β-Oxygen effect in the Barton-McCombie deoxygenation reaction: Further experimental and theoretical findings

Article abstract of DOI:10.1021/jo4012943

The chemistry of (S)-methyl xanthates derived from xylo- and ribo-furanose derivatives in the presence of the stannyl radical is investigated. Xanthate derived from β-xylo-furanose affords exclusively a deoxygenated product; whereas, under the same reacti

Full text of DOI:10.1021/jo4012943

Article
pubs.acs.org/joc
β‑Oxygen Effect in the Barton−McCombie Deoxygenation Reaction:
Further Experimental and Theoretical Findings
Alma Sanchez-Eleuterio, Jacinto Sandoval-Lira, Jenny García-Sanchez, Lorena Monterrosas-Perez,
́
́
́
Julio M. Hernandez-Perez, Leticia Quintero, and Fernando Sartillo-Piscil*
́
́
Facultad de Ciencias Químicas, Benemer
Puebla, Mexico
́
ita Universidad Auton
́
oma de Puebla (BUAP). 14 Sur Esq. San Claudio, San Manuel.72570,
́
S
* Supporting Information
ABSTRACT: The chemistry of (S)-methyl xanthates derived from
xylo- and ribo-furanose derivatives in the presence of the stannyl
radical is investigated. Xanthate derived from β-xylo-furanose affords
exclusively a deoxygenated product; whereas, under the same
reaction conditions, the α-ribo-furanose xanthate derivative produces
quantitatively a hemithioacetal compound. We reasoned that in the
case of the β-xylo-furanose derivative, a favorable β-oxygen effect in
the Barton−McCombie deoxygenation reaction is operating where,
according to theoretical calculations, unusual molecular orbital
interactions (and not strain, as previously proposed) are present.
These orbital interactions involve the SOMO (intermediary
generated from the stannyl radical addition) with the σ* orbital of
the bond undergoing cleavage and this with the two C−O antibonding orbitals anti oriented. Such molecular orbital interactions
are not present in the α-ribo-furanose; therefore, the β-scission is highly delayed, and due to the reversibly nature of the stannyl
radical addition, the ribo-furanose xanthate is forced to take an alternative route: the homolytic substitution (SH2) of the sulfide
sulfur by stannyl radical. This radical addition gives the alkoxythiocarbonyl radical, which is trapped by Bu3SnH before the
elimination of carbonyl sulfide; subsequently, radical stannyl addition followed by radical reduction produces the hemithioacetal.
via stannyl radical addition to the thiocarbonyl group; then, β-
scission of A produces secondary carbon radical B, which
undergoes reduction by Bu3SnH (route A, Scheme 1).1,2
However, an alternative mechanism for the Barton−McCombie
reaction has also been postulated: irreversible formation of the
alkoxythiocarbonyl radical C, which is formed by stannyl radical
substitution at the sulfur atom (SH2), followed by the apparent
favorable elimination of carbonyl sulfide to thus produce radical
B (route B, Scheme 1).3 Although strong experimental
evidence in favor of each mechanism have been provided,
competition experiments suggest that deoxygenation via route
B represents a less common process.4
INTRODUCTION
■
The classic Barton−McCombie reaction is the reaction that
transforms secondary alcohols (1) into their respective alkane
derivatives (2) via the temporal transformation of the hydroxyl
group into the O-methylthiocarbonyl ester (S)-methyl xanthate
(3), followed by a radical hydrogen substitution reaction
(Scheme 1).1 The prevailing reaction mechanism involves the
reversible formation of stable carbon-centered radical adduct A
Scheme 1. Barton−McCombie Reaction
A few years after the invention of this reaction, Barton
reported an interesting paper describing a favorable effect on
the deoxygenation reaction caused by the presence of an
oxygen atom located at the β-position to the carbon-centered
radical.5 Actually, it has been commented that the chemistry of
the carbon-centered radicals is only perturbed to a minor extent
by the presence of either β-hydroxy or β-alkoxy groups.6 In this
regard, to explain such unusual behavior, Jenkins postulated the
existence of polar effects in the β-scission step, wherein the
thiocarbonyl group and the C−O bond should be antiper-
iplanar oriented.7 However, on the basis of electron para-
Received: June 20, 2013
© XXXX American Chemical Society
A
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Scheme 2. Radical Deoxygenation of xylo Furanose (S)-Methyl Xanthates 4α and 4β
Scheme 3. Preparation of the xylo and ribo Furanose Xanthate Derivatives 10 and 12
a
Table 1. Reaction of xylo and ribo Furanose Xanthates 7α, 7β, 8α, and 8β with Stannyl Radical
a
Reactions conducted with 1.8 equiv of Bu3SnH at 0.068 M.
magnetic resonance (ESR) spectroscopic studies of β-
alkoxymethyl radicals, Kochi and Chen stated that the half-
filled p orbital is preferentially oriented synclinal to the β-
oxygen atom (staggered conformation).8 Additionally, using
competition experiments and computational studies, Crich and
Beckwith showed that, in conformationally labile thiocarbonyl
esters, the β-scission is not accelerated; however, in conforma-
tionally locked analogues, the β-scission is noticeably more
rapid, especially when the thiocarbonyl group is axially oriented
(i.e., the thiocarbonyl group is oriented synclinal to the β-
oxygen atom).9 They concluded that the main factor of the
origin of this β-oxygen effect comes from the greater relief of
strain on the β-scission step (steric factors), and the polar
effects do not contribute significantly to stabilization of the
transition state for the β-scission step. Although all of the
explanations concerning the β-oxygen effect in the Barton
deoxygenation reaction seem to be satisfactory for each specific
situation, it is clear that they do not cover all of the wide range
of substrates and reaction conditions. Consequently, further
experimental and theoretical studies on this very important
topic of free radical chemistry are required.
RESULTS AND DISCUSSION
■
During the course of a project directed toward the synthesis of
biologically active compounds from the chiral pool, we had the
need to use the Barton−McCombie deoxygenation reaction to
B
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a
Scheme 4. Attempts for Trapping the Putative Radical at C2 and Further Experiments
a
1
Yields and ratios determined by H NMR.
transform the mixture of α,β-methyl xylo-furanose 4 into the
respective diastereomeric mixture of tetrahydrofurans 5
(Scheme 2). The mixture of (S)-methyl xanthates 4α and 4β
was prepared by standard method from their corresponding
secondary alcohols.10 The treatment of the mixture of xanthates
4α and 4β with 1.8 equiv of Bu3SnH (0.068 M) and 1,1′-
azobis-cyclohexanecarbonitrile (ABCN) in refluxing toluene
gave two deoxygenated products 5α and 5β, and a putative
hemithioacetal 6; and, according to the 1H NMR spectrum, the
three products were formed in the ratio 26:48:26, respectively
(Scheme 2). It is important to note that purification of the
putative hemithioacetal 6 was very difficult due to its inherent
instability on silica gel, even neutralizing the silica gel with 2%
of NEt3; in its place, the secondary alcohol precursor of
xanthate 4α was obtained. However, the structure of the
hemithioacetal product was confirmed with further exper-
imentation (vide infra).
