Accepted Article

Title: Palladium-Catalyzed Thio- and Selenocarbonylation of 2-

Iodoglycals

Authors: Helio Alexandre Stefani, Mariana P. Darbem, Henrique A.

Esteves, Isadora M. de Oliveira, and Daniel C. Pimenta

This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.

To be cited as: ChemCatChem 10.1002/cctc.201901403

Link to VoR: http://dx.doi.org/10.1002/cctc.201901403

A Journal of

www.chemcatchem.org
ChemCatChem 10.1002/cctc.201901403

COMMUNICATION

Palladium-Catalyzed Thio- and Selenocarbonylation of

2- Iodoglycals
Mariana P. Darbem,[a] Henrique A. Esteves,[a] Isadora M. de Oliveira,[b] Daniel C. Pimenta,[c]
Hélio A. Stefani[a]*

Abstract: The carbonylative cross-coupling reactions of 2-iodoglycals

Accepted Manuscript
with thiols and selenols in the presence of molybdenum hexacarbonyl
as a solid source of carbon monoxide is described. This methodology
permitted the synthesis of 29 C2-glycosides bearing thioester and
selenoester functionalities in moderate to excellent yields and high
functional group tolerance. Moreover, this communication describes
the first catalytic carbonylative coupling reaction of selenols with a
carbon electrophile.

C2-Glycosides are a class of carbohydrates in which a sugar

derivative is connected to an aglycone through a C–C bond. This
modification increases the stability of these molecules towards
hydrolysis by enzymes in vivo, making them important surrogates
of natural O-glycosides in a variety of medicinal applications. [1]
Inspired by these features, many methodologies for the synthesis
of C2-glycosides based on different strategies have been
developed over the years, such as radical coupling, [2] Michael
addition[3] and the use of pre-functionalized substrates, e.g.,
glycosyl halide[4] or 2-iodoglycals. This last class of compounds is
especially important as it allows the modular connection of several
carbon and heteroatom-containing groups via cross-coupling Scheme 1. Carbonylative functionalizations of 2-iodoglycals.

chemistry. Suzuki-Miyaura,[5] Heck,[6] Sonogashira[7] and

Buchwald-Hartwig-Migita[8] reactions are some of those already
described for 2-iodoglycals.
Our group and others, on the other hand, have adopted a slightly
different approach for this substrate using carbonylative coupling
reactions, which allows a straightforward formation of useful
carbonyl-containing functional groups in a mild and atom-
economical manner.[9] Amides,[10] esters,[10a] alkynones[11] and aryl
ketones[12] bearing glycals have been obtained using this strategy
(Scheme 1).
With this approach in mind and stimulated by relevant biological
properties demonstrated by thiosaccharides, [13] we decided to
investigate the thiocarbonylation of 2-iodoglycals. The formation
of the thioester moiety could also provide an useful handle easily
convertible to ketones,[14] esters,[15] amides,[16] alkynones[17] and
aldehydes.[18]
[a] Departamento de Farmácia, Faculdade de Ciências Farmacêuticas,
Universidade de São Paulo, São Paulo, SP – Brazil
Phone (+55) 11 30913654
[b] Departamento de Química Fundamental, Instituto de Química,
Universidade de São Paulo, São Paulo, SP – Brazil.
[c] Instituto Butantan, Av. Vital Brasil 1500, São Paulo, 05503-000, Brazil.
Given our previous experience with chalcogens, [19] we also
wanted to examine the feasibility of the selenocarbonylation of 2-
iodoglycals, which is especially challenging since the
carbonylative coupling of selenols has never been reported.
Alternatively, selenol esters were previously obtained by the
carbonylation of acidic positions with CO and Se0,[20] by the
carbonylative coupling of tributylstannyl selenides [21] or by the
coupling of carboxylic acid derivatives with nucleophilic selenium
species.[22]
Herein, we describe our efforts towards the synthesis of thioesters
and selenol esters bearing glycals via the Pd-catalyzed
carbonylative coupling of thiols and selenols. We commenced our
study by synthesizing three different O-protected-2-iodoglycals
following a procedure developed by Vankar and co-workers.[6]
Next, a screening of the reaction conditions for the
thiocarbonylation reaction was carried out using tri-O-acetyl-D-
glucal (1a) and p-methoxythio-phenol as model substrates
(Table 1).

This article is protected by copyright. All rights reserved.

ChemCatChem 10.1002/cctc.201901403

COMMUNICATION
Table 1. Optimization of the reaction conditions.

Entry Pd /ligand base solvent time temp. yielda

(5 mol%) (2.0 equiv.) (h) (°C) (%)

Effect of catalyst

1 Pd2(dba)3/XantPhos NaOAc anisole 5 90 93

Accepted Manuscript
2 Pd(dba)2/XantPhos NaOAc anisole 5 90 95

3 Pd(PhCN)2Cl2/XantPhos NaOAc anisole 5 90 98

Effect of ligand

4 Pd(dppf)Cl2.DCM NaOAc anisole 5 90 75

5 Pd(PhCN)2Cl2/SPhos NaOAc anisole 5 90 0

6 Pd(PhCN)2Cl2/RuPhos NaOAc anisole 5 90 0

7 Pd(PhCN)2Cl2/DpePhos NaOAc anisole 5 90 0

Effect of temperature

8 Pd(PhCN)2Cl2/XantPhos NaOAc anisole 18 75 50

9 Pd(PhCN)2Cl2/XantPhos NaOAc anisole 5 110 72

Effect of base

10 Pd(PhCN)2Cl2/XantPhos DABCO anisole 5 90 0

11 Pd(PhCN)2Cl2/XantPhos Et3N anisole 5 90 78

12 Pd(PhCN)2Cl2/XantPhos K2CO3 anisole 5 90 79

Effect of solvent

13 Pd(PhCN)2Cl2/XantPhos NaOAc toluene 5 90 81

14 Pd(PhCN)2Cl2/XantPhos NaOAc THF 5 90 75

15 Pd(PhCN)2Cl2/XantPhos NaOAc MeCN 5 90 0

Reaction scale: 1a (0.25 mmol).

We started the screening of the reaction conditions by testing
different sources of palladium in combination with the bidentate
phosphine ligand XantPhos in anisole. [23] Excellent yields of 3a
were obtained in all cases, with Pd(PhCN) 2Cl2 giving the
carbonylated product in 98% (Entry 3). Different ligands were then
investigated and, while bidentate electron-rich phosphine dppf
delivered 3a in 75%, monodentate SPhos, RuPhos and DpePhos
completely shut down the reaction (Entries 4–7). The reason for
this trend is still not clear, however, we speculate that the
bidentate nature of XanPhos and dppf might facilitate reductive
elimination by increasing the energy of the intermediate, as
observed by Hartwig and co-workers.[24] Next, the effect of the
reaction temperature was examined: at 110 °C 3a was obtained
in 72% yield, while at 75 °C it was isolated in only 50% after 18 h
(Entries 8–9). A survey of inorganic and organic bases showed
that NaOAc was the best option for the thiocarbonylation reaction
(Entry 1), however, bases such as Et3N and K2CO3 were still
active and could deliver 3a in good yields (Entries 11–12). Finally,
the reaction solvent was investigated. Toluene and THF gave 3a
in good yields (Entries 13-14), whilst MeCN had a negative effect
in the reaction progress and no carbonylated product was
observed (Entry 15).
With the best conditions established, we then examined the
scope for the thiocarbonylation reaction for both the thiol and the
2-iodoglycal partners (Table 2).

This article is protected by copyright. All rights reserved.

ChemCatChem 10.1002/cctc.201901403

COMMUNICATION
Table 2. Scope of the thiocarbonylation reaction.

