Regio- and stereochemical aspects in synthesis of 2-allyl derivatives of glycolic, mandelic and lactic acids and their iodocyclisations to 3-hydroxy-3,4-dihydrofuran-2(5H)-ones

Article abstract of DOI:10.1016/j.tet.2005.06.045

Glyoxalic, phenylglyoxalic and pyruvic acids 1a-c undergo regio- and diastereoselective indium mediated allylations with allyl and cinnamyl bromides and ethyl 4-bromocrotonate to provide respective 2-allyl-, 2-(1-phenylallyl)- and 2-[(1-ethoxycarbonyl)all

Full text of DOI:10.1016/j.tet.2005.06.045

Tetrahedron 61 (2005) 8231–8240
Regio- and stereochemical aspects in synthesis of 2-allyl
derivatives of glycolic, mandelic and lactic acids and their
iodocyclisations to 3-hydroxy-3,4-dihydrofuran-2(5H)-ones
*
Pervinder Kaur, Palwinder Singh and Subodh Kumar
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India
Received 1 March 2005; revised 21 May 2005; accepted 9 June 2005
Available online 12 July 2005
Abstract—Glyoxalic, phenylglyoxalic and pyruvic acids 1a–c undergo regio- and diastereoselective indium mediated allylations with allyl
and cinnamyl bromides and ethyl 4-bromocrotonate to provide respective 2-allyl-, 2-(1-phenylallyl)- and 2-[(1-ethoxycarbonyl)allyl]-
derivatives of glycolic, mandelic and lactic acids 3–11. The reactions follow Cram’s chelation model for allylation and give syn addition
products as the major or the only products. Diastereoselective iodocyclisations of 3–8 and 10 provide 3-hydroxy-3,4-dihydrofuran-2(5H)-
ones (15–21), the stereochemical outcome, of which depends on the nature and position of the substituents on the substrate, choice of solvent
1
and base. The relative stereochemistries have been ascertained by X-ray structure and NOE experiments and coupling constants in the H
NMR spectra.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
functionalities.6 The presence of hydroxy-, alkoxy or amino
moieties at a- or b- to carbonyl group has led to considerable
p-facial discrimination through participation of Cram’s
chelation model.7–9 However, the participation of COOH
coordination in indium mediated allylation is not known.
2(5H)-Furanones have attained considerable significance as
the synthetic targets due to their wide-spread biological
activity, occurrence in nature and their use as synthetic
intermediates.1 Approaches towards stereoselective syn-
thesis are therefore a continued challenge in their synthesis.
The electrophile induced intramolecular cyclisation of an
appropriately substituted alkene ester constitutes one
practical approach for their synthesis.2
Now we report that 2-oxocarboxylic acids 1a–1c undergo
regio- and stereoselective indium mediated allylations with
allyl and cinnamyl bromides and ethy 4-bromoccrotonate to
provide respective 2-allyl-, 2-(1-phenylallyl)- and 2-[(1-
ethoxycarbonyl)allyl]- derivatives of glycolic, mandelic and
lactic acids 3–11.10 These allylation reactions, in general,
follow Cram’s cyclic model to provide syn addition products
as the only or the major products. 2-Hydroxypent-4-en-1-oic
acids 3–8 and 10, depending on the nature and position of the
substituents on the substrate, choice of solvent and base
undergo diastereoselective iodocyclisations to provide a
general procedure for 3-hydroxy-3,4-dihydrofuran-2(5H)-
ones 15–21. It has been observed that the balance of steric
factors on C-2 and C-3 position of respective alkenoic acids
significantly affects the outcome of stereoselectivities in
3-hydroxy-3,4-dihydrofuran-2(5H)-ones.
The availability of the appropriate alkene esters or acid
moieties constitutes the key step in the synthesis of target
furanones. The allylation of 2-oxocarboxylic acids could be
a simple and general approach for the synthesis of
functionalized alkene acids.3–5 However, the earlier
reported procedures for the allylation under Grignard type
conditions with allyl boronates3 and allyl trichloromethyl
silane4 or under Barbier type conditions by using mixed
metal combinations BiCl3–Mg(0)/BiCl3–Zn(0)5 suffer from
pre-synthesis of the reagents and non-availability of
substituted allyl organometallic reagents. In recent years,
indium mediated allylations have provided simple synthetic
procedures for the aqueous media allylation of carbonyl
compounds even in the presence of proton donor
2. Results and discussion
Keywords: Indium allylation; Diastereoselective; Iodocyclisations; Furan-
2-ones.
2.1. Allylation of 2-oxocarboxylic acids
*
Corresponding author. Tel.: C91 183 2450093; fax: C91 183 2258820;
e-mail: subodh_gndu@yahoo.co.in
A solution of glyoxalic acid 1a, allyl bromide 2a and indium
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.045

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P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
Scheme 2.
Scheme 1.
Similarly, 1b and 1c underwent indium mediated allylation
with 2c to provide respective 2-[(1-ethoxy carbonyl)allyl]
mandelic and lactic acids 10 and 11 (Scheme 2). Both 10
and 11 have been formed as a mixture of syn and anti
diastereomers, the syn diastereomer being the major product
(Table 1). In the case of 10, the diastereomeric ratio could be
increased to O98:2 by single crystallization. Therefore, allyl-
ation of 1a–c with ethyl 4-bromocrotonate leads to lower
diastero-selectivities than those found with cinnamyl bromide.
metal (suspension) (1:1.5:1) in THF–H2O (2:1) on stirring at
0 8C, following usual work-up and chromatography gave
2-allyl glycolic acid 3, as a pale yellow liquid (70%), MC
m/z 116 (Scheme 1). Similarly, phenylglyoxalic acid 1b and
pyruvic acid 1c underwent indium mediated allylation with
allyl bromide to give respective 2-allyl- mandelic and lactic
acids 4 and 5 (82–86%).
In order to extend the scope of this reaction to achieve a
diasteroselective allylation, the reactions of 1a–c have been
performed with cinnamyl bromide and ethyl
4-bromocrotonate. Glyoxalic acid 1a on indium mediated
allylation with cinnamyl bromide 2b gave 2-(1-phenylallyl)
glycolic acid 6, pale yellow liquid (96%), MC m/z 192, 116
The formation of syn addition products as the only, or major
products, in allylation of 1a–c with 2b and 2c could be
explained by the participation of Cram’s chelation model A
(Scheme 3) where the conformation of 2-oxocarboxylic acid
is locked by complexation with allylindium reagent and
allylic anion adds from the sterically less hindered face. In
case of ethyl 4-bromocrotonate, the lower diastereoselec-
tivities, could be due to partial participation of transition
state B or non-chelation model C (Scheme 3).11,12
1
(MCKC6H5) (Scheme 1). In its H NMR spectrum, the
presence of 1H double doublet at d 3.86 due to CHPh and
lack of CH2 signals in the region d 2.0–3.5 confirmed the
formation of g- addition product. The presence of only one
1
set of signals in both H and 13C NMR spectra points to a
single diastereomer being formed.
Similarly, indium mediated allylation of 1b and 1c with
cinnamyl bromide gave the respective 2-(1-phenylallyl)-
mandelic and pyruvic acids 7 and 8 (Table 1). Therefore,
2-oxocarboxylic acids 1a–c undergo indium mediated
highly g-regio- and diastereoselective Barbier type allyla-
tion with cinnamyl bromide. The stereochemistries as syn
addition products to 2-allyl carboxylic acids 6–8 have been
assigned on the basis of the X-ray crystal structure of
iodocyclised products 19a and 19b and coupling constant
Scheme 3.
