 Hz, CH¼),
4.43 (1H, d, J¼12.8 Hz, CHaHbO), 4.35 (1H, d, J¼12.8 Hz, CHbHaO),
3.14 (1H, dd, J¼13.2, 6.8 Hz, CHaHbPh), 2.64 (1H, dd, J¼13.2, 8.0 Hz,
CHbHaPh); 13C NMR (100 MHz, CDCl3) 173.6, 152.2, 146.1, 141.9,
138.5, 138.1, 137.2, 135.8, 134.7, 129.4, 129.1, 128.8, 128.6, 128.3,
128.2, 128.0, 127.8, 127.6, 127.3, 127.0, 126.9, 126.3, 126.1, 103.6, 88.6,
73.3, 66.2, 41.0, 38.4; IRymax: 3035.7, 2920.7, 1781.9, 1701.8, 1496.1,
1450.9, 1366.6, 1330.6, 1211.5, 743.8, 696.3 cmꢀ1; EI-HRMS: calcu-
lated for (C39H33NO4), 580.2410; found, 580.2395.
CHCl3); 1H NMR (400 MHz, CDCl3) 7.34e7.15 (10H, m, Ph), 6.02 (1H,
dd, J¼6.4, 1.2 Hz, CH¼), 5.30 (1H, dtd, J ¼, 8.2, 8.0, 1.2 Hz, CHCH2),
4.70 (1H, d, J¼12.4 Hz, OCHaHb), 4.62 (1H, d, J¼12.4 Hz, OCHbHa),
4.54 (1H, dd, J¼8.2, 6.4 Hz, CH¼), 4.08 (1H, d, J¼3.2 Hz, CHN), 3.23
(1H, dd, J¼13.2, 6.8 Hz, CHaHbPh), 2.81 (1H, dd, J¼13.2, 8.4 Hz,
CHbHaPh), 2.02 (1H, m, CH(CH3)2), 1.44 (3H, s, CH3), 1.22 (3H, s,
CH3), 0.85 (3H, d, J¼6.8 Hz, CH3), 0.74 (3H, d, J¼6.8 Hz, CH3); 13C
NMR (100 MHz, CDCl3) 175.0, 153.1, 146.2, 138.8, 137.1, 129.4, 128.3,
128.0,127.7,127.2,126.1,104.4, 82.4, 73.6, 66.5, 40.6, 39.2, 29.4, 28.4,
21.3, 16.5; IRymax: 2956.4, 2917.5, 1779.2, 1695.6, 1495.4, 1450.6,
1364.0, 1113.0, 1065.2, 739.6, 697.7 cmꢀ1; EI-HRMS: calculated for
(C26H31NO4), 421.2253; found, 421.2258.
4.4.8. (20S,4R,Z)-3-(40-Benzyloxyl-20-benzylbut-30-enoyl)-4,5,5-
triphenyloxazolidinone 13b. Its isolation was carried out by pre-
parative thin layer chromatography eluting with hexane-CH2Cl2
4.4.12. (20R,4R)-3-(40-Benzyloxy-20-methylbutanoyl)-4,5,5-
triphenyloxazolidinone 18. To an oven-dried 100 mL round-bottom
equipped with a magnetic stir bar, the compound 8a (100 mg,
0.20 mmol) was added followed of EtOH (3 mL), and 10% Pd/C
(20 mg). The reaction mixture was stirred for 16 h at room tem-
perature. Then, the reaction was filtered over celite and EtOH was
removed under reduced pressure. The residue was purified by flash
column chromatography eluting with hexaneeethyl acetate (95:5)
to give the respective product 18 (97.0 mg, 99%) as a white solid, mp
7:3, to give the compound 13b as a liquid (59.1 mg, 20%); ½a D25
ꢃ
þ136.4 (c 1.03, CHCl3); 1H NMR (400 MHz, CDCl3) 7.54 (2H, dt,
J¼6.4, 1.6 Hz, Ph), 7.41e7.19 (6H, m, Ph), 7.11e6.98 (6H, m, Ph), 6.15
(1H, s, CHN), 6.01 (1H, d, J¼6.0 Hz, CH¼), 5.17 (1H, m, CH), 4.67 (1H,
d, J¼12.8 Hz, CHaHbO), 4.60 (1H, d, J¼12.8 Hz, CHbHaO), 4.42 (1H,
dd, J¼8.8, 6.0 Hz, CH¼), 2.94 (1H, dd, J¼13.2, 6.8 Hz, CHaHbPh), 2.70
(1H, dd, J¼13.6, 7.6 Hz, CHbHaPh); 13C NMR (100 MHz, CDCl3) 173.2,
152.1, 146.5, 141.7, 138.5, 138.0, 137.3, 135.7, 129.1, 128.8, 128.7, 128.4,
128.0,127.9, 127.7, 127.5, 127.4, 127.3, 127.2, 126.3,126.1, 126.0, 103.4,
88.5, 73.6, 66.1, 41.5, 38.4; IRymax: 3035.7, 2920.7, 1781.9, 1701.8,
1496.1, 1450.9, 1366.6, 1330.6, 1211.5, 743.8, 696.3 cmꢀ1; FAB-
HRMS: calculated for (C39H34NO4), 580.2488; found, 580.2450.