Accepted Manuscript
Reaction conditions: 0.25 mmol (1a-g). aReaction time: 5 h. bReacton time: 15 h.

This article is protected by copyright. All rights reserved.

ChemCatChem 10.1002/cctc.201901403

COMMUNICATION
Thiols bearing strongly electron-donating groups were well
tolerated for both 2-iodoglycals 1a and 1b. Moderately donating Table 3. Scope of the selenocarbonylation reaction.
groups featuring tert-butyl and methyl groups also furnished
thioesters 3d and 3e in 81% and 95% yield, respectively.
Interestingly, o-aminothiol 2f gave product 3f in only 32% yield.
This diminished performance is likely the consequence of the
chelation of the metal center with 2f.[25] Thiophenol, on the other
hand, efficiently participated in this reaction with both 1a and 1b
and products 3g and 3h were isolated in 72% and 93% yield,
respectively. We were also pleased to find that electron-
withdrawing groups were well tolerated and 2i-k gave the
carbonylated products 3i-k in excellent yields. In the case of

Accepted Manuscript
thiophenols 2l-m we observed a slightly reduced isolated yield of
3l-m, possible due to competitive oxidative addition of the metal
catalyst. p-Nitrothiophenol gave 3m in low yield and acetamide-
containing thiophenol 2o failed to deliver thioester 3o, possible
due to Pd competitive coordination with this substrate. [26] Moving
from aromatic thiols, the benzylic substrate 2p was amenable to
this methodology and 3p was obtained in 53% yield. Aliphatic thiol
2q also allowed access to thioester 3q bearing an alcohol
functionality in 42%. A boc-protected cysteine derivative proved
to be a competent coupling partner in this transformation, yielding
products 3r-t in good to excellent yields for three different 2-
iodoglycals (1), demonstrating that different protecting groups do
not significantly impact the reaction outcome. Finally, a range of
different sugar derivatives (glucose, xylose, arabinose and Reaction conditions: 0.2 mmol (1a,b-d). Reaction time: 15 h.

galactosel) were tested, delivering thioesters 3u-y in reasonable

to good yields. In order to further demonstrate the usefulness of the methodology
The formation of 3q in significant amounts demonstrates the for sugar chemists, we performed the deprotections of 3b and 3g
orthogonality of this methodology towards 2-iodoglycals and, in using BCl3, obtaining triols 7a-b in reasonable yields (Scheme 3).
order to demonstrate this feature, this thioester was then
subjected to alkoxycarbonylation conditions previously reported
by our group,[10a] delivering highly decorated compound 4 in good
yield (Scheme 2).

Scheme 3. Deprotected compounds. Reaction conditions: BCl3 (5 equiv. per

OBn), DCM, r.t. 3h.

Our proposed mechanism for the thio- and selenocarbonylation of

2-iodoglycals is depicted in Scheme 4. Oxidative addition of Pd0
to the 2-iodoglycal gives complex I, which, after complexation with
Scheme 2. Alkoxycarbonylation of 1a (reaction scale, 0.2 mmol of 3q). CO and displacement of iodide by the corresponding
chalcogenide, forms intermediate IV. Carbonylation then forges
the key C–C bond and reductive elimination finally gives the
Encouraged by the success of the thiocarbonylation protocol, we corresponding thioester or selenol ester.
decided to subject selenols and 2-iodoglycals to similar reaction
conditions. Gratifyingly, five examples of selenol esters were
obtained in moderate yields (6a-e) after 15 h. We believe that the
reduced yields in this case are caused by the oxidation of the
selenols to diselenides.[27] Nevertheless, this methodology
represents, to the best of our knowledge, the first example of a
carbonylative coupling using selenols, an important entry to
selenol esters (Table 3).

This article is protected by copyright. All rights reserved.

