Experimental and computational investigation of the unexpected formation of β-substituted polyoxygenated furans from conveniently functionalized carbohydrates

Article abstract of DOI:10.1016/j.tet.2009.11.051

In the course of our current studies on the reactivity of alkylidenecarbenes, prepared with the trimethylsilylazide/Bu₂SnO method, on conveniently functionalized α-cyanomesylates derived from d-allose, d-arabinose, and d-threose, we have observ

Full text of DOI:10.1016/j.tet.2009.11.051

Tetrahedron 66 (2010) 736–742
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Experimental and computational investigation of the unexpected formation
of
b-substituted polyoxygenated furans from conveniently functionalized
carbohydrates
,
b
b
Romaric Cordonnier a, Albert Nguyen Van Nhien a , Elena Soriano , Jose Marco-Contelles ,
*
´
,
Denis Postel a
*
a
´
´
Laboratoire des glucides, Universite de Picardie-Jules Verne; Faculte des Sciences, 33, rue Saint Leu, 80039 Amiens, France
b Laboratorio de Radicales Libres y Qu´ımica Computacional (IQOG, CSIC), C/Juan de la Cierva, 3, 28006 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
In the course of our current studies on the reactivity of alkylidenecarbenes, prepared with the trime-
Received 12 October 2009
Received in revised form
6 November 2009
Accepted 10 November 2009
Available online 14 November 2009
thylsilylazide/Bu2SnO method, on conveniently functionalized
-arabinose, and -threose, we have observed the unexpected, but mechanistically interesting formation
of enantiomerically -substituted polyhydroxylated furans. These compounds are the result of a series of
cascade fragmentation reactions on unstable intermediates obtained during 1,5C–H insertion reactions
from alkylidenecarbenes. The mechanism of the reaction has been investigated by computational
methods using DFT analysis.
a-cyanomesylates derived from D-allose,
D
D
b
Keywords:
Sugar alkylidenecarbenes
Ó 2009 Elsevier Ltd. All rights reserved.
a
-Cyanomesylates
1,5C–H bond insertions
-Susbtituted furans
b
DFT analysis
1. Introduction
known explosive combination of sodium azide and halogenated sol-
vents.4,5 Some years ago, and also starting from
a-cyanomesylates, we
The insertion reaction of alkylidenecarbenes is demonstrated to be
an effective method for the synthesis of various cyclic systems through
1,5-, 1,6- or heteroinsertions.1 Most of the classical route to generate
these highly reactive species involved an unsaturated C,C-bond with
leaving groups. 2a–f Several authors exploited the low stability of the
unsaturated N,N-bond to generate a (alkylidene)carbene functionality.
In this context, Vasella reported a sizable work on the reactivity of
glycosylidene carbenes derived from diaziridines.3a Czernecki was the
have reported6 that the synthesis of 5-substituted tetrazoles, accord-
ing to Wittenberger’s method7 (trimethylsilylazide, dibutyltin oxide,
toluene), provided a-mesyltetrazolyl intermediates that smoothlyand
in mild reaction conditions led to the desired alkylidenecarbenes
species, giving some useful intramolecular transformations via rare
1,6C–H bond insertion reactions.8 Very recently, we have described9a
the synthesis of chiral cyclopentane intermediates for the synthesis of
neplanocin A10 and trehazolin,11 via 1,5C–H insertion processes on
suitable substituted alkylidencarbene species.
first to use a-cyanomesylates as precursor for alkylidenecarbenes:
upon treatment with sodium azide/DMF a presumed alkylidene-
carbene species was formed, that after 1,2-H shift gave acetylenic
derivatives.3b Subsequent studies have shown that the reaction of
sodium azide in methylene chloride, at room temperature, in the
Continuing with our studies on this area, we report here the
unexpected, but mechanistically interesting formation of enantio-
merically pure
have isolated in the course of the generation of alkylidenecarbenes
on conveniently functionalized -cyanomesylates derived from
-allose, -arabinose, and -threose.
b
-substituted polyhydroxylated furans,12 that we
presence of tetrabutylammonium hydrogenosulfate, with
a-cyano-
a
mesylates derived from uloses, produced alkylidenecarbenes that
were trapped in situ in intermolecular reactions with an azide anion,
the solvent, or alkenes, to give branched sugars and nucleosides.4 The
obvious interest of this methodology was hampered by the well
D
D
D
2. Results and discussion
2.1. Synthesis and reactivity of the precursors
* Corresponding authors.
E-mail addresses: albert.nguyen-van-nhien@u-picardie.fr (A.N. Van Nhien),
denis.postel@u-picardie.fr (D. Postel).
Starting with commercially available 1,2:5,6-di-O-isopropyli-
dene-a-D-allopyranose (1), after standard O-methylation, acid
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.051

R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
737
hydrolysis and peracetylation, acetyl 2,4,6-tri-O-acetyl-3-O-
methyl- )- -allopyranoside (2) was isolated as a mixture of
anomers, that without separation were submitted to glycosylation
afforded a mixture of two
b
-susbtituted furans 9 and 10, in 28% and
a
(b
D
23% chemical yields, respectively (Scheme 2). The structure of
compound 10 was assigned based on its analytical and spectro-
scopic data, and unambiguously established by comparison of these
values with those described in the literature for identical com-
pounds prepared by a different and inequivocal route.12 In the case
of compound 9, the analysis showed that it was an isomer of
compound 10, differing only in the location of the isopropylidene
moiety (see Experimental section). From a mechanistic point of
view, it is also evident that again the key alkylidenecarbene C leads
to intermediate D, that spontaneously fragments to provide a mix-
ture of compound 9 and 10 in moderate overall yield (Scheme 2).