93.4 ꢁC, ½a 2D5
ꢃ
þ121.5 (c 1.64, CHCl3); 1H NMR (400 MHz, CDCl3) 7.62
(2H, dd, J¼8.2, 1.2 Hz, Ph), 7.40e7.20 (7H, m, Ph), 7.11e7.00 (11H, m,
Ph), 6.23 (1H, s, CHN), 4.23 (1H, d, J¼12.0, CHaHbPh), 4.18 (1H, d,
J¼12.0, CHbHaPh) 3.91 (1H, m, CH), 3.38e3,26 (2H, m, CH2O), 1.98
(1H, m, CHaHb), 1.60 (1H, m, CHbHa), 1.07 (3H, d, J¼6.9 Hz, CH3); 13
C
NMR (100 MHz, CDCl3) 176.0, 152.4, 141.7, 138.3, 138.0, 135.8, 128.9,
128.8, 128.2, 128.1, 127.6, 127.5, 127.4, 127.2, 126.1, 126.0, 88.7, 72.7,
67.7, 66.0, 35.0, 33.0, 17.3; IRnmax: 2927.3, 2850.7, 1785.4, 1703.1,
1495.5, 1450.6, 986.1, 968.6, 846.0, 751.6, 692.1, 667.4 cmꢀ1; EI-
HRMS: calculated for (C33H31NO4), 505.2253; found, 505.2239.
4.4.9. (20S, 4S, Z)-3-(40-Benzyloxy-20-methylbut-30-enoyl)-4-
isopropyl-5,5-dimethyloxazolidinone 14a. Purified by flash column
chromatography eluting with hexaneeethyl acetate (95:5) to give
the compound 14a as a liquid (100 mg, 60%); ½a D25
þ67.7 (c 1.29,
ꢃ
CHCl3); 1H NMR (400 MHz, CDCl3) 7.35e7.26 (5H, m, Ph), 6.06 (1H,
dd, J¼6.0, 1.0 Hz, CH¼), 4.82 (1H, dqd, J¼8.0, 7.0, 1.0 Hz, CHCH3),
4.80 (1H, d, J¼12.4 Hz, CHaHbPh), 4.76 (1H, d, J¼12.8 Hz, CHbHaPh),
4.65 (1H, dd, J¼8.0, 6.0 Hz, CH¼), 4.12 (1H, d, J¼3.2 Hz, CHN), 2.12
(1H, m, CH(CH3)2), 1.48 (3H, s, CH3), 1.35 (3H, d, J¼7.0 Hz, CH3CH),
1.26 (3H, s, CH3), 1.01 (3H, d, J¼6.6 Hz, CH3), 0.95 (3H, d, J¼6.6 Hz,
CH3); 13C NMR (100 MHz, CDCl3) 176.3, 153.1, 145.2, 137.3, 128.4,
127.8, 127.3, 106.3, 82.6, 73.7, 66.3, 34.2, 29.5, 28.4, 21.5, 21.3, 18.9,
4.4.13. (R)-4-Benzyloxy-2-methylbutyric acid 19. To 100 mL round-
bottom equipped with a magnetic stir bar, the compound 18
(97 mg, 0.19 mmol) in THF (6 mL) and H2O (2 mL) at 0 ꢁC were
added followed of 30% H2O2 (0.13 g, 1.14 mmol) and LiOH (15.9 mg,
0.38 mmol). The reaction mixture was stirred for 1.5 h at room
temperature. Then, the reaction was quenched by the addition of an
aqueous saturated solution of Na2SO3 (5 mL) at 0 ꢁC. Then, the pH of

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J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4596
solution was adjusted in a range of 9e10 by the addition of a satu-
rated solution of NaHCO3 and the THF was removed under reduced
pressure. The organic layer was extracted with CH2Cl2 (3ꢂ30 mL),
and dried over Na2SO4, filtered and concentrated under reduced
pressure to yield the oxazolidinone. The pH of the aqueous phase
was adjusted between 1 and 2 by the addition of a aqueous solution
of 1M HCl and the organic layer was extracted with AcOEt
(3ꢂ30 mL), and dried over Na2SO4, filtered and concentrated under
compound 8a (100 mg, 0.0.20 mmol) in THF (6 mL) and H2O (2 mL)
at 0 ꢁC were added followed of 30% H2O2 (0.14 g, 1.20 mmol) and
LiOH (16.8 mg, 0.40 mmol). The reaction mixture was stirred for
1.5 h at room temperature. Then, the reaction was quenched by the
addition of an aqueous saturated solution of Na2SO3 (5 mL) at 0 ꢁC.