It can be noted from Scheme 2 that complete deoxygenation
of the β-anomer xanthate (4β) was achieved (5β); however, its
α-congener was deoxygenated (5α) and transformed into the
hemithioacetal 6 in a 1:1 ratio. Intrigued by these unexpected
results, we considered it necessary to validate and encompass
this observation by preparing a series of (S)-methyl xylo- and
ribo-furanose xanthate derivatives 7α, 7β, 8α and 8β (Scheme
3).
C1 and C3 positions, were chosen because they would provide
similar steric and stereoelectronic demand. And the ribo-
furanose substrates were chosen because they offer the
appropriate stereochemistry to study the apparent relationship
between the stereochemistry of the β-methoxyl groups on the
formation of the hemithioacetal product.
Xylo- and ribo-furanose xanthates 7α, 7β, 8α, and 8β were
separately treated under the same reaction conditions as the
mixture of 4α/4β, and according to the reaction crude, the
experiments showed complete consumption of starting material
to the respective products (Table 1).
Results shown in Table 1 not only validate the initials
findings but also set up the strong relation between the
stereochemistry of the β-CO bonds and the thiocarbonyl
ester on the product ratios. The quantitative isolation of
deoxygenation product 13 suggests a beneficial effect in the
Barton−McCombie reaction, probably due to the stereo-
electronic polar effect, as Jenkins proposed.7b Obviously, the
synperiplanar relationship between the OMe groups and the
thiocarbonyl group in 8α excludes such an effect, and hence the
formation of the respective deoxygenated product is much less
favored. Although the formation of hemithioacetals from
Barton−McCombie reactions have been reported,2,13 it is
important to note that in those cases they are formed as minor
byproducts; however, in the present work, the formation of
hemithiacetal 18 is the sole observed product. On the basis of
these results, we reasoned that the reversible attack of the
stannyl radical on the CS double bond and the lack of the
stereoelectronic polar effect in xanthate 8α might be
responsible for the formation of the hemithioacetal product
18 (and also for the reaction of 4α → 6) via the alternative
route B shown in Scheme 1. The mixed results for 7α → 14
plus 15, and 8β → 16 plus 17, can be taken as additional
The xanthate precursors 7α, 7β and 8α, 8β were prepared
from alcohols 10 and 12, respectively,12 and both alcohols were
prepared from the diacetone-D-glucose 9 by using standard
methods (Scheme 3).10−12 The assignment of the stereo-
chemistry of xanthate precursors required chemical correlation
of their respective alcohol precursors12 and two-dimensional
nuclear Overhauser effect spectroscopy (2D-NOESY) experi-
ments. It is important to mention that both methoxyl groups, in
C
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evidence to reinforce all of the just-mentioned. It is important
to comment that although all of the reaction crudes were very
clear, showing complete consumption of the starting materials
and formation of product(s), again, the isolation of the
hemithioacetals 15, 17, and 18 was quite difficult due to their
own instability. However, after a thorough purification either by
thin-layer chromatography using benzene as developing solvent
or passing the reaction crude through a short column of neutral
alumina using hexane as solvent and increasing polarity with
ethyl acetate (40:1), sufficient amounts of themithioacetals with
acceptable purity for spectroscopic analysis were obtain.
So, why does the alternative route turn into the principal
one? And what is the driving force of the exclusive formation of
the hemithioacetal product and therefore, the nonformation of
the deoxygenated product? Obviously, if we are able to address
these questions, we will provide further findings on the origin
of the β-oxygen effect in the Barton−McCombie deoxygenation
reaction, and in general, in the chemistry of β-alkoxy carbon-
centered radicals.
thus provide either cyclized product 22 or deoxygenated
product 14 (see Table 1 and Scheme 4).
The exclusive formation of the thioformate 24 from 19α at
20 °C, and the mixture of thioformate 25 and hemithioacetal
18 from 8α at the same temperature, suggests that hemi-
thioacetals are formed from their respective thioformates via
the formation of an alkoxythiocarbonyl radical. The experiment
of 8α to 18 with 2.0 equiv of Bu3SnH supports this proposal
(Scheme 4). It is worth mentioning that, although the presence
of alkoxythiocarbonyl radicals has been reported in some
Barton−McCombie deoxygenations or similar radical reactions,
in the present study, these free radicals are successfully trapped
in the form of thioformates demonstrating thus that the
elimination of alkoxythiocarbonyl radical is not so simple as
previously proposed.3,15 Additionally, it has been proposed that
the formation of hemithioacetals comes from radical adducts of
type E (e.g., 8α → E → 18);2 however, in the present
investigation, we provide experimental and theoretical evidence
(vide infra) suggesting that hemithioacetals are preferentially
formed from thioformates (e.g., H → 25 → 18).16
First of all, it was considered reasonable to investigate
whether the carbon-centered radical, which should be formed
from the β-scission of the adduct radical derived from 8α, is
actually not formed. To this end, thiocarbonyl ester 19α (and
also 19β) was prepared to trap the putative radical by means of
a rapid and favorable 5-exo-trig radical cyclization. The
thiocarbonyl esters 19α and 19β were prepared from
allofuranose 11 following the same route described in Scheme
3. Like xanthate 8α, the treatment of xanthate 19α with
Bu3SnH under more diluted conditions afforded thiohemiacetal
20 as the major product and alcohol 2114 as the minor product
(which comes from hydrolysis of the thiohemicetal 20), and no
trace of the cyclized product (not shown) was detected (eq 1).
On the other hand, xanthate 19β gave the cyclized product 22
as the major product, and thiohemiacetal 23 as the minor
product (eq 2). Purification of hemithioacetals 20 and 23 was
even more problematic than purification of hemithioacetals 15,
17, and 18; both were only observed by 1H NMR. In particular,
the chemical shifts and geminal coupling constants of
diastereotopic methylene hydrogen atoms attributable to the
On the basis of these experiments, we are in good position
for addressing the above-mentioned questions. The reversible
stannyl radical addition on both thiocabonyl groups of 7β and
8α at standard conditions should produce radical adducts D
and E, respectively; however, as above-demonstrated, the β-
scission to secondary radicals only occurs for the case of D → F
and not for E → G (Scheme 5).