ChemCatChem
COMMUNICATION
Scheme 4. Proposed reaction mechanism for the thio-and selenocarbonylation
of 2-iodoglycals.
In summary, this work presented a useful methodology for the
synthesis of chalcogen-containing C2-glycosides with high
functional group tolerance. In total 23 thioesters and 6 selenol
esters were obtained in moderate to excellent yields. Moreover,
the first example of a carbonylative coupling of nucleophilic
selenium species, with carbon electrophiles (2-iodoglycals) was
successfully accomplished and is described in this
communication.
Experimental Section
General Procedure for the thiocarbonylation and
Selenocarbonylation of 2-iodoglycals. To a vial equipped with a
magnetic stirrer bar and sealed with a rubber septum connected to a
deflated balloon with a needle were added the 2-iodoglycal (0.25 mmol for
thiols and 0.20 mmol for selenols), anisole (2.5 mL), Pd(PhCN)2Cl2 (5
mol % for thiols and 10 mol% for selenols), Xantphos (5 mol% for thiols
and 10 mol% for selenols), Mo(CO)6 (0.38 mmol, 1.5 equiv.) and NaOAc
(0.5 mmol, 2 equiv.). The reaction mixture was then vigorously stirred at
90 ºC for 5 to 15 h. The resulting mixture was washed with water and
extracted with ethyl acetate. The organic layers were then combined and
evaporated. The crude products were purified by flash chromatography
using hexanes and ethyl acetate as eluent (7:3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-methoxyphenyl)thio)carbonyl)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3a): Product 3a was obtained
as a yellow oil (107 mg, 0.245 mmol, 98%). 1H NMR (300 MHz, CDCl3): δ
= 7.82 (s, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.9 Hz, 2H), 5.72 –
5.59 (m, 1H), 5.12 (t, J = 3.0 Hz, 1H), 4.59 – 4.49 (m, 1H), 4.40 (dd, J =
12.0, 7.9 Hz, 1H), 4.12 (dd, J = 12.1, 4.5 Hz, 1H), 3.74 (s, 3H), 2.05 – 1.94
(m, 9H).13C NMR (75 MHz, CDCl3): δ = 187.1, 170.2, 169.2, 169.1, 160.8,
155.5, 136.7, 116.8, 114.9, 112.2, 75.0, 65.8, 62.0, 60.8, 55.3, 20.7, 20.6,
20.6. IR (, cm−1) = 2911, 2864, 1685, 1611, 1574, 1171, 1151, 992, 827,
804. HRMS (ESI- TOF) calc. [C20H22O9SNa+] 461.08767, found
461.08762. [α]20D = +36.2 (0.05, CHCl3).
This article is protected by copyright. All rights reserved.
10.1002/cctc.201901403
(2R,3S,4S)-S-(4-methoxyphenyl) 3,4-bis(benzyloxy)-2-
((benzyloxy)methyl)-3,4-dihydro-2H-pyran-5-carbothioate (3b):
Product 3b was obtained as a yellow oil (111 mg, 0.190 mmol, 76%).
1H NMR (300 MHz, CDCl ): δ = 7.78 (s, 1H), 7.40 – 7.11 (m, 17H), 6.86 (d,
3
J = 8.4 Hz, 2H), 4.56 (m, 2H), 4.53 – 4.29 (m, 6H), 3.79 – 3.50 (m, 5H),
3.55 (dd, J = 10.6, 5.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ = 188.9,
160.6, 155.2, 138.0, 137.7, 137.3, 136.9, 128.5, 128.4, 128.3, 128.0, 128.0,
127.8, 127.8, 127.7, 127.7, 117.9, 114.8, 114.4, 77.7, 73.3, 72.6, 71.6,
71.4, 68.2, 67.9, 55.3. IR (, cm−1) = 2959, 2928, 2766, 1601, 1566, 1540,
1445, 1248, 1136, 1052, 994. HRMS (ESI-TOF) calc. [C35H34O6SNa+]
605.1968, found 605.1997. [α]20D = +36.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-
(dimethylamino)phenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
Accepted Manuscript
diacetate (3c):Product 3c was obtained as a yellow oil (86 mg, 0.190
mmol, 76%). 1H NMR (300 MHz, CDCl3): δ = 7.82 (s, 1H), 7.19 (d, J = 2.1
Hz, 2H), 6.64 (d, J = 7.7 Hz, 2H), 5.71 – 5.63 (m, 1H), 5.17 – 5.02 (m, 1H),
4.58 – 4.51 (m, 1H), 4.40 (dd, J = 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 11.9, 4.6
Hz, 1H), 2.91 (s, 6H), 2.09 – 1.88 (m, 9H). 13C NMR (75 MHz, CDCl3): δ =
188.2, 170.2, 169.3, 169.2, 155.2, 151.2, 136.3, 112.7, 112.2, 110.6, 74.9,
65.9, 62.1, 60.8, 40.1, 20.7, 20.7, 20.6. IR (, cm−1) = 2861, 2829, 2762,
1685, 1609, 1574, 1460, 1322, 1173, 1149, 992. HRMS (ESI-TOF) calc.
[C21H25NO8SNa+], 474.1193 found 474.1156. [α]20D = +37.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-(tert-butyl)phenyl)thio)carbonyl)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3d): Product 3d was obtained
as a yellow oil (94 mg, 0.202 mmol, 81%). 1H NMR (300 MHz, CDCl3): δ =
7.92 (s, 1H), 7.55 – 7.29 (m, 4H), 5.75 (s, 1H), 5.25 – 5.14 (m, 1H), 4.67 –
4.58 (m, 1H), 4.48 (dd, J = 11.9, 7.8 Hz, 1H), 4.25 – 4.13 (m, 1H), 2.16 –
2.00 (m, 9H), 1.32 (s, 9H).13C NMR (75 MHz, CDCl3): δ = 186.6, 170.2,
169.2, 169.1, 155.6, 152.8, 134.8, 126.3, 122.8, 112.3, 75.0, 65.8, 62.0,
60.8, 34.7, 31.1, 20.7, 20.6, 20.6. IR (, cm−1) = 2862, 1693, 1575, 1350,
1326, 1181, 1153, 1020, 996. HRMS (ESI-TOF) calc. [C23H28O8SNa+]
487.1397, found 487.1383. [α]20D = +37.0 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-((p-tolylthio)carbonyl)-3,4-dihydro-
2H-pyran-3,4-diyl diacetate (3e): Product 3e was obtained as a yellow
solid (100 mg, 0.237 mmol, 95%). 1H NMR (300 MHz, CDCl3): δ = 7.90 (s,
1H), 7.32 (d, J = 7.8 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 5.74 (t, J = 3.0, 1.6
Hz, 1H), 5.19 (t, J = 2.7 Hz, 1H), 4.69 – 4.56 (m, 1H), 4.48 (dd, J = 11.9,
7.9 Hz, 1H), 4.19 (dd, J = 12.0, 4.5 Hz, 1H), 2.37 (s, 3H), 2.15 – 2.00 (m,
9H). 13C NMR (75 MHz, CDCl3): δ = 186.7, 170.2, 169.2, 169.1, 155.6,
139.8, 135.1, 130.0, 122.8, 112.2, 75.0, 65.8, 62.0, 60.8, 21.3, 20.7, 20.7,
20.6. HRMS (ESI- TOF) calc. [C20H22O8SNa+] 445.0927, found 445.0918.