Then, the pH of solution was adjusted in a range of 9e10 by the
addition of a saturated solution of NaHCO3 and the THF was re-
moved under reduced pressure. The organic layer was extracted
with CH2Cl2 (3ꢂ30 mL), and dried over Na2SO4, filtered and con-
centrated under reduced pressure to yield the oxazolidinone. The
pH of the aqueous phase was adjusted between 1 and 2 by the
addition of a aqueous solution of KHSO4 and the organic layer was
extracted with AcOEt (3ꢂ30 mL), and dried over Na2SO4, filtered
and concentrated under reduced pressure to give 22 as a liquid
reduced pressure to give 19 as a liquid (31.7 mg, 80%); ½a D25
ꢀ11.0 (c
ꢃ
1.9, CHCl3); 1H NMR (400 MHz, CDCl3) 7.33e7.31 (5H, m, Ph), 4.51
(1H, d, J¼11.6 Hz, CHaHbPh), 4.48 (1H, d, J¼11.6 Hz, CHbHaPh), 3.53
(2H, t, J¼6.4 Hz, CH2O), 2.67 (1H, m, CH), 2.04 (1H, m, CHaHb), 1.72
(1H, m, CHbHa), 1.20 (3H, d, J¼6.8 Hz, CH3); 13C NMR (100 MHz,
CDCl3) 182.7, 138.2, 128.3, 127.6, 127.5, 73.0, 67.8, 36.4, 33.1, 17.0;
IRnmax: 3450.0, 3250.0, 2919.3, 2850.5, 1704.2, 1455.6,1110.2, 1092.7,
746.1, 696.5 cmꢀ1; EI-HRMS: calculated for (C12H16O3), 208.1099;
found, 208.1074.
(33.0 mg, 80%); ½a D25
ꢃ
ꢀ54.3 (c 0.8, CHCl3); 1H NMR (400 MHz, CDCl3)
7.38e7.28 (5H, m, Ph), 6.12 (1H, dd, J¼6.0, 1.2 Hz, CH¼), 4.85 (1H,
dd, J¼12.6, CHaHb), 4.80 (1H, dd, J¼12.6, CHbHa), 4.53 (1H, dd, J¼8.8,
6.0 Hz, CH¼), 3.68 (1H, m, CH), 1.26 (3H, d, J¼6.8 Hz, CH3); 13C NMR
(100 MHz, CDCl3) 181.2, 145.7, 137.1, 128.5, 128.0, 127.3, 106.0, 74.0,
35.3, 17.8; IRnmax: 3457.0, 3257.2, 2924.0, 2912.3, 1782.6, 1700.4,
1451.0, 1360.0,1104.7, 1067.1, 905.2, 732.1, 696.9 cmꢀ1; EI-HRMS:
calculated for (C12H14O3), 206.0943; found, 206.0923.
4.4.14. (2R)-4-(Benzyloxyl)-2-methylbutan-1-ol 20. To 100 mL
round-bottom equipped with a magnetic stir bar, the compound 18
(97 mg, 0.19 mmol) in THF (6 mL) and H2O (1 mL) were added
followed of a solution of NaBH4 (28.8 mg, 0.76 mmol) in H2O (1 mL).