Scheme 5. Contrasting Behavior of Thioesters 7β and 8α
Toward Stannyl Radical
2
hemithioacetal functional group of 20 (δ: 4.92 ppm, J = 10.8
Hz; 4.96 ppm, 2J = 10.8 Hz) and 23 (δ: 4.92 ppm, 2J = 10.4 Hz;
4.96 ppm, 2J = 10.2 Hz) are quite similar to those observed for
14, 17, and 18 (δ’s in the range 4.84−4.99 ppm and 2J’s in the
range 10.2−10.8 Hz).
At this point, it was considered pertinent to varying reactions
conditions to xanthates 19α and 8α with the expectation to
obtain further mechanistic information (Scheme 4). Thus,
when xanthate 19α was reacted with Bu3SnH (1.5 equiv) and
triethylborane at 20 °C, quantitative formation of thioformate
24 was observed, and only a trace of hemithioacetal 20 was
detected (eq 3). Similarly, under the same reaction conditions,
xanthate 8α afforded thioformate 25 and hemithiocetal 18 in a
45:55 ratio, respectively (eq 4). And when the amount of
Bu3SnH was increased from 1.5 to 2.0 equiv, the hemithioacetal
18 was exclusively formed (eq 5). Evidently, these experiments
not only exclude the formation of carbon-centered radicals at
C2 when the two C−O bonds are syn oriented to the
thiocarbonyl group but also reinforce the idea of a favorable
effect for the formation of the hemithioacetal compounds
probably at the expense of an unfavorable β-oxygen effect in the
Barton deoxygenation reaction. Furthermore, it appears that at
least one C−O bond antiperiplanar oriented to a thiocarbonyl
group (19β and 8β) is necessary to trigger the β-scission to
The latter suggests that the equilibrium process between 8α
and adduct radical E is driven toward 8α, forcing it to take a
different reaction course: the stannyl radical displacement on
the sulfide sulfur atom to form the alkoxythiocarbonyl radical
H, which is reduced by Bu3SnH before elimination of carbonyl
sulfide. Then, radical stannyl addition followed by radical
reduction gives the hemithioacetal 18 (Scheme 5). At first
glance, it appears logical to assume that radical F should be
more stable than radical G; however, density functional theory
(DFT) calculations performed at B3LYP/6-311+G(d,p) level
of theory show that the radical G is 2.24 kcal/mol more stable
than radical F. On the other hand, radical precursor models L
and M show different behavior, radical L being 2.95 kcal/mol
more stable than radical M. These results might be in
accordance with the theoretical energies calculated with
molecular mechanics by Crich and Beckwith for their
D
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Figure 1. Relative energies of radicals for radical precursor models (L, F, M, and G) calculated at B3LYP/6-311+G(d,p) level of theory, and Crich−
Beckwith models calculated with Molecular Mechanics (I, J, and K).
Figure 2. Potential energy surface for the β-scission of I → TSax → K + OC(SMe)2 and J → TSeq→K + OC(SMe)2 calculated at B3LYP/6-
311+G(d,p) level of theory.
conformationally semirigid radical model adducts I and J,
wherein the radical adduct derived from the thiocarbonyl ester
syn oriented to C−O bond (I) is, by only 0.22 kcal/mol, more
unstable than the equatorial one (J). See Figure 1.
These numbers are more consistent with their experimental
results.9 Additionally, using natural bond orbital (NBO)
analysis, it was found that the stabilization energy at the TSax
transition state comes from the molecular orbital interactions
between SOMO and the σ*C5−O7 bond and unusual orbital
interaction with two antibonding orbitals17 σ*C4−H4 and
σ*C6−H6 (Table 2). The SOMO → σ*C5−O7 orbital interaction
with E(2) = 38.31 kcal/mol and two orbital interactions
σ*C5−O7 → σ*C4−H4 and σ*C5−O7 → σ*C6−H6 with E(2) = 0.84
and 0.79 kcal/mol, respectively (see Table 2 and Figure 3).
Having found that interesting and unusual orbital inter-
actions are involved in radical models I and J, we applied the
same computational treatment to radical models L and M.
Surprisingly, model adducts L and M showed inverse barriers in
the activation energy for the β-scission. Now the radical adduct
However, in the present study, the differing energies between
radical models L and M cannot be considered as strain
energies; otherwise, radical M should produce radical G more
rapidly (as it was interpreted for the case of the radical models I
and J).9 This suggests that there is something other than simple
strain energy in the β-scission. Subsequently, after an
investigation into the electronic nature of the Crich−Beckwith
radical models I and J, it was found that the activation energy
for the β-scission of I is 7.48 kcal/mol, whereas for J it is 10.05
kcal/mol; in other words, the transition state TSax is 2.57 kcal/
mol more stable than TSeq (Figure 2).
E
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σ*C1−O1 and σ*O2−C2 → σ*C3−O3 are more stabilizing than the
σ*C5−O7 → σ*C4−H4 and σ*C5−O7 → σ*C6−H6 interactions.
Therefore, it can be established that the former interactions are
responsible for the favorable β-oxygen effect in the Barton−
McCombie reaction in the β-xylo-furanose xanthate derivatives.
Table 2. NBO Analysis (Second-Order Perturbation Theory)
of Hyperconjugative Interactions in Structures TSax and TS1
Calculated at the B3LYP/6-311+G(d,p) Level of Theory
donor orbital acceptor orbital E(2) (kcal/mol) εi−εj (ua) Fij (ua)
TSax
SOMO
σ*C5−O7
σ*C5−O7
TS1
σ*C5−O7
σ*C4−H4
σ*C6−H6
38.31
0.84
0.79
0.19
0.37
0.37
0.110
0.039
0.039
CONCLUSIONS
■
On the basis of the experimental and theoretical efforts
presented herein, we can conclude that the β-oxygen effect in
the Barton−McCombie reaction is highly favored by unusual
orbital interactions between the σ* orbital of the bond
undergoing cleavage with C−O antibonding orbitals placed in
β-position anti oriented. These orbital interactions lower
considerably the transition state energy of the β-scission,
favoring thus the deoxygenation step; however, when those
interactions are not present, the transition state is highly
destabilized so the β-scission is repressed (or delayed);
therefore, the deoxygenation does not proceed. Under this
critical scenario and due to the reversibly nature of the first step
of the Barton−McCombie reaction (the stannyl addition to
thiocarbonyl group), the stannyl radical prefers to attack the
SMe group (homolytic displacement: SH2) to afford the
alkoxythiocarbonyl radical, which is trapped by Bu3SnH and
subsequently transformed into the hemithioacetal compound.
