Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis

Article abstract of DOI:10.1021/acs.joc.1c00706

A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.

Full text of DOI:10.1021/acs.joc.1c00706

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Article
Highly Stereoselective Glycosylation Reactions of Furanoside
Derivatives via Rhenium (V) Catalysis
Emanuele Casali, Sirwan T. Othman, Ahmed A. Dezaye, Debora Chiodi, Alessio Porta,
and Giuseppe Zanoni*
Cite This: J. Org. Chem. 2021, 86, 7672−7686
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ABSTRACT: A novel approach for the formation of anomeric
carbon-functionalized furanoside systems was accomplished
through the employment of an oxo-rhenium catalyst. The
transformation boasts a broad range of nucleophiles including
allylsilanes, enol ethers, and aromatics in addition to sulfur,
nitrogen, and hydride donors, able to react with an oxocarbenium
ion intermediate derived from furanosidic structures. The excellent
stereoselectivities observed followed the Woerpel model, ultimately
providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center
with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory
calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine
heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.
Among the different synthetic strategies to assembly-
substituted THFs,1 one of the classical approaches is the
venerable Sakurai−Hosomi reaction (Scheme 1), which
INTRODUCTION
■
Decorated tetrahydrofurans (THFs) are prevalent motifs in the
structures of a myriad of natural products. In particular, the
trans-1,4-dialkyl-substituted THF ring is a common function-
ality in biologically active compounds, polyether antibiotics,
acetogenins, C-glycosides, and amphidinolides.1 Figure 1
illustrates a few examples of natural products that contain this
THF ring systems, such as haterumalides NA 1, amphidinolide F
2, (−)-obtusallene III 3, and oxylipid 4.
Scheme 1. General Approach to the Trisubstituted THF Core
via the Sakurai−Hosomi Reaction
operates through the exposure of a suitable THF acetal, such
as 6, to a strong Lewis acid (e.g., TMSOTf, SnCl4, BF3·Et2O, or
TiCl4) and soft, nucleophilic allylsilanes to afford the
corresponding allylated THF product 7.2
However, this reaction is limited by the highly corrosive and
moisture-sensitive Lewis acids that are required in stoichio-
metric amounts to provide the desired products. Therefore, an
affordable and reliable catalytic system that could promote an
efficient and stereoselective reaction would be advantageous
considering both the commercial availability and the low
synthetic manipulation of THF acetals. To the best of our
Received: March 25, 2021
Published: May 25, 2021
Figure 1. Representative members of the trans-2,5-dialkyl-substituted
THF family.
© 2021 The Authors. Published by
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knowledge, only two catalytic approaches have been developed
for the allylation of THF acetals. In 2009, Yadav reported a
protocol using molecular iodine in CH2Cl2 at cryogenic
temperatures.3 In the same year, Fiestad delivered an alternative
approach to solve the innate stereochemical problems of cyclic,
five-membered oxocarbenium ions, developing an allylation
reaction on a 2,7-dioxabicyclo[2.2.1]heptane ring system which
uses a catalytic amount of TiCl4 as a Lewis acid.4 As a part of our
program aimed to explore the chemistry of rhenium (V),5
herein, we report a new talent of oxo−rhenium complex 8,
namely, its ability to promote the formation of an oxocarbenium
species in a catalytic fashion (Scheme 2).
Table 1. Optimization of Reaction Conditions: General
Reaction Conditions: 9 (1 mmol), Allyltrimethylsilane (2.5
mmol), Oxo-Re Catalyst 8 (15 mol %), and Cocatalyst (5 mol
a
%) Were Reacted in CH2Cl2 (10 mL) at −50 °C
time
(h)
yield
(%)
entry
oxo-rhenium catalyst
cocatalyst
none
Cu(OTf)2
Cu(OTf)2
CuI
b
1
Re(O)Cl3(OPPh3)(Me2S) 8
Re(O)Cl3(OPPh3)(Me2S) 8
Re(O)Cl3(OPPh3)(Me2S) 8
Re(O)Cl3(OPPh3)(Me2S) 8
Re(O)Cl3(OPPh3)(Me2S) 8
none
none
(dppe)ReOCl3
(dppp)ReOCl3
(dppm)ReOCl3
0.5
12
16
26
26
12
12
12
12
12
45
92
n.d.
80
85
n.d.
n.d.
n.d.
n.d.
n.d.
Scheme 2. Catalytic Approaches to the Allylation Reaction
2
a
c
via a Five-Membered Ring-Oxocarbenium Intermediate
3
d
4
5
CoCl2
e
6
e
CoCl2−Me2S
Co(OTf)2−Me2S
none
none
none
7
8
9
10
a
Temperature was then increased to −30 °C for a given time
b
indicated in the table. Without the cocatalyst and the reaction
mixture was warmed to rt for 0.5 h. 15 mol % Cu cocatalyst. 30 mol
% of cocatalyst. 5 mol % of Me2S, without catalyst 8, has been used.
c
d
e
We speculate that this low reactivity could be attributed to the
inability of acetal 9 to displace the dimethylsulfide ligand from
the complex 8, a pre-equilibrium necessary to initiate the
catalytic cycle (vide infra). We hypothesized that a thiophilic
cocatalyst would facilitate the displacement of the sulfide ligand
to form the active, oxophilic 12e− Re complex and by
consequence improve the reaction kinetics. A brief screening
of copper salts was performed, as they maintain a high affinity for
sulfur.9 We were delighted to find that catalyst 8 (15 mol %) in
the presence of Cu(OTf)2 (5 mol %) afforded the desired
product 10 even at low temperature (−50 to −30 °C) with 92%
isolated yield (Table 1, entry 2). Increasing the catalyst loading
of Cu(OTf)2 to 15 mol %, no reaction was observed (Table 1,
entry 3). Switching to a softer copper (I) salt, such as CuI,10 the
reaction proceeded promptly but only when the catalyst loading
was increased to 35 mol % of both Re catalyst 8 and CuI
cocatalyst (Table 1, entry 4). This behavior could be ascribed to
the stronger electrophilicity of Cu(II) compared to that of
Cu(I), which causes Cu(II) to bind Me2S molecules more
strongly. The essential role of the Me2S scavenging in the
catalytic cycle was further demonstrated by employing CoCl2
instead of Cu(OTf)2.11
a
DCE = dichloroethane and DCM = dichloromethane.
RESULTS AND DISCUSSION
■
In the course of our studies on rhenium (V) chemistry, we
discovered that Lewis acidic oxo-rhenium complex 8 was
catalytically competent in the promotion of Meyer Schuster
rearrangements and one-pot Meyer Schuster/Diels−Alder
reaction sequences. Indeed, the 14e− complex 8 exhibited an
efficiency even higher than that of hallmark Lewis acids (e.g.
Cu(OTf)2, BF3·Et2O) usually employed in the Meyer Schuster
rearrangement.5a−c
Therefore, we reasoned that substoichiometric metal-oxo
complex 8 could promote the Sakurai−Hosomi reaction
between suitable THF acetals and allyltrimethylsilane.5d
In the event, the reaction of simple ethoxyl-acetal 9 (Table 1)6
with allyltrimethylsilane (250 mol %) in the presence of 15 mol
% catalyst 8 in CH2Cl2 was initially carried out in a range of
temperatures from −50 to −30 °C, but no significant trace of
product was observed. Only after 30 min at room temperature,
the expected products 10 (Table 1) were obtained, albeit in
moderate 45% isolated yields and as a 55:45 trans−cis epimeric
mixture at C-1 (Table 1, entry 1).7
Indeed, allylated products 10 have been obtained in a slightly
lower isolated yield (85%) using CoCl2 in the presence of 8 (15
mol %) (Table 1, entry 5). A background reaction promoted by
the Lewis acidity of the cocatalyst was ruled out by carrying out
the allylation reaction with the sole Cu(OTf)2 and CoCl2 in the
presence of an equimolecular amount, with respect to the
cocatalyst, of Me2S (Table 1, entries 6 and 7). CoCl2 was
inactive to promote the allylation reaction, while Cu(OTf)2
induced an extensive decomposition of acetal 9.
Not surprisingly, when alternative 14e− Re-complexes, such as
(dppm)ReOCl3, (dppe)ReOCl3, and (dppp)ReOCl3, were
employed, no reactions were observed, even upon warming
the reaction mixture at room temperature (Table 1, entries 8−
10).
Substrate 9 has been used as a 1:1 mixture at C1 by virtue of
the control experiment and the literature precedent that revealed
that the stereoselectivity was not influenced by the anomeric
composition of the starting glycoside.8
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Scheme 3. Oxo-Rhenium-Mediated Allylation of O-Methyl bis-TBDSO-Protected Furanoside Acetals with Various
a
Nucleophiles
a
Conditions: 1.0 equiv of furanoside 11, 2.5 equiv of nucleophile, 15 mol % oxo-Re complex 8, 5 mol % Cu(OTf)2, CH2Cl2 (0.05 M), from −50
°C to −30 °C; (a) reaction temperature was increased to 0 °C; (b) 30 mol % oxo-Re complex 8 and 15 mol % Cu(OTf)2 were used; and (c) 1.5
equiv of furan nucleophile was used. Unless otherwise noted, alkylated furanosides displayed a 1,3-cis - 1,4-trans stereochemistry.
1
Diastereoselectivities, except for compound 16, were determined from the H NMR spectrum.
With an allylation protocol in hands, we tested the versatility
of our synthetic method by reacting oxo-Re catalyst 8 with
different nucleophiles using (3S,4R)-bis-TBDPS-protected
methoxy-acetal 11 (Scheme 3).
Allyltrimethylsilane was added to an oxocarbenium ion
intermediate with an exquisite 99:1, 1,3-syn (1,4-anti) stereo-
selectivity with a 93% isolated yield. Relative stereochemistry of
12 has been established by chemical correlation with the known
Borhan allylated diol, previously reported as diol 4.12 This
complete selectivity is remarkable in light of the fact that other
catalytic approaches3 afford the corresponding TBS-protected
12 in 90:10 selectivity. Indeed, in order to achieve the same level
of stereoselectivity, the reaction requires an equimolar amount
of Lewis acids such as BF3 etherate13 or SnBr4.14 We could
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a
Scheme 4. Oxo-Rhenium-Mediated Allylation Reaction on Decorated O-Alkyl Furanoside Acetals
a
Conditions: 1 equiv of furanoside substrate, 2.5 equiv of allyltrimethyl silane, 15 mol % oxo−Re complex 8, 5 mol % Cu(OTf)2, CH2Cl2 (0.05 M),
from −50 to −30 °C. Unless otherwise noted, reactions were carried out on the corresponding O-methyl furanoside. (a) Reaction was carried out
on the corresponding O-allyl acetal; (b) 30 mol % oxo-Re complex 8 and 15 mol % Cu(OTf)2 were used. Unless otherwise noted, alkylated
1
furanosides displayed a 1,3-cis/1,4-trans stereochemistry. Diastereoselectivities were determined from the H NMR spectrum.
anticipate that the stereochemical outcome, for products from
13 to 24, is in good agreement with the inside attack model
proposed by Woerpel and co-workers for ribose-derived
analogues.8a,15
formed rather than the 1,3-cis stereoisomer.21 The synthesis of
aryl-C-glycosides via Lewis acid catalysis has been reported in
the literature to afford primarily the β-stereoisomer (1,4-cis in
our scenario) over the α-stereoisomer (1,4-trans).22 Albeit the
origin of observed stereoselectivity has been attributed to a
Lewis/Brønsted acid thermodynamic isomerization, a clear
mechanistic picture is not described in the literature.22a−c,e,23
The formation of 25 therefore could be explained by an initial
Friedel−Crafts reaction on the electron-rich 2-
(trimethylsilyloxy)furan and then epimerization followed by
furan ring dearomatization. Not surprisingly, a deviation from
the Woerpel stereochemical model was observed when electron-
rich, aromatic C-nucleophiles were subjected to our glyco-
sidation protocol. In the event, anisole (para regioisomer only),
1,3-benzodioxole, and furan afforded the corresponding aryl-C-
glycosides 26, 27, and 28, respectively, in high yields and
The same levels of both stereoselectivities and yields have
been observed using substituted allylsilanes such as 2-
bromoallyltrimethylsilane, ethyl 3-(trimethylsilyl)-4-pente-
noate, and methallyltrimethylsilane, delivering alkylated prod-
ucts 13, 14, and 15, respectively. The latter was obtained with a
1,3-syn stereoselectivity of 95:5, a remarkable result in light of
the poor selectivity obtained by Yadav for an analogous
compound.3 The use of 2-(trimethylsilyl)-2,3-pentadiene
afforded product 16, with a pendant alkyne, in good yield and
high 1,3-syn stereoselectivity and 7:3 (UPLC analysis) at a C-4′
(S)-stereocenter.16 Noncarbon-based nucleophiles such as
nitrogen (Me3SiN3), sulfur (Me3SiSPh), and hydride
(Et3SiH)17 afforded the corresponding azido- (17) and thio-
(19) glycosides and 1,4-anhydro-2-deoxy-glycitol (18) in high
yield and good selectivity. Other TMS-enol ether nucleophiles
proved to be excellent partners in the oxocarbenium coupling;
glycosylation with acetal 11 proceeded smoothly under the
previous C-allylation conditions. All the reactions provided the
desired C-glycosides (20−24) in high yields and stereo-
selectivity. An NOE enhancement observed by NMR analysis
of 23 (see the Supporting Information for details) supported its
1,3-cis, 1,4-trans relative configurations, thus establishing the
expected stereochemical Woerpel outcome. Of note, 1,3-syn
stereoselectivity has been imposed without aid of either a
directing group18 or by ortho-alkynylbenzoate glycosyl deriva-
tives.19 This showcases the high atom economy of our
glycosidation protocol. When vinylogous heterocyclic TMS-
ether 2-(trimethylsilyloxy)furan was used,20 an interesting
stereochemical inversion was observed. Indeed, glycoside 25
was obtained in 57% isolated yield higher than a 99:1 mixture of
diastereoisomers, in which the 1,3-trans stereoisomer was
stereoselectivity. Vorbuggen stereoselectivity, that is, 1,3-anti
̈
and 1,4-syn, was inferred by NOE experiments (see the
Supporting Information) and tentatively explained using
quantum chemical calculations (vide infra).