1
We envisioned that the increased ease of participation of
carboxylic acid moiety in forming cyclic transition state with
allylindium reagent could increase the participation of Cram’s
chelation model and thus the diastereoselectivity. The
conversion of carboxylic acid to carboxylate anion (12a–c),
due to the presence of negative charge, would facilitate
chelation during the allyl transfer process. Alternatively, the
conversion of acid to amide 13, due to delocalisation of the
nitrogen lone pair of electrons with carbonyl, is expected to
increase the participation of amide oxygen towards com-
plexation with indium and thus higher diastereoselectivities.
and NOE experiments on the H NMR spectra of 18–20
(Scheme 1).
Table 1. Reactions of 2-oxocarboxylic acids 1a–c with 2b and 2c
S.no.
R1
R2
Product
Yield (%)
dr (syn:
anti)
1
2
3
4
5
6
H
C6H5
C6H5
C6H5
CO2C2H5
CO2C2H5
CO2C2H5
6
7
8
9
10
11
96
95
92
66
97
96
O99:1
O99:1
O99:1
86:14
C6H5
CH3
H
C6H5
CH3
90:10a
86:14
However, sodium pyruvate 12c did not undergo allylation
with ethyl 4-bromocrotonate in THF–H2O. On performing
a After single crystallization increases to O98:2.

P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
8233
the reaction at pH 4.7G0.2, the allylation proceeded quite
2.2. Synthesis of 3-hydroxy-3,4-dihydrofuran-2(5H)-
ones (15–21)
smoothly and in a highly diastereoselective manner to
provide 11 (drO98:2), but the yield of 11 was lowered to
50%. On using 2 equiv of indium metal and 3 equiv of 2c,
the yield of 11 could be increased to 90%. During the
reaction, the pH of the solution was maintained by adding
4 N NaOH solution from time to time. Similarly, 12a
and 12b underwent diastereoselective allylation with 2c
at pH 4.7G0.2 to provide 9 and 10, respectively, in drO
98:2 (Scheme 4). The allylation of 12a–c was completed
in shorter times (4–6 h) than the time taken for the
reactions of respective 2-oxocarboxylic acids 1a–c (18–
24 h). Both higher diastereoselectivities and shorter
reaction time for allylation at pH 4.7G0.2 could be
assigned to better participation of the carboxylate anion in
chelation than the carboxylic acid moiety. In an
alternative approach, the pH of the solution of 1a–c
in THF–H2O (2:1) was adjusted to 6G0.2 by adding
NaOH solution and then ethyl 4-bromocrotonate and indium
was added and the stirring was continued. The reactions
were completed in 4–6 h and 9–11 were formed with
diastereoselectivities O98:2.
A solution of 3 in dry CH3CN containing I2 and suspended
NaHCO3 (3 equiv) on stirring at 0 8C after work-up gave
15a, mp 69 8C, MC m/z 242 in diastereomeric ratio O99:1
(Scheme 6). The 1H NMR spectrum of 15a exhibits five 1H
signals with well defined multiplicities and one 1H signal as
multiplet and shows that each proton is magnetically non-
equivalent. The decoupling of 1H multiplet at d 4.41–4.45
coverts dt at d 1.98 to triplet, and ddd’s at d 2.89 to double
doublet, two dd’s at d 3.31 and 3.45 to doublets and has been
assigned the 5-H proton. The decoupling of the dd at d 4.62
(H3) modulates dt at d 1.98, and doublet of dd at d 2.89 and
confirms the signals at d 1.98 and 2.89 due to ring CH2
protons. The higher coupling constants (JZ10.4 Hz)
between H-c, and H-5 with signal at d 1.98 and lower
coupling constants (JZ5.4/8.6 Hz) with signal at d 2.89
support the stereochemistries defined in Figure 1. The
positive NOE of signal Hc (d 2.89) with H3 and H5 signals
and lack of NOE of Hd with these protons conspicuously
assigns these stereochemistries. Therefore 3 undergoes
highly diastereoselective iodocyclisation to provide
(3R*,5R*)-3-hydroxy-5-iodomethylfuran-2(5H)-one (15a).
Scheme 6.
2-Allylmandelic acid 4 on iodocyclisation (I2–CH3CN–
NaHCO3) provided the crude reaction mixture, which in its
1H NMR spectrum shows two multiplets at d 4.33–4.41 (1H)
and 4.68–4.79 (1H) due to CH in 66:34 ratio and pointed it
to be a mixture of two diastereomeric furan-2(5H)-ones 16a
and 16b. However, even on repeated chromatography and
crystallization, the two components could not be separated.
Since the diastereoselectivity in iodocyclisation reactions is
significantly affected by the choice of solvent and base, the
iodocyclisation of 4 was attempted under various conditions
by using solvents of varied polarities and NaC/RNH4C
carboxylates in place of COOH (Table 2).
Scheme 4.
Similarly, indium mediated allylation of 13, with ethyl
4-bromocrotonate in THF–H2O proceeded quite smoothly
(4–5 h) and in a highly diastereoselective manner (drO
98:2) to provide 14 (Scheme 5). Both higher diastereos-
electivities and shorter reaction time for allylation point to
the increased participation of amide oxygen towards
complexation with indium.
On performing the reaction of 4 in dry THF, the dr 16a/16b
was increased to 80:20, which was further increased to 91:9
on carrying out the reaction in dry DMF. The sodium salt of
Figure 1. The relative stereochemistries in 15a from NOE and coupling
constant experiments.
Scheme 5.

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P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
Table 2. Disatereoselectivities in iodocyclisations of 4
The signals for the minor component 16b were picked from
the 2:1 mixture of 16a and 16b. The irradiation of H-5 signal
at d 4.68–4.79 does not show NOE with the phenyl protons
and has been assigned the structure 16b.
S. no.
Base
Solvent
Time (h)
dr
Yield %
Effect of solvent
1
2
3
NaHCO3
NaHCO3
NaHCO3
CH3CN
THF
DMF
72
6
1–2
66:34
80:20
91:9
82
83
56
2-Allyl lactic acid 5 on iodocyclisation provided 80:20
mixture of two diastereomers, which on column chroma-
tography followed by repeated crystallization resulted in
isolation of major diastereomer 17a. The assignment of the
signals to each proton and carbon has been made on the
basis of 1H, 13C NMR, decoupling experiments and 1H–13C
COSY spectra. The relative stereochemistries at C-3 and
C-5 carbons have been ascertained from NOE experiment.
The irradiation of H-5 multiplet at d 4.44–4.49 shows
positive NOE for CH3 (12.6%) and Hc (d 2.54) (5.2%).
These observations show that H-4, CH3 and H-5 are on the
same side of furan-2(5H)-one ring and have been assigned
the structure (3R*,5R*)-3-hydroxy-3-methyl-5-iodomethyl-
furan-2(5H)-one (17a).
Effect of base
4
5
6
7
8
9
Benzyl amine THF
3–5
3–5
1–2
3–5
1–2
3–5
86:14
89:11
93:7
91: 9
95: 5
90:10
63
90
56
82
70
62
a
a
b
b
THF
DMF
THF
DMF
THF
Pyrrolidine
a Phenylethylamine.
b Diisopropylamine.