These results suggest that the alkoxythiocarbonyl radical is
formed during the deoxygenation reaction as long as the barrier
in the activation energy for the β-scission is considerably high,
and that the elimination of the carbonyl sulfide is not that
easy.15,17 Probably, similar molecular orbital interactions are
necessary to favor the β-scission of the alkoxythiocarbonyl
radical to thus produce deoxygenation through the alternative
route B. Finally, the implications of these findings might be
extended to similar carbon-centered free radicals where their
behavior is also strongly perturbed by the presence of a βC−O
bond (i.e., nucleotide C3′,C′4 radical cation).6,24
SOMO
σ*C2−O2
σ*C2−O2
σ*C2−O2
σ*C1−O1
σ*C3−O3
36.47
1.30
1.56
0.20
0.32
0.31
0.110
0.046
0.051
Figure 3. NBO orbital interaction SOMO → σ*C5−O7 and two orbital
interactions σ*C5−O7 → σ*C4−H4 and σ*C5−O7 → σ*C6−H6 at the
transition state (TSax).
L, derived from the xanthate that orients the thiocarbonyl ester
group anti to C−O bonds, possesses the lower energy barrier
for the formation of secondary radical F (ΔE‡L→TS1 = 9.70 kcal/
mol); on the other hand, its radical congener M requires
considerably more energy for the formation of the secondary
radical G (ΔE‡M→TS2 = 13.28 kcal/mol) (Figure 4). In fact, the
latter high barrier is more than enough to destabilize transition
state TS2 and therefore is responsible for the nonformation of
the radical G. Hence, this high destabilizing energy may explain
why the equilibrium between 8α and adduct radical E,
described in Scheme 5, is driven toward 8α, and it also may
explain the formation of the hemithioacetal product.
EXPERIMENTAL SECTION
■
General Information. All reagents purchased commercially were
used without purification. The solvents were used as technical grade
and freshly distilled prior to use unless otherwise noted. 1H NMR and
13C NMR spectra were recorded with 400 and 100 MHz
spectrometers, respectively. 1H NMR and 13C NMR spectra were
recorded in CDCl3 and are reported in ppm relative to
Analyzing electronic transitions states structures TS1 and
TS2, we found that the lowering of the transition state energy
of TS1 is due to the same unusual molecular orbital
interactions of the SOMO with σ*O2−C2 and two antibonding
orbitals σ*C1−O1 and σ*C3−O3. The remarkably low energy
barrier of TS1 is due to the higher acceptor capacity of the two
antibonding orbitals σ*C1−O1 and σ*C3−O3 (compared to those
for the two antibonding orbitals σ*C4−H4 and σ*C6−H6 of TSax).
The energy of SOMO → σ*O2−C2 orbital interaction is on the
order of E(2) = 36.47 kcal/mol, and two orbital interactions
σ*O2−C2 → σ*C1−O1 and σ*O2−C2 → σ*C3−O3 with E(2) energies
of 1.37 and 1.56 kcal/mol, respectively (Table 2 and Figure 5).
These electronic interactions are not present in the TS2.
The energy and occupancy of the antibonding orbitals were
calculated to explain this double hyperconjugative interaction
(Table 3). The orbital occupancy value for the antibonding
orbitals TSax and TS1 are very similar: σ*C5−O7 = 0.283 and
σ*C2−O2 = 0.276, indicating that both β-scission for radical I and
radical L are quite favorable. The reason for these high
occupancy values is due to the interaction energy of the SOMO
→ σ*C5−O7 in TSax (38.31 kcal/mol) and the SOMO →
σ*C2−O2 in TS1 (36.47 kcal/mol). Additionally, the NBO
1
tetramethylsilane (TMS). Data for H NMR are reported as follows:
chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet), coupling constant (Hz), and
integration. Data for 13C NMR are reported in terms of chemical shift.
Optical rotations (Na lamp, 589 nm, 20 °C), and [α]D values are
reported in 10−1 dg cm2 g−1; concentration (c) is in g/100 mL.
Computational Studies. All calculations were performed using
Gaussian 09,18 and all structures were visualized using the Chemcraft
1.6 program.19 We carried out the complete set of calculations for the
reactions under study with DFT using the B3LYP hybrid functional20
and Tao, Perdew, Staroverov, and Scuseria (TPSS) meta-generalized
gradient approximation (meta-GGA) functional21 with the 6-311+G-
(d,p) basis set. All minima and transition state structures were
validated by subsequent frequency calculations at the same level of
theory. The minimum structures have a set of positive second
derivatives, while transition states have one imaginary frequency. The
searching of the transition states was conducted by implying the Berny
algorithm (opt = TS).22 Electronic structures of radicals were studied
by using NBO analysis, and the stabilizing energies are calculated by
second-order perturbation theory analysis.23 Unrestricted calculations
were used for open shell system. No spin contamination was found for
radicals; begin the ⟨S2⟩ value about 0.750 in all cases. B3LYP and
analysis revealed that the orbital interactions σ*O2−C2
→
F
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Figure 4. Potential energy surface for the β-scission of L → TS1 → OC(SMe)2 + F and M → TS2 → OC(SMe)2 + G calculated at the B3LYP/6-
311+G(d,p) level.
TPSS results show the same trend in all cases. Only discussed results
of B3LYP and TPSS results are available in the Supporting
Information.
General Procedure for the Formations of Alcohols 10α , 10β,
12α, and 12β.12 1,2-O-Isopropyliden-α-D-xylo-furanose was dissolved
in a solution of HCl (4 mL, 4 N) and MeOH (8 mL) and the solution
was heated at refluxing temperature for 1.3 h. After this time, the
reaction mixture was treated with a saturated aqueous solution of
NaHCO3 (5 mL) and extracted three times with ethyl acetate (30
mL). The organic phase was dried with Na2SO4 and evaporated under
reduced pressure, and resultant residue was purified by column
chromatography on silica gel.
Figure 5. NBO orbital interaction SOMO → σ*O2−C2 and two orbital
interactions: σ*O2−C2 → σ*C1−O1 and σ*O2−C2 → σ*C3−O3 at the
5-O-Benzyl-1,3-O-dimethyl-β-D-ribo-furanose 12β. Purified by
column chromatography on silica gel (eluent: hexane/ethyl acetate
4:1), 2.54 g (70%) of 12β was obtained as a yellow oil: [α]D20 = −18.4
transition state (TS1).