Next, the rhenium oxo-complex-mediated allylation proce-
dure was next extended to more decorated and synthetically
useful THF acetal substrates (Scheme 4). Acetates and benzyl
ethers on carbons C-4 and C-5 and tosylate on C-4 (ribose
numbering system)1 are well-tolerated, affording the corre-
sponding allylated diacetate 29, bis-benzyl ethers 30, and
tosylate 31, in high yields and selectivities. The potential of this
catalytic Re-mediated process compares favorably with those
reported in the literature that typically require a stoichiometric
amount of the Lewis acid trimethylsilyltrifluoromethanesulfo-
nate (TMSOTf).24 The stereochemical behavior predicted by
Woerpel was demonstrated by reacting the corresponding C-3
epimer of 11 (not shown) under our Re-mediated allylation
reaction. Glycoside 32 was thus obtained in 86% isolated yield as
a 73:27 1,3-cis/1,3-trans mixture of C-1 isomers, respectively.
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The stereochemical inversion could be ascribed to the pseudo-
equatorial orientationinstead of the preferred pseudo-axial
oneof the C-3 alkoxy group in the five-membered-ring
oxocarbenium systems, as observed by Woerpel.8a,15b
corresponding 2,4-cis diastereoisomer 41 was obtained in more
than a 99:1 ratio in 63% isolated yield. According to the data
available in the literature, stereoisomer 41 corresponds to the
thermodynamic product.29b
Fully decorated THF afforded the corresponding allylated
products 33 and 34 in 93% and 77% isolated yields, respectively.
The 91:9 stereoselectivity in favor of the 1,3-cis stereoisomer of
33, confirmed by two-dimensional NOESY experiments, is of
particular importance in light of the conflicting results found in
the literature and which prompted Vogel to publish an in-depth
examination of the synthesis of 33 using alternative
approaches.25 Our robust and reliable allylation protocol
could therefore be used to prepare a stereochemically defined
allyl-C-glycoside such as 33 without any doubt about the C-1
allyl stereochemistry. Finally, aryl-C-glycoside could be prepared
on a decorated THF ring as demonstrated by the high yield and
stereoselective preparation of compound 35. This complete
stereoselectivity is due to an anchimeric assistance of the acetate
group at the C-2 position of the ribose, which shields the α-face
of the oxocarbenium intermediate.26a The regioselectivity of the
Friedel−Craft reaction is in line with the data in the literature, as
only the ortho product has been obtained. This is intriguing, in
light of the fact that the stereoselectivity in our case is
complete.26b
Another key feature of 31 and 32 formation lies in the nature
of substituent at C-1, namely, the allyloxy group. This group
could be easily ionized under our Re catalysis, to form the
corresponding oxocarbenium ion. Of note, the direct use of
allyloxy-protected glycosides in glycosidation reactions, for
example, allows us to save the deprotection-activation sequence
procedure which usually involves the use of Pd, Ir, or even Hg
salts.27
COMPUTATIONAL STUDIES
■
To shed some light on the peculiar stereochemical behavior of
aryl-C-glycoside formation, some computational density func-
tional theory (DFT) calculations have been carried out.
The reaction starts with the initial approach of the anisole
reactant toward the α- or β-face of the oxocarbenium species 5,
by forming two quasi-isoenergetic adducts, adduct-α and
adduct-β, respectively (Scheme 6a). The system undergoes
the Friedel−Crafts reaction passing through the attachment to
the α side, a largely favored (ΔΔE = 3.22 kcal/mol) approach
over the β one, as indicated by the energy of the TS1-α and TS1-
β transition states (TSs), −1.32 and 1.90 kcal/mol, respectively.
After the first TS, the two next Wheland intermediates are
reported as INT1-α and INT1-β, which maintain the same
distribution in selectivity as in the previous TSs.
The results obtained so far, seemed to be in disagreement with
the experimental data: literature methods for C-1 epimerization
of the furanoside derivative require harsh conditions in order to
be accomplished. Strong acids, such as benzenesulfonic acid or
TFA, in refluxing toluene22g or in over stoichiometric
concentrations are usually required.23b Under these conditions,
the formation of a carbocation intermediate has been
demonstrated by NMR studies.23b However, in our case, the
equilibration occurred at −30 °C in the presence of a catalytic
amount of a Lewis acid; therefore, a different scenario should be
operative.
Specifically, INT1 species could undergo an intramolecular
hydrogen transfer of the two corresponding Wheland cationic
intermediates to the furan oxygen atom and the concomitant
opening of the THF ring. The TSs obtained for this
transformation appear to be the rate-determining step in both
the cases, with an activation energy of 25.00 kcal/mol to
overcome TS2-α and 25.30 kcal/mol for TS2-β. The resulting
intermediates INT2 correspond to the opened-ring cationic
structures, where the alcohol obtained from the protonation of
the furane oxygen is opposed to the trigonal planar cationic
counterpart (see Scheme 6a). Also, in this step, the α-approach
is favored over the β-one. These two transition states are
fundamental to explain the reactivity of this reaction: indeed, the
population of INT2-α as a main intermediate occurs under a
kinetic-dominated scenario. Furthermore, INT2-α can be easily
interconverted in the more stable INT2-β through TS3-α-β
with a very low energy barrier (2.71 kcal/mol) under
thermodynamic equilibration. This negligible C−C bond energy
rotation is the key step for the equilibration between the two C-1
epimers, thus resulting in the formation of the β-arylated
product as a main isomer. By applying a Boltzmann population
analysis of the direct (α to β, ΔE = 2.71 kcal/mol) and reverse (β
to α, ΔE = 3.40 kcal/mol) reactions at the equilibrium, we found
that theoretical values of 76:24 (α/β) are fully consistent with
the selectivity trend observed in our experiments, 78:22 (α/β)
(Scheme 6a).
Dihydroisobenzofuran, pyrrolidine, and oxazolidine hetero-
cycles could also be employed as substrates for this oxo-Re-
mediated allylation (Scheme 5). In the event, 1-methoxy-1,3-
dihydroisobenzofuran 36 and 2-methoxy-1-methoxycarbonyl-
pyrrolidine 3828 afforded the corresponding allylated product
37 and 39 in 86 and 90% isolated yields, respectively.
Interestingly, when chiral29a (4S)-4-benzyl-2-methoxy-3-tosyl-
1,3-oxazolidine 40 was subjected to the allylation reaction, the
Scheme 5. Oxo-Rhenium-Mediated Allylation Reaction on
a
Different Oxocarbenium Ions
a
In Scheme 6b, the structures of the final deprotonated
products 26-TMS-α and 26-TMS-β are reported together with
the relative energy, showing the higher stability of the β product
over the α one (ΔΔE = 1.54 kcal/mol).
Conditions: 1 equiv of furanoside substrate, 2.5 equiv of
allyltrimethyl silane, 15 mol % oxoRe complex 8, 5 mol % Cu(OTf)2,
CH2Cl2 (0.05 M), from −50 to −30 °C. Diastereoselectivities were
determined from the H NMR spectrum.
1
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Scheme 6. (a) Proposed Mechanism for the Aryl-C-glycoside Formation Based on DFT Calculations (ΔE in kcal/mol); (b)
a
Relative Energy between Products 26-TMS-β and 26-TMS-α
a
[B3LYP/6-31G(d,p)&6-31+G(d,p)/CH2Cl2(PCM)//B3LYP/6-31G(d,p)&6-31+G(d,p)]
Compounds were visualized by UV irradiation at a wavelength of 254
nm or stained by exposure to a 0.5% solution of vanillin in H2SO4−
EtOH followed by charring. Flash column chromatography was
CONCLUSIONS
■
In summary, a new methodology for the formation of
oxocarbenium ions and subsequent addition of a wide range
of nucleophiles was developed, exploiting the advantage of using
commercially available THF O-methoxy-acetals as starting
materials in combination with a Re (V) complex catalyst. The
peculiarity of this method is the use of catalytic amounts of a
stable and easy to handle Re (V) catalyst as a Lewis acid,
together with the Cu(OTf)2 cocatalyst, achieving high yields
and stereoselectivities. The wide scope for both the nucleophile
and the oxocarbenium species paves the way for further
investigation in this research field, also opening to a fast and
reliable approach for other heterocyclic substrates. Moreover,
the computational explanation of the diastereoselectivity
observed in the case of electron-rich aromatic nucleophiles
uncovered the presence of an equilibration step, which is
ultimately responsible for the regulation of the observed anti-
Woerpel selectivity.
performed using Kieselgel 60 Merck (40−63 μm). Yields are reported
for chromatographically and spectroscopically pure isolated com-
pounds. NMR spectra were recorded on 200, 300, and 400 MHz
spectrometers. Chemical shifts are reported in δ units relative to the
employed solvent; the main abbreviations used have the following
meaning: s = singlet, d = doublet, t = triplet, q = quartet, qu =
quintuplet, m = multiplet, and br = broad. Coupling constants (J) are
given in Hz. The multiplicity (in parentheses) of each carbon atom was
determined by DEPT experiments, while * indicates the presence of
anomers. A relative configuration of the anomeric center of compounds
Ba-trans and Bb-cis was determined with NOE experiments.
Synthesis of Acetals. (5R)-2-Ethoxy-5-hexyltetrahydrofuran (9).
DIBAL-H (2.50 mL, 1 M solution in hexane, 2.50 mmol, 1.2 equiv) was
added dropwise to a solution of γ-decalactone (0.35 g, 2.10 mmol, 1.0
equiv) in dry CH2Cl2 (13 mL) at −78 °C under an argon atmosphere.
After been stirred for 30 min, the mixture was quenched by adding a
saturated solution of NH4Cl (50 mL). CH2Cl2 (80 mL) was then
added, and the resulting mixture was warmed to rt before the addition
of saturated solution of Rochelle’s salt. The layers were separated, and
the aqueous phase was extracted with CH2Cl2 (4 × 10 mL). The
combined organic phases were washed with brine, dried with MgSO4,
filtered, and concentrated under reduced pressure. The resulting
residue was dissolved in CH2Cl2/EtOH (2:1, 24 mL) and cooled to 4
°C, and then, PTSA (cat.) was added. After 12 h, excess solid NaHCO3
was added, and the resulting mixture was stirred for 15′, filtered, and
concentrated under reduced pressure. The residue was dissolved in
CH2Cl2 (50 mL), and a saturated solution of NaHCO3 (50 mL) was
added. The layers were separated, and the aqueous phase was extracted
with CH2Cl2 (3 × 20 mL). The combined organic phases were dried
with Na2SO4, filtered, and concentrated under reduced pressure. The
resulting residue was purified by flash chromatography on silica gel.
Elution with hexane/EtOAc (98:2) gave compound 9 (386 mg, 92%),
colorless oil as a 1:1 mixture of unseparable anomers; 1H NMR (300
EXPERIMENTAL SECTION
■
General Methods. All the reactions were performed in glassware
which has been dried in an oven at 140 °C for at least 3 h prior to use
and allowed to cool in a desiccator over self-indicating silica gel pellets.
Anhydrous solvents were distilled from appropriate drying agents.