The reaction mixture was stirred for 3 h at room temperature. Then,
the reaction was quenched by the addition of a aqueous solution of
2N HCl (3 mL), and THF was removed under reduced pressure. The
organic layer was extracted with CH2Cl2 (3ꢂ30 mL), and washed
with brine, dried over Na2SO4, filtered and concentrated under
reduced pressure. The oily residue was purified by preparative thin
layer chromatography eluting with CH2Cl2-hexane 9:1, to give the
4.4.17. (R,Z)-4-(Benzyloxy)-2-methylbut-3-en-1-ol 23a. To 100 mL
round-bottom equipped with a magnetic stir bar, the compound 8a
(100 mg, 0.19 mmol) in THF (6 mL) at 0 ꢁc were added followed of
a solution of NaBH4 (30 mg, 0.79 mmol) in H2O (2 mL). The reaction
mixture was stirred for 16 h at room temperature. Then, the re-
action was quenched by the addition of a saturated solution of NaCl
(10 mL), and THF was removed under reduced pressure. The or-
ganic layer was extracted with AcOEt (3ꢂ20 mL), and dried over
Na2SO4, filtered and concentrated under reduced pressure. The oily
residue was purified by preparative thin layer chromatography
eluting with Hexane/AcOEt 8:2, to give the oxazolidinone as a white
solid (50 mg, 80%) and the compound 23a as a liquid (32 mg, 84%);
compound 20 as a liquid (30.6 mg, 83%); ½a D25
þ10.5 (c 0.35, CHCl3);
ꢃ
1H NMR (400 MHz, CDCl3) 7.37e7.28 (5H, m, Ph), 4.52 (2H, s,
CH2Ph), 3.60 (1H, m, CHaHbO), 3.52 (1H, m, CHbHaO), 3.51 (1H, dd,
J¼11.0, 4.8 Hz, CHaHbOH), 3.43 (1H, dd, J¼11.0, 6.8 Hz, CHbHaOH),
1.82 (1H, m, CHCH3), 1.70 (1H, m, CHaHb), 1.60 (1H, m, CHbHa), 0.92
(3H, d, J¼6.8 Hz, CH3); 13C NMR (100 MHz, CDCl3) 137.8, 128.4,
127.8, 127.7, 73.1, 68.5, 68.1, 34.2, 34.0, 17.2; IRnmax: 3422.3, 2917.3,
2844.1, 1454.5, 1269.9, 1092.2, 1022.6, 737.0, 695.2 cmꢀ1; EI-HRMS:
calculated for (C12H18O2), 194.1307; found, 194.1306.
½
a 2D5
ꢃ
þ3.5 (c 2.5, CHCl3); 1H NMR (400 MHz,CDCl3) 7.38e7.28 (5H,
m, Ph), 6.12 (1H, dd, J¼6.2, 1.2 Hz, ¼CH), 4.80 (2H, s, CH2Ph), 4.23
(1H, dd, J¼8.8, 6.2 Hz, ¼CH), 3.51 (1H, dd, J¼10.2, 5.4 Hz, CHaHbO),
3.36 (1H, dd, J¼10.2, 8.2 Hz, CHbHaO), 2.88 (1H, m, CH), 1.80 (1H, br
s, OH), 0.96 (3H, d, J¼6.8 Hz, CH3); 13C NMR (100 MHz, CDCl3) 145.6,
137.2, 128.5, 128.0, 127.3, 110.0, 73.8, 67.0, 32.4, 17.1; IRnmax: 3449.0,
2927.0, 2871.0, 2362.0, 2339.0, 1663.0, 1457.0, 1029.0, 743.0,
(3R,
5S)-5-(benzyloxy)-3-methyldihidrofuran-2-(3H)-one
21a; Purified by preparative thin layer chromatography eluting
with hexane-AcOEt 8:2, to give the compound 21a as a liquid
(10 mg, 30%); ½a 2D5
ꢃ
ꢀ42.4 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3)
7.38e7.31 (5H, m, Ph), 5.55 (1H, dd, J¼5.6, 4.3 Hz, H-4), 4.90 (1H, d,
J¼11.6 Hz, CHaHbPh), 4.61 (1H, d, J¼11.6 Hz, CHbHaPh), 2.64 (1H,
dqd, 9.5, 7.0, 6.5 Hz, H-1), 2.62 (1H, ddd, J¼13.0, 9.5, 5.6 Hz, H-3),
1.87 (1H, ddd, J¼13.0, 6.5, 4.3, Hz, H-2), 1.35 (3H, d, J¼7.0 Hz, CH3);
13C NMR (100 MHz, CDCl3) 178.7, 136.3, 128.5, 128.2, 128.1, 101.7,
71.4, 36.3, 34.4, 16.6; IRnmax: 2926.6, 1779.6, 1455.6, 1162.8, 953.9,
904.1, 738.7, 698.9 cmꢀ1; FAB-HRMS: calculated for (C12H15O3),
207.1021; found, 207.1044.
698.0 cmꢀ1
found,192.1145.