[α]20D = +35.6 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-aminophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3f): Product 3f was obtained as a
yellow solid (34 mg, 0.08 mmol, 32%). 1H NMR (300 MHz, CDCl3): δ =
7.84 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.58 (s, 1H), 7.40 – 7.33
(m, 1H), 7.25 (td, J = 7.6, 1.3 Hz, 1H), 5.95 (dd, J = 3.4, 1.4 Hz, 1H), 5.24
(t, J = 3.6 Hz, 1H), 4.46 (m, 2H), 4.20 (dd, J = 11.7, 4.0 Hz, 1H), 2.07 –
1.98 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 182.6, 170.3, 169.8, 169.3,
153.4, 149.5, 133.4, 126.1, 124.8, 122.6, 121.2, 108.1, 74.5, 66.6, 64.3,
61.0, 20.8, 20.8, 20.6. IR (, cm−1) = 3258, 3152, 1685, 1586, 1326, 1145,
1062, 992. HRMS (ESI- TOF) calc. [C19H21NO8Na+] 446.0880, found
446.0872. [α]20D = +33.6 (0.05, CHCl3).
(2R,3S,4S)-S-phenyl 3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-3,4-
dihydro-2H-pyran-5-carbothioate (3g): Product 3g was obtained as a
coreless oil (99 mg, 0.18 mmol, 72%). 1H NMR (300 MHz, CDCl3): δ = 7.80
(s, 1H), 7.47 – 7.13 (m, 20H), 4.61 – 4.34 (m, 7H), 3.76 – 3.53 (m, 4H). 13C
NMR (75 MHz, CDCl3): δ = 187.9, 155.3, 138.0, 137.7, 137.3, 135.3, 129.2,
129.0, 128.5, 128.4, 128.3, 128.0, 128.0, 127.8, 127.7, 127.7, 127.7, 127.4,
114.4, 77.7, 73.3, 72.6, 71.6, 71.4, 68.1, 67.9. IR (, cm−1) = 2968, 2937,
2772, 1604, 1569, 1540, 1443, 1228, 1115, 1005, 992. HRMS (ESI-TOF)
calc. [C34H32O5SNa+] 575.1863, found 575.1858. [α]20D = +35.2 (0.05,
CHCl3).
ChemCatChem
COMMUNICATION
(2R,3S,4S)-2-(acetoxymethyl)-5-((phenylthio)carbonyl)-3,4-dihydro-
2H-pyran-3,4-diyl diacetate (3h): Product 3h was obtained as a yellow oil
(95 mg, 0.232 mmol, 93%). 1H NMR (300 MHz, CDCl3): δ = 7.84 (s, 1H),
7.41 – 7.29 (m, 5H), 5.67 (t, J = 3.0, 1.6 Hz, 1H), 5.12 (t, J = 2.9 Hz, 1H),
4.59 – 4.47 (m, 1H), 4.41 (dd, J = 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 12.0, 4.4
Hz, 1H), 2.09 – 1.92 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 186.2, 170.2,
169.2, 169.1, 155.7, 135.1, 129.5, 129.1, 126.4, 112.2, 75.1, 65.8, 62.0,
60.8, 20.7, 20.6, 20.6. IR (, cm−1) = 2961, 2916, 1687, 1611, 1574, 1549,
1395, 1326, 1173, 1153, 1018, 992. HRMS (ESI-TOF) calc.
[C19H20O8SNa+] 431.0771, found 431.0767. [α]20D = +38.4 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((3-methoxyphenyl)thio)carbonyl)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3i): Product 3i was obtained as
a yellow oil (101 mg, 0.230, 92%). 1H NMR (300 MHz, CDCl3): δ = 7.83 (s,
1H), 7.33 – 7.15 (m, 1H), 7.01 – 6.84 (m, 3H), 5.66 (dd, J = 3.0, 1.6 Hz,
1H), 5.12 (t, J = 2.9 Hz, 1H), 4.55 (m, J = 6.0, 2.9, 1.4 Hz, 1H), 4.40 (dd, J
= 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 12.0, 4.5 Hz, 1H), 3.72 (s, 3H), 2.04 –
1.96 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 185.1, 169.2, 168.2, 168.1,
158.8, 154.7, 128.9, 126.4, 126.3, 119.3, 114.6, 111.2, 74.1, 64.8, 60.9,
59.8, 54.3, 19.7, 19.6, 19.6. IR (, cm−1) = 2916, 2868, 2745, 1685, 1611,
1574, 1324, 1169, 1147, 991, 840. HRMS (ESI-TOF) calc. [C20H22O9SNa+]
461.0877, found 461.0883. [α]20D = +37.8 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-
(trifluoromethyl)phenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
diacetate (3j): Product 3j was obtained as a yellow oil (114 mg, 0.240
mmol, 96%). 1H NMR (300 MHz, CDCl3): δ = 7.83 (s, 1H), 7.70 (d, J = 7.1
Hz, 1H), 7.55 – 7.42 (m, 3H), 5.67 (dd, J = 3.2, 1.6 Hz, 1H), 5.14 (t, J = 3.3
Hz, 1H), 4.58 – 4.50 (m, 1H), 4.39 (dd, J = 12.1, 7.6 Hz, 1H), 4.15 (dd, J =
12.1, 4.5 Hz, 1H), 2.09 – 1.91 (m, 9H). 13C NMR (75 MHz, CDCl3): δ =
183.8, 169.2, 168.3, 168.1, 155.1, 138.6, 132.5 (q, J = 30.1 Hz), 131.1,
129.0, 126.1 (q, J = 5.4 Hz), 124.2, 120.3, 111.3, 74.3, 64.8, 61.2, 59.7,
19.6, 19.5, 19.5. 19F NMR (282 MHz, THF-d8): δ = -61.1. IR (, cm−1) =
2972, 2846, 1693, 1622, 1575, 1551, 1272, 1179, 1158, 1002.
HRMS (ESI-TOF) calc. [C20H19O8F3SNa+] 499.0644, found 499.0625.
[α]20D = +36.8 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-fluorophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3k): Product 3k was obtained as a
yellow oil (100 mg, 0.235, 94%). 1H NMR (300 MHz, CDCl3): δ = 7.90 (s,
1H), 7.45 – 7.40 (m, 2H), 7.16 – 7.05 (m, 2H), 5.77 – 5.64 (m, 1H), 5.20 (t,
J = 3.0 Hz, 1H), 4.72 – 4.58 (m, 1H), 4.48 (dd, J = 12.0, 7.8 Hz, 1H), 4.20
(dd, J = 12.1, 4.5 Hz, 1H), 2.19 – 1.98 (m, 9H). 13C NMR (75 MHz, CDCl3):
δ = 186.1, 170.2, 169,2, 169,1, 163.5 (d, J = 250.2 Hz), 155.9, 137.2 (d, J
= 8.6 Hz), 121.7 (d, J = 3.3 Hz), 116.4 (d, J = 22.1 Hz), 112.1, 75.2, 65.7,
61.9, 60.7, 20.6, 20.6, 20.5. 19F NMR (282 MHz, THF-d8): δ =
-113.2. IR (, cm−1) = 2924, 1685, 1574, 1443, 1324, 1169, 1149, 992,
806. HRMS (ESI-TOF) calc. [C19H19FO8Na+] 449.0676, found 449.0680.
[α]20D = +35.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-chlorophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3l): Product 3l was obtained as a
coreless oil (63 mg, 0.142 mmol, 57%). 1H NMR (300 MHz, CDCl3): δ =
7.82 (s, 1H), 7.34 – 7.25 (m, 4H), 5.66 (dd, J = 3.1, 1.7 Hz, 1H), 5.12 (t, J
= 3.0 Hz, 1H), 4.60 – 4.52 (m, 1H), 4.41 (dd, J = 12.1, 7.9 Hz, 1H), 4.12
(dd, J = 12.1, 4.5 Hz, 1H), 2.06 – 1.95 (m, 9H). 13C NMR (75 MHz, CDCl3):
δ = 185.6, 170.2, 169.2, 169.1, 156.0, 136.3, 136.0, 129.4, 124.9, 112.1,
75.2, 65.7, 61.9, 60.7, 20.7, 20.6, 20.6. IR (, cm−1) = 2915, 1689, 1574,