4 in dry DMF also gave 16a and 16b in 91:9 ratio but failed
to react in THF or CH3CN, probably due to its poor
solubility in latter solvents. It seems that on moving from
THF and CH3CN, to DMF, the nature of the nucleophile
shifts from carboxylic acid to carboxylate ion. Since
ammonium salts find more solubility in non-polar solvents,
the reactions of 4 were performed in the presence of various
amines. The iodocyclisation of 4 in I2-benzylamine/phenyl
ethyl amine by using THF as solvent gave 16a/16b in dr
86:14–89:11 (Table 2, s. no. 4,5), which was further
increased to 90:10–91:9 by using secondary alkyl amines
as base (s. no. 7, 9). On performing iodocyclisation of 4 in
the presence of primary and secondary amines and by using
DMF as solvent, the dr 16a/16b was enhanced to 93:7 and
95:5 (s. no. 6, 8), respectively. The 95:5 mixture of 16a/16b
on crystallization gave pure 16a, mp 70 8C, MC m/z 318.
2-(1-Phenylallyl)glycolic acid 6 on iodocyclisation gave
only one diastereomer 18a (85%), mp 84 8C, MC m/z 318
(Scheme 7). The JZ10.2 Hz coupling constant between H-5
(d 4.25–4.31) and H-4 (d 3.42) and JZ10.2 Hz coupling
constant between H-3 (d 4.77) and H-4 (d 3.42) assign trans,
trans stereochemistry between H-3, H-4 and H-5. The
irradiation of H-3 doublet at d 4.77 shows NOE
enhancement of H-5 (3.7%) and Ph (6.1%) protons and
irradiation of H-5 multiplet (d 4.25–4.31) shows NOE
enhancement of H-3 (2.2%) and Ph (5.7%) protons and
confirms the structure (3R*,4R*,5R*)-3-hydroxy-4-phenyl-
5-iodomethyl-furan-2 (5H)-one (18a) for this compound.
1
Compound 16a. in its H NMR spectrum shows four 1H
double doublets and one 1H multiplet along with aromatic
(5H) protons. The decoupling of multiplet at d 4.33–4.41
converts all the four double doublets to doublets and
unambiguously assigns H-5 proton to this multiplet. In its
1H-13C COSY spectrum, the correlation of most up-field
negative carbon (CH2I) signal at d 5.13 (due to iodine effect)
with two double doublets at d 3.34 and 3.47 assigns them to
be CH2I protons. The irradiation of 1H multiplet at d 4.33–
4.41 (H-5) enhances the signals for Hc (d 2.87) and phenyl
protons by 7.6 and 13.6%, respectively, (Fig. 2) and points
to the presence of H-5, Hc and 3-Ph moieties on the same
face of furan-2(5H)-one ring. The higher coupling constant
between H-5 and Hd (JZ10 Hz) than between H-5 and Hc
(JZ5.4 Hz) (Fig. 2) also supports the presence of Hd proton
trans to H-5 proton. This data confirms the structure
(3S*,5R*)-3-hydroxy-3-phenyl-5-iodomethylfuran-2(5H)-
one (16a) to this compound.
Scheme 7.
2-(1-Phenylallyl)mandelic acid 7 on iodocyclisation in
CH3CN–NaHCO3 gave 75:25 mixture of two diastereomers
19a (61%) and 19b (20%). On using DMF–NaHCO3 the
diastereoselectivity decreased to 50:50. In 1H NMR
spectrum of major component JH-4, H-5Z10.4 Hz shows
the presence of H-4 and H-5 on the opposite side of furan-
2(5H)-one ring (19a). The minor component in its 1H NMR
spectrum exhibits JH-4, H-5Z5.4 Hz and points to the
presence of H-4 and H-5 protons on the same side of
furan-2(5H)-one ring (19b). However, the relative stereo-
chemsitries at C-3 and C-4 in 19a and 19b could not be
assigned on the basis of NMR or NOE experiments and have
been confirmed by X-ray structure analysis.
The X-ray crystal structures of both 19a (Fig. 3) and 19b
(Fig. 4), show the presence of two aryl rings on the same
face of furan-2(5H)-one ring and confirm the formation
of syn homoallylic alcohol 7. In 19a, the CH2I and OH
Figure 2. The relative stereochemistries in 16a from NOE and coupling
constant experiments.

P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
8235
JH4,5Z4.8 Hz shows the presence of H-4 and H-5 protons
on the same side of furan-2(5H)-one ring and lack of NOE
of H-5 with phenyl and methyl protons points the placement
of methyl and phenyl groups on the opposite face than H-5
and confirms structure (3R*,4R*,5S*)-3-methyl-4-phenyl-
3-hydroxy-5-idomethyl-furan-2(5H)-one (20b) to the minor
product.
Compound 10 underwent diastereoselective iodocyclisation
to provide 21 in drO98:2 (Scheme 8). The assignment of
1
1
signals has been made on the basis of H NMR and H
decoupling experiments. The coupling constant JZ9 Hz
between H-4 (d, d 3.62) and H-5 (m, d 4.64–4.69), shows the
presence of H-4 and H-5 protons on the opposite side of
furan-2(5H)-one ring. The irradiation of H-5 multiplet
shows positive NOE for phenyl ring multiplet (5.0%) and
COOCH2 multiplet (7.67%) and points to the presence of
phenyl ring, COOEt and H-5 moieties on the same side of
furan-2(5H)-one ring. Therefore, iodine mediated cyclisa-
tion of 10 gives only (3S*,4S*, 5R*)-3-hydroxy-4-ethox-
ycarbonyl-5-iodomethylfuran-2(5H)-one 21.
Figure 3. The ORTEP view (50% ellipsoide) of 19a.
moieties are on the same face. This results in placement of
H-3 and H-4 protons on the opposite face of furan-2(5H)-
one ring and is in agreement with JH-4, 5Z10.4 Hz observed
1
in its H NMR spectrum. Similarly, in the case of 19b,
JH-4,5Z5.4 Hz is in agreement with placement of H-3 and
H-4 protons on the same side of furan-2(5H)-one ring as
confimed by X-ray structure. In both 19a and 19b C(4)–
O(1)–C(1)–C(2) make one mean plane (Tables 3 and 4) and
C-3 carbon moves out of plane by an angle of 23G18. The
two phenyl rings on C-2 and C-3 carbons are placed at
dihedral angle of 44.6(3)8 in 19a and 39.2(3)8 in 19b. The
placement of CH2I unit in two different orientations in 19a
and 19b controls the placement of C-2 and C-3 phenyl rings.
In the case of 19a, 3-phenyl ring is placed at equatorial
position [C(6)–C(3)–C(4)–O(1) –163.5(2)8] and 2-phenyl is
placed at axial position [O(1)–C(1)–C(2)–C(12) 97.3(3)8].
But in the case of 19b, 2-phenyl ring is placed at equatorial
position [O(1)–C(1)–C(2)–C(12) K151.4(2)8] and 3-phenyl
is placed at axial position [C(6)–C(3)–C(4)–O(1) 86.9(3)8].
Scheme 8.