Allyltrimethylsilane, anisole, methyl trimethylsilyl dimethylketene
acetal, γ-decalactone, 1-O-methyl-2-deoxy-d-ribose, 2-deoxy-D-ribose,
methyl D-ribofuranoside, methyl D-arabinofuranoside, methyl 3,5-di-O-
acetyl-2-deoxy-d-ribofuranoside S29, 1-methoxy-1,3-dihydro-2-benzo-
furan 36, 2-methoxy-pyrrolidine-1-carboxylic acid methylester 38, and
complex ReOCl3(OPPh3)(SMe2) 8 were purchased and used as
received. The reactions were carried out under a slightly positive static
pressure of argon. Routine monitoring of reactions was performed using
GF- 254 Merck (0.25 mm) aluminum-supported TLC plates.
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MHz, CD2Cl2): δ 5.10 (dd, J = 4.9, 2.0 Hz, 1H), 5.03 (dd, J = 3.7, 1.5
Hz, 1 H), 4.01 (m, 1H), 3.71 (m, 1H), 3.43 (dq, J = 16.1, 8.6 Hz, 1H),
2.04−1.33 (m, 14H), 1.12 (t, J = 7.1 Hz, 3H), 0.92 (t, J = 6.9 Hz, 3H)
ppm; 13C{1H} NMR (75 MHz, CD2Cl2): δ 104.4 (CH), 104.1* (CH),
81.2 (CH), 78.6 (CH), 63.2 (CH2), 62.7* (CH2), 38.5 (CH2), 36.4*
(CH2), 34.0 (CH2), 33.1 (CH2), 32.7* (CH2), 30.3 (CH2), 30.2*
(CH2), 27.1 (CH2), 26.9 (CH2), 23.4 (CH2), 15.9 (CH3), 14.7 (CH3)
ppm; IR (film, cm−1): 2980, 1464, 1369, 1107, 739; HRMS (ESI) m/z:
[M + H]+ calcd. for C12H25O2, 201.1849; found, 201.1852.
mg, 20.25 mmol, 3 equiv) and TBDPSCl (3.80 mL, 14.85 mmol,
2.2 equiv) were added under magnetic stirring. The resulting
solution has been stirred for 10 h and then was quenched by
adding a saturated solution of NaHCO3 (50 mL). The layers
were separated, and the aqueous phase was extracted with
CH2Cl2 (3 × 50 mL). The combined organic phases were dried
with Na2SO4, filtered, and concentrated under reduced pressure.
The resulting residue was purified by flash chromatography on
silica gel. Elution with hexane/EtOAc (99:1) gave compound 11
(3922 mg, 95%), colorless oil as a 1:1 mixture of unseparable
anomers. The spectroscopic data correspond with those
reported in the literature (See the Supporting Information for
1H NMR spectra).30
tert-Butyl(((2R,3S)-3-((tert-butyldiphenylsilyl)oxy)-5-methoxyte-
trahydrofuran-2-yl)methoxy)diphenylsilane (11).
(2R,3S,5S)-5-(Allyloxy)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-ol (Ba) and (2R,3S,5R)-5-(allyloxy)-2-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-3-ol (Bb).
The commercially available 1-O-methyl-2-deoxy-D-ribose (1000
mg, 6.75 mmol) was dissolved in dry CH2Cl2 (67.5 mL) at room
temperature under an argon atmosphere; then, imidazole (1379
2-Deoxy-D-ribose (134.1 mg, 1.0 mmol) was dissolved in
CH2Cl2/2-propen-1-ol (15:1, 16 mL) and cooled to 4 °C, and
then, PTSA (cat.) was added. After 14 h, excess solid NaHCO3
was added, and the resulting mixture was stirred for 15′ and
concentrated under reduced pressure. The residue was dissolved
in CH2Cl2 (50 mL), and a saturated solution of NaHCO3 (50
mL) was added. The layers were separated, and the aqueous
phase was extracted with CH2Cl2 (3 × 20 mL). The combined
organic phases were dried with Na2SO4, filtered, and
concentrated under reduced pressure. The resulting residue
was purified by flash chromatography on silica gel. Elution with
hexane−EtOAc (2:8) gave a desired allyl acetal A as a 1:1
mixture of unseparable anomers. Allyl acetal A (120.1 mg, 0.7
mmol) was dissolved in dry CH2Cl2 (6 mL) at room
temperature under an argon atmosphere; then, imidazole
(120.1 mg, 1.7 mmol, 3.0 equiv) and TBDPSCl (0.16 mL,
0.61 mmol, 1.1 equiv) were added under magnetic stirring. The
resulting solution has been stirred for 16 h and then was
quenched by adding a saturated solution of NaHCO3 (4 mL).
The layers were separated, and the aqueous phase was extracted
with CH2Cl2 (3 × 8 mL). The combined organic phases were
dried with Na2SO4, filtered, and concentrated under reduced
pressure. The resulting residue was purified by flash chromatog-
raphy on silica gel. Elution with a gradient from hexane/MTBE
(99:1) to hexane/MTBE (9:1) gave compound Ba-trans (139
mg) and compound Bb-cis (88.1 mg), colorless oil, overall yield
= 96%, trans/cis ratio = 1.58/1;
+ H]+ calcd. for C24H33O4Si, 413.2143; found, 413.2139; [α]2D0 + 58.0, c
= 0.96 in CH2Cl2.
1
(Bb)-cis. H NMR (300 MHz, CD2Cl2): δ 7.75 (m, 4H), 7.40 (m,
6H), 5.85 (m, 1H), 5.25−5.05 (m, 3H), 4.50 (dt, J = 6.3, 4.2 Hz, 1H),
4.15 (dd, J = 13.0, 5.0 Hz, 1H), 3.90 (m,1H), 3.80 (dd, J = 10.3, 5.4 Hz,
1H), 3.70 (dd, J = 10.3, 7.3 Hz, 1H), 2.24 (ddd, J = 13.4, 6.7, 2.3 Hz,
1H), 2.08 (m, 1H), 1.05 (s, 9H); 13C{1H} NMR (75 MHz, CD2Cl2): δ
136.3 (CH), 135.5 (CH), 134.2 (CH), 130.5 (C), 130.4 (C), 128.5
(CH), 128.4 (CH), 116.9 (CH2), 104.1 (CH), 86.9 (CH), 73.9 (CH),
69.0 (CH2), 66.3 (CH2), 42.1 (CH2), 27.4 (CH3), 19.9 (C); IR (film,
cm−1): 2931, 1568, 1475, 1431, 1118; HRMS (ESI) m/z: [M + H]+
calcd. for C24H33O4Si, 413.2143; found, 413.2139; [α]2D0 = −41.7, c =
0.94 CH2Cl2.
(2R,3S)-3-(benzyloxy)-2-((benzyloxy)methyl)-5-methoxytetrahy-
drofuran (S30).
The commercially available 1-O-methyl-2-deoxy-D-ribose (200
mg, 1.35 mmol) was dissolved in dry DMF (6.75 mL) at room
temperature under an argon atmosphere. Then, the solution was
cooled down to 0 °C, and NaH (71 mg, 2.97 mmol, 2.2 equiv)
was added under magnetic stirring. The resulting solution was
stirred for 30 min, and then, benzyl-bromide (481 μL, 4.05
mmol, 3 equiv) was added dropwise. The so-obtained mixture
was then warmed to room temperature and left under stirring
overnight. The quench was operated by the addition of a
saturated solution of NH4Cl (10 mL). The layers were
separated, and the aqueous phase was extracted with Et2O (3
× 10 mL). The combined organic phases were dried with
Na2SO4, filtered, and concentrated under reduced pressure. The
resulting residue was purified by flash chromatography on silica
gel. Elution with hexane/EtOAc (9:1) gave compound S30 (353
mg, 80%), colorless oil as a 1:1 mixture of unseparable anomers.
The spectroscopic data correspond with those reported in the
(Ba)-trans. 1H NMR (300 MHz, CD2Cl2): δ 7.70 (m, 4H), 7.40 (m,
6H), 5.85 (m, 1H), 5.35−5.15 (m, 3H), 4.28 (dd, J = 13.0, 5.1 Hz, 2H),
4.18 (t, J = 4.9 Hz, 1H), 4.02 (dd, J = 13.0, 5.9 Hz, 1H), 3.80 (dd, J =
10.9, 3.8 Hz, 1H), 3.68 (dd, J = 10.9, 4.8 Hz, 1H), 2.80 (dd, J = 10.6, 1.9
Hz, 1H), 2.25 (ddd, J = 13.6, 6.1, 4.7 Hz, 1H), 1.05 (s, 9H); 13C{1H}
NMR (75 MHz, CD2Cl2): δ 136.5 (CH), 135.5 (CH), 134.2 (C), 130.6
(CH), 134.6 (CH), 128.6 (CH), 117.3 (), 104.8 (CH), 88.8 (CH),
73.9 (CH), 68.9 (CH2), 65.4 (CH2), 42.1 (CH2), 27.5 (C), 20.0 (C);
IR (film, cm−1): 2933, 1564, 1472, 1432, 1115; HRMS (ESI) m/z: [M
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literature (see the Supporting Information for 1H NMR
filtered, and concentrated under reduced pressure. The resulting
residue was purified by flash chromatography on silica gel.
Elution with hexane/AcOEt (9:1) gave compound S31 (122.3
mg, 90%) as colorless oil; 1H NMR (300 MHz, CD3CN): δ 7.75
(d, J = 8.3 Hz, 2H), 7.61 (m, 4H), 7.50−7.40 (m, 8H), 6.05−
5.85 (m, 1H), 5.32−5.12 (m, 3H), 5.02 (dt, J = 7.6, 1.5 Hz, 1H),
4.25−4.15 (m, 2H), 4.05−3.91 (m, 1H), 3.60−3.48 (dd, J =
11.3, 3.0 Hz, 2H), 2.45 (s, 3H), 2.25-2.37-1.90 (m, 2H), 1.08 (s,
9H) ppm; 13C{1H} NMR (75 MHz, CD3CN): δ 145.5 (C),
135.4 (CH), 135.3 (CH), 134.8 (CH), 133.0 (C), 132.9 (C),
130.1 (CH), 129.9 (CH), 129.9 (CH), 127.8 (CH), 127.7
(CH), 115.9 (CH2), 103.2 (CH), 83.5 (CH), 80.6 (CH), 67.9
(CH2), 63.2 (CH2), 39.2 (CH2), 26.1 (CH3), 20.7 (CH), 18.7
(C) ppm; IR (film, cm−1): 3068, 2855, 1471, 1424, 1261, 1102,
1004, 940, 713; HRMS (ESI) m/z: [M + H]+ calcd. for
C31H39O6SSi, 567.2231; found, 567.2233; [α]2D0 = +65.3, c =
2.72 CH2Cl2.
spectra).31
(2R,3S,5S)-5-(Allyloxy)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl 4-methylbenzenesulfonate (S31).
Free alcohol Ba (100.1 mg, 0.24 mmol) was dissolved in dry
pyridine (4.0 mL) at room temperature under an argon
atmosphere; then, tosyl chloride (185.0 mg, 0.96 mmol, 4.0
equiv) and 4-dimethylaminopyridine (2.9 mg, 0.02 mmol, 0.1
equiv) were added under magnetic stirring. The resulting
solution has been stirred for 15 h and then was quenched by
adding a saturated solution of NaHCO3 (5 mL). The layers were
separated, and the aqueous phase was extracted with Et2O (3 × 5
mL). The combined organic phases were dried with Na2SO4,
(2R,3R)-5-(Allyloxy)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-ol (D).
Synthetical Sequence for the Preparation of Inverted Acetal S32.
(2R,3R)-5-(Allyloxy)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl 4-nitrobenzoate (C).