; EI-HRMS: calculated for (C12H16O2), 192.1150;
4.4.18. (R, Z)-2-[(2-Bezyloxy)vinyl]pent-4-en-1-ol 24a. Purified by
preparative thin layer chromatography eluting with Hexane/AcOEt
8:2, to give the oxazolidinone as a white solid (23.8 mg, 80%) and
the compound 24a as a liquid (16.4 mg, 80%); ½a D25
þ14.7 (c 1.9,
ꢃ
CHCl3); 1H NMR (400 MHz,CDCl3) 7.38e7.30 (5H, m, Ph), 6.18 (1H,
dd, J¼6.0, 1.2 Hz, ¼CH), 5.77 (1H, ddt, J¼17.0, 10.0, 6.8 Hz, ¼CH),
5.03 (1H, ddd, J¼17.0, 3.6, 1.6 Hz, ¼CH), 5.00 (1H, ddt, J¼10.0, 1.6,
1.2 Hz, ¼CH), 4.80 (2H, s, CH2Ph), 4.24 (1H, dd, J¼9.2, 6.0 Hz, ¼CH),
3.60 (1H, dd, J¼10.0, 5.2 Hz, CHaHbO), 3.42 (1H, dd, J¼10.0, 7.6 Hz,
CHbHaO), 2.88 (1H, m, CH), 2.18 (1H, ddd, J¼14.0, 6.4, 6.4 Hz,
CHaHb), 2.04 (1H, ddd, J¼14.0, 7.2, 7.2 Hz CHbHa), 1.70 (1H, br s,
OH); 13C NMR (100 MHz, CDCl3) 146.4, 137.2, 136.6, 128.5, 128.0,
127.0, 116.0, 107.8, 73.8, 66.2, 37.5, 36.2; IRnmax: 3422.0, 2925.0,
2873.0, 2368.0, 2340.0, 1663.0, 1455.0, 1103.0, 1071.0, 737.0, 694.0.
cmꢀ1; FAB-HRMS: calculated for (C14H20O2), 220.1463; found,
220.1435.
4.4.15. (3R,
5R)-5-(Benzyloxy)-3-methyldihidrofuran-2-(3H)-one
21b. Purified by preparative thin layer chromatography eluting
with hexane-AcOEt 8:2, to give the compound 21b as a liquid
(30 mg, 69%); ½a 2D5
ꢃ
þ109.1 (c 0.7, CHCl3); 1H NMR (400 MHz, CDCl3)
7.37e7.31 (5H, m, Ph), 5.52 (1H, d, J¼5.6 Hz, H-4), 4.82 (1H, d,
J¼11.6 Hz, CHaHbPh), 4.57 (1H, d, J¼11.6 Hz, CHbHaPh), 2.87 (1H,
ddq, J¼10.8, 8.6, 7.2 Hz, H-1), 2.42 (1H, dd, J¼13.2, 8.5 Hz, H-3), 2.00
(1H, ddd, J¼13.2, 10.8, 5.6 Hz, H-2), 1.26 (3H, d, J¼7.2 Hz, CH3); 13
C
NMR (100 MHz, CDCl3) 179.6, 136.4, 128.5, 128.2, 100.5, 70.6, 37.2,
32.5, 15.2; IRnmax: 2926.6, 1779.6, 1455.6, 1162.8, 953.9, 904.1, 738.7,
698.9 cmꢀ1; EI-HRMS: calculated for (C12H14O3), 206.0943; found,
206.0923.
4.4.19. (R, Z)-2-Benzyl-4-(benzyloxy)but-3-en-1-ol 25a. Purified by
preparative thin layer chromatography eluting with Hexane/
AcOEt 8:2, to give the oxazolidinone as a white solid (34.4 mg,
4.4.16. (2R, Z)-4-Benzyloxyl-2-methylbut-3-enoic acid 22. To
100 mL round-bottom equipped with a magnetic stir bar, the
80%) and the compound 25a as a liquid (29.6 mg, 80%); ½a D25
þ4.4
ꢃ

ꢀ
J. Jimenez et al. / Tetrahedron 71 (2015) 4590e4597
4597
(c 2.3, CHCl3); 1H NMR (400 MHz, CDCl3) 7.34e7.16 (10H, m, Ph),
Supplementary data
6.10 (1H, dd, J¼6.2, 1.2 Hz, ¼CH), 4.73 (1H, d, J¼12.8 Hz,
OCHaHbPh), 4.67 (1H, d, J¼12.8 Hz, OCHbHaPh), 4.25 (1H, dd, J¼9.2,
6.2 Hz, ¼CH), 3.60 (1H, dd, J¼10.4, 5.2 Hz, OCHaHb), 3.44 (1H, dd,
J¼10.4, 7.4 Hz, OCHbHa), 3.11 (1H, m, CH), 2.75 (1H, dd, J¼13.6,
6.8 Hz, CHaHbPh), 2.56 (1H, dd, J¼13.6, 8.0 Hz, CHbHaPh), 1.80 (1H,
br s, OH); 13C NMR (100 MHz, CDCl3) 146.5, 140.0, 137.2, 129.0,
Supplementary data (1H NMR and 13C NMR, spectra of all
compounds.) related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.05.037.