The formation of two diastereomers of furan-2(5H)-ones
could be visualized to proceed through intermediates A and
B (Scheme 9) formed by the addition of iodine on either of
the two faces of double bond. Iodonium ion intermediate
A would result in the formation of 3,5-substituted product
with OH and CH2I groups placed syn to each other, while
iodonium ion intermediate B would result in formation of
product with OH and CH2I groups on the opposite faces of
furane ring. The present iodine mediated intramolecular
cyclisations of 2-hydroxy-4-pentene-1-oic acid and its
derivatives result in formation of the products with OH
and CH2I moieties present on same side either exclusively
or predominantly and involve the preferential participation
of intermediate A. This preference arises probably due to
stabilisation of iodonium ion intermediate by its electro-
static interactions with lone pair of oxygen in intermediate
A. Such participation of oxygen lone pairs in the
Iodine mediated intramolecular cyclisation of 8 in CH3CN
provided 70:30 mixture of 20a and 20b. In the case of 20a
the irradiation of H-5 multiplet (d 4.57–4.64) shows
NOE enhancement of CH3 (22.6%) and phenyl (21.8%)
protons. Therefore, H-5, CH3 and phenyl are on the
same side of furan-2(5H)-one ring and confirms the
structure (3R*,4R*,5R*)-3-hydroxy-3-methyl-4-phenyl-5-
iodo methyl-furan-2(5H)-one (20a). In the case of 20b,
Figure 4. The ORTEP view (50% ellipsoide) of 19b.
Scheme 9.

8236
P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
stabilization of iodonium ion has earlier been suggested in
iodocyclizations of 4-hydroxy-pentenoic acids.13
pale yellow liquid; FAB mass MC m/z 116 (MC); 1H NMR
(CDCl3): d 2.34–2.63 (m, 2H, CH2), 4.22–4.32 (m, 1H, CH),
4.60–4.92 (b, 1H, OH, exchanges with D2O), 5.04–5.17 (m,
2H, ]CH2), 5.62–5.85 (m, 1H, ]CH), 6.24–6.55 (bs, 1H,
OH, exchanges with D2O); 13C NMR (normal/DEPT-135)
(CDCl3): d 38.47 (Kve, CH2), 69.65 (Cve, CH), 118.07
(Cve, CH), 132.93 (Kve, CH2), 176.23 (ab, C); IR nmax
(neat): 1722 (C]O), 3440 (OH) cmK1. (For Na salt: mpO
300 8C. Found: C, 43.2; H, 5.1. C5H7O3Na requires C,
43.48; H, 5.07%).
3. Conclusions
Thus, 2-oxocarboxylic acids undergo facile indium
mediated allylation in aqueous media with allyl bromide,
cinnamyl bromide and ethyl 4-bromocrotonate to provide
the corresponding 2-allyl derivatives of glycolic, mandelic
and lactic acids. In the case of reactions with cinnamyl
bromide and ethyl 4-bromocrotonate, the allylation
reactions proceed with high g-regio- and diastereoselec-
tivities. The formation of syn addition products confirms
possible chelation of carboxylic acid moiety with indium
during allyl transfer process. The iodine mediated intra-
molecular cyclizations of 3–8 and 10 provide furan-2(5H)-
one derivatives with OH and CH2I moieties placed syn to
each other as the major or the only product.
4.2.2. 2-Allylmandelic acid (4). Procedure A. White solid
825 mg, 86%; mp 110 8C (CHCl3); FAB mass MC m/z 192
(MC); 1H NMR (CDCl3): d 1.87 (s, 1H, OH, exchanges with
D2O), 2.71 (dd, J1Z13.8 Hz, J2Z6.8 Hz, 1H of CH2), 2.96
(dd J1Z13.8 Hz, J2Z6.8 Hz, 1H of CH2), 5.11–5.22 (m,
2H, ]CH2), 5.69–5.89 (m, 1H, ]CH), 7.19–7.64 (m, 5H,
ArH); 13C NMR (normal/DEPT-135) (CDCl3): d 44.32
(Kve, CH2), 78.08 (ab, C), 119.72 (Kve, CH2), 125.67
(Cve, CH), 127.89 (Cve, CH), 128.45 (Cve, CH), 133.78
(Cve, CH), 140.85 (ab, C), 178.79 (ab, C); IR nmax (neat):
1720 (C]O), 3442 (OH) cmK1. Found C, 61.4; H, 5.3%.
C11H11O3Na requires C, 61.68; H, 5.14%.
4. Experimental
4.1. General details
4.2.3. 2-Allyllactic acid (5). Procedure A. 533 mg, 82%;
colourless liquid; FAB mass MC m/z 130 (MC), 111
Melting points were determined in capillaries and are
uncorrected. H NMR spectra were recorded on JEOL Al
1
1
(MCKallyl); H NMR (CDCl3): d 1.49 (s, 3H, CH3), 2.41
300 MHz instrument using CDCl3 solution containing
tetramethylsilane as an internal standard. The chemical
shifts are reported in d values relative to TMS and coupling
constants (J) are expressed in Hz. 13C NMR spectra were
recorded at 75 MHz and values are reported relative to
CDCl3 signal at d 77.0. Chromatography was performed
with silica 100–200 mesh and the reactions were monitored
by thin-layer chromatography (TLC) with glass plates
coated with silca gel HF-254.
(dd, 1H, J1Z10 Hz, J2Z6 Hz, 1H of CH2), 2.57 (dd, 1H,
J1Z10 Hz, J2Z6 Hz, 1H of CH2), 5.16–5.29 (m, 2H,
]CH2), 5.74–5.87 (m, 1H, ]CH); 13C NMR (normal/
DEPT-135) (CDCl3): d 25.22 (Kve, CH2), 44.51 (Cve,
CH3), 74.41 (ab, C), 119.33 (Cve, CH), 131.79 (Kve,
CH2), 180.18 (ab, C); IR nmax (neat): 1724 (C]O), 3446
(OH) cmK1. (For Na salt: mpO300 8C. Found: C, 47.3; H,
5.7. C6H10O3Na requires C, 47.36; H, 5.92%).
4.2.4. (2R*,3R*)-2-(1-Phenylallyl)-glycolic acid (6). Pro-
cedure A. 920 mg, 96%; light yellow liquid; FAB mass MC
m/z 192 (MC), 116 (MCKC6H5); 1H NMR (CDCl3): d 2.18
(s, 1H, OH, exchanges with D2O), 3.86 (dd, J1Z7.6 Hz,
J2Z4 Hz, 1H, CH), 4.59 (d, JZ4 Hz, 1H, CH), 5.20–5.29
(m, 2H, ]CH2), 6.25 (ddd, J1Z17.4 Hz, J2Z10 Hz, J3Z
7.4 Hz, 1H, ]CH), 7.22–7.37 (m, 5H, ArH); 13C NMR
(normal/DEPT-135) (CDCl3): d 52.82 (Cve, CH), 73.74
(Cve, CH), 117.29 (Kve, CH2), 127.37 (Cve, CH), 128.46
(Cve, CH), 128.74 (Cve, CH), 137.72 (ab, C), 136.88
(Cve, CH), 177.72 (ab, C); IR nmax (neat): 1687 (C]O),
3521 (OH) cmK1. (For Na salt: mp O300 8C. Found C,
61.4; H, 5.3%. C11H11O3Na requires C, 61.68; H, 5.14%).
4.2. General procedure
Procedure A. The 2-oxocarboxylic acid 1 (5 mmol), allyl
bromide (7.5 mmol) and indium metal (fine flakes)
(5 mmol) were taken in THF–H2O (2:1) mixture and the
reaction mixture was stirred in an ice bath until the indium
metal dissolved (18–24 h). The turbid reaction mixture was
treated with 4 N HCl and extracted with CHCl3. The organic
solvent was distilled off and the residue was column
chromatographed (silica gel, 60–120 mesh) to isolate the
allyl addition product.