To a magnetically stirred solution of C (236 mg, 0.42 mmol) in
dry MeOH (8 mL) were added few crystals of K2CO3. The
reaction mixture was stirred at room temperature, and the
reaction was completed after 16 h. Methanol was removed in
vacuo, and the residue was purified on silica gel using hexane/
AcOEt 80:20 as an eluent to afford the desired alcohol D as
1
colorless oil (164.6 mg, yield = 95%); H NMR (300 MHz,
(CD3)2CO): δ 7.86−7.67 (m, 4H), 7.56−7.36 (m, 6H), 5.95
(ddt, J = 17.1, 10.6, 5.4 Hz, 1H), 5.39−5.02 (m, 3H), 4.48 (p, J =
4.4 Hz, 1H), 4.28−3.78 (m, 5H), 2.14 (t, J = 4.4 Hz, 2H), 1.07
(s, 9H); 13C{1H} NMR (75 MHz, (CD3)2CO): δ 136.9 (CH),
136.8 (CH), 136.7 (CH), 136.7 (CH), 134.9 (C), 134.8 (C),
130.9 (CH), 129.0 (CH), 128.9 (CH), 116.5 (CH2), 103.9
(CH), 82.80 (CH), 72.21 (CH), 69.3 (CH2), 64.3 (CH2), 44.1
(CH2), 27.7 (CH3), 27.5 (CH3), 20.1 (C); IR (film, cm−1):
2934, 1566, 1475, 1431, 1117; HRMS (ESI) m/z: [M + H]+
To a magnetically stirred solution of anomeric mixture of Ba and
Bb (80.9 mg, 0.196 mmol) in dry toluene (2 mL) under an Ar
atmosphere at −78 °C were added PPh3 (66.8 mg, 0.255 mmol,
1.3 equiv), 4-NO2-C6H4-CO2H (36.1 mg, 0.216 mmol, 1.1
equiv), and DEAD (41 mL, 0.262 mmol). The reaction mixture
was allowed to warm to room temperature, and the reaction was
completed after 16 h. The reaction mixture was thus
concentrated under vacuum. The residue was purified by
column chromatography on silica gel using hexane/AcOEt 92:8
as an eluent to afford the ester C as white foam (97.9 mg, yield =
calcd. for C24H33O4Si, 413.2143; found, 413.2145.
(((2R,3R)-5-(Allyloxy)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl)oxy) (tert-butyl)diphenylsilane (S32).
1
89%); H NMR (300 MHz, CDCl3): δ 8.40−8.09 (m, 4H),
7.75−7.66 (m, 3H), 7.65−7.57 (m, 2H), 7.51−7.25 (m, 8H),
5.96 (dddd, J = 17.3, 10.6, 5.8, 5.0 Hz, 1H), 5.82 (dt, J = 5.3, 3.7
Hz, 1H), 5.41 (dd, J = 5.0, 3.7 Hz, 1H), 5.29 (dq, J = 17.3, 1.8
Hz, 1H), 5.15 (dq, J = 10.5, 1.6 Hz, 1H), 4.46 (td, J = 6.2, 4.0 Hz,
1H), 4.23 (ddt, J = 13.2, 5.0, 1.6 Hz, 1H), 4.10−3.91 (m, 4H),
2.50−2.40 (m, 2H), 1.00 (s, 9H); 13C{1H} NMR (75 MHz,
CDCl3): δ 164.9 (C), 151.9 (C), 136.7 (C), 136.6 (C), 136.3
(C), 134.4 (C), 131.9 (CH), 131.1 (CH), 131.0 (CH), 129.0
(CH), 128.9 (CH), 124.8 (C), 116.9 (CH2), 103.7 (CH), 80.6
(CH), 76.3 (CH), 69.6 (CH2), 63.0 (CH2), 41.4 (CH2), 27.41
(CH3), 20.01 (C); IR (film, cm−1): 3071, 2932, 2857, 1719,
1529, 1479, 1429, 1281, 1103, 1003, 935; HRMS (ESI) m/z: [M
+ H]+ calcd. for C31H36NO7Si2, 562.2256; found, 562.2253.
The epimeric alcohol D (42 mg, 0.1 mmol) was dissolved in dry
CH2Cl2 (2 mL) under Ar, and at room temperature, imidazole
(28 mg, 0.41 mmol, 4.1 equiv) and TBDPSCl (32 mL, 0.11
mmol, 1.1 equiv) were added. The reaction mixture was stirred
at room temperature for 16 h and was quenched with H2O (2
mL). The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (3 × 5 mL). The combined organic layers
were dried over Na2SO4, filtered, and concentrated under
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combined organic phases were dried with Na2SO4, filtered, and
concentrated under reduced pressure. The resulting residue was
purified by flash chromatography on silica gel. Elution with a suitable
solvent mixture (see conditions for each compound) gave the final
product (see yield for each compound).
vacuum. The residue was purified by column chromatography
on silica gel using hexane/MTBE 95:5 as an eluent to afford the
product S32 as colorless oil (59.9 mg, yield = 92%); 1H NMR
(300 MHz, (CD3)2CO): δ 7.77 (ddt, J = 12.8, 6.3, 1.8 Hz, 4H),
7.64 (ddt, J = 6.6, 3.7, 1.9 Hz, 4H), 7.52−7.32 (m, 12H), 6.00−
5.76 (m, 1H), 5.28−5.02 (m, 3H), 4.65 (dt, J = 6.0, 3.9 Hz, 1H),
4.20−3.88 (m, 5H), 2.15−2.01 (m, H, overlapped with solvent),
1.85 (ddd, J = 13.8, 6.2, 2.8 Hz, 1H), 1.10 (s, 9H), 1.00 (s, 9H)
ppm; 13C{1H} NMR (75 MHz, (CD3)2CO): δ 136.9 (CH),
136.8 (CH), 136.8 (CH), 136.7 (CH), 136.7 (CH), 136.5
(CH), 135.1 (C), 135.0 (C), 134.9 (C), 134.4 (C), 131.1 (CH),
131.1 (CH), 130.9 (CH), 129.1 (CH), 128.9 (CH), 128.9
(CH), 116.6 (CH2), 103.5 (CH), 82.9 (CH), 74.6 (CH), 69.2
(CH2), 65.0 (CH2), 43.7 (CH2), 27.7 (CH3), 27.6 (CH3), 20.2
(C), 20.1 (C) ppm; IR (film, cm−1): 3065, 2858, 1470, 1421,
1257, 1106, 1002, 941, 751, 713, 601; HRMS (ESI) m/z: [M +
(2S,5R)-2-Allyl-5-hexyltetrahydrofuran (10a) and (2R,5R)-2-allyl-
5-hexyltetrahydrofuran (10b). See Table 1 for yields associated to
each reaction conditions; for entry 2, purification with hexane/MTBE
1
(99:1) gave 186.2 mg, 95%, as colorless oil; H NMR (300 MHz,
CDCl3): δ 5.82 (ddt, J = 10.1, 2.7, 0.9 Hz, 1H), 5.12 (dd, J = 2.1, 0.9 Hz,
1H), 5.04 (dd, J = 2.7, 0.9 Hz, 1H), 3.95 (dt, J = 32.0, 7.4 Hz, 1H), 3.89
(dt, J = 43.3, 6.2 Hz, 1H), 2.37 (m, 1H), 2.24 (m, 1H), 1.99 (m, 2H),
1.59−1.29 (m, 12H), 0.89 (t, J = 6.9 Hz, 3H) ppm; 13C{1H} NMR (75
MHz, CDCl3): δ 134.6 (CH), 116.1 (CH2), 79.1 (CH), 78.5 (CH),
77.9 (CH), 77.3 (CH), 34.0 (CH2), 39.9 (CH2), 35.6 (CH2), 35.5
(CH2), 31.4 (CH2), 31.3 (CH2), 30.9 (CH2), 30.4 (CH2), 29.9 (CH2),
28.9 (CH2), 25.6 (CH2), 22.1 (CH2), 13.6 (C) ppm; IR (film, cm−1):
3070, 2974, 2869, 1641; HRMS (ESI) m/z: [M + H]+ calcd. for
C13H25O, 197.1900; found, 197.1903.
(((2R,3S,5R)-5-Allyl-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl)oxy)(tert-butyl)diphenylsilane (12). Purifica-
tion with hexane/MTBE (98:2) gave 59.1 mg, yield 93%, as colorless
oil; 1H NMR (300 MHz, CDCl3): δ 7.75 (m, 8H), 7.45 (m, 12H), 6.00
(dddd, J = 17.2, 10.2, 6.9, 6.9 Hz, 1H), 5.27 (dd, J = 16.5, 0.8 Hz, 1H),
5.20 (dd, J = 9.6, 0.8 Hz, 1H), 4.62 (ddd, J = 6.8, 3.5, 3.5 Hz, 1H), 4.20
(m, 2H), 3.62 (dd, J = 10.9, 3.5 Hz, 1H), 3.40 (dd, J = 10.9, 3.8 Hz, 1H),
2.65 (ddd, J = 13.9, 6.9, 6.9 Hz, 1H), 2.52 (ddd, J = 13.9, 6.9, 6.9 Hz,
1H), 2.19 (ddd, J = 8.4, 6.0, 1.8 Hz, 1H), 1.89 (ddd, J = 12.5, 5.6, 4.9 Hz,
1H), 1.20 (s, 9H), 1.05 (s, 9H) ppm; 13C{1H} NMR (75 MHz,
CDCl3): δ 135.7 (CH), 135.5 (CH), 135.4 (CH), 135.3 (CH), 133.7
(C), 133.6 (C), 133.3 (C), 129.6 (CH), 129.4 (CH), 129.4 (CH),
127.6 (CH), 127.5 (CH), 116.5 (CH2), 86.6 (CH), 78.6 (CH), 74.8
(CH), 64.4 (CH2), 40.8 (CH2), 40.3 (CH2), 26.8 (CH3), 26.6 (CH3),
19.0 (C) ppm; IR (film, cm−1): 3069, 2933, 2855, 1475, 1431, 1261,
1113, 1002, 935, 777, 741, 702, 614; HRMS (ESI) m/z: [M + H]+
calcd. for C40H51O3Si2, 635.3371; found, 635.3370; [α]2D0 + 38.0, c =
1.9, CH2Cl2.
H]+ calcd. for C40H51O4Si2, 651.3320; found, 651.3322.
(2R,3R,4R)-2-(Acetoxymethyl)-5-methoxytetrahydrofuran-3,4-
diyl diacetate (S33).
The commercially available methyl D-ribofuranoside (90.7 mg,
0.55 mmol) was dissolved in dry CH2Cl2 (8 mL) at room
temperature under an argon atmosphere; then, pyridine (0.35
μL, 3.92 mmol, 7.1 equiv) and Ac2O (0.20 μL, 1.93 mmol, 3.5
equiv) were added under magnetic stirring. The resulting
solution has been stirred for 15 h and then was quenched by
adding a saturated solution of NaHCO3 (5 mL). The layers were
separated, and the aqueous phase was extracted with CH2Cl2 (3
× 5 mL). The combined organic phases were dried with Na2SO4,
filtered, and concentrated under reduced pressure. The resulting
residue was purified by flash chromatography on silica gel.
Elution with hexane/MTBE (9:1) gave compound S33 (145.3
mg, 91%) as colorless oil as a mixture of unseparable anomers.
The spectroscopic data correspond with those reported in the
literature (See the Supporting Information for 1H NMR
((2R,3S,5R)-3-Acetoxy-5-allyltetrahydrofuran-2-yl)methyl ace-
tate (29). Purification with hexane/AcOEt (9:1) gave 22.3 mg, yield
1
92%, as colorless oil; H NMR (300 MHz, CDCl3): δ 5.82 (m, 1H),
5.07 (m, 3H), 4.18 (m, 4H), 2.25−2.45 (m, 3H), 2.08 (s, 3H), 2.06 (s,
3H), 1.75 (dt, J = 13.1, 5.3 Hz, 1H) ppm; 13C{1H} NMR (75 MHz,
CDCl3): δ 170.6 (C), 170.5 (C), 134.0 (CH), 117.4 (CH2), 80.8 (CH),
78.1 (CH), 75.6 (CH), 63.9 (CH2), 39.9 (CH2), 36.7 (CH2), 20.9
(CH3), 20.7 (CH3) ppm; IR (film, cm−1): 2953, 1749, 1494, 1451,
1367, 1243, 1171, 1125, 1085, 1026, 992, 896, 768, 721; HRMS (ESI)
m/z: [M + H]+ calcd. for C12H19O5, 243.1227; found, 243.1230; [α]D20
+ 34.7, c = 1.16, CH2Cl2.
spectra).32
(2R,3R,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-5-methoxy-
tetrahydrofuran (S34).