with methanol to give stereospecifically methyl 2,4,6-tri-O-acetyl-
3-O-methyl-b-D
-allopyranoside (3)13 in good overall yield
(Scheme 1). Basic hydrolysis of peracetate 3 followed by reaction
with benzaldehyde dimethyl acetal provided compound 4, that was
submitted to the ‘OCS’ (¼Oxidation to give the known, not isolated,
methyl
4,6-O-benzylidene-3-O-methyl-b-D-ribo-hexopyranosid-
2-ulose14þCyanhydrin formationþSulfonation) three-step protocol
to provide intermediate 5 as a mixture of isomers at C2 (see Ex-
perimental section), ready to react under our standard methodol-
ogy (TMSN3, Bu2SnO, toluene)6,9 for the preparation of the
alkylidenecarbene species. Unfortunately, under these conditions,
the reaction was very complex, and only compound 6 could be
isolated and characterized, albeit in low yield (10%) (Scheme 1). The
full analysis of this molecule clearly showed that this compound
did not correspond with the expected dihydrofuran-type of com-
pound obtained previously by us under similar conditions, in re-
lated substrates.9b Conversely, the electron impact spectrum mass
showed a molecular mass in agreement with a C16H18O5 molecular
formula. In the IR spectrum, a wide band at 2919 cmꢀ1 indicated
the presence of at least one free hydroxyl group. The 1H NMR
analysis revealed that the phenyl, the methoxy, and five protons
(H–C–O: 4.46–3.66 ppm) possibly bonded to oxygen atoms still
remained in the molecule; these signals showed their corre-
sponding data in the 13C NMR spectrum. In addition, we observed
O
O
O
O
H
OCH
OMs
O
OCH
a
O
O
b
O
1
O
O
O
OH
NC
C
7
8
OH
3
O
O-
O
H
O
5
O
O
O
O
O
+
O
H
4
O
2
1'
O
HO
O
2'
H
H
D
10 (23%)
9 (28%)
Scheme 2. Reagents and conditions: (a) (i). PDC, Ac2O, molecular sieves, CH2Cl2, reflux,
(ii) Ti(OiPr)4, TMSCN, MeOH, (iii) MsCl, Et3N, CH2Cl2, rt (57%); (b) TMSN3, Bu2SnO,
toluene, 100 ꢁC.
Based on the previous results, next we selected the known
protected threitol 1116 to prepare a suitable precursor 12 in order to
test if in this substrate a similar series of events leading to furan
derivatives could be possible. To our delight, under the standard
conditions (see Experimental Part) compound 12 gave the known
furan 1317 in 20% yield (Scheme 3). In this case, the initial formation
of alkylidenecarbene E is followed by 1,5 O–Si insertion to give
dihydrofuran F, that is, followed by t-butyldimetylsilyl migration18
to provide intermediate G, ready for the fragmentation cascade
process that ends with the formation of compound 13 (Scheme 3).
three signals for three protons [
7.49 (H-10), and 6.50 (H-20), and four carbons [
at 143.5 (C-1), 141.3 (C-10), 118.9 (C-2), 108.9 (C-20), that perfectly fit
with a -susbtituted furan. Accordingly, the structure of (2R,4R,5R)-
d
(sugar numbering)] at 7.51 (H-1),
d
(sugar numbering)]
b
4-((S)-furan-3-yl(methoxy)methyl)-2-phenyl-1,3-dioxan-5-ol was
assigned to compound 6. The formation of this compound was
unexpected, and reveals that the 1,5C–H insertion on the alkyli-
denecarbene A (Scheme 1) was very regioselective implicating
exclusively the protons in the methyl group at the oxygen in the
anomeric center, to give the presumed intermediate B (Scheme 1),
essentially unstable, that in a fragmentation process, possibly
promoted by the excess of the TMSN3 used, would yield the final
observed molecule.
Ph
O
Ph
TBDMSO
12
O
O
Ph
TBDMSO
11
O
a
OMs
CN
b
OH
O
O
O
(H3C)3CMe2Si
E
O
O
AcO
AcO
AcO
AcO
Ph
O
O
O
Ph
O
O
OMe
O
OH
OAc
b
O
a
c
O
O
H
HO
PhCHO
TBDMS
MeO
OAc
MeO
OAc
O
O
O
H
3
TBDMS
TBDMS
2
O
O
(H3C)3CMe2Si
O
1
13
G
F
O
O
O
O
O
Ph
Ph
O
Ph
O
d
e
Scheme 3. Reagents and conditions: (a) (i). Swern oxidation, (ii) KCN, NaHCO3, CH2Cl2,
H2O, rt, (iii) MsCl, Et3N, CH2Cl2, rt (32%); (b) TMSN3, Bu2SnO, toluene, 100 ꢁC (20%).
OMe
O
OMe
O
H
OMs
CN
x
MeO
OH
MeO
O
Hx
4
5
A
2.2. Reactivity and mechanisms based on a DFT study
6
O
O
O
O
O
Ph
O
Ph
5
OH
Ph
O
The results described above leading to the b-substituted furans
O
O
O
O
H
4
1
3
H
6, 9, 10, and 13 (Schemes 1–3) have not been optimized, but al-
though limited from the synthetic point of view, deserve further
investigation and interest regarding the mechanism of the diverse
reactions implicated. In order to investigate these aspects and ex-
plain the reactivity of the key intermediates and regiochemistry of
these processes, we decided to carry out a DFT-based computa-
tional study.
2
1'
MeO
MeO
MeO
2'
6
B
Scheme 1. Reagents and conditions. (a) (i). NaOH, CH3I, acetone, rt, (ii). Dowex resin
50 W-X8, H2O, 80 ꢁC, (iii). Ac2O, pyridine, DMAP (89%); (b) (i). HBr, CH2Cl2, 0 ꢁC, ii.
CaSO4, CH2Cl2–MeOH, HgO, Hg2O (52%); (c) (i). MeONa, MeOH, ii. C6H5C(OMe)2,
camphorsulfonic acid (49%); (d) (i). Dess–Martin (71%), (ii). Ti(i-PrO)4, TMSCN, MeOH
(14%) (iii). ClMs, Py (80%); (e) TMSN3, Bu2SnO (10%).
Firstly, we have focussed on an alkylidenecarbene at C-2 derived
from 5 (A, Scheme 1), and accordingly, we have analyzed carbene I
(Scheme 4) as theoretical model. As described above, the 1,5C–H
insertion on the alkylidenecarbene A (Scheme 1) was very regio-
selective since the process involved exclusively the methoxy group
at the anomeric position.
In view of this results, and in order to check the generality and
scope of this reactivity, next we prepared precursor 8 from known
methyl 3,4-O-isopropylidene-b-D
-arabinopyranoside (7),15 follow-
ing the standard synthetic sequence (Scheme 2) (see Experimental
Part). Under the same experimental conditions, compound 8

738
R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
O
O
the empty p orbital of the carbene carbon, the transition structure
O
O
O
O
O
O
O
TSIII adopts a less stable conformation: the forming heterocycle
adopts an envelope conformation, which forces the pyranose ring
to a skew-boat type conformation. The moving H atom shows
a larger deviation from the plane defined by the carbon atom and
the doubly bound carbon atoms of the carbene (deviation of 14.7ꢁ,
Fig. 1).
O
H
OMe
O
H
H
O
O
MeO
H
H
H
I
II
III
From an energetic point of view, our results clearly reveal a ki-
netic preference for the formation of the regioisomer II over III (3.6
vs 4.9 kcal molꢀ1, Fig. 1), due to the structural distortion needed to
get an efficient orbital overlap and achieve the transition state.