Procedure B. The sodium salt of 2-oxocarboxylic acid 1
(5 mmol), 2c (15 mmol) and indium metal (fine falkes)
(10 mmol) were taken in THF–H2O (2:1) mixture. The pH
4.7 of the reaction was controlled initially by addition of
acetic acid. The reaction mixture was stirred in an ice bath
until the indium metal dissolved. During the course of
reaction the pH was controlled 4.7G0.2 by the addition of
aqueous NaOH (4 N). After completion of the reaction, the
turbid reaction mixture was treated with 4 N HCl and
extracted with CHCl3.The organic solvent was distilled off
and the residue was column chromatographed (silica gel,
60–120 mesh) to isolate the allyl addition product.
4.2.5. (2R*,3R*)-2-(1-Phenylallyl)-mandelic acid (7).
Procedure A. White solid 206 g, 95%; mp 168 8C
(CH2Cl2); FAB mass MC m/z 269 (MCC1); 1H NMR
(CDCl3): d 4.39 (s, 1H, OH, exchanges with D2O), 4.40 (d,
JZ9.6 Hz, 1H, CH), 4.79–4.99 (m, 2H, ]CH2), 5.96 (ddd,
J1Z17.4 Hz, J2Z9.6 Hz, J3Z8.1 Hz, 1H, ]CH), 7.19–
7.41 (m, 8H, ArH), 7.72–7.73 (m, 2H, ArH); 13C NMR
(normal/DEPT-135) (CDCl3): d 57.13 (Cve, CH), 80.75
(ab, C), 118.49 (Kve, CH2), 126.42 (Cve, CH), 127.26
(Cve, CH), 127.89 (Cve, CH), 128.12 (Cve, CH),
128.21(Cve, CH), 129.43 (Cve, CH), 135.29 (Cve, CH),
138.93 (ab, C), 139.17 (ab, C), 177.75 (ab, C); IR nmax
4.2.1. 2-Allylglycolic acid (3). Procedure A. 406 mg, 70%;

P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
8237
(KBr): 1685 (C]O), 3519 (OH) cmK1. (Found C, 76.3; H,
5.9. C17H16O3 requires C, 76.12; H, 5.97%).
4.3. Synthesis of 2-oxo-N-phenyl-propionamide (13)
The mixture of ethyl lactate (1 mmol, 2 g) and aniline
(1 mmol, 1.6 g) was heated without solvent for 5–6 h on
water bath. The progress of the reaction was monitored by
TLC. On completion of reaction (TLC) the reaction mixture
was diluted with 10 ml of water and extracted with CHCl3
(3!20 ml). The organic phase was washed with water and
dried over sodium sulphate. The removal of solvent
provided yellow liquid. The crude reaction mixture was
column chramotaographed over silica gel to isolate pure
2-hydroxy-N-phenylpropionamide (2.23 g, 80%). It was
treated with Jones reagent. On completion the reaction
mixture was diluted with 10 ml of water and extracted with
CHCl3 (3!20 ml). The organic phase was washed with
water and dried over sodium sulphate. The crude reaction
mixture was column chromatographed over silica gel to
isolate pure (13) (1.14 g, 52%);white solid, mp 62 8C
(CHCl3); FAB mass MC m/z 163 (MC); 1H NMR (CDCl3):
d 2.55 (s, 3H, CH3), 7.16 (t, JZ7.4 Hz, 1H, ArH), 7.35 (t,
JZ7.4 Hz, 2H, ArH), 7.62 (d, JZ9 Hz, 2H, ArH), 8.70 (br
s, 1H, NH, exchanges with D2O); 13C NMR (normal/DEPT-
135) (CDCl3): d 24.40 (Cve, CH3), 119.68 (Cve, CH),
125.26 (Cve, CH), 129.20 (Cve, CH), 136.21 (ab, C),
162.56 (ab, C), 197.29 (ab, C); IR nmax (KBr): 1674 (C]O),
1710 (C]O), 3321 (NH) cmK1. (Found: C, 66.2; H, 5.3; N,
8.3. C9H9NO2 requires C, 66.3; H, 5.52; N, 8.59%).
4.2.6. (2R*,3R*)-2-(1-Phenylallyl)-lactic acid (8). Pro-
cedure A. 948 mg, 92%; light yellow liquid; FAB mass MC
m/z 206 (MC); 1H NMR (CDCl3): d 1.49 (s,3H, CH3), 3.55
(d, JZ9.6 Hz, 1H, CH), 5.16–5.31 (m, 2H, ]CH2), 6.26
(dt, J1Z16.8 Hz, J2Z9.6 Hz, 1H, ]CH), 7.24–7.29
(m, 5H, ArH); 13C NMR (normal/DEPT-135) (CDCl3): d
24.42 (Cve, CH3), 57.61 (Cve, CH), 76.77 (ab, C), 118.80
(Kve, CH2), 127.19 (Cve, CH), 128.38 (Cve, CH), 128.53
(Cve, CH), 135.39 (Cve, CH), 139.39 (ab, C), 180.41 (ab,
C); IR nmax (neat): 1728 (C]O), 3481 (OH) cmK1. (For Na
salt: mpO300 8C. Found C, 63.1; H, 6.1. C12H13O3Na
requires C, 63.16; H, 5.70%).
4.2.7. (2R*,3S*)-2-[(1-Ethoxy carbonyl)allyl] glycolic
acid (9). Procedure B. 798 mg, 85%; light yellow liquid;
1
FAB mass MC m/z 188 (MC), 143 (MCKCOOH); H
NMR (CDCl3): d 1.31 (t, JZ7 Hz, 3H, CH3), 2.09 (s,
1H,OH, exchanges with D2O), 3.62 (dd, J1Z8.4 Hz, J2Z
3.6 Hz, 1H, CH), 4.20 (s, 1H, OH, exchanges with D2O),
4.22 (q, JZ7 Hz, 2H, OCH2), 4.47 (d, JZ3.6 Hz,1H, CH),
5.26–5.38 (m, 2H, ]CH2), 5.92 (dt, J1Z17.4 Hz, J2Z
8.4 Hz, 1H, ]CH); 13C NMR (normal/DEPT-135)
(CDCl3): d 14.21 (Cve, CH3), 50.21 (Cve, CH), 60.32
(Kve, CH2), 71.20 (Cve, CH), 121.23 (Kve, CH2), 136.13
(Cve, CH), 173.22 (ab, C), 175.59 (ab, C); IR nmax (neat):
1728 (C]O), 3481 (OH) cmK1. (For Na salt: mpO300 8C.
Found C, 45.4; H, 4.9. C8H11O5Na requires C, 45.71; H,
5.24%).