References and notes
128.4, 128.0, 127.8, 127.2, 125.7, 107.6, 73.6, 65.8, 39.3, 38.0; IRn
:
max
3447.0, 2926e0, 2862.0, 2361.0, 2343.0, 1658.0, 1496.0, 1456.0,
739.0, 700.0 cmꢀ1; EI-HRMS: calculated for (C18H20O2), 268.1463;
found, 268.1469.
1. (a) Kende, A. S.; Constantinides, D.; Lee, S. J.; Liebeskind, L. Tetrahedron Lett.
1975, 16, 405e408; (b) Krebs, E.-P. Helv. Chim. Acta 1981, 64, 1023e1025; (c)
Kende, A. S.; Toder, B. H. J. Org. Chem. 1982, 47, 167e169; (d) Alcock, S. G.;
Baldwin, J. E.; Bohlmann, R.; Harwood, L. M.; Seeman, J. J. Org. Chem. 1985, 50,
3526e3535; (e) Galatsis, P.; Manwell, J. J. Tetrahedron Lett. 1995, 36, 8179e8182;
(f) Galatsis, P.; Manwell, J. J.; Millan, S. D. Tetrahedron Lett. 1996, 37, 5261e5264.
2. Tomooka, K.; Nagasawa, A.; Wei, S.-Y.; Nakai, T. Tetrahedron Lett. 1996, 37,
8895e8898.
3. Tomooka, K.; Nagasawa, A.; Nakai, T. Chem. Lett. 1998, 27, 1049e1050.
4. (a) Guha, S. K.; Shibayama, A.; Abe, D.; Ukaji, Y.; Inomata, K. Chem. Lett. 2003,
32, 778e779; (b) Guha, S. K.; Shibayama, A.; Abe, D.; Sakaguchi, M.; Ukaji, Y.;
Inomata, K. Bull. Chem. Soc. Jpn. 2004, 77, 2147e2157 and references therein.; (c)
Nakano, T.; Soeta, T.; Endo, K.; Inomata, K.; Ukaji, Y. J. Org. Chem. 2013, 78,
12654e12661; (d) Inomata, K. J. Synth. Org. Chem. Jpn. 2009, 67, 1172e1182; (e)
Horii, S.; Ishimaru, I.; Ukaji, Y.; Inomata, K. Chem. Lett. 2011, 40, 521e523; (f)
Tayama, E.; Toma, Y. Tetrahedron 2015, 71, 554e559.
4.4.20. (S,Z)-4-(Benzyloxy)-2-methylbut-3-en-1-ol 23b. Purified by
preparative thin layer chromatography eluting with Hexane/AcOEt
8:2, to give the oxazolidinone as a white solid (25 mg, 80%) and the
compound 23b as a liquid (16 mg, 84%); ½a D25
ꢃ
ꢀ3.3 (c 0.5, CHCl3); 1H
NMR (400 MHz,CDCl3) 7.38e7.31 (5H, m, Ph), 6.13 (1H, d, J¼6.2 Hz,
¼CH), 4.80 (2H, s, CH2Ph), 4.23 (1H, dd, J¼9.2, 6.2 Hz, ¼CH), 3.52
(1H, dd, J¼10.4, 5.2 Hz, CHaHbO), 3.36 (1H, dd, J¼10.4, 8.0 Hz,
CHbHaO), 2.89 (1H, m, CH), 0.96 (3H, d, J¼6.8 Hz, CH3); 13C NMR
(100 MHz, CDCl3) 145.6, 137.2, 128.5, 128.0, 127.4, 110.0, 73.8, 68.0,
32.5, 17.1; IRnmax: 3449.0, 2927.0, 2871.0, 2362.0, 2339.0, 1663.0,
5. (a) Abe, T.; Suzuki, T.; Sekiguchi, K.; Hosokawa, S.; Kobayashi, S. Tetrahedron
Lett. 2003, 44, 9303e9305; (b) Shirokawa, S.-I.; Kamiyama, M.; Nakamura, T.;
Okada, M.; Nakasaki, A.; Hosokawa, S.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126,
13604e13605.