1
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 7.38−7.25 (m, 5H),
Table 3. NBO Energies and Occupancy for the SOMO
Orbital and Antibonding Orbitals Calculated at the B3LYP/
6-311+G(d,p) level for structures TSax and TS1
4.86 (s, 1H), 4.61 (s, 2H), 4.16 (q, J = 5.6 Hz, 1H), 4.09 (d, J = 4.8
Hz, 1H), 3.86 (dd, J = 6.0, 4.8 Hz, 1H), 3.61−3.55 (m, 2H), 3.41 (s,
3H), 3.33 (s, 3H), 2.74 (d, J = 3.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 138.1, 128.3, 127.6, 108.5, 81.6, 80.3, 73.2, 72.9, 71.8, 58.4,
55.0; HRMS (FAB-QMS) [M + H]+ calcd for C14H21O5 269.1389,
found 269.1414
TSax
TS1
orbital
energy (ua) occupancy
orbital
energy (ua) occupancy
5-O-Benzyl-1,3-O-dimethyl-α-D-ribo-furanose 12α: Purified by
column chromatography on silica gel (eluent: hexane/ethyl acetate
2:1), 0.72 g (20%) of 12α was obtained as a yellow oil: [α]D20 = +69.2
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 7.39−7.31 (m, 5H),
4.88 (d, J = 4.7 Hz, 1H), 4.60 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 12.0
Hz, 1H), 4.19−4.13 (m, 2H), 3.61−3.56 (m, 4H), 3.48 (s, 3H), 3.44
SOMO
σ*C5−O7
σ*C4−H4
σ*C6−H6
−0.2120
−0.2093
0.3494
0.758
0.283
0.022
0.019
SOMO
σ*C2−O2
σ*C1−O1
σ*C3−O3
−0.2206
−0.0185
0.3050
0.752
0.276
0.040
0.025
1
0.3534
0.2949
G
dx.doi.org/10.1021/jo4012943 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(s, 3H), 2.87 (d, J = 11.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
138.0, 128.4, 127.7, 127.6, 103.0, 81.7, 79.5, 73.5, 71.9, 70.5, 59.4, 55.9;
HRMS (FAB-QMS) [M + H]+ calcd for C14H21O5 269.1389, found
269.1370
(FAB-QMS) [M + H]+ calcd for C16H23O5S2 359.0987, found
359.0977.
3-O-Allyl-5-O-benzyl-1-O-methyl-2-O-[(methylthio)-
thiocarbonyl]-α-D-ribo-furanose 19α. Purified by column chroma-
tography on silica gel (eluent: hexane/ethyl acetate 8:1), 625 mg
5-O-Benzyl-1,3-O-dimethyl-β-D-xylo-furanose 10β: Purified by
column chromatography on silica gel (eluent: hexane/ethyl acetate
4:1), 2.1 g (60%) of 10β was obtained as a yellow oil: [α]D20 = −65.5
20
(24%) of 19α was obtained as a yellow oil: [α]D = +65.8 (c = 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.42−7.21 (m, 5H), 5.85−
1
5.75 (m, 1H), 5.64 (dd, J = 7.2, 4.8 Hz, 1H), 5.20 (d, J = 4.4 Hz, 1H),
5.13 (m, 2H), 4.63(d, J = 12.0 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.26
(q, 3.6 Hz, 1H), 4.12−4.071 (m, 2H), 3.94 (dd, J = 13.2, 6.4 Hz, 1H),
3.65 (dd, J = 10.8, 3.6 Hz, 1H), 3.60 (dd, J = 10.8, 4.2 Hz, 1H), 3.45
(s, 3H), 2.60 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 215.7, 137.8,
134.4, 128.3, 127.7, 127.6, 117.6, 101.5, 81.7, 78.9, 74.8, 73.4, 72.4,
69.4, 55.7, 19.2; HRMS (FAB-QMS) [M + H]+ calcd for C18H25O5S2
385.1143, found 385.1156.
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 7.35−7.26 (m, 5H),
4.81(s, 1H), 4.61(d, J = 12.0 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.50
(ddd, J = 7.2, 6, 4.8 Hz, 1H), 4.17 (s,1H), 3.74−3.70 (m, 2H), 3.63
(dd, J = 10.4, 7.6 Hz, 1H), 3.39 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 138.2, 128.3, 127.8, 127.6, 109.6, 85.9, 80.2, 78.8, 73.4, 69.6, 58.6,
55.75; HRMS (FAB-QMS) [M − H]+ calcd for C14H19O5 267.1232,
found 267.1258
5-O-Benzyl-1,3-O-dimethyl-α-D-xylo-furanose 10α. Purified by
column chromatography on silica gel (eluent: hexane/ethyl acetate
3:1), 1.08 g (30%) of 10α was obtained as a yellow oil: [α]D20 = +52.8
3-O-Allyl-5-O-benzyl-1-O-methyl-2-O-[(methylthio)-
thiocarbonyl]-β-D-ribo--furanose 19β. Purified by column chroma-
tography on silica gel (eluent: hexane/ethyl acetate 15:1), 1.95 g
1
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 7.35−7.33 (m, 5H),
20
(76%) of 19β was obtained as a yellow oil: [α]D = +25.2 (c = 1.0,
4.97 (d, J = 4.8 Hz, 1H), 4.64 (d, J = 12.0 Hz, 1H), 4.52 (d, J = 12.0
Hz, 1H), 4.38 (ddd, J = 6.8, 6.0, 4 Hz,1H), 4.19 (dt, J = 6, 4 Hz, 1H),
3.76 (dd, J = 6, 4 Hz, 1H), 3.67 (dd, J = 10.8, 4 Hz, 1H), 3.58 (dd, J =
10.8, 7.2 Hz, 1H), 3.49 (s, 3H), 3.40 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 138.2, 128.3, 127.7, 127.5, 101.7, 85.8, 77.3, 76.4, 73.4, 68.8,
57.9, 55.8; HRMS (FAB-QMS) [M − H]+ calcd for C14H19O5
267.1232, found 267.1210
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.42−7.21 (m, 5H), 5.92 (d,
J = 4.4 Hz, 1H), 5.81 (m, 1H), 5.24 (dm, J = 17.2 Hz, 1H), 5.12 (dm, J
= 10.4 Hz, 1H), 5.00 (s, 1H), 4.64 (d, J = 12.0 Hz, 1H), 4.60 (d, J =
12.0 Hz, 1H), 4.28 (ddd, J = 8.0, 6.0, 3.6 Hz, 1H), 4.19 (dd, J = 7.6, 4.0
Hz, 1H), 4.01 (ddt, J = 12.4, 5.6, 1.6 Hz, 1H), 3.94 (ddt, J = 12.4, 4.4,
1.6 Hz, 1H), 3.70 (dd, J = 10.4, 3.6 Hz, 1H), 3.59 (dd, J = 10.4, 6 Hz,
1H), 3.37 (s, 3H), 2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
215.2, 138.3, 133.9, 128.3, 127.6, 117.9, 105.7, 81.7, 80.9, 77.5, 73.3,
72.1, 71.0, 55.2, 18.0; HRMS (FAB-QMS) [M + H]+ calcd for
C18H25O5S2 385.1143, found 385.1109.