(2R,3S,5R)-5-Allyl-3-(benzyloxy)-2-((benzyloxy)methyl)-
tetrahydrofuran (30). Purification with hexane/MTBE (97:3) gave
1
30.1 mg, yield 89%, as colorless oil; H NMR (300 MHz, CDCl3): δ
The commercially available methyl D-arabinofuranoside was
involved in the same procedure abovereported for the synthesis
of compound S30, by giving compound S34 in 85% of isolated
yield as colorless oil as a mixture of unseparable anomers. The
spectroscopic data correspond with those reported in the
literature (see the Supporting Information for 1H NMR
spectra).33
General Procedure for Allylation with Allyl-TMS. A suitable
acetal (0.08 mmol) was dissolved in dry CH2Cl2 (30 mM) at room
temperature under an argon atmosphere; then, allyltrimethylsilane
(0.40 mmol, 5.0 equiv or less, see manuscript for details) was added
under magnetic stirring. The resulting solution was cooled at −50 °C,
and complex 8 (15 mol %) followed by Cu(OTf)2 (5 mol %) were
added in one portion. The reaction mixture was allowed to warm at −30
°C and stirred at this temperature until the starting material was
completely consumed. The reaction was then quenched with a
saturated solution of NaHCO3 (2 mL). The layers were separated,
and the aqueous phase was extracted with CH2Cl2 (3 × 4 mL). The
7.57−7.10 (m, 10H), 5.86 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.23−5.02
(m, 2H), 4.67−4.46 (m, 4H), 4.29−4.07 (m, 3H), 3.65−3.47 (m, 2H),
2.54 (dtt, J = 13.2, 6.5, 1.4 Hz, 1H), 2.45−2.23 (m, 2H), 1.82 (ddd, J =
12.5, 7.0, 5.2 Hz, 1H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 138.2
(C), 138.1 (C), 134.7 (CH), 128.3 (CH), 128.2 (CH), 127.5 (CH),
127.5 (CH), 127.5 (CH), 116.9 (CH2), 82.1 (CH), 80.7 (CH), 78.1
(CH), 73.3 (CH2), 71.5 (CH2), 70.7 (CH2), 40.3 (CH2), 37.2 (CH2)
ppm; IR (film, cm−1): 3061, 2927, 1445, 1367, 1219, 1081, 1017, 957,
737, 703; HRMS (ESI) m/z: [M + H]+ calcd. for C22H27O3, 339.1955;
found, 339.1953; [α]2D0 + 39.5, c = 1.5, CH2Cl2.
(2R,3S,5R)-5-Allyl-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl 4-methylbenzenesulfonate (31). Purification
with hexane/MTBE (92:8) gave 51.1 mg, yield 93%, as colorless oil; 1H
NMR (300 MHz, CDCl3): δ 7.75 (d, J = 8.3 Hz, 2H), 7.62 (m, 4H),
7.40 (m, 6H), 7.25 (d, J = 8.3 Hz, 2H), 5.85 (m, 1H), 5.25 (dt, J = 3.9,
0.8 Hz, 1H), 5.16−5.07 (m, 2H), 4.24 (quintet, J = 6.7 Hz, 1H), 4.16
(m, 1H), 3.60 (dd, J = 11.0, 4.0 Hz, 2H), 2.50 (s, 3H), 2.25−2.37 (m,
3H), 1.90 (m, 1H), 1.08 (s, 9H) ppm; 13C{1H} NMR (75 MHz,
CDCl3): δ 144.7 (C), 135.4 (CH), 134.2 (CH), 133.6 (C), 132.9 (C),
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132.8 (C), 129.8 (CH), 129.7 (CH), 129.6 (CH), 127.7 (CH), 127.6
(CH), 127.6 (CH), 117.2 (CH2), 83.35 (CH), 82.3 (CH), 78.6 (CH),
63.9 (CH2), 40.1 (CH2), 37.6 (CH2), 26.6 (CH3), 21.5 (CH3), 19.0
(C) ppm; IR (film, cm−1): 2856, 1473, 1429, 1268, 1098, 1009, 951;
HRMS (ESI) m/z: [M + H]+ calcd. for C31H39O5SSi, 551.2282; found,
551.2285; [α]2D0 + 34.7, c = 0.6 CH2Cl2.
reaction mixture was allowed to warm at −30 °C and stirred at this
temperature for 12 h. The reaction was then quenched with a saturated
solution of NaHCO3 (5 mL). The layers were separated, and the
aqueous phase was extracted with CH2Cl2 (3 × 7 mL). The combined
organic phases were dried with Na2SO4, filtered, and concentrated
under reduced pressure. The resulting residue was purified by flash
chromatography on silica gel.
(((2R,3R,5S)-5-Allyl-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl)oxy)(tert-butyl)diphenylsilane (32). Purifica-
tion with hexane/MTBE (98:2) gave 54.2 mg, yield 86%, as colorless
oil; 1H NMR (300 MHz, CD2Cl2): δ 7.81−7.27 (m, 20H), 6.01−5.74
(m, 1H), 5.29−4.97 (m, 2H), 4.64−4.39 (m, 1H), 4.25−3.75 (m, 4H),
2.51 (dtt, J = 14.5, 6.5, 1.4 Hz, 1H), 2.41−2.25 (m, 1H), 2.14−1.59 (m,
2H), 1.11 (s, 9H), 1.01 (s, 9H) ppm; 13C{1H} NMR (75 MHz,
CD2Cl2): δ 136.7 (CH), 136.6 (CH), 136.5 (CH), 136.5 (CH), 136.4
(CH), 136.1 (CH), 135.8 (CH), 134.8 (CH), 134.7 (CH), 134.6 (C),
134.1 (C), 134.0 (C), 130.5 (CH), 130.5 (CH), 130.4 (CH), 130.3
(CH), 130.3 (CH), 128.5 (CH), 128.4 (CH), 128.4 (CH), 128.3
(CH), 117.1 (CH2), 116.9 (CH2), 83.9 (CH), 82.5 (CH), 77.7 (CH),
74.8 (CH), 64.6 (CH2), 43.3 (CH2), 41.4 (CH2), 41.15 (CH2), 27.5
(CH3), 27.5 (CH3), 27.5 (CH3), 27.4 (CH3), 19.9 (C), 19.8 (C) ppm;
IR (film, cm−1): 3068, 2934, 2853, 1473, 1435, 1262, 1112, 1000, 936,
774, 742, 701, 618; HRMS (ESI) m/z: [M + H]+ calcd. for
C40H51O3Si2, 635.3371; found, 635.3375.
(2R,3R,4S,5R)-2-(Acetoxymethyl)-5-Allyltetrahydrofuran-3,4-diyl
diacetate (33). Purification with hexane/AcOEt (85:15) gave 27.9 mg,
yield 93%, as pale-yellow oil; 1H NMR (300 MHz, CDCl3): δ 5.74 (ddt,
J = 17.1, 10.2, 7.0 Hz, 1H), 5.46 (dd, J = 4.6, 3.4 Hz, 1H), 5.34−5.25 (m,
1H), 5.18−5.04 (m, 2H), 4.39−4.02 (m, 4H), 2.56−2.29 (m, 2H),
2.20−2.01 (m, 9H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 170.6
(C), 169.7 (C), 169.6 (C), 132.9 (CH), 117.7 (CH2), 78.8 (CH), 76.5
(CH), 72.2 (CH), 72.0 (CH), 63.6 (CH2), 33.8 (CH2), 20.7 (CH3),
20.4 (CH3), 20.4 (CH3) ppm; IR (film, cm−1): 2957, 1745, 1494, 1447,
1367, 1243, 1101, 1083, 1047, 891, 771, 723; HRMS (ESI) m/z: [M +
H]+ calcd. for C14H21O7, 301.1282; found, 301.1283; NOESY
correlations (see the Supporting Information).
(2R,3R,4R,5R)-2-Allyl-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)-
tetrahydrofuran (34). Purification with hexane/MTBE (9:1) gave 34.2
mg, yield 77%, as colorless oil; 1H NMR (300 MHz, CDCl3): δ 7.46−
7.19 (m, 15H), 5.94−5.72 (m, 1H), 5.24−4.97 (m, 2H), 4.69−4.32 (m,
4H), 4.17−3.99 (m, 2H), 3.99−3.79 (m, 2H), 3.73−3.46 (m, 2H), 2.52
(tq, J = 7.0, 1.4 Hz, 2H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ
138.2 (C), 137.8 (C), 137.7 (C), 134.8 (CH), 134.1 (C), 128.3 (CH),
128.3 (CH), 128.3 (CH), 128.2 (CH), 128.2 (CH), 127.7 (CH), 127.6
(CH), 127.6 (CH), 127.5 (CH), 127.5 (CH), 127.4 (CH), 116.8
(CH2), 83.7 (CH), 82.7 (CH), 82.5 (CH), 80.9 (CH), 73.2 (CH2),
71.3 (CH2), 71.2 (CH2), 70.5 (CH2), 33.07 (CH2) ppm; IR (film,
cm−1): 2957, 1445, 1367, 1209, 1081, 1017, 737, 703; HRMS (ESI) m/
z: [M + H]+ calcd. for C29H33O4, 445.2373; found, 445.2378; NOESY
correlations (see the Supporting Information).
General Procedures for the Glycosylation Scope. Procedure
A. The acetal for the specific reaction (0.2 mmol) was dissolved in dry
CH2Cl2 (4 mL) at room temperature under an argon atmosphere; then,
the trimethylsilyl-substituted alkyl-based reagent (0.5 mmol, 2.5 equiv)
was added under magnetic stirring. The resulting solution has been
cooled at −50 °C, and complex 5 (15 mol %) followed by Cu(OTf)2 (5
mol %) were added in one portion. The reaction mixture was allowed to
warm at −30 °C and stirred at this temperature for 12 h (except for
compound 16 which was warmed up to 0 °C). The reaction was then
quenched with a saturated solution of NaHCO3 (5 mL). The layers
were separated, and the aqueous phase was extracted with CH2Cl2 (3 ×
7 mL). The combined organic phases were dried with Na2SO4, filtered,
and concentrated under reduced pressure. The resulting residue was
purified by flash chromatography on silica gel.
Methyl 3-(((2R,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)methyl)but-3-
enoate (13-Procedure A). Purification with hexane/MTBE (85:15)
gave 104.5 mg, yield 74%, as colorless oil; 1H NMR (400 MHz,
(CD3)2CO): δ 7.67−7.47 (m, 8H), 7.43−7.25 (m, 12H), 5.62−5.46
(m, 2H), 4.49 (ddd, J = 6.6, 4.6, 3.4 Hz, 1H), 4.07−3.89 (m, 2H), 3.54
(s, 3H), 3.44 (dd, J = 11.0, 3.4 Hz, 1H), 3.32 (dd, J = 11.0, 4.0 Hz, 1H),
2.97 (dt, J = 4.2, 1.1 Hz, 2H), 2.45−2.22 (m, 2H), 2.04 (dt, J = 13.4, 6.7
Hz, 1H), 1.72 (ddd, J = 12.6, 6.4, 4.6 Hz, 1H), 1.00 (s, 9H), 0.85 (s, 9H)
ppm; 13C{1H} NMR (101 MHz, (CD3)2CO: δ 171.5 (C), 135.7 (CH),
135.6 (CH), 135.5 (CH), 135.4 (CH), 133.6 (C), 133.6 (C), 133.3
(C), 130.6 (CH), 129.9 (CH), 129.9 (CH), 129.7 (CH), 129.6 (CH),
127.8 (CH), 127.7 (CH), 127.6 (CH), 124.3 (CH), 86.4 (CH), 78.5
(CH), 74.9 (CH), 64.4 (CH2), 50.9 (CH3), 40.3 (CH2), 39.3 (CH2),
37.4 (CH2), 26.5 (CH3), 26.2 (CH3), 18.8 (C), 18.7 (C) ppm; IR (film,
cm−1): 2937, 1746, 1651, 1562, 1475, 1429, 1113, 1001, 826, 729;
HRMS (ESI) m/z: [M + H]+ calcd. for C43H55O5Si2, 707.3583; found,
707.3581; [α]2D0 + 33.6, c = 0.72, CH2Cl2.