The 1,5-insertion reaction with C–H is strongly exothermic
(z ꢀ70 kcal molꢀ1, Fig. 1), and hence irreversible, although the
formation of II is thermodynamically favored (by 4 kcal molꢀ1) over
III. These results are supported by the experimental results, which
describe the formation of the furan 6 from 5 (Scheme 1).
The close proximity of the endocyclic oxygen atoms in the
presumed fused furopyran intermediate B (Scheme 1) likely pro-
motes the fragmentation process to yield the final furan product.
Two plausible routes can be envisaged to account for this trans-
formation. First, a spontaneous opening to relieve the annular
tension could take place where the breaking alkoxy group would
take the H atom away from the five-membered ring II to afford the
furan scaffold V (path a). However, we have found that this process
implies a very high activation barrier and leads to high-energy in-
termediate IV, which suggests that it is most likely promoted by the
excess of the TMSN3 used. Accordingly, we have conducted the
analysis of the reaction pathway b depicted in Scheme 5.
Scheme 4.
Previous observations9 onrelated alkylidenecarbenes have shown
us that they exist in singlet state, S0, as ground state. According to the
traditional assumption, in S0 there is an empty pp orbital on the car-
bene carbon, and the non-bonding unshared spin-paired electrons
electrons occupy a sp.-like orbital in the plane of the molecule.
Two regioisomers can be formed by 1,5C–H insertion of the
alkylidencarbene, II and III (Scheme 4). The reactive carbene in-
termediate I shows short H/CCARB (1.943 Å) distance and long C–H
bond (1.117 Å) with the methoxy moiety at C-2 (Fig. 1), so it can be
view as a precursor complexes19 or even ylide-like complexes, since
it possess a similar ylide structure. The formation of II takes place
through the half chair-like transition structures TSII showing the
moving hydrogen atom in a plane defined by the carbon atom to
which it originally is attached and the doubly bound carbon atoms
of the carbene (deviation of 11.1ꢁ). In this arrangement (Fig. 1), the
alkane C–H bond molecular orbital is periplanar with and therefore
can overlap with the empty orbital of the alkylidenecarbene.20
Analogously to our previous results,9 the key geometric parameters
of the transition state structure [long C–H (1.551 Å) and CCARBENE–C
(2.224 Å) distances and a nearly formed C–H bond (1.144 Å)] reveal
that the new carbon–hydrogen bond forms much faster than does
the new carbon–carbon bond. Therefore, the cyclization is a con-
certed process, although strongly asynchronous.9
O
OH
O
O
H
N
path a
O
O
O
O
MeO
H
O
OH
IV
O
O
H
H
TMSN3
MeO
MeO
O
O
path b
II
V
O
H
O
N
N
TMS
MeO
H
VI
Scheme 5.
The intermolecular azide-assisted proton abstraction seems
more likely since it requires a softer steric distortion than the un-
assisted intramolecular mechanism. The two-step pathway pro-
ceeds first through the late transition structure TSVI, which shows
the nearly full C–H bond cleavage (1.954 Å, Fig. 2). This transition
structure drives to the formation of the unstable triazene VI by
development of the C–N (1.448 Å) and N–H (1.013 Å) bonds, as IRC
calculations confirm. Although the preparation of triazene struc-
tures is usually fruitless because of the high unstability, silylated
triazenes have been successfully isolated under certain condi-
tions.21 The transient triazene then fragments via the transition
structure TSV by formation of the O–H (1.474 Å) bond and cleavage
Figure 1. Enthalpy profile (in kcal molꢀ1) for the 1,5C–H insertion processes of the
alkylidencarbene I into the substituents at C-2 and C-4. (Free energy differences are
shown in parenthesis).
A different picture is found in the formation of III. In order to
achieve the required orbital interaction of the sC–H electrons with
Figure 2. Computed structures for the azide-assisted fragmentation.

R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
739
of the C–N bond (1.985 Å). At this point, the opening of the dihy-
dropyrane by breaking of the O–C bond seems evident (1.675 Å) as
a result of the incipient formation of the alcohol moiety. There is
a nearly linear arrangement N/H/O in the transition state (160.7ꢁ),
with the hydrogen atom being clearly transferred from nitrogen to
oxygen. Finally, TSV leads to the furan derivative V. The formation of
the triazene VI from II proceeds with a barrier of 32.8 kcal/mol
(ꢀ42.8 kcal/mol from I) and is thermoneutral in terms of enthalpy
(0.1 kcal/mol), although it is endothermic if entropy effects are
taken into account (9.8 kcal/mol). The last step takes place with
a similar barrier 30.1 kcal/mol (ꢀ45.4 kcal/mol from I) but is clearly
exothermic thus ensuring the formation of the product. The overall
distance (2.264 Å) is still rather large, suggesting a remarkable
asynchronicity in the insertion. However, IRC calculations have
ruled out additional steps and TSVIII evolves to the expected dihy-
drofuran VIII, able to provide the furan derivative through the
assisted fragmentation mechanism described above.
In summary, as was found for the 1,5C–H insertion, the process
is concerted as the insertion is concomitant with the 1,2-silyl shift.
3. Conclusions
In our current studies on the reactivity of alkylidenecarbenes,
prepared with the trimethylsilylazide/Bu2SnO method, on conve-
transformation of I into V is very exothermic (
D
G¼ꢀ82.8 kcal/mol).
niently functionalized
-arabinose, and -threose, we have observed the unexpected,
certainly low-yielding, but mechanistically interesting formation of
enantiomerically -substituted polyhydroxylated furans. These
compounds are the result of a series of cascade fragmentation re-
actions on unstable intermediates obtained during 1,5C–H in-
sertion reactions from alkylidenecarbenes. As the computational
chemistry on the reactivity of carbine species, and in particular in
alkylidenecarbenes, has been scarcely investigated, the mechanism
of the 1,5C–H and Si–O insertion reactions from alkylidenecarbenes
has been studied by DFT-based computational methods. The results
account for the regiochemical bond insertion and show an analo-
gous concerted path for the insertion/1,2-shift events. The follow-
a-cyanomesylates derived from D-allose,
The drawings of the computed structures are presented in Figure 2.
The formation of 13 is also interesting since, besides the ring
fragmentation, points to a 1,5 Si–O insertion on the alkylidene-
carbene. For this simulation, the TBDM moiety has been replaced
for the computationally less expensive TMS group.