Xanthates Were Prepared According the Traditional
Procedure.1 5-O-Benzyl-1,3-O-methyl-2-O-[(methylthio)-
thiocarbonyl]-α-D-xylo-furanose 7α. Purified by column chromatog-
raphy on silica gel (eluent: hexane/ethyl acetate 20:1), 798 mg (30%)
of 7α was obtained as a yellow oil: [α]D20 = +103.1 (c = 1.0, CHCl3);
1H NMR (400 MHz, CDCl3) δ 7.40−7.25 (m, 5H), 5.67 (t, J = 4.8
Hz, 1H), 5.28 (d, J = 4.8 Hz, 1H), 4.65 (d, J = 12.1 Hz, 1H), 4.55 (d, J
= 12.2 Hz, 1H), 4.45 (td, J = 6.7, 3.9 Hz, 1H), 4.29 (dd, J = 6.9, 5.4
Hz, 1H), 3.71 (dd, J = 10.7, 4.0 Hz, 1H), 3.62 (dd, J = 10.7, 6.5 Hz,
1H), 3.38 (s, 3H), 3.37 (s, 3H), 2.59 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 215.5, 138.2, 128.3, 127.7, 127.6, 99.7, 85.6, 82.1, 75.9, 73.5,
68.6, 58.3, 55.8, 19.4; HRMS (FAB-QMS) [M + H]+ calcd for
C16H23O5S2 359.0987, found 359.0952.
5-O-Benzyl-1,3-O-methyl-2-O-[(methylthio)thiocarbonyl]-β-D-
xylo-furanose 7β. Purified by column chromatography on silica gel
(eluent: hexane/ethyl acetate 15:1), 1.59 g (60%) of 7β was obtained
as a yellow oil: [α]D25 = −48.7 (c = 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 7.41−7.22 (m, 5H), 5.84 (s, 1H), 5.04 (s, 1H), 4.63 (d, J =
12.0 Hz, 1H), 4.56 (d, J = 12.0 Hz, 1H), 4.49 (dt, J = 7.2, 5.2 Hz, 1H),
3.93 (d, J = 5.6 Hz, 1H), 3.78 (dd, J = 10.0, 5.2 Hz, 1H), 3.70 (dd, J =
10.0, 7.2 Hz, 1H), 3.47 (s, 3H), 3.42 (s, 3H), 2.57 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 214.4, 138.1, 128.3, 127.8, 127.6, 107.0, 86.9,
82.7, 81.3, 73.4, 69.0, 59.1, 55.9, 19.3; HRMS (FAB-QMS) [M + H]+
calcd for C16H23O5S2 359.0987, found 359.0948.
5-O-Benzyl-1,3-O-methyl-2-O-[(methylthio)thiocarbonyl]-α-D-
ribo-furanose 8α. Purified by column chromatography on silica gel
(eluent: hexane/ethyl acetate 15:1), 532 mg (20%) of 8α was obtained
as a yellow oil: [α]D20 = +50.0 (c = 1.0 CHCl3); 1H NMR (400 MHz,
CDCl3) δ 7.37−7.26 (m, 5H), 5.65 (dd, J = 7.0, 4.6 Hz, 1H), 5.20 (d, J
= 4.8 Hz, 1H), 4.64 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 12.0 Hz, 1H),
4.27 (q, J = 3.8 Hz, 1H), 3.96 (dd, J = 7.0, 4.0 Hz, 1H), 3.64 (m, 2H),
3.46 (s, 3H), 3.38 (s, 3H), 2.60 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 215.8, 137.8, 128.4, 127.7, 127.65, 101.4, 81.7, 79.2, 77.7, 73.5, 69.9,
59.6, 55.8, 19.3; HRMS (EI-QMS) [M]+ calcd for C16H22O5S2
358.0909, found 358.0914.
Barton−McCombie Deoxygenation. To a solution of xanthate
(100 mg) in dry and degassed benzene (5.0 mL) at 80 °C was added
slowly Bu3SnH (1.8 equiv) and 1,1′-azobis-cyclohexanecarbonitrile
(ABCN, 0.5 equiv) dissolved in 1 mL of benzene. The reaction
mixture was stirred for 2 h at 80 °C. The resulting mixture was
evaporated under reduced pressure and analyzed directly by 1H NMR,
and then the residue was purified by column chromatography on silica
gel to give the corresponding product. For the case of hemithiocetals,
the purification was performed either by thin-layer chromatography
using benzene as developing solvent or passing the crude reaction
mixture through a short column of neutral alumina using hexane as
solvent and increasing polarity with ethyl acetate (40:1). And for the
case of thioformates, the tin resides were removed by evaporation of
the solvent under reduced pressure followed by liquid−liquid
extraction using acetonitrile and hexane. The polar phase (acetonitrile)
is evaporated under reduced pressure and the thioformates were
1
characterized by H-and 13C NMR.
5-O-Benzyl-2-deoxy-1,3-O-dimethyl-β-D-xylo-furanose 13. Puri-
fied by column chromatography on silica gel (eluent: hexane/ethyl
20
acetate 15:1), 67 mg (95%) of 13 was obtained as a yellow oil: [α]D
1
= −85.3 (c = 1.0, CHCl3); H NMR (400 MHz CDCl3) δ 7.40−7.25
(m, 5H), 5.03 (t, J = 3.6 Hz, 1H), 4.63 (d, J = 12.3 Hz, 1H), 4.58 (d, J
= 12.3 Hz, 1H), 4.26 (dt, J = 7.5, 5.1 Hz, 1H), 3.92 (m, 1H), 3.78 (dd,
J = 10.2, 4.8 Hz, 1H), 3.68 (dd, J = 10.2, 7.5 Hz, 1H), 3.38 (s, 3H),
3.32 (s, 3H), 2.12 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 138.4,
128.3, 127.8, 127.5, 104.9, 81.4, 80.0, 73.4, 69.7, 57.9, 55.6, 37.8;
HRMS (FAB-QMS) [M − H]+ calcd for C14H19O4 251.1283, found
251.1255.
5-O-Benzyl-2-deoxy-1,3-O-dimethyl-α-D-xylo-furanose 14.