1457.0, 1029.0, 743.0, 698.0 cmꢀ1
(C12H16O2), 192.1150; found,192.1145.
; EI-HRMS: calculated for
6. Davies, S. G.; Elend, D. L.; Jones, S.; Roberts, P. M.; Savory, E. D.; Smith, A. D.;
Thomson, J. E. Tetrahedron 2009, 65, 7837e7851.
4.4.21. (S, Z)-2-[(2-Bezyloxy)vinyl]pent-4-en-1-ol 24b. Purified by
preparative thin layer chromatography eluting with Hexane/AcOEt
8:2, to give the oxazolidinone as a white solid (28.5 mg, 80%) and
the compound 24b as a liquid (19.7 mg, 80%); Liquid, Yield 80%;
ꢀ
ꢀ
ꢀ
7. Jimenez, J.; Meza-Leon, R.; Piscil-Sartillo, F.; Melendez, F. J.; Sansinenea, E.;
Ortiz, A. Tetrahedron Lett. 2012, 53, 4775e4778.
8. (a) Han, H.; Cho, C.-W.; Janda, K. D. Chem.dEur. J. 1999, 5, 1565e1569; (b) Ito,
M.; Clark, C. W.; Mortimore, M.; Goh, J. B.; Martin, S. F. J. Am. Chem. Soc. 2001,
123, 8003e8010; (c) Trost, B. M.; Li, C.-J. J. Am. Chem. Soc. 1994, 116,
10819e10820.
9. Abraham, E.; Cookie, J. W. B.; Davies, S. G.; Naylor, A.; Nicholson, R. L.; Price, P.
D.; Smith, A. D. Tetrahedron 2007, 63, 5855e5872.
10. Ihara, M.; Katsumata, A.; Setsu, F.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1996,
61, 677e684.
11. (a) Dobarro, A.; Velasco, D. Tetrahedron 1996, 52, 13733e13738; (b) Henderson,
J. R.; Parvez, M.; Keay, B. A. Org. Lett. 2009, 11, 3178e3181.
12. (a) Bull, S. D.; Davies, S. G.; Jones, S.; Polywya, M. E. C.; Prasad, R. S.; Sanganee,
H. J. Synlett 1998, 519e521; (b) Davies, S. G.; Sanganee, H. J.; Szolcsanyi, P.
Tetrahedron 1999, 55, 3337e3354; (c) Davies, S. G.; Sanganee, H. J. Tetrahedron:
Asymmetry 1995, 6, 671e674; (d) Bull, S. D.; Davies, S. G.; Garner, A. C.; Kru-
chinin, D.; Key, M.-S.-; Roberts, P. M.; Savory, E. D.; Smith, D.; Thomson, J. E. Org.
Biomol. Chem. 2006, 4, 2945e2964.
13. Like (L) Stereodescriptor for Diastereomers with two Stereogenic Centers where
both are R or both S within a Given Molecule. Unlike (U), one is R and the Other is S
or the reverse. Stereochemistry of Organic Compounds; Eliel, E. L., Wilen, S. H.,
Mander, L. N., Eds.; John Wiley and Sons: USA, 1994; pp 1191e1210.
14. The alkylation reaction of 8 was carried out in the presence of HMPA as additive
too, with the intention to observe any change in yield or stereoselectivity of
alkylated products 8aeb. However, the compounds were achieved with same
yield and the same stereoselectivity.
15. The vinylketene silyl N,O-acetyl 17 was unstable and unable to purify it by any
chromatographic technique, its 1H NMR spectrum showed a single product and
it was enough clean to allow measuring the important coupling constants: 5.85
(J¼6.4, 1.2 Hz), 5.76 (J¼11.0, 1.2 Hz), 5.01 (J¼11.0, 6.4 Hz). These NMR data
couldn’t be compared with literature data due to the fact that similar structures
are not found in the literature.