1549, 1430, 1326, 1173, 1154, 994, 983, 825. HRMS (ESI-TOF) calc.
[C19H19ClO8SNa+] 465.0381, found 465.0385. [α]20D = +36.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-bromophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3m):Product 3m was obtained as
a yellow solid (74 mg, 0.152 mmol, 61%). 1H NMR (300 MHz, CDCl3): δ =
7.89 (s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 5.74 (dd, J
= 3.2, 1.6 Hz, 1H), 5.23 – 5.15 (m, 1H), 4.69 – 4.61 (m, 1H), 4.48 (dd, J =
12.1, 7.9 Hz, 1H), 4.18 (dd, J = 12.1, 4.6 Hz, 1H), 2.18 – 2.03 (m, 9H). 13C
NMR (75 MHz, CDCl3): δ = 185.5, 170.2, 169.2, 169.1, 156.0, 136.6, 132.4,
This article is protected by copyright. All rights reserved.
10.1002/cctc.201901403
125.5, 124.3, 112.1, 75.2, 65.8, 61.9, 60.7, 20.7, 20.6, 20.6. IR (, cm−1) =
2862, 2834, 1681, 1613, 1574, 1549, 1326, 1179, 1156, 996, 827, 791.
HRMS (ESI-TOF) calc. [C19H19BrO8Na+] 508.9876, found 508.9883. [α]20D
= +36.8 (0.1, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-nitrophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3n): Product 3n was obtained as a
brown solid (41 mg, 0.09 mmol, 36%). 1H NMR (300 MHz, CDCl3): δ = 7.81
(s, 1H), 7.18 (d, J = 8.2 Hz, 2H), 6.51 (d, J = 8.5 Hz, 2H), 5.72 – 5.60 (m,
1H), 5.11 (t, J = 3.0 Hz, 1H), 4.60 – 4.48 (m, 1H), 4.47 – 4.34 (m, 1H), 4.19
– 4.01 (m, 1H), 2.07 – 1.91 (m, 9H).13C NMR (75 MHz, CDCl3): δ = 187.9,
170.2, 169.3, 169.2, 155.3, 148.0, 136.6, 133.8, 125.7, 115.3, 74.9, 65.9,
62.0, 60.8, 20.7, 20.7, 20.6. IR (, cm−1) = 2820, 1568, 1542, 1685, 1447,
1192, 1140, 1013, 802. HRMS (ESI-TOF) calc. [C19H19NO10SNa+]
Accepted Manuscript
476.0621, found 437.0622. [α]20D = +26.0 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-((benzylthio)carbonyl)-3,4-dihydro-
2H-pyran-3,4-diyl diacetate (3p): Product 3p was obtained as a yellow oil
(56 mg, 0.13 mmol, 53%). 1H NMR (300 MHz, CDCl3): δ = 7.69 (s, 1H),
7.22 (d, J = 4.2 Hz, 5H), 5.75 – 5.63 (m, 1H), 5.09 (t, J = 3.1 Hz, 1H), 4.58
– 4.45 (m, 1H), 4.40 – 4.27 (m, 1H), 4.21 – 4.03 (m, 3H), 2.06 – 1.92 (m,
9H). 13C NMR (75 MHz, CDCl3): δ = 187.4, 170.2, 169.3, 169.1, 155.1,
137.4, 128.9, 128.6, 127.3, 112.3, 75.0, 65.8, 62.0, 60.8, 32.5, 20.7, 20.6,
20.6. IR (, cm−1) = 2931, 1689, 1601, 1575, 1549, 1177, 1153, 1020, 996.
HRMS (ESI-TOF) calc. [C20H22O8SNa+] 445.0927, found 445.0920. [α]20D
= +34.0 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-hydroxyethyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3q): Product 3q was obtained as a
coreless oil (40 mg, 0.11 mmol, 42%). 1H NMR (300 MHz, CDCl3): δ =
7.81 (s, 1H), 5.77 – 5.71 (m, 1H), 5.17 (t, J = 3.1 Hz, 1H), 4.64 – 4.56 (m,
1H), 4.45 (dd, J = 11.7, 8.2 Hz, 1H), 4.17 (dd, J = 12.0, 4.5 Hz, 1H), 3.79
(t, J = 5.9 Hz, 2H), 3.17 (t, J = 6.2 Hz, 2H), 2.11 – 2.06 (m, 9H). 13C NMR
(75 MHz, CDCl3): δ = 188.3, 170.2, 169.3, 1691, 155.5, 112.4, 77.4, 75.0,
65.8, 61.9, 60.8, 31.3, 20.7, 20.6, 20.6. IR (, cm−1) = 3330, 3244, 2844,
1687, 1600, 1575, 1547, 1326, 1153, 1177, 1017, 994. HRMS (ESI-TOF)
calc. [C15H20O9SNa+] 399.0720, found 399.0729. [α]20D = +34.8 (0.05,
CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-((((R)-2-((tert-
butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3r): Product 3r was obtained as a
yellow oil (113 mg, 0.212 mmol, 85%). 1H NMR (300 MHz, CDCl3): δ =
7.72 (s, 1H), 5.65 (s, 1H), 5.23 (s, 1H), 5.11 (t, J = 3.3 Hz, 1H), 4.59 – 4.31
(m, 3H), 4.11 (m, 1H), 3.68 (d, J = 3.0 Hz, 3H), 3.37 (t, J = 4.3 Hz, 2H),
2.02 (m, 9H), 1.37 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 186.8, 170.8,
170.1, 169.2, 169.1, 155.7, 155.0, 112.3, 80.1, 75.1, 65.7, 61.9, 60.7, 53.2,
52.5, 30.3, 28.2, 20.6, 20.6, 20.5. IR (, cm−1) = 3267, 2877, 1687, 1661,
1587, 1549, 1324, 1153, 1175, 994, 836. HRMS (ESI-TOF) calc.
[C22H31NO12SNa+] 556.1459, found 556.1490. [α]20D = +33.8 (0.05, CHCl3).
(R)-methyl 3-(((2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-
3,4-dihydro-2H-pyran-5-carbonyl)thio)-2-((tert-
butoxycarbonyl)amino)propanoate (3s): Product 3s was obtained as a
yellow oil (130 mg, 0.192 mmol, 77%). 1H NMR (300 MHz, CDCl3): δ =
7.66 (s, 1H), 7.34 – 7.09 (m, 15H), 4.64 – 4.29 (m, 10H), 3.78 – 3.73 (m,
1H), 3.68 – 3.62 (m, 4H), 3.55 – 3.48 (m, 1H), 3.35 (d, J = 4.8 Hz, 2H),
1.37 – 1.32 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 188.7, 171.1, 155.4,
155.1, 137.8, 137.7, 137.3, 128.5, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7,
127.7, 114.4, 80.1, 77.6, 77.3, 73.3, 72.3, 71.5, 71.1, 68.0, 67.8, 53.5, 52.5,
30.3, 28.2. IR (, cm−1) = 3254, 2929, 2853, 2877, 1689, 1657, 1601, 1449,
1158, 1035, 678. HRMS (ESI-TOF) calc. [C37H43NO9SNa+] 700.2551,
found 700.2516. [α]20D = +33.4 (0.05, CHCl3).
(R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(((2R,3S,4S)-3,4-
dimethoxy-2- (methoxymethyl)-3,4-dihydro-2H-pyran-5-
carbonyl)thio)propanoate (3t): Product 3t was obtained as a yellow oil
(103 mg, 0.230 mmol, 92%). 1H NMR (300 MHz, CDCl3): δ = 7.03 (s, 1H),
ChemCatChem
COMMUNICATION
5.22 (s, 1H), 4.54 (s, 1H), 4.06 – 3.98 (m, 1H), 3.90 (dd, J = 8.0, 5.0 Hz,
1H), 3.80 – 3.71 (m, 4H), 3.67 – 3.61 (m, 2H), 3.50 – 3.38 (m, 11H), 1.45
– 1.42 (s, 9H).13C NMR (75 MHz, CDCl3): δ = 188.4, 171.1, 170.8, 137.8,
137.3, 94.7, 80.2, 71.9, 71.1, 68.2, 59.3, 57.1, 56.2, 52.6, 52.5, 41.3, 30.7.
IR (, cm−1) = 3226, 2879, 2855, 2736, 1689, 1654, 1618, 1460, 1451,