Thirty-three milligrams (48%) of 14 was obtained as a pale yellow
oil: [α]D25 = +28.8 (c = 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ
1
5-O-Benzyl-1,3-O-methyl-2-O-[(methylthio)thiocarbonyl]-β-D-
ribo-furanose 8β. Purified by column chromatography on silica gel
(eluent: hexane/ethyl acetate 20:1), 1.86 g (70%) of 8β was obtained
as a yellow oil: [α]D20 = +14.2 (c = 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 7.41−7.23 (m, 5H), 5.95 (d, J = 4.4 Hz, 1H), 4.99 (s, 1H),
4.65 (d, J = 12.0 Hz, 1H), 4.61 (d, J = 12.0 Hz, 1H), 4.26 (ddd, J = 7.6,
5.6, 3.6 Hz, 1H), 4.06 (dd, J = 7.2, 4.4 Hz, 1H), 3.70 (dd, J = 10.4, 3.6
Hz, 1H), 3.60 (dd, J = 10.4, 6.0 Hz, 1H), 3.37 (s, 3H), 3.35 (s,3H),
2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 215.4, 138.1, 128.3,
127.6, 127.6, 105.6, 81.4, 80.8, 79.8, 73.3, 71.1, 59.0, 55.2, 19.0; HRMS
7.38−7.30 (m, 3H), 5.13 (dd, J = 5.6, 2.4 Hz, 1H), 4.66 (d, J = 12.2
Hz, 1H), 4.53 (d, J = 12.2 Hz, 1H), 4.23 (dt, J = 6.4, 4.6 Hz, 1H), 3.99
(ddd, J = 6.1, 4.7, 3.0 Hz, 1H), 3.75 (dd, J = 10.4, 4.6 Hz, 1H), 3.66
(dd, J = 10.4, 8.0 Hz, 1H), 3.37 (s, 3H), 3.26 (s, 3H), 2.19 (ddd, J =
14.1, 5.6, 3.0 Hz, 1H), 2.04 (ddd, J = 14.1, 6.4, 2.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 138.3, 128.3, 127.7, 127.5, 104.2, 104.2, 80.5,
79.0, 77.3, 77.0, 76.7, 73.4, 73.3, 68.5, 57.1, 55.3, 55.2, 38.8; HRMS
(FAB-QMS) [M − H]+ calcd for C14H19O4 251.1283, found 251.1259.
5-O-Benzyl-1,3-O-dimethyl-2-O-tributylstannylmethyltio-α-D-
xylo-furanose 15. After repeated purifications, 33 mg (20%) of 15 was
H
dx.doi.org/10.1021/jo4012943 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
25
1
obtained as a pale yellow oil: [α]D = +40.2 (c = 1.0, CHCl3); H
NMR (400 MHz, CDCl3) δ 7.38−7.25 (m, 5H), 4.96 (d, J = 10.2 Hz,
1H), 4.94 (d, J = 4.4 Hz, 1H), 4.84 (d, J = 10.2 Hz, 1H), 4.65 (d, J =
12.3 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.40 (m, 2H), 3.98 (dd, J =
6.6, 5.7 Hz, 1H), 3.69 (dd, J = 10.5, 4.2 Hz, 1H), 3.58 (dd, J = 10.2, 6.9
Hz, 1H), 3.43 (s, 3H), 3.38 (s, 3H), 1.56 (m, 6H), 1.32 (m, 6H), 1.18
(m, 6H), 0.90 (t, J = 7.5 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ
138.2, 128.3, 127.7, 127.5, 100.8, 83.6, 79.9, 76.2, 73.4, 69.4, 69.1, 58.7,
55.3, 28.6, 27.0, 13.7; HRMS (FAB-QMS) [M − H]+ calcd for
C27H47O5SSn 603.2166, found 603.2139.
by the slow addition of Bu3SnH (0.111 mL, 0.417 mmol). The
reaction mixture was allowed to stir for 1.3 h and then concentrated
under reduced pressure. Analysis of the H NMR spectra revealed
1
clean formation of 25 and 18 in a 45:55 ratio, respectively. For the
case of xanthate 19α, thioformate 24 was observed as the sole product.
Unfortunately, all the efforts for purification the thioformates 25 and
24 on silica gel were unsuccessful; the hydrolysis of the thioformate
group occurred, and the alcohol precursors of their corresponding
xanthates (8α and 19α) were obtained. Furthermore, the stannyl
impurities were efficiently removed by dissolving the reaction crude
with acetonitrile and extraction with hexane. Thus, thioformates 24
and 25 were obtained with moderate purity.
5-O-Benzyl-2-deoxy-1,3-O-dimethyl-β-D-ribo-furanose 16.
Twenty-eight milligrams (40%) of 16 was obtained as a pale yellow
25
1
5-O-Benzyl-1,3-di-O-methyl-2-thioformyl-α-D-ribo-furanose 25.
oil: [α]D = −36.2 (c = 1.0, CHCl3); H NMR (400 MHz, CDl3) δ
7.39−7.24 (m, 5H), 5.08 (dd, J = 5.7, 2.4 Hz, 1H), 4.59 (s, 2H), 4.18
(td, J = 6.3, 3.6 Hz, 1H), 3.93 (ddd, J = 6.9, 5.9, 3.6 Hz, 1H), 3.52 (m,
2H), 3.31 (s, 6H), 2.22 (ddd, J = 13.5, 6.9, 2.1 Hz, 1H), 2.06 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 138.2, 128.3, 127.6, 127.6, 105.4, 82.6,
Twenty-five milligrams (29%) was obtained as a pale yellow oil.
25
[α]D = +32.6 (c 1.0, CHCl3). NMR data are reported as a rotamer
mixture: 1H NMR (400 MHz, CDCl3) δ 9.75 (s), 8.16 (s), 7.35−7.27
(m), 5.55 (ddd, J = 6.0, 4.4, 1.2 Hz), 5.23 (d, J = 4.4 Hz), 5.14 (d, J =
4.4 Hz), 4.98 (ddd, J = 5.6, 4.8, 1.2 Hz), 4.64−4.54 (m), 4.30 (q, J =
4.0 Hz), 4.24 (q, J = 4.0 Hz), 4.01 (dd, J = 6.8, 3.2 Hz), 3.89 (dd, J =
6.8, 3.2 Hz), 3.62−3.55 (m), 3.46 (s), 3.45 (s), 3.37 (s), 3.35 (s); 13C
NMR (100 MHz, CDCl3) δ 205.5, 160.1, 137.9, 137.7, 128.4, 127.8,
127.6, 101.6, 101.2, 81.8, 81.4, 77.9, 73.6, 72.0, 70.1, 70.0, 59.5, 59.2,
55.7.
82.0, 73.3, 72.0, 57.2, 55.0, 38.9; HRMS (FAB-QMS) [M − H]+ calcd
for C14H19O4 251.1283, found 251.1260.
5-O-Benzyl-1,3-O-dimethyl-2-O-tributylstannylmethyltio-β-D-
ribo-furanose 17. After repeated purifications, 40 mg (24%) of 17 was
25
1
obtained as a pale yellow oil: [α]D = −25.8 (c = 1.0, CHCl3); H
NMR (400 MHz, CDl3) δ 7.38−7.27 (m, 5H), 4.99 (d, J = 10.8 Hz,
1H) 4.94 (d, J = 10.4 Hz, 1H), 4.93 (s, 1H), 4.60 (m, 2H), 4.29 (d, J =
4.8 Hz, 1H), 4.19 (m, 1H), 3.84 (dd, J = 6.0, 4.8 Hz, 1H), 3.63 (dd, J =
10.4, 3.6 Hz, 1H), 3.55 (dd, J = 10.0, 6.4 Hz, 1H), 3.39 (s, 3H), 3.35
(s, 3H), 1.56 (m, 6H), 1.34 (m, 6H), 1.19 (m, 6H), 0.90 (t, J = 7.3 Hz,
9H); 13C NMR (100 MHz, CDCl3) δ 138.3, 128.3, 127.6, 127.5,
106.5, 80.9, 80.2, 76.9, 73.2, 71.5, 69.7, 58.3, 55.1, 28.6, 27.0, 13.7,
13.6; HRMS (FAB-QMS) [M − H]+ calcd for C27H47O5SSn
603.2166, found 603.2186.