(((2R,3S,5S)-5-(2-bromoallyl)-2-(((tert-butyldiphenylsilyl)oxy)-
methyl)tetrahydrofuran-3-yl)oxy)(tert-butyl)diphenylsilane (14-
Procedure A). Purification with hexane/MTBE (98:2) gave 140.9
mg, yield 99%, as colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.60−
7.39 (m, 8H), 7.38−7.16 (m, 12H), 5.61 (q, J = 1.2 Hz, 1H), 5.42 (d, J =
1.6 Hz, 1H), 4.44 (dt, J = 6.0, 2.9 Hz, 1H), 4.36 (tdd, J = 7.4, 5.9, 4.7 Hz,
1H), 3.97 (td, J = 3.7, 2.4 Hz, 1H), 3.38 (dd, J = 11.0, 3.8 Hz, 1H), 3.19
(dd, J = 11.0, 3.6 Hz, 1H), 2.88 (ddd, J = 14.5, 7.3, 1.1 Hz, 1H), 2.62
(ddd, J = 14.5, 5.9, 1.1 Hz, 1H), 2.08 (ddd, J = 13.4, 7.5, 6.2 Hz, 1H),
1.69 (ddd, J = 13.0, 4.8, 3.2 Hz, 1H), 0.99 (s, 9H), 0.84 (s, 9H) ppm;
13C{1H} NMR (101 MHz, CDCl3): δ 135.8 (CH), 135.8 (CH), 135.6
(CH), 135.6 (CH), 133.7 (C), 133.6 (C), 133.3 (C), 133.2 (C), 131.1
(C), 129.8 (CH), 129.6 (CH), 129.6 (CH), 127.7 (CH), 127.6 (CH),
118.5 (CH2), 87.2 (CH), 77.4 (CH), 77.1 (CH), 77.0 (CH), 76.7
(CH), 75.0 (CH), 64.5 (CH2), 48.3 (CH2), 39.9 (CH2), 27.0 (CH3),
26.8 (CH3), 19.1 (C), 19.1 (C) ppm; IR (film, cm−1): 3067, 2931,
2861, 1459, 1257, 1119, 1008, 931; HRMS (ESI) m/z: [M + H]+ calcd.
for C40H50O3Si2Br, 713.2476; found, 713.2478; [α]2D0 + 32.2, c = 0.68,
CH2Cl2.
tert-butyl(((2R,3S,5R)-3-((tert-butyldiphenylsilyl)oxy)-5-(2-
methylallyl)tetrahydrofuran-2-yl)methoxy)diphenylsilane (15-Pro-
cedure A). Purification with hexane/MTBE (9:1) gave 112.7 mg, yield
87%, as colorless oil; 1H NMR (300 MHz, CDCl3): δ 7.78−7.23 (m,
20H), 4.90−4.73 (m, 2H), 4.53 (ddd, J = 6.8, 4.2, 3.0 Hz, 1H), 4.27 (p, J
= 6.7 Hz, 1H), 4.07 (q, J = 3.5 Hz, 1H), 3.52 (dd, J = 11.0, 3.6 Hz, 1H),
3.43−3.23 (m, 1H), 2.54 (dd, J = 14.0, 7.2 Hz, 1H), 2.34 (dd, J = 14.1,
6.4 Hz, 1H), 2.11 (dt, J = 13.2, 6.8 Hz, 1H), 1.84−1.71 (m, 4H), 1.17−
1.02 (s, 9H), 0.94 (s, 9H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ
143.1 (C), 135.7 (CH), 135.6 (CH), 135.5 (CH), 135.4 (CH), 133.8
(C), 133.7 (C), 133.3 (C), 133.2 (C), 129.6 (CH), 129.4 (CH), 129.4
(CH), 127.6 (CH), 127.5 (CH), 127.4 (CH), 111.9 (CH2), 86.5 (CH),
77.5 (CH), 74.8 (CH), 64.4 (CH2), 44.7 (CH2), 40.7 (CH2), 26.8
(CH3), 26.6 (CH3), 22.7 (C), 19.0 (C) ppm; IR (film, cm−1): 3070,
2933, 2857, 1479, 1429, 1261, 1115, 1002, 935, 702, 614; HRMS (ESI)
m/z: [M + H]+ calcd. for C41H53O3Si2, 649.3528; found, 649.3529;
[α]2D0 + 37.4, c = 0.5, CH2Cl2; NOESY correlations (see the Supporting
Information).
tert-butyl(((2R,3S,5S)-3-((tert-butyldiphenylsilyl)oxy)-5-((S)-pent-
3-yn-2-yl)tetrahydrofuran-2-yl)methoxy)diphenylsilane (16-Proce-
dure A). Purification with hexane/MTBE (99:1) gave 108.2 mg, yield
82%, as colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.55−7.30 (m,
8H), 7.29−7.05 (m, 12H), 4.29 (ddd, J = 6.1, 4.7, 3.3 Hz, 1H), 3.85 (q, J
= 3.6 Hz, 1H), 3.64 (dt, J = 8.5, 6.3 Hz, 1H), 3.32 (dd, J = 11.0, 3.6 Hz,
1H), 3.22−3.14 (m, 1H), 2.59 (ddq, J = 9.0, 6.8, 2.3 Hz, 1H), 1.97−
1.87 (m, 2H), 1.62 (d, J = 2.4 Hz, 3H), 1.03 (s, 9H), 0.89 (s, 9H) ppm;
Procedure B. The acetal for the specific reaction (0.2 mmol) was
dissolved in dry CH2Cl2 (4 mL) at room temperature under an argon
atmosphere; then, the trimethylsilyl-substituted aromatic reagent (0.5
mmol, 2.5 equiv) was added under magnetic stirring (except for
compound 28 where furan was used in 1.5 equiv). The resulting
solution has been cooled at −50 °C, and complex 5 (30 mol %)
followed by Cu(OTf)2 (15 mol %) were added in one portion. The
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Article
13C{1H} NMR (101 MHz, CDCl3): δ 135.9 (CH), 135.8 (CH), 135.8
(C), 133.6 (C), 133.4 (C), 129.7 (CH), 129.5 (CH), 129.5 (CH),
127.7 (CH), 127.7 (CH), 127.7 (CH), 127.6 (CH), 127.59, 127.6
(CH), 86.4 (CH), 83.0 (CH), 73.8 (CH), 64.2 (CH2), 51.8 (CH3),
46.0 (C), 36.9 (CH2), 26.9 (CH3), 26.7 (CH3), 21.1 (CH3), 20.5
(CH3), 19.1 (C), 19.0 (C) ppm; IR (film, cm−1): 2935, 1748, 1653,
1561, 1475, 1429, 1113, 824, 738; HRMS (ESI) m/z: [M + H]+ calcd.
for C42H55O5Si2, 695.3583; found, 695.3585.
(CH), 135.7 (CH), 135.6 (CH), 135.6 (CH), 135.5 (CH), 133.9 (C),
133.8 (C), 133.5 (C), 133.4 (C), 129.8 (CH), 129.7 (CH), 129.5
(CH), 129.5 (CH), 129.4 (CH), 127.7 (CH), 127.6 (CH), 127.6
(CH), 127.6 (CH), 86.9 (CH), 82.9 (C), 81.3 (C), 74.5 (CH), 64.4
(CH2), 39.4 (CH), 32.3 (CH3), 26.8 (CH3), 26.6 (CH3), 19.2 (C),
19.1 (C), 3.7 (CH3) ppm; IR (film, cm−1): 3071, 2923, 2857, 1447,
1477, 1425, 1263, 1112, 1003, 937, 706; HRMS (ESI) m/z: [M + H]+
calcd. for C42H53O3Si2, 661.3528; found, 661.3526.
2-((2S,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-1-phenyle-
than-1-one (21-Procedure A). Purification with hexane/AcOEt (9:1)
gave 95.4 mg, yield 67%, as colorless oil; 1H NMR (400 MHz, CDCl3):
δ 7.96−7.87 (m, 2H), 7.61−7.11 (m, 23H), 4.70−4.59 (m, 1H), 4.48−
4.41 (m, 1H), 4.04 (td, J = 4.0, 2.2 Hz, 1H), 3.54 (dd, J = 16.4, 6.2 Hz,
1H), 3.33 (dd, J = 11.0, 4.2 Hz, 1H), 3.27 (d, J = 7.1 Hz, 1H), 3.25−3.18
(m, 1H), 2.21 (ddd, J = 13.4, 7.6, 6.1 Hz, 1H), 1.75 (ddd, J = 13.1, 4.4,
2.9 Hz, 1H), 0.98 (s, 9H), 0.83 (s, 9H) ppm; 13C{1H} NMR (101 MHz,
CDCl3): δ 198.9 (C), 198.4* (C), 137.3 (C), 137.2* (C), 135.8*
(CH), 135.8 (CH), 135.6 (CH), 135.6 (CH), 135.6 (CH), 133.9* (C),
133.9* (C), 133.60 (C), 133.4 (C), 133.3 (C), 133.1 (CH), 129.8
(CH), 129.7 (CH), 129.6* (CH), 129.6 (CH), 128.6 (CH), 128.3
(CH), 128.3 (CH), 127.8 (CH), 127.8 (CH), 127.7 (CH), 127.6
(CH), 87.9* (CH), 87.2 (CH), 75.9 (CH), 75.6* (CH), 75.4 (CH),
75.2* (CH), 64.5 (CH2), 64.3* (CH2), 45.7 (CH2), 44.5* (CH2),
42.0* (CH2), 40.8 (CH2), 27.0 (CH3), 26.8 (CH3), 26.8 (CH3), 19.2*
(C), 19.1 (C), 19.1 (C) ppm; IR (film, cm−1): 3070, 3050, 2998, 2957,
2931, 2893, 2857, 1961, 1897, 1823, 1684, 1597, 1472, 1448, 1428,
1389, 1361, 1306, 1263, 1208, 1112, 1039, 999, 938, 822, 741, 702, 612,
506, 446, 413; HRMS (ESI) m/z: [M + H]+ calcd. for C45H53O4Si2,
713.3477; found, 713.3474.
1-((2S,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)propan-2-one
(22-Procedure A). Purification with hexane/AcOEt (9:1) gave 101.5
mg, yield 78%, as colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.61−
7.14 (m, 20H), 4.47−4.33 (m, 2H), 3.97 (q, J = 3.7 Hz, 1H), 3.35 (dd, J
= 11.0, 3.9 Hz, 1H), 3.20 (dd, J = 11.0, 3.9 Hz, 1H), 2.93 (dd, J = 16.0,
7.3 Hz, 1H), 2.66 (dd, J = 16.0, 6.0 Hz, 1H), 2.17−2.04 (m, 4H), 1.63
(ddd, J = 13.0, 5.0, 3.5 Hz, 1H), 0.99 (s, 9H), 0.84 (s, 9H) ppm;
13C{1H} NMR (101 MHz, CDCl3): δ 207.8 (C), 135.8 (CH), 135.8
(((2R,3S,5S)-5-Azido-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl)oxy)(tert-butyl)diphenylsilane (17-Procedure
A). Purification with hexane/MTBE (7:3) gave 114.3 mg, yield 90%,
1
as pale-yellow oil; H NMR (300 MHz, CDCl3): δ 7.82−7.22 (m,
20H), 5.49 (dd, J = 6.4, 1.7 Hz, 1H), 4.47 (ddt, J = 6.9, 4.7, 2.8 Hz, 1H),
4.29 (q, J = 3.0 Hz, 1H), 3.63−3.41 (m, 1H), 3.26 (dd, J = 11.3, 3.3 Hz,
1H), 2.32−1.94 (m, 2H), 1.10 (s, 9H), 0.98 (s, 9H) ppm; 13C{1H}
NMR (75 MHz, CDCl3): δ 135.7 (CH), 135.7 (CH), 135.6 (CH),
135.4 (CH), 135.4 (CH), 133.42 (C), 133.4 (C), 133.0 (C), 132.9 (C),
129.8 (CH), 129.7 (CH), 129.6 (CH), 127.7 (CH), 127.6 (CH), 91.9
(CH), 89.0 (CH), 73.4 (CH), 63.7 (CH2), 26.8 (CH3), 26.6 (CH3),
19.0 (C), 18.9 (C) ppm; IR (film, cm−1): 3071, 2937, 2859, 2137, 1487,
1427, 1261, 1111, 1009, 931, 703; HRMS (ESI) m/z: [M + H]+ calcd.
for C37H46O3N3Si2, 636.3072; found, 636.3075.
tert-butyl(((2R,3S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-
tetrahydrofuran-3-yl)oxy)diphenylsilane (18-Procedure A). Purifica-
tion with hexane/MTBE (99:1) gave 114.1 mg, yield 96%, as colorless
oil; 1H NMR (300 MHz, CDCl3): δ 7.89−7.53 (m, 8H), 7.49−7.22 (m,
12H), 4.47 (td, J = 3.9, 2.0 Hz, 1H), 4.14−3.92 (m, 3H), 3.42 (qd, J =
10.9, 4.3 Hz, 2H), 1.87 (dtd, J = 8.7, 4.6, 1.4 Hz, 2H), 1.11 (s, 9H), 0.99
(s, 9H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 135.7 (CH), 135.5
(CH), 135.4 (CH), 133.9 (C), 133.7 (C), 133.3 (C), 133.3 (C), 129.6
(CH), 129.5 (CH), 129.4 (CH), 127.6 (CH), 127.6 (CH), 127.5
(CH), 127.5 (CH), 87.1 (CH), 75 (CH), 67.5 (CH2), 64.5 (CH2), 35.6
(CH2), 26.9 (CH3), 26.7 (CH3), 19.1 (C), 19.0 (C) ppm; IR (film,
cm−1): 3067, 2939, 2861, 1485, 1421, 1264, 1112, 1011, 927, 705;
HRMS (ESI) m/z: [M + H]+ calcd. for C37H47O3Si2, 595.3058; found,
595.3059; [α]2D0 + 23.7, c = 1.7, CH2Cl2.