D
D
b
Alkylidenecarbenes are known to undergo intramolecular 1,5
O–Si insertion reactions to yield 2,3-dihydrofuran derivatives, and
this pathway has been shown to proceed more rapidly than 1,5C–
H insertion.6,18,22 Two possible pathways have been postulated to
account for this process: a concerted route and through the for-
mation of an ylide intermediate followed by the 1,2-alkylsilyl
shift.18b To note that, as we described previously for related sys-
tems, the reactive alkylidenecarbene VII resembles a oxonium
ylide structure,23 as it shows a strong interaction of the vacant
orbital on the carbene with an oxygen lone pair of the O-TMS
oxygen (C–O¼1.739, Fig. 3). In fact, it has been reported that the
absence of expected 1,5 O–Si insertion products can be ascribed to
the need to adopt a conformation that allows this required orbital
overlap.24 In this case, the lone pairs on oxygen is periplanar to the
p orbital on the carbene in the lowest energy conformation,25 so
the alkylidenecarbene can indeed be viewed as the initial ylide-
like complex.
ing fragmentation cascade to the b-substituted polyhydroxylated
furan most probably proceeds by an azide-assisted intermolecular
proton abstraction mechanism, which is supported by the
calculations.
4. Experimental section
4.1. Materials and methods
Melting points were determined on a digital melting-point ap-
paratus (Electrothermal) and are uncorrected. Optical rotations
were recorded in CH2Cl2, CHCl3, MeOH, with a digital polarimeter
using a 1 dm cell. 1H NMR and 13C NMR spectra were recorded in
At the transition state TSVIII (Fig. 3), the attacked O–Si bond is
slightly enlarged (1.840 Å), whereas the forming C–O distance
(1.526 Å) suggests an advanced bond formation. The Si–CCARBENE
Figure 3. Enthalpy profile (in kcal molꢀ1) for the 1,5 O–Si insertion processes of the alkylidenecarbene VII. (Free energy differences are shown in parenthesis).

740
R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
CDCl3, acetone-d6, Me2SO-d6, or MeOD-d3 (internal SiMe4), re-
spectively, at 300.13 MHz and at 75.47 MHz. TLC was performed on
Silica F254 and detection by UV light at 254 nm or by charring with
phosphomolybdic acid-H2SO4 reagent. Column chromatography
was effected on Silica Gel 60 (230 mesh). Acetone, hexane, cyclo-
hexane, ethyl acetate, and diethyl ether were distilled before use.
Bases and solvents were used as supplied. 13C NMR resonances have
been assigned by using standard NMR (DEPT, COSY, HSQC) exper-
iments. FTIR spectra were obtained neat using ATR and are reported
concentrated under vacuum and the crude cyanohydrins were used
in the next step without further purification.
4.6. General method for alkylidenecarbene generation (C)
To a solution of cyanomesylate in dry toluene under argon,
dibutyltin oxide (1 equiv) and TMSN3 (2 equiv) were added. The
reaction was heated to 100 ꢁC and stirred for 22–23 h and then the
solvent was removed under vacuo. The crude product was sub-
mitted to flash chromatography (EtOAc/cyclohexane).
in cmꢀ1
.
4.2. General method for Dess–Martin periodinane
oxidation (A1)
4.7. Acetyl 2,4,6-tri-O-acetyl-3-O-methyl-a(b)-D-
allopyranoside (2)
To a solution of Dess–Martin reagent (3 or 4 equiv) in anhydrous
CH2Cl2 was slowly added a solution of starting material in anhy-
drous CH2Cl2. The mixture was stirred at rt under argon overnight.
Diethyl ether (100 mL), a saturated solution of NaHCO3 (100 mL)
and Na2S2O3 (10 g) were added and stirred for 5 min. After ex-
traction, the organic layer was successively washed with a satu-
rated solution of NaHCO3 (100 mL) and water (100 mL). The organic
phase was separated, dried (Na2SO4), filtered and evaporated to
dryness. The crude ulose was used in the next step without further
purification.
To a solution of commercial ‘diacetone-D-allose’ (1) (18 g,
0.07 mol) in acetone (250 mL) was added NaOH (2.8 g, 0.084 mol)
and iodomethane (4.35 mL, 0.077 mol). After stirring at rt for 4 h,
the reaction mixture was filtered and the filtrate evaporated to
dryness to afford crude 1,2:5,6-di-O-isopropylidene-3-O-methyl-
a-
D
-allopyranose in a quantitative yield, which was used in the next
step without further purification. Then, the diacetonide was treated
with resin Dowex 50 W-X8-100(Hþ), and stirred in distilled water
(250 mL) for 10 h at 80 ꢁC. After cooling at rt, the resin was removed
by filtration and the solvent eliminated under reduced pressure.
Pyridine (113 mL) was added to the reaction mixture at 0 ꢁC fol-
lowed by addition of DMAP (catalytic) and Ac2O (97 mL). After
stirring for 13 h at rt, the solvent was eliminated and the residue
extracted with ethyl acetate (3ꢂ100 mL). The organic layers were
gathered, dried (Na2SO4) and filtered. After flash chromatography
(EtOAc/cyclohexane, 4/6), compound 2 (22.4 g, 89%) was obtained
4.3. General method for oxidation with PDC (A2)
To a solution of starting material in CH2Cl2 and powder mole-
cular sieves 3 Å (2.5 equiv w/w), Ac2O (3.5 equiv) was added and
the mixture was refluxed. PDC (0.7 equiv) was added portionwise
and the reaction mixture was stirred for 4–22 h. After evaporation
of the solvent, the reaction mixture was dissolved with EtOAc, and
filtered through a silica pad. The filtrate was concentrated under
vacuum and the crude ulose was used in the next step without
further purification.
as a slight yellow syrup; IR(ATR)
n
1733, 1366, 1242, 1118,
d 5.94/5.91 (m, 2H, H-1),
1040 cmꢀ1 1H NMR (CDCl3, 300 MHz)
;
4.76 (m, 4H, H-2, H-5), 4.11 (m, 2H, H-6a), 4.03 (m, 2H, H-4, H-3),
4.00 (m, 2H, H-6b), 3.95 (dd, J3,4¼9.5 Hz, J4,5¼6.8 Hz, 2H, H-4), 3.42/
3.28 (s, 6H, OCH3), 2.01 (m, 24H, 6ꢂCOCH3); 13C NMR (CDCl3,
75 MHz)
d
171.0, 170.9, 170.3, 169.9, 169.8, 169.4, 169.0 (8ꢂCOCH3),
4.4. General method for oxidation (Swern) (A3)
98.6/90.5 (C-1), 80.4/7.2 (C-4), 79.9/1.2 (C-3), 73.4/1.0 (C-2), 71.7/8.5
(C-5), 62.8/2.4 (C-6), 61.8/9.3 (OCH3), 20.9 (8ꢂCOCH3). HRMS
C15H22O10Na: calcd 385.1111, found 385.1114.