5-O-Benzyl-3-O-allyl-1-O-methyl-2-O-thioformyl-α-D-ribo-fura-
nose 24. Thirty milligrams (34%) yield was obtained as a pale yellow
25
oil. [α]D = +29.1 (c = 1.0, CHCl3). NMR data are reported as a
1
rotamer mixture: H NMR (400 MHz, CDCl3) δ 9.75 (s), 8.16 (s),
7.35 (m), 5.82 (m), 5.57 (m) 5.23 (m), 5.17−5.10 (m), 5.01 (m),
4.64−4.52 (m), 4.28 (q, J = 3.6 Hz), 4.23 (q, J = 4.0 Hz), 4.17 (dd, J =
7.2, 3.6 Hz), 4.10−4.02 (m), 3.97 (m) 3.63−3.53 (m), 3.47 (s, 3H),
3.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 205.6, 160.06, 137.8,
134.4, 128.4, 127.8, 127.7, 118.0, 117.9, 101.6, 101.3, 82.1, 81.6, 76.2,
75.07, 74.6, 73.5, 72.6, 72.4, 71.7, 69.5, 69.4, 55.7, 28.6, 27.0, 13.6,
13.01.
5-O-Benzyl-1,3-O-dimethyl-2-O-tributylstannylmethyltio-α-D-
ribo-furanose 18. After repeated purifications, 28 mg (17%) of 18 was
obtained as a pale yellow oil: 1H NMR (400 MHz,CDl3) δ 7.35−7.27
(m, 5H), 4.95 (d, J = 10.8 Hz, 1H), 4.93 (s, 1H) 4.92 (d, J = 10.8 Hz,
1H), 4.62 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 12.0 Hz, 1H), 4.46 (dd, J =
6.8, 4.8 Hz, 1H), 4.27 (td, J = 4.4, 2.4 Hz, 1H), 3.67 (dd, J = 7.2, 2.8
Hz, 1H), 3.60−3.55 (m, 2H), 3.43 (s, 3H), 3.38 (s, 3H), 1.61−1.53
(m, 6H), 1.36−1.30 (m, 6H), 1.21−1.16 (m, 6H), 0.90 (t, J = 7.3 Hz,
9H); 13C NMR (100 MHz, CDCl3) δ 137.9, 128.3, 127.5, 127.5,
102.2, 81.9, 78.5, 74.0, 73.4, 70.6, 69.1, 58.7, 55.4, 28.5, 27.0, 13.6;
HRMS (FAB-QMS) [M − H]+ calcd for C27H47O5SSn 603.2166,
found 603.2141.
ASSOCIATED CONTENT
■
S
* Supporting Information
NMR copies for new compounds, calculated energies and
thermodynamic parameters for all optimized structures,
structure XYZ coordinates for molecules, optimized structure
for all transition states, and activation energy diagram for the β-
scission calculated at TPSS/6-311+G(d,p) level of theory for
key radical models are provided. This material is available free
of charge via the Internet at http://pubs.acs.org.
3-O-Allyl-5-O-benzyl-1-O-methyl-α-D-ribo-furanose 21.14 Sixty-
five milligrams (85.5%) of 21 was obtained as a pale yellow oil:
25
1
[α]D = +119.7 (c = 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ
7.37−7.26 (m, 5H), 5.91−5.81(m, 1H), 5.23 (dm, J = 17.2 Hz 1H),
5.16 (dm, J = 10.4 Hz, 1H), 4.88 (d, J = 4.8 Hz, 1H), 4.60 (d, J = 12.0
Hz, 1H), 4.52 (d, J = 12.0 Hz, 1H), 4.17−4.03 (m, 4H), 3.77 (dd, J =
6.8, 2.8 Hz, 1H), 3.56 (d, J = 4.0 Hz, 2H), 3.47 (s, 3H), 2.89 (d, J =
11.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 137.8, 134.4, 128.4,
127.7, 127.6, 117.7, 102.9, 82.0, 76.5, 73.4, 72.3, 71.7, 70.0, 55.7;
HRMS (FAB-QMS) [M + H]+ calcd for C16H23O5 295.1545, found
295.1570
AUTHOR INFORMATION
■
Corresponding Author
*F. Sartillo-Piscil. Tel.:+52 222 2955500 ext. 7391. Fax: + 52
222 2454972. E-mail: fernando.sartillo@correo.buap.mx.
Notes
The authors declare no competing financial interest.
6-Bencyloxy-melthyl-4-methyloxy-3-methylhexahydrofuro[3,4b]-
furan 22. Purified by column chromatography on silica gel (eluent:
hexane/ethyl acetate 8:1), 61 mg (85%) of 22 was obtained as an
inseparable diastereoisomerica mixture (4:1). [α]D25 = −33.3 (c = 1.0,
CHCl3). NMR data are reported for the major diastereomers: 1H
NMR (400 MHz, CDCl3) δ 7.39−7.26 (m, 5H), 4.94 (d, J = 1.7 Hz,
1H), 4.56 (s, 3H), 4.28−4.22 (m, 1H), 3.89 (dd, J = 8.4, 6.9 Hz, 1H),
3.56−3.47 (m, 3H), 3.34−3.31 (m, 1H), 3.30 (d, J = 0.6 Hz, 3H), 2.74
(ddd, J = 8.8, 6.7, 1.6 Hz, 1H), 2.45−2.36 (m, 1H), 1.09 (dd, J = 6.9,
2.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 138.1, 128.3, 127.6,
127.6, 106.3, 85.4, 85.2, 74.0, 73.2, 71.6, 54.9, 53.5, 35.4, 12.1; HRMS
(FAB-QMS) [M − H]+ calcd for C16H21O4 277.1440, found 277.1468
Reaction of the Xanthate 8α in the Presence of Triethylbor-
ane. To a solution of xanthate 8α (0.100 g, 0.278 mmol) dissolved in
6 mL of benzene was added BEt3 (0.139 mL of 1 M solution, 0.139
mmol) at 20 °C. The reaction mixture was stirred for 5 min followed
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from CONACyT
(CB-2012/179074) and the Benemer
ma de Puebla (BUAP-VIEP).
́
ita Universidad Auton
́
o-
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