4.3.1. (2R*,3S*)-2-[(1-Ethoxy carbonyl)allyl]-N-phenyl-
propionamide (14). Procedure A. White solid 1.135 g,
82%; mp 71 8C (CHCl3); FAB mass MC m/z 277 (MC); 1H
NMR (CDCl3): d 1.23 (t, JZ7.2 Hz, 3H, CH3), 1.37 (s, 3H,
CH3), 3.83 (d, JZ9.2 Hz, 1H, CH), 4.09–4.22 (m, 2H,
OCH2), 4.95 (s, 1H, OH, exchanges with D2O), 5.35–5.44
(m, 2H, ]CH2), 5.90 (ddd, J1Z17.2 Hz, J2Z10.8 Hz, J3Z
9.2 Hz, 1H, ]CH) 7.13 (t, JZ7.2 Hz, 1H, ArH), 7.35 (t,
JZ7.5 Hz, 2H, ArH), 7.55 (d, JZ9 Hz, 2H, ArH), 8.73 (br
s, 1H, NH, exchanges with D2O); 13C NMR (normal/DEPT-
135) (CDCl3): d 14.03 (Cve, CH3), 24.01 (Cve, CH3),
54.20 (Cve, CH), 61.65 (Kve, CH2), 76.73 (ab, C), 119.59
(Cve, CH), 122.16 (Kve, CH2), 124.36 (Cve, CH), 128.95
(Cve, CH), 130.15(Cve, CH), 137.11(ab, C), 173.81(ab, C),
175.13 (ab, C); IR nmax (KBr): 1668 (C]O), 1701 (C]O),
3355 (NH), 3421 (OH) cmK1. (Found: C, 64.8; H, 7.1; N, 4.9.
C15H19NO4 requires C, 64.98; H, 6.86; N, 5.05%).
4.2.8. (2S*,3S*)-2-[(1-Ethoxy carbonyl)allyl] mandelic
acid (10). Procedure B. White solid 991 mg, 75%; mp 97–
98 8C (CH2Cl2); FAB mass MC m/z 219 (MCKCOOH); 1H
NMR (CDCl3): d 1.29 (t, JZ7.2 Hz, 3H, CH3), 2.20 (s, 1H,
OH, exchanges with D2O), 4.14 (d, JZ8.2 Hz, 1H, CH),
4.22 (q, JZ7.2 Hz, 2H, OCH2), 5.02–5.17 (m, 2H, ]CH2),
5.56–5.62 (ddd, J1Z17.4 Hz, J2Z7.2 Hz, J3Z6.4 Hz, 1H,
]CH), 7.29–7.42 (m, 8H, ArH), 7.58–7.63 (m, 2H, ArH);
13C NMR (normal/DEPT-135) (CDCl3): d 13.90 (Cve,
CH3), 56.88 (Cve, CH), 61.31 (Kve, CH2), 78.73 (ab, C),
120.64(Kve, CH2), 125.66 (Cve, CH), 127.66 (Cve, CH),
128.01 (Cve, CH), 130.23 (Cve, CH), 138.51 (ab, C),
173.22 (ab, C), 175.63 (ab, C); IR nmax (KBr): 1706 (C]O),
1730 (C]O), 3504 (OH) cmK1. (Found: C, 63.3; H, 6.0.
C14H16O5 requires C, 63.63; H, 6.06%).
4.4. Iodine mediated cyclization of homoallylic alcohols
Procedure C. Sodium hydrogen carbonate (0.009 mol) was
added to an ice cold solution of homoallylic alcohol (0.
003 mol) in dry acetonitrile and resulting suspension was
stirred for 15 min at 0 8C. Iodine (0.009 mol) was added and
stirring was continued for 24–72 h at 0 8C in dark (TLC
monitoring). The reaction mixture was diluted with water
and extracted with CHCl3. The organic layer was washed
with saturated aqueous sodium thiosulphate to remove
excess of iodine. The organic layer was dried over
anhydrous sodium sulphate and was distilled off. The
residue was column chromatographed (silica gel 100–200)
to isolate substituted furan-2(5H)-one derivatives.
4.2.9. (2R*,3S*)-2-[(1-Ethoxy carbonyl)allyl] lactic acids
(11). Procedure B. 909 mg, 90%; light yellow liquid; FAB
1
mass MC m/z 202 (MC); H NMR (CDCl3): d 1.33 (t, JZ
8 Hz, 3H, CH3), 1.39 (s, 3H, CH3), 2.84 (br s, 1H, OH,
exchanges with D2O), 4.17 (dd, J1Z8.4 Hz, J2Z3.6 Hz,
1H, CH), 4.20 (s, 1H, OH, exchanges with D2O), 4.22 (q,
JZ7 Hz, 2H, OCH2), 5.31–5.44 (m, 2H, ]CH2), 5.89 (ddd,
J1Z17 Hz, J2Z9 Hz, J3Z8.4 Hz, 1H, ]CH); 13C NMR
(normal/DEPT-135) (CDCl3): d 12.91 (Cve, CH3), 22.87
(Cve, CH3), 55.96 (Cve, CH), 59.54 (Kve, CH2), 73.18
(ab, C), 119.46 (Kve, CH2), 130.59 (Cve, CH), 176.96 (ab,
C), 176.23 (ab, C); IR nmax: 1730 (C]O), 1785 (C]O),
3558 (OH) cmK1. (For Na salt of 11: mp O300 8C. Found:
C, 48.0; H, 6.1. C9H13NaO5 requires C, 48.21; H, 5.8%).
Procedure D. Di-isopropylamine (0.009 mol) was added to
an ice cold solution of homoallylic alcohol (0.003 mol) in

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P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
dry DMF and resulting solution was stirred for 15 min at
0 8C. Iodine (0.009 mol) was added and stirring was
continued for 24 h at 0 8C in dark (TLC monitoring). The
reaction mixture was diluted with water and extracted with
ether. The organic layer was washed with saturated aqueous
sodium thiosulphate to remove excess of iodine. The
organic layer was dried over anhydrous sodium sulphate
and was distilled off. The residue was column chromato-
graphed (silica gel 100–200) to isolate substituted furan-
2(5H)-one derivatives.
decoupling of H5 multiplet at d 4.44–4.49, converts two dd d
3.32 and d 3.46 (CH2I) and at d 2.18 (Hd) and 2.54 (Hc) into
doublets NOE experiments: the irradiation of H5 multiplet
at d 4.44–4.49 shows positive NOE for CH3 (12.6%) and Hc
(d 2.54) (5.2%); 13C NMR (normal/DEPT-135) (CDCl3): d
5.65 (Kve, CH2I), 24.647 (Cve, CH3), 42.82 (Kve, CH2K
4), 73.93 (ab, C-3), 75.82 (Cve, CH-5), 178.44 (ab, C]O);
IR nmax (KBr): 1762 (C]O), 3442 (OH) cmK1. (Found: C,
28.4; H, 3.6. C6H9IO3 requires C, 28.13; H, 3.52%).
4.4.5. (3R*,4R*,5R*)-3-Hydroxy-4-phenyl-5-iodomethyl-
furan-2(5H)-one (18a). Procedure C. White solid 810 mg,
85%; mp 84 8C (benzene); FAB mass MC m/z 318 (MC);