DMSO (3.0 equiv) in CH2Cl2 was added dropwise to oxalyl
chloride (2.0 equiv) in CH2Cl2 at ꢀ55 ꢁC and the solution stirred
(0.5 h). The alcohol (1.0 equiv) in CH2Cl2 was then added dropwise
to the solution and the resulting solution stirred at ꢀ55 ꢁC (1.5 h).
The solution was then warmed to ꢀ30 ꢁC followed by the dropwise
addition of Et3N (3.0 equiv). The solution was then warmed to room
temperature and a standard workup (CH2Cl2) yielded the ketone
that was used in the next step without any further purification.
4.8. Methyl 2,4,6-tri-O-acetyl-3-O-methyl-b-D-
allopyranoside (3)13
To a solution of compound 2 (10 g, 0.03 mol) in CH2Cl2 cooled at
0 ꢁC was slowly added bromhydric acid (250 mL). After stirring for
1 h at rt, the reaction was quenched with cold water (500 mL) and
extracted. The organic phase was washed with a saturated solution
of NaHCO3 (ꢂ2) and water (500 mL). The organic layers were
gathered, dried (Na2SO4) and filtered. The crude (10.7 g, 0.03 mol)
was dissolved in CH2Cl2 (85 mL) and MeOH (30 mL) and then CaSO4
(10.4 g, 0.06 mol) was added. After stirring for 15 min, HgO (5.2 g,
0.024 mol) and Hg2O (0.26 g, 0.72 mmol) were added and the re-
action mixture was stirred for 13 h. After filtration through a silica
pad, the filtrate was concentrated under reduced pressure and
purified by flash chromatography (EtOAc/cyclohexane, 25/75) to
4.5. General method for cyanomesylation (B)
To a solution of crude ulose in CH2Cl2 was added a solution of
NaHCO3 (2 equiv) in water and KCN (2.1 equiv). The resulting
mixture was stirred vigorously at rt then extracted with CH2Cl2
(ꢂ2) or the crude ulose was added to a solution of diethyl ether/
H2O (2/1), NaCN (1 equiv), and NaHCO3 (2 equiv) and vigorously
stirred at rt. The organic phase was separated, dried (Na2SO4), fil-
tered and evaporated to dryness. The crude cyanohydrins were
dissolved in CH2Cl2 followed by addition of Et3N (8 equiv) and MsCl
(5.5 equiv) at 0 ꢁC. After stirring at rt, the mixture was extracted by
slow addition of water and CH2Cl2. The residue was purified by
flash chromatography. Alternatively, to a solution of crude ulose in
MeOH was added Ti(OiPr)4 (2 equiv) and the solution was stirred at
rt for 5 h or overnight; then, TMSCN (2 equiv) was added. After
24 h, a few drops of water was added, and EtOAc to dilute the so-
lution. After evaporation of the solvent, the reaction mixture was
dissolved in EtOAc and filtered through a silica pad. The filtrate was
give compound 313 (4.84 g, 52%) as a yellow syrup; IR(ATR)
n 1739,
1372, 1221, 1112, 1032 cmꢀ1; 1H NMR (CDCl3, 300 MHz)
d
4.82 (dd,
J4,3¼2.7 Hz, J4,5¼10.0 Hz 1H, H-4), 4.69 (m, 2H, H-1, H-2), 4.24 (dd,
J6a,5¼4.6 Hz, J6a,6b¼12.2 Hz, 1H, H-6a), 4.13 (dd, J6b,5¼2.4 Hz, 1H,
H-6b), 4.06 (ddd, 1H, H-5), 3.94 (t, 1H, H-3), 3.47 (s, 6H, OCH3), 2.10,
2.06, 2.03 (s, 9H, COCH3); 13C NMR (CDCl3, 75 MHz)
d 170.8, 169.6,
169.5 (COCH3), 99.5 (C-1), 77.1 (C-2), 71.6 (C-4), 69.8 (C-3), 68.7 (C-
5), 62.5 (C-6), 61.5, 56.9 (2ꢂOCH3), 20.9, 20.8 (COCH3). HRMS
C14H22O9Na: calcd 357.1162, found 357.1154.

R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
741
4.9. Methyl 4,6-O-benzylidene-3-O-methyl-
b
-D
-
4.12. Methyl 2-C-cyano-3,4-O-isopropylidene-2-O-mesyl-
b-D-
allopyranoside (4)
ribo(arabino)pyranoside (8)
Compound 3 (1.22 g, 3.65 mmol) and MeONa (0.59 g, 0.01 mol)
were dissolved in MeOH (10 mL), and stirred for 2 h at rt. The re-
action mixture was filtered through a silica pad and the filtrate was
concentrated to afford crude deacetylated (0.75 g, 3.61 mmol),
which was dissolved in CH3CN (20 mL). After addition of benzal-
dehyde dimethyl acetal (0.65 mL, 4.33 mmol) and camphorsulfonic
acid (3.0 g), the reaction mixture was stirred at rt for two days.
Neutralization with Et3N (pH¼7) followed by filtration and usual
work-up afforded after flash chromatography (EtOAc/cyclohexane,
Following general method A2, compound 715 (1.8 g, 8.82 mmol),
Ac2O (2.90 mL, 30.88 mmol), and PDC (2.32 g, 6.17 mmol) reacted
for 20 h to give the corresponding crude ulose. This ulose, following
the general method B [Ti(OiPr)4 (3.16 mL, 10.58 mmol) and TMSCN
(2.36 mL, 17.64 mmol) in MeOH (20 mL)] gave the crude cyanohy-
drins, which were dissolved in CH2Cl2 (50 mL), and treated with
Et3N (9.91 mL, 70.56 mmol) and CH3SO2Cl (3.75 mL, 48.51 mmol).