1123, 1061, 1017. HRMS (ESI-TOF) calc. [C19H31O9SNa+] 472.1611,
found 472.1618. [α]20D = +25.2 (0.05, CHCl3).
(2R,3R,4S,5R,6R)-2-(((2R,3S,4R)-4-acetoxy-2-(acetoxymethyl)-5-(((4-
methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3-yl)oxy)-6-
(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3u):
Product 3u was obtained as a yellow solid (172 mg, 0.237 mmol, 95%).
1
H NMR (300 MHz, CDCl3):  = 7.85 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 6.87
(d, J = 8.4 Hz, 2H), 5.46 (s, 1H), 5.40 – 5.28 (m, 2H), 5.02 – 4.90 (m, 1H),
4.86 – 4.63 (m, 2H), 4.33 (t, J = 10.3 Hz, 1H), 4.15 – 3.95 (m, 4H), 3.92 (s,
1H), 3.75 (s, 3H), 2.08 – 1.92 (m, 18H).13C NMR (75 MHz, CDCl3): =
187.4, 170.5, 170.2, 170.1, 170.0, 169.6, 169.5, 160.8, 155.3, 136.7, 116.9,
114.9, 111.5, 97.0, 75.8, 72.7, 70.1, 69.9, 68.4, 68.2, 61.9, 61.7, 60.8, 55.3,
20.7, 20.6, 20.6, 20.6, 20.5, 20.4. IR (, cm−1) = 2864, 1687, 1605, 1572,
1542, 1442, 1184, 1154, 1004, 992. HRMS (ESI-TOF) calc.
[C32H38O17SNa+] 749.1722, found 749.1696. [α]20D = +2.00 (0.05, CHCl3).
(3R,4R)-5-(((4-methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-
3,4-diyl diacetate (3v): Product 3v was obtained as a yellow oil (78 mg,
0.215 mmol, 86%). 1H NMR (300 MHz, CDCl3):  = 7.90 (s, 1H), 7.28 (d, J
= 8.9 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 5.61 (t, J = 2.2 Hz, 1H), 4.37 (d, J
= 13.2 Hz, 1H), 3.98 (d, J = 12.6 Hz, 1H), 3.74 (s, 3H), 2.02 (s, 3H), 2.00
(s, 3H). 13C NMR (75 MHz, CDCl3): = 187.5, 169.4, 169.0, 160.7, 157.8,
136.7, 117.1, 114.8, 112.0, 65.3, 64.7, 61.0, 55.3, 20.9, 20.8. IR (, cm−1)
= 2884, 1689, 1605, 1557, 1442, 1174, 1152, 1001, 990. HRMS (ESI-
TOF) calc. [C17H18O7SNa+] 389.0665, found 389.0669. [α]20D = -210 (0.05,
CHCl3).
(3S,4R)-5-(((4-methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-
3,4-diyl diacetate (3x): Product 3x was obtained as a yellow oil (90 mg,
0.245 mmol, 93%). 1H NMR (300 MHz, CDCl3):  = 7.77 (s, 1H), 7.24 (d, J
= 8.2 Hz, 2H), 6.84 (d, J = 8.3 Hz, 2H), 6.04 (d, J = 3.5 Hz, 1H), 5.14 –
5.01 (m, 1H), 4.17 – 4.06 (m, 1H), 4.02 – 3.92 (m, 1H), 3.72 (s, 3H), 2.01
(s, 3H), 1.95 (s, 3H). 13C NMR (75 MHz, CDCl3): = 186.8, 169.6, 169.3,
160.7, 157.6, 136.4, 117.0, 114.8, 112.7, 65.1, 63.0, 60.8, 55.3, 20.8, 20.5.
IR (, cm−1) = 2949, 2852, 2878, 1686, 1657, 1605, 1447, 1158, 1035.
HRMS (ESI-TOF) calc. [C17H18O7SNa+] 389.0665, found 389.0661. [α]20D
= -176 (0.05, CHCl3).
(2R,3R,4R)-2-(acetoxymethyl)-5-(((4-methoxyphenyl)thio)carbonyl)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3y): Product 3y was obtained
as a yellow oil (58 mg, 0.132 mmol, 53%). 1H NMR (300 MHz, CDCl3):  =
7.73 (s, 1H), 7.25 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.99 (d, J =
4.4 Hz, 1H), 5.37 (t, J = 4.0 Hz, 1H), 4.50 – 4.37 (m, 2H), 4.30 – 4.18 (m,
1H), 3.75 (s, 3H), 2.20 – 1.98 (m, 9H). 13C NMR (75 MHz, CDCl3): =
185.5, 169.5, 168.7, 168.3, 159.8, 154.3, 135.7, 115.9, 113.9, 112.3, 73.2,
63.6, 60.3, 60.1, 54.3, 19.7, 19.6, 19.5. IR (, cm−1) = 2948, 2859, 1689,
1657, 1607, 1449, 1150, 1001. HRMS (ESI-TOF) calc. [C20H22O9SNa+]
461.0877, found 461.0863. [α]20D = +42.0 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-(((2R,3S,4S)-3,4-diacetoxy-
2- (acetoxymethyl)-3,4-dihydro-2H-pyran-5-
carbonyl)oxy)ethyl)thio)carbonyl)-3,4- dihydro-2H-pyran-3,4-diyl
diacetate (4): Product 4 was synthesized according to a previously
published procedure1 and was obtained as a yellow solid (97 mg, 0.144
mmol, 72%). 1H NMR (300 MHz, CDCl3): δ = 7.74 (s, 2H), 5.71 – 5.63 (m,
2H), 5.10 (t, J = 3.1 Hz, 2H), 4.60 – 4.48 (m, 2H), 4.38 (dd, J = 12.2, 7.7
Hz, 2H), 4.16 – 4.07 (m, 2H), 3.72 (t, J = 5.9 Hz, 2H), 3.10 (t, J = 6.0 Hz,
2H), 2.06 – 1.97 (m, 18H). 13C NMR (75 MHz, CDCl3): δ = 188.3, 170.2,
169.3, 169.2, 169.1, 155.5, 112.4, 75.0, 65.8, 61.9, 60.8, 31.2, 20.7, 20.6,
20.6. IR (, cm−1) = 2872, 1685, 1601, 1549, 1326, 1175, 1151, 1015, 992,
836. HRMS (ESI-TOF) calc. [C28H34O17SNa+] 472.1611, found 472.1618.
[α]20D = +35.6 (0.05, CHCl3).
This article is protected by copyright. All rights reserved.
10.1002/cctc.201901403
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-
methoxyphenyl)selanyl)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
diacetate (6a): Product 6a was obtained as a yellow oil (56 mg, 0.116
mmol, 58%). 1H NMR (300 MHz, CDCl3): δ = 7.77 (s, 1H), 7.47 – 7.32 (m,
2H), 6.84 (d, J = 8.7 Hz, 2H), 5.63 (dd, J = 3.1, 1.7 Hz, 1H), 5.11 (t, J = 3.0
Hz, 1H), 4.61 – 4.53 (m, 1H), 4.40 (dd, J = 12.0, 7.8 Hz, 1H), 4.11 (dd, J =
12.1, 4.6 Hz, 1H), 3.75 (s, 3H), 2.09 – 1.91 (m, 9H). 13C NMR (75 MHz,
CDCl3): δ = 188.9, 170.2, 169.2, 169.1, 160.5, 156.6, 137.9, 115.2, 115.1,
114.3, 75.3, 65.8, 62.1, 60.7, 55.2, 20.7, 20.7, 20.6. IR (, cm−1) = 2862,
2747, 1685, 1631, 1574, 1443, 1324, 1177, 1154, 1136, 992, 799. HRMS
(ESI-TOF) calc. [C20H22O9SeNa+] 509.0321, found 509.0316. [α]20D
= +33.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-
Accepted Manuscript
methoxyphenyl)selanyl)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
diacetate (6b): Product 6b was obtained as a yellow solid (39 mg, 0.08
mmol, 41%). 1H NMR (300 MHz, CDCl3): δ = 7.82 (s, 1H), 7.49 – 7.44 (m,
1H), 7.33 (t, J = 7.8 Hz, 1H), 6.90 (t, J = 7.1 Hz, 2H), 5.68 – 5.60 (m, 1H),