tert-butyl(((2R,3S,5R)-3-((tert-butyldiphenylsilyl)oxy)-5-
(phenylthio)tetrahydrofuran-2-yl)methoxy)diphenylsilane (19-Pro-
cedure A). Purification with hexane/AcOEt (99:1) gave 134.8 mg, yield
96%, as colorless oil; 1H NMR (300 MHz, CDCl3): δ 7.80−7.15 (m,
25H), 5.68 (dd, J = 7.5, 4.1 Hz, 1H), 4.47 (dt, J = 8.0, 4.0 Hz, 1H),
4.40−4.27 (m, 1H), 3.70 (dd, J = 11.3, 2.7 Hz, 1H), 3.54−3.41 (m,
1H), 2.49 (dt, J = 14.1, 7.2 Hz, 1H), 2.12 (dt, J = 13.6, 4.0 Hz, 1H), 1.15
(s, 9H), 0.98 (s, 9H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 137.0
(C), 135.8 (CH), 135.7 (CH), 135.6 (CH), 135.6 (CH), 135.5 (CH),
135.5 (CH), 135.5 (CH), 135.1 (C), 133.6* (C), 133.6* (C), 133.5*
(C), 133.4* (C), 133.3* (C), 133.2* (C), 133.1* (C), 133.1* (C),
131.2* (CH), 130.4 (CH), 129.7 (CH), 129.7* (CH), 129.5* (C),
129.5 (CH), 128.7* (CH), 128.7 (CH), 127.7 (CH), 127.6 (CH),
127.5* (CH), 127.5* (CH), 127.5* (CH), 126.8* (CH), 126.4 (CH),
88.8* (CH), 87.2 (CH), 86.2 (CH), 85.8* (CH), 74.3* (CH), 72.8
(CH), 64.1* (CH2), 63.4 (CH2), 42.5 (CH2), 41.3* (CH2), 29.6
(CH2), 26.8 (CH3), 26.7* (CH3), 26.6 (CH3), 19.1 (C), 19.1 (C)
ppm; IR (film, cm−1): 3134, 3071, 3050, 3015, 2957, 2931, 2893, 2857,
2773, 2739, 2710, 2316, 1960, 1891, 1825, 1775, 1731, 1660, 1587,
1472, 1427, 1390, 1256, 1112, 702, 612, 505, 436, 423, 413; HRMS
(ESI) m/z: [M + H]+ calcd. for C43H51O3SSi2, 703.3092; found,
703.3094.
Methyl 2-((2R,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-2-methylpro-
panoate (20-Procedure A). Purification with hexane/MTBE (85:15)
gave 102.7 mg, yield 74%, as colorless oil; 1H NMR (400 MHz,
CDCl3): δ 7.60−7.42 (m, 8H), 7.38−7.16 (m, 12H), 4.44 (ddd, J = 7.1,
6.2, 4.6 Hz, 1H), 4.16 (dd, J = 9.3, 6.8 Hz, 1H), 3.85−3.78 (m, 1H),
3.56 (s, 3H), 3.54−3.48 (m, 1H), 3.31−3.22 (m, 1H), 1.92 (dt, J = 12.6,
7.0 Hz, 1H), 1.72 (ddd, J = 12.6, 9.3, 6.2 Hz, 1H), 1.19 (s, 3H), 1.08 (s,
3H), 0.98 (d, J = 9.4 Hz, 9H), 0.84 (d, J = 5.1 Hz, 9H) ppm; 13C{1H}
NMR (101 MHz, CDCl3): δ 177.0 (C), 135.8 (CH), 135.8 (CH),
135.8 (CH), 135.7 (CH), 135.6 (CH), 135.6 (CH), 133.8 (C), 133.7
(CH), 135.6 (CH), 135.6 (CH), 135.5 (CH), 133.6 (C), 133.5 (C),
133.3 (C), 133.2 (C), 129.8 (CH), 129.8 (CH), 129.6 (CH), 127.8
(CH), 127.7 (CH), 127.6 (CH), 87.0 (CH), 75.3 (CH), 75.0 (CH),
64.4 (CH2), 50.6 (CH2), 40.8 (CH2), 30.8 (CH3), 27.0 (CH3), 26.7
(CH3), 19.1 (C), 19.1 (C) ppm; IR (film, cm−1): 3134, 3071, 3049,
2998, 2958, 2931, 2893, 2858, 2709, 1961, 1892, 1825, 1715, 1589,
1472, 1428, 1360, 1242, 1189, 1111, 1007, 936, 823, 741, 703, 612, 506,
443; HRMS (ESI) m/z: [M + H]+ calcd. for C40H51O4Si2, 651.3320;
found, 651.3324.
(S)-2-((2R,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-2-
((trimethylsilyl)oxy)cyclobutan-1-one (23-Procedure A). Purification
with hexane/MTBE (94:6) gave 132.0 mg, yield 88%, as colorless oil;
1H NMR (400 MHz, CD2Cl2): δ 7.56−7.13 (m, 20H), 5.21−5.14 (m,
1H), 4.36 (ddd, J = 7.1, 5.7, 4.2 Hz, 1H), 3.92−3.84 (m, 1H), 3.40 (dd, J
= 11.2, 2.8 Hz, 1H), 3.19 (dd, J = 11.2, 3.9 Hz, 1H), 2.78−2.45 (m, 3H),
2.03−1.91 (m, 1H), 1.90−1.79 (m, 2H), 0.94 (s, 9H), 0.79 (s, 9H),
0.00 (s, 9H) ppm; 13C{1H} NMR (101 MHz, CD2Cl2): δ 210.8 (C),
209.8* (C), 135.5* (CH), 135.5 (CH), 135.4 (CH), 135.4* (CH),
135.3* (CH), 135.2 (CH), 135.2 (CH), 135.2* (CH), 135.1* (CH),
133.4* (C), 133.3 (C), 133.3 (C), 133.2* (C), 133.0 (C), 132.9 (C),
129.5 (CH), 129.4* (CH), 129.3 (CH), 129.2 (CH), 129.2 (CH),
129.2 (CH), 127.4 (CH), 127.4 (CH), 127.3* (CH), 127.3* (CH),
127.3 (CH), 127.3 (CH), 127.2* (CH), 125.1* (CH), 93.8 (C), 93.2*
(C), 87.8* (CH), 87.7* (CH), 87.0 (CH), 85.6* (CH), 80.9* (CH),
80.3* (CH), 79.6 (CH), 79.0* (CH), 74.4* (CH), 73.3 (CH), 72.6*
(CH), 64.1 (CH2), 63.6* (CH2), 40.2 (CH2), 40.1* (CH2), 36.6
(CH2), 36.1* (CH2), 33.8* (CH), 29.8 (CH), 29.4* (CH), 26.4
(CH3), 26.4* (CH3), 26.2* (CH3), 26.2 (CH3), 23.8 (CH2), 23.3*
(CH2), 20.5* (CH3), 18.7 (C), 18.6 (C), 0.9 (CH3) ppm; IR (film,
cm−1): 3640, 3135, 3071, 3050, 2999, 2957, 2931, 2894, 2858, 2710,
1960, 1891, 1789, 1661, 1589, 1472, 1428, 1389, 1362, 1308, 1252,
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1180, 1111, 1008, 980, 937, 844, 740, 702, 612, 504, 421; HRMS (ESI)
m/z: [M + H]+ calcd. for C44H59O5Si3, 751.3665; found, 751.3668;
NOESY correlations (see the Supporting Information).
(CH), 133.8 (C), 133.7 (C), 133.1 (CH), 133.0 (CH), 129.6 (CH),
129.5 (CH), 129.5 (CH), 129.4 (CH), 127.6 (CH), 127.6 (CH), 127.5
(CH), 119.5 (CH), 107.8 (CH), 106.7 (CH), 100.8 (CH2), 88.1 (CH),
80.2 (CH), 75.7 (CH), 64.4 (CH2), 44.7 (CH2), 26.9 (CH3), 26.7
(CH3), 19.0 (C) ppm; IR (film, cm−1): 3071, 2921, 2857, 1502, 1481,
1463, 1233, 1115, 1092, 1041, 939, 739; HRMS (ESI) m/z: [M + H]+
calcd. for C44H51O5Si2, 715.3270; found, 715.3269; NOESY
correlations (see the Supporting Information).
tert-Butyl(((2R,3S,5R)-3-((tert-butyldiphenylsilyl)oxy)-5-(furan-2-
yl)tetrahydrofuran-2-yl)methoxy)diphenylsilane (28-Procedure B).
Purification with hexane/MTBE (9:1) gave 75.4 mg, yield 57%, as
colorless oil; 1H NMR (400 MHz, (CD3)2CO): δ 7.78−7.29 (m, 21H),
6.39−6.30 (m, 2H), 5.25 (dd, J = 10.4, 5.4 Hz, 1H), 4.74−4.63 (m,
1H), 4.12 (td, J = 4.3, 1.7 Hz, 1H), 3.54−3.46 (m, 1H), 3.41 (dd, J =
10.9, 4.1 Hz, 1H), 2.25−2.09 (m, 2H), 1.13 (s, 9H), 0.95 (s, 9H) ppm;
13C{1H} NMR (101 MHz, (CD3)2CO): δ 154.1 (C), 142.4 (CH),
135.7 (CH), 135.7 (CH), 135.7 (CH), 135.5 (CH), 135.5 (CH), 135.4
(CH), 133.6 (C), 133.5 (C), 133.1 (C), 133.1 (C), 130.0 (CH), 129.9
(CH), 129.7 (CH), 129.6 (CH), 127.9 (CH), 127.7 (CH), 127.6
(CH), 110.1 (CH), 107.3 (CH), 87.8 (CH), 75.3 (CH), 73.2 (CH),
64.3 (CH2), 40.0 (CH2), 26.5 (CH3), 26.4 (CH3), 18.76 (C) ppm; IR
(film, cm−1): 3067, 2939, 2861, 1693, 1483, 1421, 1382, 1167, 1061,
992, 745; HRMS (ESI) m/z: [M + H]+ calcd. for C41H49O4Si2,
661.3164; found, 661.3166.
(R)-2-((2R,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)cyclohexan-1-
one (24-Procedure A). Purification with hexane/AcOEt (9:1) gave
114.5 mg, yield 83%, as colorless oil; 1H NMR (400 MHz, CDCl3): δ
7.56−7.40 (m, 8H), 7.35−7.18 (m, 12H), 4.37 (dt, J = 6.4, 3.3 Hz, 1H),
4.10 (ddd, J = 9.1, 7.2, 5.2 Hz, 1H), 3.96−3.83 (m, 1H), 3.33 (dd, J =
10.9, 4.0 Hz, 1H), 3.21 (dd, J = 11.0, 4.2 Hz, 1H), 2.74 (ddd, J = 11.8,
9.2, 5.4 Hz, 1H), 2.43 (dt, J = 13.4, 3.9 Hz, 1H), 2.31−2.20 (m, 3H),
2.00 (d, J = 9.2 Hz, 1H), 1.81 (dp, J = 18.9, 6.4, 5.2 Hz, 2H), 1.73−1.53
(m, 2H), 1.41 (dtd, J = 22.6, 11.2, 10.2, 4.5 Hz, 1H), 0.97 (s, 9H), 0.84
(s, 9H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 212.8 (C), 135.9*
(CH), 135.8 (CH), 135.8 (CH), 135.8* (CH), 135.7* (CH), 135.6
(CH), 133.7 (C), 133.6 (C), 133.4 (C), 133.4 (C), 129.8 (CH), 129.8
(CH), 129.5 (CH), 129.5 (CH), 127.7 (CH), 127.7* (CH), 127.6*
(CH), 127.6 (CH), 127.6 (CH), 86.4 (CH), 78.0 (CH), 74.9 (CH),
64.4 (CH2), 56.8 (CH), 42.8 (CH2), 42.0 (CH2), 40.5 (CH2), 31.4
(CH2), 28.4 (CH2), 27.0 (CH2), 27.0 (CH3), 26.7 (CH3), 25.0*
(CH2), 24.9 (CH2), 19.1 (C), 19.1 (C) ppm; IR (film, cm−1): 3071,
3049, 2956, 2931, 2893, 2858, 2739, 2710, 1960, 1891, 1825, 1709,
1589, 1472, 1428, 1390, 1264, 1112, 999, 970, 823, 740, 703, 612, 506;
HRMS (ESI) m/z: [M + H]+ calcd. for C43H55O4Si2, 691.3633; found,
691.3630.