The reaction mixture was stirred overnight then extracted and the
residue purified by flash chromatography (EtOAc/cyclohexane, 50/
50) to give compound 8 (1.54 g, 56%) as a mixture (56/44) of di-
10/90) the desired compound 4 (0.53 g, 49%) as a yellow syrup;
20
[
a
]
þ76 (c 0.09, MeOH); IR (ATR)
n
2932, 1253, 1164, 1093,
7.51–7.28 (m, 5H, C6H5),
astereoisomers: yellow syrup; IR (ATR)
n
2943, 1365, 1253, 1217,
5.32, 5.17
D
1036 cmꢀ1
;
1H NMR (CDCl3, 300 MHz)
d
1182, 1145, 1082, 1031 cmꢀ1; 1H NMR (CDCl3, 300 MHz)
d
5.84 (s, 1H, CHC6H5), 4.52 (d, J1,2¼7.9 Hz, 1H, H-1), 4.40 (q,
J3,2¼5.2 Hz, J4,3¼10.3 Hz, 1H, H-3), 3.96 (m, 2H, H-6), 3.76 (s, 1H, H-
2), 3.61 (m, 2H, H-4, H-5), 3.67, 3.58 (s, 6H, OCH3); 13C NMR (CDCl3,
(s, 2H, H-1), 4.57 (d, J3,4¼5.7 Hz,1H, H-3), 4.25 (m,1H, H-4), 3.99 (m,
4H, 4ꢂH-5), 3.45, 3.43 (s, 6H, 2ꢂOCH3), 3.20, 3.19 (s, 6H,
2ꢂOSO2CH3), 1.50, 1.32 (s, 12H, 4ꢂCH3); 13C NMR (CDCl3, 75 MHz)
75 MHz)
d
137.8–126.5 (C6H5), 103.2 (CHC6H5), 102.4 (C-1), 80.7 (C-
d
115.5 (CN), 111.1 [OC(CH3)2], 97.9/97.8 (C-1), 74.0 (2ꢂC-2), 75.3/
2), 78.9 (C-4), 71.6 (C-3), 69.6 (C-6), 63.8 (C-5), 61.6, 57.8 (2ꢂOCH3).
73.7 (C-4), 72.8/70.5 (C-3), 59.4/58.6 (C-5), 57.2/57.1 (OCH3), 40.7/
40.4 (OSO2CH3), 26.1, 25.9, 25.8, 25.3 (4ꢂCH3); HMRS C11H17NO7-
NaS: calcd 330.0623, found 330.0635.
HRMS C15H20O6Na: calcd 319.1158, found 319.1169.
4.10. Methyl 4,6-O-benzylidene-2-C-cyano-2-O-mesyl-3-O-
4.13. ((4R,5S)-5-(Furan-3-yl)-2,2-dimethyl-1,3-dioxolan-4-
yl)methanol (9)/(S)-((R)-2,2-dimethyl-1,3-dioxolan-4-
yl)(furan-3-yl)methanol (10)12
methyl-
a-D-allo(altro)pyranoside (5)
Following the general method A1, compound
4
(0.63 g,
2.13 mmol) in dry CH2Cl2 (20 mL) was treated with Dess–Martin
reagent (3.61 g, 2.13 mmol) in dry CH2Cl2 (20 mL) for 11 h to give
the crude ulose (0.44 g, 71%). Following the general method B, to
a solution of the crude ulose14 in MeOH (5 mL), reacted with
Ti(OiPr)4 (0.45 mL, 1.51 mmol) and TMSCN (0.41 mL, 3.02 mmol) to
provide the crude cyanohydrins (67 mg,14%), which were dissolved
in pyridine (5 mL). After addition of CH3SO2Cl (0.05 mL, 0.62 mmol)
at 0 ꢁC, the reaction mixture was stirred for 16 h at rt; then,
extracted and the residue purified by flash chromatography (EtOAc/
Following the general method C, compound
8 (983 mg,
3.20 mmol), Bu2SnO (797 mg, 3.20 mmol), and TMSN3 (0.86 mL,
6.40 mmol) in toluene (32 mL) for 18 h at 100 ꢁC gave after flash
chromatography (EtOAc/cyclohexane, 35/65) compounds 9 (171 mg,
28%) and 10 (144 mg, 22.7%) as pure diastereoisomers. Compound 9:
20
yellow syrup; [
a]
D þ28 (c 0.51, CHCl3); IR (ATR)
n
3421, 3342, 1985,
1H NMR
(sugar numbering) 7.41, 7.36 (m, 2H, H-1, H-10),
2887, 1506, 1373, 1246, 1217, 1153, 1066, 1039, 1016 cmꢀ1
(CDCl3, 300 MHz)
;
d
6.37 (m, 1H, H-20), 4.77 (d, J3,4¼4.6 Hz, 1H, H-3), 4.23 (dt,
J5a,4¼J5b,4¼6.5 Hz, 1H, H-4), 3.95 (dd, J5a,5b¼8.1 Hz, 1H, H-5a), 3.90
(dd, 1H, H-5b), 1.43, 1.35 (s, 6H, 2ꢂCH3); 13C NMR (CDCl3, 75 MHz)
cyclohexane, 30/70) to give
stereoisomers 5 (67 mg, 80%) as a slight yellow syrup: IR (ATR):
2942, 1353, 1316, 1061 cmꢀ1; 1H NMR (CDCl3, 300 MHz)
7.52–7.30
a mixture (9/1 ratio) of dia-
n
d
d
(sugar numbering) 143.7, 140.0 (C-1, C-10), 125.1 (C-2), 110.0
(m, 5H, 2ꢂC6H5), 5.59 (s, 1H, CHC6H5), 4.84 (s, 1H, H-1), 4.63 (d,
J3,4¼2.1 Hz, 1H, H-3), 4.44 (dd, J6a,6b¼10.5 Hz, 1H, H-6a), 4.12 (m,
J6,5¼4.9 Hz, 1H, H-5), 4.04 (dd, J4,5¼3.8 Hz, 1H, H-4), 3.86 (d, 1H, H-
6b), 3.73, 3.64 (s, 6H, 2ꢂOCH3), 3.31 (s, 3H, SO2CH3); 13C NMR
[OC(OCH3)], 108.9 (C-20), 79.0 (C-4), 67.0 (C-3), 65.3 (C-5), 26.8, 25.5
(CH3). HRMS. C10H14O4Na: calcd 221.0790, found 221.0800. Com-
20
pound 1012: yellow syrup; [
a]
þ130 (c 0.02, CHCl3); IR (ATR)
n
D
3423, 2987, 2935, 1504, 1371, 1211, 1157, 1026 cmꢀ1; 1H NMR (CDCl3,
(CDCl3, 75 MHz)
d
136.8–126.1 (2ꢂC6H5), 113.6 (2ꢂCN), 102.3,
300 MHz) d
(sugar numbering) 7.40 (m, 2H, H-1, H-10), 6.35 (m,1H, H-
102.1(2ꢂCHC6H5), 99.5/99.3(C-1), 79.4/78.8(C-3), 78.1/76.7(C-4),
75.4 (2ꢂC-2), 68.5/65.3(C-6), 64.3/64.1(C-5), 62.1, 61.8, 58.6, 58.0
(4ꢂOCH3), 40.1/39.9 (O2SCH3). HRMS C17H21O8SNa: calcd 422.0886,
found 422.0875.