1H NMR (CDCl3): d 2.04 (br s, 1H, OH, exchanges with
D2O), 3.27 (dd, J1Z11.4 Hz, J2Z5.4 Hz, 1H, 1H of CH2I),
3.42 (t, JZ10.4 Hz, 1H, H4), 3.52 (dd, J1Z11.4 Hz, J2Z
3.3 Hz, 1H, 1H of CH2i), 4.25–4.31 (m, 1H, H5), 4.77 (d,
JZ10.4 Hz, 1H, H3), 7.28–7.45 (m, 5H, Arh); Decoupling
of 1H multiplet at d 4.25–4.31 changes two double
doublets at d 3.27, 3.52 into doublets and triplet at d 3.42
into doublet; 13C NMR (normal/DEPT-135) (CDCl3): d
4.77(Kve, CH2I), 55.65 (Cve, CH), 74.16 (Cve, CH),
79.75 (Cve, CH), 127.72 (Cve, CH), 128.52 (Cve, CH),
129.33 (Cve, CH), 134.48 (ab, C), 175.02 (ab, C); IR nmax
(KBr): 1791 (C]O), 3384 (OH) cmK1. (Found: C, 41.2; H,
3.6. C11H11IO3 requires C, 41.51; H, 3.46%).
4.4.1. (3R*,5R*)-3-Hydroxy-5-iodomethylfuran-2(5H)-
one (15a). Procedure C. White solid 566 mg, 78%; mp
1
69 8C (benzene); FAB mass MC m/z 242 (MC); H NMR
(CDCl3): d 1.98 (dt, J1Z12.6 Hz, J2Z10.4 Hz, 1H of CH2
[Hd]), 2.89 (ddd, J1Z12.6 Hz, J2Z8.6 Hz, J3Z5.4 Hz, 1H,
1H of CH2 [Hc]), 3.31 (dd, J1Z10.4 Hz, J2Z7.5 Hz, 1H, 1H
of ICH2), 3.45 (dd, J1Z10.4 Hz, J2Z5.4 Hz, 1H, 1H of
ICH2), 3.82 (br s, 1H, OH, exchanges with D2O), 4.41–4.45
(m, 1H, H5), 4.62 (dd, J1Z10.4 Hz, J2Z8.6 Hz, 1H, H3);
13C NMR (normal/DEPT-135) (CDCl3): d 5.41(Kve,
CH2I), 37.41 (Kve, CH2K4), 68.84 (Cve, CH-3), 75.52
(Cve, CH-5), 176.53 (ab, C]O); IR nmax (KBr): 1772
(C]O), 3361 (OH) cmK1. (Found: C, 25.2; H, 2.9.
C5H7IO3 requires C, 24.79; H, 2.89%).
4.4.2. (3S*,5R*)-3-Hydroxy-3-phenyl-5-iodomethyl-
furan-2(5H)-one(16a). Procedure D. White solid 562 mg,
59%; mp 70 8C (benzene); FAB mass MC m/z 318 (MC);
1H NMR (CDCl3): d 2.46 (dd, J1Z13.2 Hz, J2Z10 Hz,1H,
1H of CH2 [Hd]), 2.87 (dd, J1Z13.2 Hz, J2Z5.4 Hz, 1H of
CH2 [Hc]), 3.11 (br s, 1H, OH, exchanges with D2O), 3.34
(dd, J1Z10.5 Hz, J2Z7.8 Hz,1H, 1H of CH2i), 3.47 (dd,
J1Z10.5 Hz, J2Z5.4 Hz,1H, 1H of CH2i), 4.33–4.41
(m,1H, H5), 7.23–7.46 (m, 5H,Arh); 13C NMR (normal/
DEPT-135) (CDCl3): d 5.13 (Kve, CH2I), 44.64 (Kve,
CH2-4), 75.53 (Cve, CH-5), 79.12 (ab, C-3), 125.16 (Cve,
CH), 129.09 (Cve, CH), 129.13 (Cve, CH), 139.55 (ab, C),
176.99 (ab, C]O); IR nmax (KBr): 1778 (C]O), 3429
(OH) cmK1. (Found: C, 41.8; H, 3.3. C11H11IO3 requires C,
41.51; H, 3.46%).
4.4.6. (3S*,4R*,5R*)-3-Hydroxy-3-phenyl-4-phenyl-5-
iodomethyl-furan-2(5H)-one (19a). Procedure C. White
solid 721 mg, 61%; mp 203 8C; FAB mass MC m/z 394
1
(MC); H NMR (CDCl3): d 1.71 (br s, 1H, OH, exchanges
with D2O), 3.27 (dd, J1Z12.0 Hz, J2Z6.0 Hz, 1H, 1H of
CH2I), 3.53 (dd, J1Z12.0 Hz, J2Z4.0 Hz, 1H, 1H of CH2i),
3.79 (d, JZ10.6 Hz, H4), 4.40–4.49 (m, 1H, H5), 6.66–6.71
(m, 2H, Arh), 6.71–6.95 (m, 2H, Arh), 7.13–7.26 (m, 2H,
Arh); 13C NMR (normal/DEPT-135) (CDCl3): d 4.43 (Kve,
CH2), 59.96 (Cve, CH), 77.42 (Cve, CH), 82.17 (absent, C),
127.13 (Cve, CH), 127.71 (Cve, CH), 127.77 (Cve, CH),
128.21 (Cve, CH), 128.37 (Cve, CH), 129.47 (Cve, CH),
131.94 (ab, C), 136.17 (ab, C),176.62 (ab, C); IR nmax (KBr):
1760 (C]O), 3377 (OH) cmK1. (Found: C, 51.5; H, 3.6%.
C17H15IO3 requires C, 51.78; H, 3.81%).
4.4.3. (3S*,5S*)-3-Hydroxy-3-phenyl-5-iodomethyl-
furan-2(5H)-one (16b). From the spectrum of 1:2 mixture
of 16a and 16b the lower concentration signals have been
chosen. 1H NMR (CDCl3):d 2.21(dd, J1Z18 Hz, J2Z8.2 Hz,
1H, 1H of ring CH2), 2. 83 (dd, J1Z18 Hz, J2Z6 Hz, 1H, 1H
of ring CH2), 3.29 (dd, J1Z10 Hz, J2Z1.8 Hz, 1H, 1H of
CH2I) and 3.45 (dd, J1Z10 Hz, J2Z4.4 Hz, 1H, 1H of
4.4.7. (3S*,4R*,5S)-3-Hydroxy-3-phenyl-4-phenyl-5-
iodomethyl-furan-2(5H)-one (19b). Procedure C. White
solid 235 mg, 20%; mp 257 8C (benzene); FAB mass MC
m/z 394 (MC); 1H NMR (CDCl3): d 2.91 (t, JZ9.6 Hz, 1H
of CH2I), 3.51 (br s, 1H, OH, exchanges with D2O), 3.38
(dd, J1Z9.6 Hz, J2Z6.3 Hz, 1H, 1H of CH2i), 3.90 (d, JZ
5.4 Hz, H4), 5.41–5.47 (m, 1H, H5), 6.90–7.92 (m, 2H, Arh),
7.02–7.11 (m, 2H, Arh), 7.34–7.36 (m, 6H, Arh);
Decoupling: the decoupling of H5 multiplet at d 5.41–5.47,
converts triplet at d 2.91, dd at d 3.55 into doublet and doublet
at d 3.61 into singlet; 13C NMR (normal/DEPT-135) (CDCl3):
d 0.79(Kve, CH2), 57.24(Cve, CH), 58.92(Cve, CH), 80.82
(Cve, CH), 81.83 (ab, C), 127.12 (Cve, CH), 127.77 (Cve,
CH), 128.21 (Cve, CH), 128.37 (Cve, CH), 129.47 (Cve,
CH), 132.32 (ab, C), 132.65 (ab, C), 176.58 (ab, C); IR nmax
(KBr): 1775 (C]O), 3438 (OH) cmK1. (Found: C, 52.1; H,
3.6. C17H15IO3 requires C, 51.78; H, 3.81%).
CH2I), 4.68–4.79 (m, 1H, H5), 7.23–7.46 (m, 5H, ArH); 13
C
NMR (normal/DEPT-135) (CDCl3): d 7.78 (Kve, CH2),
45.87 (Kve, CH2), 76.11 (Cve, CH), 78.79 (ab, C), 125.55
(Cve, CH), 128.46(Cve, CH), 139.65(ab, C), 176.21(ab, C).