5.11 (t, J = 3.1 Hz, 1H), 4.62 – 4.50 (m, 1H), 4.39 (dd, J = 12.1, 7.8 Hz,
1H), 4.12 (dd, J = 12.1, 4.5 Hz, 1H), 3.77 (s, 3H), 2.21 – 1.86 (m, 9H). 13C
NMR (75 MHz, CDCl3): δ = 186.2, 169.2, 168.3, 168.1, 158.1, 155.5, 137.3,
130.2, 120.4, 113.6, 113.1, 110.3, 74.3, 64.9, 61.2, 59.8, 55.0, 19.7, 19.7,
19.6. IR (, cm−1) = 2877, 2112, 1685, 1564, 1177, 1328, 1197, 1154, 1143,
991. HRMS (ESI-TOF) calc. [C20H22O9SeNa+] 509.0321, found 509.0326.
[α]20D = +32.6 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-((phenylselanyl)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (6c): Product 6c was obtained as a
yellow oil (51 mg, 0.112 mmol, 56%). 1H NMR (300 MHz, CDCl3): δ = 7.79
(s, 1H), 7.46 (d, J = 7.5 Hz, 2H), 7.36 – 7.29 (m, 3H), 5.64 (s, 1H), 5.11 (s,
1H), 4.56 (d, J = 3.1 Hz, 1H), 4.40 (dd, J = 12.1, 7.9 Hz, 1H), 4.12 (dd, J =
11.9, 4.4 Hz, 1H), 2.13 – 1.91 (m, 9H). 13C NMR (75 MHz, CDCl3): δ
=188.0, 170.2, 169.2, 169.1, 156.7, 136.3, 129.3, 129.0, 124.9, 114.3, 75.4,
65.8, 62.1, 60.7, 20.7, 20.7, 20.6. IR (, cm−1) = 2861, 2827, 2762, 1691,
1629, 1574, 1326, 1184, 1158, 1018, 996. HRMS (ESI-TOF) calc.
[C19H20O8SeNa+] 479.0216, found 479.0207. [α]20D = +34.0 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-((naphthalen-1-ylselanyl)carbonyl)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate (6d): Product 6d was obtained
as a yellow oil (46 mg, 0.09 mmol, 46%). 1H NMR (300 MHz, CDCl3): δ =
8.07 (s, 1H), 7.98 – 7.72 (m, 4H), 7.62 – 7.49 (m, 3H), 5.78 – 5.70 (m, 1H),
5.25 – 5.16 (m, 1H), 4.73 – 4.60 (m, 1H), 4.49 (dd, J = 12.2, 8.0 Hz, 1H),
4.20 (dd, J = 12.2, 4.6 Hz, 1H), 2.17 – 2.05 (m, 9H). 13C NMR (75 MHz,
CDCl3): δ = 188.2, 170.2, 169.2, 169.1, 156.8, 136.2, 133.8, 133.2, 132.7,
128.7, 127.8, 127.8, 126.9, 126.4, 122.2, 114.4, 75.4, 65.8, 62.1, 60.7,
20.7, 20.7, 20.6. IR (, cm−1) = 2862, 2821, 2756, 1689, 1629, 1574. 1326,
1182, 1156, 1018, 996. HRMS (ESI-TOF) calc. [C23H22O8SeNa+] 529.0372,
found 529.0378. [α]20D = +32.8 (0.05, CHCl3).
(2R,3S,4S)-Se-naphthalen-1-yl 3,4-bis(benzyloxy)-2-
((benzyloxy)methyl)-3,4-dihydro-2H-pyran-5-carboselenoate (6e):
Product 6e was obtained as a yellow oil (56 mg, 0.09 mmol, 43%). 1H NMR
(300 MHz, CDCl3): δ = 8.02 (s, 1H), 7.78 (m, 4H), 7.53 (d, J = 8.5 Hz, 1H),
7.49 – 7.37 (m, 2H), 7.31 – 7.15 (m, 15H), 4.60 – 4.35 (m, 7H), 3.82 – 3.69
(m, 3H), 3.57 (dd, J = 10.7, 5.0 Hz, 1H). 13C NMR (75 MHz, CDCl3):
δ = 189.8, 156.6, 137.8, 137.6, 137.2, 136.2, 133.9, 133.1, 133.0, 128.5,
128.5, 128.5, 128.4, 128.4, 128.3, 128.3, 128.0, 127.8, 127.8, 127.7, 127.7,
126.7, 126.2, 123.1, 116.4, 78.1, 73.3, 72.5, 71.6, 71.3, 68.1, 68.1.
HRMS (ESI-TOF) calc. [C38H34O5SeNa+] 673.1464, found 673.1466. [α]20D
= +34.4 (0.05, CHCl3).
(3S,4R)-5-((naphthalen-1-ylselanyl)carbonyl)-3,4-dihydro-2H-pyran-
3,4-diyl diacetate (6f): Product 6f was obtained as a yellow oil (38 mg,
0.09 mmol, 44%). 1H NMR (300 MHz, CDCl3): δ = 8.05 (s, 1H), 7.83 (d, J
= 9.4 Hz, 3H), 7.51 (m, 4H), 6.22 – 6.05 (m, 1H), 5.63 (d, J = 4.2 Hz, 1H),
4.30 – 4.20 (m, 1H), 4.15 – 3.94 (m, 1H), 2.14 (s, 3H), 2.14 (s, 3H). 13C
NMR (75 MHz, CDCl3): = 187.8, 169.7, 169.3, 158.5, 150.9, 136.2, 132.7,
127.8, 127.7, 127.7, 126.8, 126.5, 126.4, 126.3, 114.9, 68.5, 65.9, 65.1,
ChemCatChem
COMMUNICATION
20.8, 20.7. IR (, cm−1) = 2876, 2826, 2755, 1689, 1627, 1574. 1321, 1182,
1155, 1020, 990. HRMS (ESI-TOF) calc. [C20H18O6SeNa+] 457.0161,
found 457.0164. [α]20D = +4.00 (0.05, CHCl3).
(2R,3S,4R)-S-(4-methoxyphenyl) 3,4-dihydroxy-2-(hydroxymethyl)-
3,4-dihydro-2H-pyran-5-carbothioate (7a): Product 7a was obtained as
a yellow oil (37 mg, 0.117 mmol, 69%). 1H NMR (300 MHz, CDCl3): δ =
8.15 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.9 Hz, 2H), 4.89 (t, 1H),
4.28 (dd, J = 5.9, 3.6 Hz, 1H), 3.99 – 3.93 (m, 2H), 3.90 (s, 3H), 3.78 –
3.68 (m, 1H). 13C NMR (75 MHz, CDCl3): = 183.0, 159.8, 154.7, 144.5,
135.4, 113.9, 104.6, 76.0, 67.1, 67.1, 63.8, 54.3. IR (, cm−1) = 3330, 3024,
2954, 2910, 2832, 1688, 1615, 1557, 1454, 1190, 1027, 982, 697.
HRMS (ESI-TOF) calc. [C14H16O6SNa+] 335.0560, found 335.0557. [α]20D
= +46.0 (0.05, CHCl3).
(2R,3S,4R)-S-phenyl 3,4-dihydroxy-2-(hydroxymethyl)-3,4-dihydro-
2H-pyran-5-carbothioate (7b): Product 7b was obtained as a yellow oil
(27 mg, 0.096 mmol, 56%). 1H NMR (300 MHz, CDCl3): δ = 8.03 (s, 1H),
7.42 – 7.30 (m, 5H), 5.22 – 5.13 (m, 1H), 4.35 (d, J = 8.8 Hz, 1H), 3.86 –
3.77 (m, 2H), 3.61 – 3.56 (m, 1H), 3.44 – 3.38 (m, 2H), 2.72 (s, 1H).13C
NMR (75 MHz, CDCl3): = 185.4, 143.1, 138.4, 134.4, 132.4, 127.1, 126.7,
103.0, 92.1, 68.1, 65.5, 61.6, 59.7. IR (, cm−1) = 3323, 3015, 2945, 2909,
2823, 1684, 1615, 1557, 1454, 1192, 1027, 988, 697. HRMS (ESI-TOF)
calc. [C13H14O5S+Na+] 305.0454, found 305.0449 [α]20D = +46.0 (0.05,
CHCl3).
Acknowledgements
The authors thank the São Paulo Research Foundation, FAPESP
for financial support (grant 2017/24821-4 to HAS, 2016/24396-9
to MPD, 2017/26673-2 to HAE, 2016/04289-3 to IMO). We are
also thankful for the financial support provided by The National
Council for Scientific and Technological Development (CNPq) for
the fellowship 306119/2014-5 to HAS.
Keywords: Thiocarbonylation, selenocarbonylation,
C2-Branched sugars, glycals, molybdenum hexacarbonyl.
[1] a) Y. Yang, B. Yu, Chem. Rev. 2017, 117, 12281-12356; b) D.-C. Xiong, C.
Gao, W. Li, Y. Wang, Q. Li, X.-S. Ye, Org. Chem. Front. 2014, 1, 798-