20), 5.21 (d, J3,4¼6.7 Hz, 1H, H-3), 4.35 (m, 1H, H-4), 3.43 (dd,
J5a,4¼7.7 Hz, J5a,5b¼11.6 Hz, 1H, H-5a), 3.33 (dd, J5b,4¼4.4 Hz, 1H, H-
5b), 2.12 (br s, 1H, OH), 1.55, 1.42 (s, 6H, 2ꢂCH3); 13C NMR (CDCl3,
75 MHz)
d
(sugar numbering) 143.9, 140.7 (C-1, C-10), 121.8 (C-2),
109.5 (C-20), 109.1 [OC(OCH3)], 78.7 (C-4), 72.3 (C-3), 63.0 (C-5), 27.9,
25.4 (2ꢂCH3). HRMS C10H14O4Na: calcd 221.0790, found 221.0792.
4.11. (2R,4R,5R)-4-((S)-Furan-3-yl(methoxy)methyl)-2-
phenyl-1,3-dioxan-5-ol (6)
4.14. 1,3-O-(Phenylmethylene-4-O-tert-butyldimethylsilyl-3-
C-cyano-3-O-mesyl-thre(erythr)itol) (12)
Following the general method C, compound
0.17 mmol), TMSN3 (45 L, 0.34 mmol), and Bu2SnO (41.6 mg,
0.17 mmol) after 15 h led after flash chromatography (EtOAc/cy-
5 (66.8 mg,
m
Following the general method A3, compound 1116 (4.0 g,
12.34 mmol), DMSO (2.63 mL, 37.03 mmol), oxalyl chloride
(2.12 mL, 24.68 mmol), and Et3N (5.2 mL, 37.03 mmol) in CH2Cl2
(50 mL) gave the intermediate crude ulose (3.69 g), that was used in
the next step without further purification; following the general
method B. To a solution of crude ulose in CH2Cl2 (143 mL) was
added NaHCO3 (2.07 g, 24.68 mmol) in water (28.6 mL) and KCN
(1.71 g, 26.4 mmol). After stirring for 19 h, the crude cyanohydrins
were dissolved in CH2Cl2 (143 mL) followed by addition of Et3N
(13.8 mL, 98.72 mmol) and MsCl (5.25 mL, 67.87 mmol). After 3 h
and work-up, the residue was purified by flash chromatography
(EtOAc/cyclohexane, 15/85) to give an unseparable mixture (3/97)
20
clohexane, 2/8) to compound 6 (5 mg, 10%) as a yellow syrup; [a]
þ42 (c 0.6, MeOH); IR(ATR)
n
2919, 1369, 1259, 1058, 1011 cmꢀ1; 1DH
NMR (CDCl3, 300 MHz)
d
(sugar numbering) 7.51 (m, 1H, H-1), 7.49
(m, 1H, H-10), 7.44–7.30 (m, 5H, C6H5), 6.50 (d, J1 ,2 ¼1.1 Hz, 1H, H-
20), 5.45 [s, 1H, CH(C6H5)], 4.46 (d, J3,4¼8.2 Hz, 1H, H-3), 4.38 (dd,
J5,6a¼5.3 Hz, 1H, H-6a), 3.96 (m, 1H, H-5), 3.74 (t, J4,5¼8.2 Hz, 1H, H-
4), 3.66 (dd, J6a,6b¼11.8, J5,6b¼7.8 Hz, 1H, H-6b), 3.38 (s, 3H, OCH3);
0
0
13C NMR (CDCl3, 75 MHz)
d (sugar numbering) 143.5 (C-1), 141.3 (C-
10), 136.1, 128.4–125.9 (C6H5), 118.9 (C-2), 108.9 (C-20), 100.5
[CH(C6H5)], 81.5 (C-4), 79.7 (C-3), 70.3 (C-6), 66.0 (C-5), 56.7
(OCH3). HRMS C16H18O5Na: calcd 313.1052, found 313.1059.

742
R. Cordonnier et al. / Tetrahedron 66 (2010) 736–742
3. (a) Wenger, W.; Vasella, A. Helv. Chim. Acta 2000, 83, 1542 and references cited
of diastereoisomers 12 (1.58 g, 32%) as an orange syrup: IR (ATR)
2962–2856, 1462, 1360, 1259, 1185, 1118, 1027 cmꢀ1 1H NMR
(CDCl3, 300 MHz) 7.53–7.41 (m, 5H, C6H5), 5.59 (s, 1H, H-5), 5.02
n
´
herein; (b) Czernecki, S.; Valery, J.-M. J. Carbohydr. Chem. 1986, 5, 235.
;
4. (a) Pe´rez.Pe´rez, M. J.; Camarasa, M. J. J. Chem. Soc., Chem. Commun. 1992, 1403;
d
´
´
(b) Perez.Perez, M. J.; Camarasa, M. J. Tetrahedron 1994, 50, 7269.
5. For some useful transformations of alkylidenecarbenes in sugar templates, see:
(a) Tronchet, J. M. J.; Gonza´lez, A.; Zumwald, J.-B.; Perret, F. Helv. Chim. Acta
1974, 57, 1505; (b) Hauske, J. R.; Guadliana, M.; Desai, K. J. Org. Chem. 1982, 47,
5019; (c) Ohira, S.; Sawamoto, T.; Yamato, M. Tetrahedron Lett. 1995, 36, 1537;
(d) Niizuma, S.; Shuto, S.; Matsuda, A. Tetrahedron 1997, 53, 13621; (e) Wardrop,
D. J.; Zhang, W.; Frtz, J. Org. Lett. 2002, 4, 489.
(d, J4A,4B¼11.1 Hz, 1H, H-4A), 4.15–4.04 (m, 4H, H-2, 2ꢂH-1, H-4B),
3.19 (s, 3H, OSO2CH3), 0.94 [s, 9H, SiC(CH3)3], 0.13, 0.10 [s, 6H,
2ꢂSiCH3]; 13C NMR (CDCl3, 75 MHz)
d 136.1–126.8 (C6H5), 115.0
(CN), 102.8 (C-5), 81.4 (C-2), 72.1 (C-4), 71.6 (C-3), 62.7 (C-1), 40.4
(OSO2CH3), 26.2 [SiC(CH3)3], 18.8 [SiC(CH3)3], ꢀ4.8, ꢀ4.9 [2ꢂSiCH3].