(2R,3R,4S,5S)-2-(Acetoxymethyl)-5-(2-methoxyphenyl)-
tetrahydrofuran-3,4-diyl diacetate (35-Procedure B). Purification
with hexane/AcOEt (8:2) gave 57.8 mg, yield 79%, as colorless oil; 1H
NMR (300 MHz, CDCl3): δ 7.52 (ddd, J = 7.6, 1.8, 0.8 Hz, 1H), 7.32−
7.20 (m, 1H), 6.97 (td, J = 7.5, 1.1 Hz, 1H), 6.81 (dd, J = 8.2, 1.0 Hz,
1H), 5.83 (dd, J = 4.4, 3.1 Hz, 1H), 5.56 (d, J = 3.1 Hz, 1H), 5.45 (dd, J
= 8.1, 4.5 Hz, 1H), 4.51−4.37 (m, 2H), 4.29−4.17 (m, 1H), 3.80 (s,
3H), 2.23−1.99 (m, 6H), 1.77 (s, 3H) ppm; 13C{1H} NMR (75 MHz,
CDCl3): δ 170.7 (C), 169.7 (C), 169.3 (C), 155.7 (C), 128.6 (CH),
127.2 (CH), 124.1 (C), 119.9 (CH), 109.5 (CH), 76.8 (CH), 76.5
(CH), 72.6 (CH), 72.0 (CH), 63.6 (CH2), 55.1 (CH3), 20.8 (CH3),
20.4 (CH3), 20.2 (CH3) ppm; IR (film, cm−1): 2961, 1743, 1497, 1446,
1367, 1245, 1043, 1047, 891, 701; HRMS (ESI) m/z: [M + H]+ calcd.
for C18H23O8, 367.1387; found, 367.1384; NOESY correlations (see
the Supporting Information). The spectroscopic data are in agreement
with those reported in the literature26b but refer to a single anomeric
compound.
Allylation Scope on Different Heterocyclic Cores. The
procedure herein adopted is the same as described for the previous
allylation reactions.
1-Allyl-1,3-dihydroisobenzofuran (37). Purification with hexane/
MTBE (99:1) gave 27.6 mg, yield 86%, as colorless oil; the
spectroscopic data correspond with those reported in the literature
(See the Supporting Information for 1H NMR spectra).34
(R)-5-((2R,4S,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-2-yl)furan-2(5H)-
one (25-Procedure B). Purification with hexane/AcOEt (9:1) gave 74.3
1
mg, yield 55%, as colorless oil; H NMR (400 MHz, CDCl3): δ 7.68
(dd, J = 5.7, 1.5 Hz, 1H), 7.60−7.17 (m, 20H), 6.10 (dd, J = 5.7, 1.9 Hz,
1H), 5.17 (dt, J = 8.5, 1.7 Hz, 1H), 4.39 (td, J = 4.1, 1.8 Hz, 1H), 4.03
(tt, J = 3.8, 2.1 Hz, 1H), 3.78 (dt, J = 8.6, 5.6 Hz, 1H), 3.31 (dd, J = 11.1,
4.0 Hz, 1H), 3.13 (dd, J = 11.1, 3.7 Hz, 1H), 2.20−2.10 (m, 2H), 0.99
(s, 9H), 0.83 (s, 9H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 173.2
(C), 156.2 (CH), 135.8 (CH), 135.7 (CH), 135.5 (CH), 135.5 (CH),
135.5 (CH), 133.4 (C), 133.1 (C), 133.1 (C), 133.0 (CH), 130.0
(CH), 129.9 (CH), 129.7 (CH), 127.9 (CH), 127.8 (CH), 127.7
(CH), 127.6 (CH), 121.7 (CH), 88.4 (CH), 85.0 (CH), 80.6 (CH),
75.0 (CH), 64.4 (CH2), 38.4 (CH2), 27.0 (CH3), 26.7 (CH3), 19.1
(C), 19.0 (C) ppm; IR (film, cm−1): 3071, 3049, 2956, 2931, 2894,
2858, 1787, 1760, 1589, 1472, 1428, 1390, 1362, 1155, 1113, 1046,
1007, 950, 886, 822, 703, 613, 506, 442, 410; HRMS (ESI) m/z: [M +
H]+ calcd. for C41H49O5Si2, 677.3113; found 677.3117; NOESY
correlations (see the Supporting Information).
tert-butyl(((2R,3S,5R)-3-((tert-butyldiphenylsilyl)oxy)-5-(4-
methoxyphenyl)tetrahydrofuran-2-yl)methoxy)diphenylsilane (26-
Procedure B). Purification with hexane/MTBE (93:7) gave 99.4 mg,
yield 71%, as colorless oil; 1H NMR (300 MHz, CDCl3): δ 7.79−7.20
(m, 22H), 6.88−6.79 (m, 2H), 5.25 (dd, J = 11.0, 4.7 Hz, 1H), 4.61 (d, J
= 5.2 Hz, 1H), 4.16 (td, J = 3.9, 1.5 Hz, 1H), 3.81 (s, 3H), 3.60 (dd, J =
11.0, 4.0 Hz, 1H), 3.51−3.33 (m, 1H), 2.22−2.10 (m, 1H), 1.85 (ddd, J
= 12.7, 11.0, 5.2 Hz, 1H), 1.14 (s, 9H), 0.99 (d, J = 5.1 Hz, 9H) ppm;
13C{1H} NMR (75 MHz, CDCl3): δ 158.9 (C), 135.7 (CH), 135.5
(CH), 135.5 (CH), 133.9 (C), 133.8 (C), 133.7 (C), 133.2 (C), 133.1
(C), 129.6 (CH), 129.5 (CH), 129.4 (CH), 127.6 (CH), 127.6 (CH),
127.5 (CH), 127.5 (CH), 127.5 (CH), 113.5 (CH), 88.0 (CH), 80.0
(CH), 75.72 (CH), 64.4 (CH2), 55.2 (CH3), 44.6 (CH2), 26.9 (CH3),
26.67 (CH3), 19.1 (C) ppm; IR (film, cm−1): 3067, 2929, 2861, 1491,
1247, 1117, 1019, 931, 827, 734; HRMS (ESI) m/z: [M + H]+ calcd.
for C44H53O4Si2, 701.3477; found, 701.3479; NOESY correlations (see
the Supporting Information).
(((2R,3S,5R)-5-(benzo[d][1,3]dioxol-5-yl)-2-(((tert-
butyldiphenylsilyl)oxy)methyl)tetrahydrofuran-3-yl)oxy)(tert-
butyl)diphenylsilane (27-Procedure B). Purification with hexane/
MTBE (92:8) gave 100.0 mg, yield 70%, as colorless oil; 1H NMR (300
MHz, CDCl3): δ 7.76−7.53 (m, 8H), 7.52−7.26 (m, 12H), 7.08−6.71
(m, 3H), 5.96 (dd, J = 10.3, 1.3 Hz, 2H), 5.28−4.97 (m, 1H), 4.74−
4.49 (m, 1H), 4.31−4.11 (m, 1H), 3.72−3.54 (m, 1H), 3.52−3.38 (m,
1H), 2.51−1.72 (m, 2H), 1.10 (dd, J = 23.2, 1.3 Hz, 8H), 0.99 (dd, J =
4.4, 1.3 Hz, 9H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 147.5 (C),
146.7 (C), 135.8 (CH), 135.7 (CH), 135.6 (CH), 135.5 (CH), 135.4
Methyl 2-allylpyrrolidine-1-carboxylate (39). Purification with
hexane/MTBE (78:22) gave 30.4 mg, yield 90%, as colorless oil; the
spectroscopic data correspond with those reported in the literature (See
the Supporting Information for 1H NMR spectra).35
(2S,4S)-2-Allyl-4-benzyl-3-tosyloxazolidine (41).36 Purification
with hexane/MTBE (7:3) gave 45.0 mg, yield 63%, as colorless oil;
1H NMR (300 MHz, CDCl3): δ 7.83−7.70 (m, 2H), 7.42−7.14 (m,
7H), 5.89 (ddt, J = 17.2, 10.1, 7.0 Hz, 1H), 5.30−5.13 (m, 2H), 5.00
(dd, J = 7.5, 3.2 Hz, 1H), 3.84 (ddq, J = 10.1, 7.1, 3.6 Hz, 1H), 3.74 (dd,
J = 9.1, 3.1 Hz, 1H), 3.28−3.09 (m, 2H), 2.91−2.65 (m, 2H), 2.57−
2.36 (m, 4H) ppm; 13C{1H} NMR (75 MHz, CDCl3): δ 144.1 (C),
137.3 (C), 134.1 (C), 132.3 (CH), 129.8 (CH), 129.7 (CH), 129.4
(CH), 129.2 (CH), 128.6 (CH), 128.6 (CH), 128.5 (CH), 127.7
(CH), 126.7 (CH), 118.4 (CH2), 91.81, 68.8 (CH2), 60.50, 40.9
(CH2), 40.46 (CH2), 21.43 (CH3) ppm; IR (film, cm−1): 2985, 2923,
2885, 2254, 1598, 1456, 1337, 1232, 1157, 1093, 904, 725; HRMS
(ESI) m/z: [M + H]+ calcd. for C20H24NO3S, 358.1471; found,
358.1475; [α]2D0 − 65.0, c = 0.55 in CH2Cl2; NOESY correlations (see
the Supporting Information).
Large-Scale Synthesis. The allylation reaction of 11 to give 12 was
tested on a larger scale to prove the scale up of the synthesis.
Specifically, an identical procedure for the synthesis of 12 was followed,
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using 750 mg of the starting acetal 11 (1.2 mmol) and the
corresponding percentages of Re catalyst 8 (15 mol %, 0.18 mmol,
117 mg) and Cu(OTf)2 (5 mol %, 0.06 mmol, 22 mg). Purification with
hexane/MTBE (98:2) gave 700 mg of product 12 (1.1 mmol) with an
isolated yield 92%, as colorless oil. NMR spectra correspond with those
obtained for the sub-millimolar scale.
E46D17000110009) and the Italian MIUR (funds PRIN 2017)
for financial support, Professor Mariella Mella for the NMR
spectra measurement, and Professors Giovanni Vidari and Lucio
Toma for helpful discussions.
Computational Methods. All structures studied during the DFT
investigation of the anisole reaction mechanism were optimized with
the Gaussian 09 program package.37 Previously reported studies on the
allylation reaction of five-membered ring oxocarbenium ions, by
Woerpel and co-workers, showed that the use of B3LYP could results in
difficulties in locating the transitions states when allyltrimethylsilane
was involved in the reaction, thus suggesting the use of M06-2X.38
Considering the different types of reactants involved, we decided to use
the more parametrized B3LYP functional anyway, by specifying a
differentiated basis set.39 This resulted in the absence of any problem in
locating the corresponding TSs. Specifically, C and H atoms were
described using the 6-31G(d,p) basis set, whereas O and Si atoms were
described with the 6-31+G(d,p) basis set.40 Vibrational frequencies
were computed at the same level of theory to verify that the optimized
structures were minima or TSs. For TS, IRC calculations were
computed at the same level of theory in order to confirm the structures
at the ends. Solvent effects were then evaluated by running single-point
calculations at the same level of theory, the polarizable continuum
solvent model (PCM) was used for CH2Cl2. NPA charges on C1
(furanoside numbering system) are calculated in CH2Cl2 at the same
level of theory. TMS was used to model the presence of a TBDPS-
protecting group.41
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00706.
■
̀
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AUTHOR INFORMATION
Corresponding Author
Giuseppe Zanoni − Department of Chemistry, University of
Pavia, Pavia 27100, Italy; orcid.org/0000-0003-1530-
9409; Email: gz@unipv.it
■
Authors
Emanuele Casali − Department of Chemistry, University of
Pavia, Pavia 27100, Italy; orcid.org/0000-0001-7501-
5213
Sirwan T. Othman − Department of Chemistry, College of
Science, Salahaddin University-Erbil, Erbil 44002, Iraq
Ahmed A. Dezaye − International University of Erbil, Erbil-
Kurdistan 44001, Iraq
Debora Chiodi − Department of Chemistry, University of Pavia,
Pavia 27100, Italy
Alessio Porta − Department of Chemistry, University of Pavia,
Pavia 27100, Italy; orcid.org/0000-0002-2564-9696
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compounds XLV: Structure analysis of 2-alkoxy-5-alkyl-tetrahydrofur-
ans. Chirality 1991, 3, 76−83.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00706
(7) Rhenium catalyst 8 was used in the synthesis of glycosides by
Toste and subsequently by Zhu. However, the peculiar mechanism of
Nu-H activation via a protonated Re-oxo species cannot be operative in
our scenario. For more details, see: (a) Sherry, B. D.; Loy, R. N.; Toste,
F. D. Rhenium(V)-Catalyzed Synthesis of 2-Deoxy-α-glycosides. J. Am.
Chem. Soc. 2004, 126, 4510−4511. (b) Baryal, K. N.; Adhikari, S.; Zhu,
J. Catalytic Stereoselective Synthesis of β-Digitoxosides: Direct
Synthesis of Digitoxin and C1′-epi-Digitoxin. J. Org. Chem. 2013, 78,
12469−12476.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Regione Lombardia - project VIPCAT (Value Added
Innovative Protocols for Catalytic Transformations - CUP:
■
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