806.
[2] a) S. Colombel, N. Van Hijfte, T. Poisson, E. Lecler, X. Pannecoucke, Chem.
Eur. J. 2013, 19, 12778-12787; b) A. M. Gomez, M. Casillas, S. .Valverde,
J. C. Lopez, Tetrahedron: Asymmetry 2001, 12, 2175-2183.
[3] K. Pachamuthu, A. Gupta, J. Das, R. R. Schmidt, Y. D. Vankar, Eur. J. Org.
Chem. 2002, 1479-1483
[4] a) S. Barroso, S. Lemaire, V. Farina, A. K. Steib, R. Blanc, P. Knochel, J.
Org. Chem. 2016, 81, 2804-2816; b) S. Lemaire, I. N. Houpis, T. Xiao, J.
Li, E. Digard, C. Gozlan, R. Liu, A. Gavryushin, C. Diene, Y. Wang, V.
Farina, P. Knochel, Org. Lett. 2012, 14, 1480-1483; c) D. Mukherjee, S.
K. Sarkar, U. S. Chowdhury, S. C. Taneja, Tetrahedron Lett. 2007, 48,
663-667.
[5] I. Cobo, M. I. Matheu, S. Castillon, O. Boutureira, B. G. Davis, Org. Lett.
2012, 14, 1728-1731.
[6] S. Dharuman, Y. D. Vankar, Org. Lett. 2014, 16, 1172-1175.
[7] A. Shamim, S. N. Vasconcelos, B. Ali, L. S. Madureira, J. Zukerman-
Schpector, H. A. Stefani, Tetrahedron Lett. 2015, 56, 5836-5842.
[8] R. A. A. AL-Shuaeeb, D. Montoir, M. Alami, S. Messaoudi, J. Org. Chem.
2017, 82, 6720-6728.
[9] a) J.-B. Peng, F.-P. Wu, X.-F. Wu, Chem. Rev. 2019, 119, 4, 2090-2127; b)
B. Gabriele, R. Mancuso, G. Salerno, Eur. J. Org. Chem. 2012, 6825-
6839; c) Q. Liu, H. Zhang, A. Lei, Angew. Chem. Int. Ed. 2011, 50, 10788-
10799; d) X.-F. Wu, H. Neumann, M. Beller, Chem. Soc. Rev. 2011, 40,
This article is protected by copyright. All rights reserved.
10.1002/cctc.201901403
4986-5009; e) A. Brennführer, H. Neumann, M. Beller, Angew. Chem. Int.
Ed. 2009, 48, 4114-4133.
[10] a) M. P. Darbem, K. S. Kanno, I. M. de Oliveira, C. H. A. Esteves, D. C.
Pimenta, H. A. Stefani, New J. Chem. 2019, 43, 696-699; b) A. Bordessa,
A. Ferry, N. Lubin-Germain, J. Org. Chem. 2016, 81, 12459-12465.
[11] M. P. Darbem, C. H. A. Esteves, I. M. de Oliveira, J. S. Reis, D. C. Pimenta,
H. A. Stefani, RSC Adv. 2019, 9, 9468-9474.
[12] a) M. de Robichon, A. Bordessa, N. Lubin-Germain, A. Ferry, J. Org. Chem.
2019, 84, 3328-3339; b) N. Hussain, M. Bhardwaj, A. Ahmed, D.
Mukherjee, Org. Lett. 2019, 21, 3034-3037.
[13] a) G. Lian, X. Zhang, B. Yu, Carbohydr. Res. 20015, 403, 13-22; b) M.
Samuni-Blank, I. Izhaki, M. D. Dearing, Y. Gerchman, B. Trabelcy, A. L.
W. H. Karasov, Z. Arad, Curr. Biol. 2012, 22, 1218-1220.
[14] a) N. Yoshikai, R. Iida, E. Nakamura, Adv. Synth. Catal. 2008, 350, 1063–
Accepted Manuscript
1072; b) R. J. Anderson, C. A. Henrick, L. D. Rosenblum, J. Am. Chem.
Soc. 1974, 96, 3654–3655.
[15] S. Kim and J. I. Lee, J. Org. Chem. 1984, 49, 1712–1716.
[16] M. Ueda, K. Seki and Y. Imai, Synthesis 1981, 12, 991–993.
[17] H. Tokuyama, T. Miyazaki, S. Yokoshima, T. Fukuyama, Synlett 2003, 10,
1512–1514.
[18] a) T. Miyazaki, Y. Han-Ya, H. Tokuyama, T. Fukuyama, Synlett 2004, 3,
477-480; b) T. Fukuyama, S. C. Lin, L. Li, J. Am. Chem. Soc. 1990, 112,
7050–7051.
[19] a) I. M. de Oliveira, C. H. A. Esteves, M. P. Darbem, D. C. Pimenta, J.
Zukerman-Schpector, A. G. Ferreira, H. A. Stefani, F. Manarin, Adv.
Synth. Catal., DOI: 10.1002/adsc.201900142; b) I. M. de Oliveira, M. P.
Darbem, C. H. A. Esteves, D. C. Pimenta, J. Zukerman-Schpector, H. A.
Stefani, F. Manarin, Tetrahedron Lett. 2018, 59, 3907-3911; c) I. M. de
Oliveira, S. N. Vasconcelos, C. S. Barbeiro, T. C. Correra, A. Shamim,
D. C. Pimenta, I. Caracelli, J. Zukerman-Schpector, H. A. Stefani, F.
Manarin, New J. Chem. 2017, 41, 9884-9888; d) M. P. D. Rocha, A. R.
Oliveira, T. B. Albuquerque, C. D. G. da Silva, R. Katla N. L. C.
Domingues, RSC Adv. 2016, 6, 4979–4982.
[20] H. Maeda, S.-i. Fujiwara, T. S.-I., N. Kambe, N. Sonoda, J. Am. Chem. Soc.
1996, 118, 8160-5161.
[21] Y. Nishiyama, K. Tokunaga, H. Kawamatsu, N. Sonoda, Tetrahedron Lett.
2002, 43, 1507-1509.
[22] a) A. Temperini, F. Piazzolla, L. Minuti, M. Curini, C. Siciliano, J. Org. Chem.
2017, 82, 4588-4603; b) L. Sancineto, J. P. Vargas, B. Monti, M. Arca, V.
Lippolis, G. Perin, E. J. Lenardao, C. Santi, Molecules 2017, 22, 953; c)
P. A. Grieco, Y. Yokoyama, E. Williams, J. Org. Chem. 1978, 43, 1283–
1285; d) H.-J. Gais and T. Lied, Angew. Chemie Int. Ed. 1978, 17, 267-
268.
[23] M. N. Burhardt, A. Ahlburg, T. Skydstrup, J. Org. Chem. 2014, 79, 11830-
11840.
[24] a) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998, 120, 7369-7370;
b) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998, 120, 3694-
3703.
[25] a) S. Bharti, M. Choudhary, B. Mohan, S. P. Rawat, S. R. Sharma, J. Mol.
Struct. 2018, 1164, 137-154; b) R. Lertlapwasin, N. Bhawawet, A. Imym,
S. Fuangswasdi, Sep. Pur. Tech. 2010, 72, 70-76.
[26] S. Durand, G. Jugie, J.-P. Laurent, Transition Met. Chem. 1982, 7, 310-312.
[27] P. Zhong, M.-P. Guo, Synth. Commun. 2001, 31, 1507-1510.
ChemCatChem 10.1002/cctc.201901403

COMMUNICATION
Entry for the Table of Contents (Please choose one layout)

Layout 1:

COMMUNICATION
Text for Table of Contents Mariana P. Darbem,[a] Henrique A.
Esteves,[a] Isadora M. de Oliveira,[b]
Daniel C. Pimenta,[c] Hélio A. Stefani[a]*

Accepted Manuscript
Page No. – Page No.

Palladium-Catalyzed Thio- and

Selenocarbonylation of 2-Iodoglycals

Layout 2:

COMMUNICATION
Author(s), Corresponding Author(s)*

Page No. – Page No.

Title

Text for Table of Contents

This article is protected by copyright. All rights reserved.