HRMS C19H29NO6SSiNa: calcd 450.1374, found 450.1383.
6. Van Nhien, A. N.; Leo´n, R.; Postel, D.; Carreiras, M. C.; Garcı´a, A. G.; Marco-
Contelles, J. J. Carbohydr. Chem. 2005, 24, 369.
7. (a) Wittenberger, S. J.; Donner, B. G. J. Org. Chem. 1993, 58, 4139; (b) For a review
on the synthesis of 5-substituted 1H-tetrazoles, see: Herr, R. J. Bioorg. Med.
Chem. 2002, 10, 3379.
4.15. 2-tert-Butyldimethylsilyl-3-hydroxymethylfuran (13)
8. Examples of 1,6-C–H insertions on alkylidenecarbenes are rare: (a) Feldman, K.
S.; Perkins, A. L. Tetrahedron Lett. 2001, 42, 6031; (b) Gilbert, J. C.; Blackburn, B.
K. Tetrahedron Lett. 1990, 31, 4727; (c) Brown, R. F. C.; Eastwood, F. W.; Har-
rington, K. J.; McMullen, G. L. Aust. J. Chem. 1974, 27, 2393.
9. (a) Van Nhien, A. N.; Soriano, E.; Marco-Contelles, J.; Postel, D. Carbohydr. Res.
2009, 344, 1605; (b) Van Nhien, A. N.; Cordonnier, R.; Le Bas, M.-D.; Delacroix,
S.; Soriano, E.; Marco-Contelles, J.; Postel, D. Tetrahedron 2009, 65, 9378.
10. (a) Ohira, S.; Sawamoto, T.; Yamato, M. Tetrahedron Lett. 1995, 36, 1537;
(b) Niizuma, S.; Shuto, S.; Matsuda, A. Tetrahedron 1997, 53, 13621.
11. Akiyama, M.; Awamura, T.; Kimura, K.; Hosomi, Y.; Kobayashi, A.; Tsuji, K.;
Kuboki, A.; Ohira, S. Tetrahedron Lett. 2004, 45, 7133.
Following the general method C, compound 12 (590 mg,
1.49 mmol), Bu2SnO (372 mg, 1.49 mmol), and TMSN3 (0.40 mL,
2.98 mmol) in toluene (14.9 mL) for 19 h at 100 ꢁC gave after flash
chromatography (EtOAc/cyclohexane, 1/9), compound 13 (63 mg,
20%), which showed spectroscopic data [1H NMR (CDCl3, 300 MHz)
d
7.61 (d, J4,5¼1.6 Hz,1H, H-5), 6.49 (d, 1H, H-4), 4.59 (s, 2H, CH2OH),
t
1.69 (s, 1H, OH), 0.92 (s, 9H, Bu), 0.31 (s, 6H, 2ꢂSiCH3); 13C NMR
(CDCl3, 75 MHz)
d 156.2 (C-3), 147.1 (C-5), 136.2 (C-2), 110.9 (C-1),
57.5 (CH2OH), 26.7 (tBu), 17.7 (Cq Bu), ꢀ5.3 (2ꢂCH3Si)] in accor-
t
12. (a) Hui, C. W.; Lee, H. K.; Wong, H. N. C. Tetrahedron Lett. 2001, 43, 123;
(b) Marco, J. L.; Hueso-Rodrı´guez, J. A. Tetrahedron Lett. 1988, 29, 2459.
13. Gorin, P. A. J.; Mazurek, M. Carbohydr. Res. 1978, 67, 479.
dance with the literature.17
14. Yoshimura, J.; Sato, K.; Funabashi, M. Bull. Chem. Soc. Jpn. 1979, 52, 2630.
´
´
15. Popsavin, V.; Benedekovic, G.; Popsavin, M.; Divjakovic, V.; Armbruster, T.
Tetrahedron 2004, 60, 5225.
4.16. Computational methods
16. Ihara, M.; Takino, Y.; Fukomoto, K.; Kametani, T. Tetrahedron Lett. 1988, 29, 4135.
17. (a) Bures, E. J.; Keay, B. A. Tetrahedron Lett. 1988, 29, 1247; (b) Keay, B. A.;
Bontront, J. L. J. Can. J. Chem. 1991, 69, 1326.
18. The intramolecular 1,5-oxygen-silicon insertion reactions are very well known:
(a) See Ref. 6; (b) Kim, S.; Cho, C.-M. Tetrahedron Lett. 1995, 36, 4845; (c) Hobley,
G.; Stuttle, K.; Wills, M. Tetrahedron 2003, 59, 4739.
19. Gilbert, J. C.; Giamalva, D. H.; Baze, M. E. J. Org. Chem. 1985, 50, 2557.
20. Taber, D. F.; Meagley, R. P.; Doren, D. J. J. Org. Chem. 1996, 61, 5723.
21. Wiberg, N.; Fischer, G.; Karampatses, P. Angew. Chem., Int. Ed. Engl. 1984, 23, 59.
22. (a) Miwa, K.; Aoyama, T.; Shioiri, T. Synlett 1994, 461; (b) Feldman, K. S.;
Wrobleski, M. L. J. Org. Chem. 2000, 65, 8659; (c) Gais, H.-J.; Reddy, L. R.; Babu,
G. S.; Raabe, G. J. Am. Chem. Soc. 2004, 126, 4859.
All calculations were performed with Gaussian 03.26 The
method applied for optimizing structures was B3LYP.27 The basis
set was 6ꢀ31þG(d,p) including polarization and diffuse functions.
Basis sets with diffuse functions are recommended for molecules
with lone pairs, for anions, and for systems with significant nega-
tive charge. All geometry optimizations were complete, and the
stationary points were identified as local minima or transition
states through the number of negative eigenvalues in their hessian
matrices. IRC calculations28 were used to connect the transition
state to its respective precedent and ensuing minima. Vibrational
frequency analyses were carried out also to obtain the zero-point
vibrational energies (ZPVEs) and thermodynamic parameters.
23. Sueda, T.; Nagaoka, T.; Goto, S.; Ochiai, M. J. Am. Chem. Soc. 1996, 118, 10141.
24. Grainger, R. S.; Owoare, R. B. Org. Lett. 2004, 6, 2961.
25. The rotation of the O–C–C–C dihedral angle provides conformers 4.17.
2 kcal molꢀ1 higher in energy than that depicted in Figure 3.
26. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
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Acknowledgements
´
A.N.V.N. and DP thanks the Conseil Regional de Picardie and the
`
Ministere de la Recherche for financial support. ES and JMC are
grateful to CESGA for supercomputer time.
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