4.4.4. (3R*,5R*)-3-Hydroxy-3-methyl-5-iodomethyl-
furan-2(5H)-one (17a). Procedure C. White solid
430 mg, 56%; mp 95 8C (benzene); FAB mass MC m/z
256 (MC); 1H NMR (CDCl3): d 1.52 (s, 3H, CH3), 2.18 (dd,
J1Z13.2 Hz, J2Z8.4 Hz, 1H, 1H of CH2 [Hd]), 2.54 (dd,
J1Z13.2 Hz, J2Z10.8 Hz, 1H, 1H of CH2 [Hc]), 2.61 (br s,
1H, OH, exchanges with D2O), 3.32 (dd, J1Z10.4 Hz, J2Z
8.1 Hz, 1H, 1H of CH2i), 3.46 (dd, J1Z10.4 Hz, J2Z4.8 Hz,
1H, 1H of CH2i), 4.44–4.49 (m, 1H, H5); Decoupling: the
4.4.8. (3R*,4R*,5R*)-3-Hydroxy-3-methyl-4-phenyl-5-
iodomethyl-furan-2(5H)-one (20a). Procedure C. White

P. Kaur et al. / Tetrahedron 61 (2005) 8231–8240
8239
solid 558 mg, 56%; mp 134 8C (benzene); FAB mass MC
m/z 332 (MC); 1H NMR (CDCl3): d 1.59 (s, 3H, CH3), 2.82
(s, 1H, OH, exchanges with D2O), 3.34 (dd, J1Z11.4 Hz,
J2Z6.0 Hz, 1H, 1H of CH2I), 3.53–3.66 (m, 2H, 1H of CH2i
and H4), 4.57–4.64 (m, 1H, H5), 7.22–7.26 (m, 2H, Arh),
7.33–7.44 (m, 3H, Arh); 13C NMR (normal/DEPT-135)
(CDCl3): d 4.80 (Kve, CH2I), 21.06 (Cve, CH3), 57.62
(Cve, CH-4), 78.08 (Cve, CH-5), 81.12 (ab, C), 128.271
(Cve, CH), 128.38 (Cve, CH), 128.99 (Cve, CH), 129.05
(Cve, CH), 129.29 (Cve, CH),132.91 (ab, C), 177.47 (ab,
C); IR nmax (KBr): 1764 (C]O), 3365 (OH) cmK1. (Found:
C, 43.7; H, 4.2. C12H13IO3 requires C, 43.37; H, 3.92%).
which converged to RZ0.037. Refinement method: full-
matrix least squares on F2, goodness of fitZ1.105.
4.5.2. Compound 19b. CCDC 261098, Mol. formulae
˚
C17H15IO3; triclinic space group P-1, aZ8.3040(14) A, bZ
˚
˚
9.6450(15) A, cZ10.6990(17) A, aZ76.422(13)8, bZ
3
˚
89.511(13)8, gZ70.592(15)8, vZ783.4(2) A , zZ2, dcZ
3
˚
1.671 mg/m , Mo KaZ0.70930 A, q range for data collec-
tion 1.96–24.938. The structure solution is based on 2636
reflections, which converged to RZ0.023. Refinement
method: full-matrix least squares on F2, goodness of fitZ
1.069.
4.4.9. (3R*,4R*,5S*)-3-Hydroxy-3-methyl-4-phenyl-5-
iodomethyl-furan-2(5H)-one (20b). Procedure C. White
solid 231 mg, 24%; mp 145 8C (benzene); FAB mass MC
m/z 322 (MC); 1H NMR (CDCl3): d 1.20 (s, 3H, CH3), 2.37
(br s, 1H, OH, exchanges with D2O), 2.82 (t, JZ9.6 Hz, 1H,
1H of CH2I), 3.33 (dd, J1Z9.6 Hz, J2Z6.0 Hz, 1H, 1H of
CH2i), 3.61 (d, JZ4.8 Hz, 1H, H4), 5.29–5.36 (m, 1H, H5),
7.07–7.12 (m, 2H, Arh), 7.31–7.76 (m, 3H, ArH);
Decoupling: the decoupling of H5 multiplet at d 5.29–
5.34, converts two dd’s at d 2.82, d 3.55 into doublet and
doublet at d 3.61 into singlet; 13C NMR (normal/DEPT-135)
(CDCl3): d 0.77 (Kve, CH2I), 19.48 (Cve, CH3), 57.24
(Cve, CH-4), 80.10 (Cve, CH-5), 76.87 (absent, C-3),
127.23 (Cve, CH), 128.16 (Cve, CH), 128.56 (Cve, CH),
135.16 (absent, C), 176.58 (absent, C]O); IR nmax (KBr):
1772 (C]O), 3404 (OH) cmK1. (Found: C, 43.5; H, 4.1.
C12H13IO3 requires C, 43.37; H, 3.92%).
Acknowledgements
We thank CSIR [01(1795)/02/EMR-II] for financial
assistance and DST, New Delhi for the FIST programme,
IIT Bombay, Mumbai for X-ray structure data and CDRI
Lucknow for FAB Mass and elemental analysis.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.06.
045
4.4.10. (3S*,4S*,5R*)-3-Hydroxy-3-phenyl-4-ethoxycar-
bonyl-5-iodomethyl-furan-2(5H)-one (21). Procedure C.
807 mg, 69%; light yellow liquid; FAB mass MC m/z 390
References and notes
1
(MC); H NMR (CDCl3): d 1.05 (t, JZ7.2 Hz, 3H, CH3),
1.67 (br s, 1H, OH, exchanges with D2O), 3.45 (dd, J1Z
11.4 Hz, J2Z4.8 Hz, 1H, 1H of CH2I), 3.62 (d, JZ9 Hz,
1H, CH), 3.66 (dd, J1Z11.4 Hz, J2Z4.8 Hz, 1H, 1H of
CH2i), 3.88–3.93 (m, 2H, OCH2), 4.64–4.69 (m,1H, CH),
7.28–7.45 (m, 5H, Arh); Decoupling: the decoupling of 1H
multiplet (d 4.64–4.69) converts double doublet at d 3.45
and d 3.66 into doublet and doublet at d 3.62 into singlet;
13C NMR (normal/DEPT-135) (CDCl3): d 5.83 (Kve,
CH2I), 13.77 (Cve, CH3), 59.04 (Cve, CH), 61.77 (Kve,
CH2), 75.62 (Cve, CH), 80.16 (ab, C), 125.12 (Cve, CH),
128.79 (Cve, CH), 129.48 (Cve, CH), 136.34 (ab, C),
167.16 (ab, C), 175.02 (ab, C). IR nmax (neat): 1726 (C]O),
1787 (C]O), 3614 (OH) cmK1. (Found: C, 43.2; H, 3.9.
C14H15IO5 requires C, 43.10; H, 3.87%).
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4.5.1. Compound 19a. CCDC 261510, Mol. formulae
˚
C17H15IO3; triclinic space group P-1, aZ8.039 A, bZ
˚
˚
10.102 A, cZ10.590 A, aZ88.40(13)8, bZ80.13(13)8, gZ
3
3
˚
70.17(15)8, VZ796.6(2) A , zZ2, dcZ1.643 mg/m ,
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24.978. The structure solution is based on 3021 reflections,
˚

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