½
a 2D5
ꢃ
ꢀ14.7 (c 1.6, CHCl3); 1H NMR (400 MHz,CDCl3) 7.38e7.30 (5H,
m, Ph), 6.18 (1H, dd, J¼6.0, 1.2 Hz, ¼CH), 5.77 (1H, ddt, J¼17.0, 10.0,
6.8 Hz, ¼CH), 5.03 (1H, ddd, J¼17.0, 3.6, 1.6 Hz, ¼CH), 5.00 (1H, ddt,
J¼10.0, 1.6, 1.2 Hz, ¼CH), 4.80 (2H, s, CH2Ph), 4.24 (1H, dd, J¼9.2,
6.0 Hz, ¼CH), 3.60 (1H, dd, J¼10.0, 5.2 Hz, CHaHbO), 3.42 (1H, dd,
J¼10.0, 7.6 Hz, CHbHaO), 2.88 (1H, m, CH), 2.18 (1H, ddd, J¼14.0, 6.4,
6.4 Hz, CHaHb), 2.04 (1H, ddd, J¼14.0, 7.2, 7.2 Hz CHbHa), 1.70 (1H, br
s, OH); 13C NMR (100 MHz, CDCl3) 146.4, 137.2, 136.6, 128.5, 128.0,
127.0, 116.0, 107.8, 73.8, 66.2, 37.5, 36.2; IRnmax: 3422.0, 2925.0,
2873.0, 2368.0, 2340.0, 1663.0, 1455.0, 1103.0, 1071.0, 737.0, 694.0.
cmꢀ1; FAB-HRMS: calculated for (C14H20O2), 220.1463; found,
220.1435.
4.4.22. (S, Z)-2-Benzyl-4-(benzyloxy)but-3-en-1-ol 25b. Purified by
preparative thin layer chromatography eluting with Hexane/AcOEt
8:2, to give the oxazolidinone as a white solid (26.1 mg, 80%) and
the compound 25b as a liquid (22.2 mg, 80%); ½a D25
ꢀ4.7 (c 1.5,
ꢃ
CHCl3); 1H NMR (400 MHz, CDCl3) 7.34e7.16 (10H, m, Ph), 6.10 (1H,
dd, J¼6.2, 1.2 Hz, ¼CH), 4.73 (1H, d, J¼12.8 Hz, OCHaHbPh), 4.67 (1H,
d, J¼12.8 Hz, OCHbHaPh), 4.25 (1H, dd, J¼9.2, 6.2 Hz, ¼CH), 3.60
(1H, dd, J¼10.4, 5.2 Hz, OCHaHb), 3.44 (1H, dd, J¼10.4, 7.4 Hz,
OCHbHa), 3.11 (1H, m, CH), 2.75 (1H, dd, J¼13.6, 6.8 Hz, CHaHbPh),
2.56 (1H, dd, J¼13.6, 8.0 Hz, CHbHaPh), 1.80 (1H, br s, OH); 13C NMR
(100 MHz, CDCl3) 146.5,140.0,137.2, 129.0,128.4,128.0,127.8, 127.2,
125.7, 107.6, 73.6, 65.8, 39.3, 38.0; IRnmax: 3447.0, 2926.0, 2862.0,
2361.0, 2343.0, 1658.0, 1496.0, 1456.0, 739.0, 700.0 cmꢀ1; EI-HRMS:
calculated for (C18H20O2), 268.1463; found, 268.1469.
16. (a) Morita, M.; Ishiyama, S.; Koshino, H.; Nakata, T. Org. Lett. 2008, 10,
D
1675e1678 R-4-(benzyloxy)-2-methylbutan-1-ol, Lit.
[a
]
þ10.1 (c 1.0,
25
D
CHCl3). Our result [
a
]
25 þ10.5 (c 0.35, CHCl3); (b) Shi, C. J. U.S. Patent 4461835,
1984 (ꢀ)-4-benzyloxy-2-methylbutyric acid.
17. Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett. 1987, 28, 6141e6144.
18. (a) Prashad, M.; Har, D.; Kim, H.-Y.; Repic, O. Tetrahedron Lett. 1998, 39,
7067e7070; (b) Palomo, C.; Oiarbide, M.; Dias, F.; Ortiz, A.; Linden, A. J. Am.
Chem. Soc. 2001, 123, 5602e5603.
19. The stereochemistry of
g-lactones was estimated using theoretical calculations,
see Ref. 7.
20. (a) Lee, E.; Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S. K. J. Am. Chem. Soc. 2001,
ꢀ
123, 10131e10132; (b) Ortiz, A.; Quintero, L.; Hernandez, H.; Maldonado, S.;
Acknowledgements
ꢀ
Mendoza, G.; Bernes, S. Tetrahedron Lett. 2003, 44, 1129e1132; (c) Palomo, C.;
Oiarbide, M.; Lopez, R.; Gonzalez, P. B.; Gomez-Bengoa, E.; Jose, M.; Saa, J. M.;
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
We thank VIEP (projects) for financial support.
Linden, A. J. Am. Chem. Soc. 2006, 128, 15236e15247.