Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis of C-linked Glycoconjugates

Article abstract of DOI:10.1002/anie.202009828

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C-linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate-DNA conjugates.

Full text of DOI:10.1002/anie.202009828

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its
Use in the Synthesis of C-linked Glycoconjugates
Authors: Weidong Shang, Sheng-Nan Su, Rong Shi, Ze-Dong Mou,
Guo-Qiang Yu, Xia Zhang, and Dawen Niu
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10.1002/anie.202009828
Angewandte Chemie International Edition
COMMUNICATION
Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its
Use in the Synthesis of C-linked Glycoconjugates
Weidong Shang,[a] Sheng-Nan Su,[a] Rong Shi,[a] Ze-Dong Mou,[a] Guo-Qiang Yu,[b] Xia Zhang*[a] and
Dawen Niu*[a]
Dedicated to Professor Thomas R. Hoye on the occasion of his 70th birthday.
[a]
[b]
W. Shang, S.-N. Su, R. Shi, Z.-D. Mou, Prof. X. Zhang, Prof. D. Niu
Department of Emergency, State Key Laboratory of Biotherapy, West China Hospital, and School of Chemical Engineering, Sichuan University
No. 17 Renmin Nan Road, Chengdu, 610041, China.
E-mail: zhang-xia@scu.edu.cn; niudawen@scu.edu.cn
Homepage: www.theniugroup.com
G.-Q. Yu
Discovery Chemistry Unit, HitGen Inc.
Building 6, No. Huigu 1st East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu, China 610200
Supporting information for this article is given via a link at the end of the document.
a. C-Glycosylation via glycosyl radical species
Abstract: We here report glycosyl sulfoxides appended with an aryl
iodide moiety as readily available, air and moisture stable precursors
to glycosyl radicals. These glycosyl sulfoxides could be converted to
glycosyl radicals by way of a rapid and efficient intramolecular radical
substitution event. The use of this type of precursors enabled the
synthesis of various complex C-linked glycoconjugates under mild
conditions. This reaction could be performed in aqueous media and is
amenable to the synthesis of glycopeptidomimetics and
carbohydrate-DNA conjugates.
O
Conditions
O
(PO)n
O
(PO)n
(PO)n
LG
R
1
2
3
Representative radical precursors:
O
O
O
O
Br
S
OR
XR
O
S
X = S/Sn/Se/Te
b. This Work
C–I
cleavage
O
H
HO
O
H
O
O
HO
HO
HO
I
X
unimolecular
substitution
bimolecular
trapping
Introduction
X
FG
X = S or S(=O)
Glycosyl radicals[1-8] (2, Scheme 1a) are among the most
well studied and versatile species in carbohydrate chemistry.
These species show unique utility in the preparation of C-linked
glycoconjugates[9] (1 to 3 via 2), compounds that are extensively
studied as isosteres of their O-linked analogues[10] but more inert
toward enzymatic degradation. Glycosyl radicals exhibit
interesting stereoselectivity profiles when engaged in C–C bond
forming reactions, usually providing C-glycosides with good to
excellent axial selectivity.[1] From the perspective of
chemoselectivity, radical-based reactions generally demonstrate
excellent functional group compatibility.[11] Taken together, these
features should render glycosyl radicals particularly attractive
intermediates in the preparation of structurally complex C-linked
glycoconjugates. However, it remains a challenge to apply
glycosyl radical chemistry in aqueous media for the preparation of
valuable, water-soluble glycoconjugates.
Our group has been interested in the development of efficient
methods to prepare carbohydrate derivatives.[ 12 ] In a project
aimed at making libraries of complex C-glycosides, a mild method
to produce glycosyl radicals in aqueous media from bench-stable
and readily available precursors is needed. Toward this end, we
propose the sequence shown in Scheme 1b, in which glycosyl
sulfides or sulfoxides 4 are intended as precursors to glycosyl
radicals. Glycosyl sulfides or sulfoxides have long been employed
in carbohydrate synthesis,[13] but mostly as precursors of glycosyl
cations. We reason that the aryl iodide moiety in 4 could be readily
converted to aryl radical 5 under mild conditions. Once the aryl
4
5
6
7
(air and moisture stable)
(easy to access)
(required)
Representative products:
OH
O
HO
HO
O
O
OH
HO
O
Ph
NH
O
H
N
N
H
OEt
N
H
O
O
Me
Me
DNA headpiece
Scheme 1. (a) Glycosyl radicals as valuable intermediates in C-glycoside
synthesis. (b) Our strategy to generate glycosyl radicals.
radical is generated, it would then attack the sulfur atom at the
anomeric position via a radical substitution process[14] and result
in the requisite glycosyl radical 6. Subsequent bimolecular
trapping of 6, if viable and efficient, would afford various C-
glycoconjugates. In this case, the task of generating glycosyl
radicals is simplified to one that produces aryl radicals. The
unimolecular radical substitution reaction on higher heteroatoms
(e.g., S or P) is an established process.[14- 16 ] However, the
synthetic potential of radicals generated by this process remains
relatively unexplored. In our design, we were curious, 1) if the aryl
radical in 5 would attack the sulfur atom (solid double-headed
arrow) faster than abstracting the hydrogen atom from the weak
C–H bonds within the substrate (dashed double-headed arrow),
such as the one at the anomeric position[17] 2) if complex C-linked
glycoconjugates could be made by uniting the unimolecular
radical substitution with a bimolecular radical trapping reaction. In
1
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10.1002/anie.202009828
Angewandte Chemie International Edition
COMMUNICATION
this work, we report the realization of the transformation. The
general stability of 4 render them convenient substrates in
synthesis, and meanwhile endow the process with remarkable
functional group tolerance. This reaction is compatible with
aqueous conditions, and amenable to the synthesis of various
complex C-glycoconjugates, including glycopeptidomimetics and
carbohydrate–DNA conjugates.
furnish aryl radical 17, which then triggers the intramolecular
radical substitution step to produce the desired glycosyl radical 18.
Further reaction of 18 with radical acceptors yields the final C-
glycoside products via a-carbonyl radical 20.
Control experiments in Table 1 indicate some key factors that
affect the performance of this transformation. First, we found both
sulfoxide 9 (entry 1) and the corresponding sulfide 8 (entry 2)
could be employed as radical precursor. However, when the latter
was used, product 13 was furnished in lower yield, along with a
significant amount of the deiodinated byproduct 24. These results
suggest that: 1) aryl radicals could attack both the trivalent sulfur
in the sulfoxide or the divalent sulfur in the sulfide group; and 2)
the attack at sulfide is likely a slower process (see below).[22] The
use of sulfone 10 failed to deliver any of the desired product, and
only the deiodinated product 25 was formed (entry 3).[23] The use
of carbene-borane complex 12 was critical. When silane 21 was
employed instead, significant amount of byproduct 23 was formed
(entry 4). We attribute the formation of 23 to the more rapid
hydrogen donation to glycosyl radical 22 by 21 than by 12.[24] We
have examined the possibility of generating the aryl radicals under
photocatalytic conditions[ 25 ] (entry 5). Although the desired
product was indeed obtained in decent yield, concomitant
formation of 23 was a problem. We have attempted heating AIBN
as a way of generating the initiating radical (entry 6). In this case,
the formation of 2-deoxy sugar derivative 26 was observed as a
byproduct, presumably via the known 1,2-acyloxyl migration
process [26] of 22. We lastly investigated the impact of solvent
properties on this reaction (entries 7-13). Interestingly, this
reaction proceeds well in both polar and nonpolar solvents. Protic
solvents such as MeOH could be employed, which bodes well for
the use of water as (co)solvent in our future investigations (see
below). However, the use of solvents such as THF and toluene
that contain weak C–H bonds led to increased amount of 23 as
byproduct.
Results and Discussion
Table 1. Condition Optimization.a
OAc
OAc
Et3B (1.5 eq.), air
O
I
+
AcO
AcO
CO2Me
O
AcO
AcO
X
Me
AcO
CO2Me
N
OAc
11 (2.0 eq.)
BH3
O
O
O
13
N
S
S
S
12 (1.5 eq.)
DCM, rt
X =
Me
8
9
10
O
Product
AcO
+
+
12
Et3B + O2
CO2Me
NHC–BH2
•
20
14
I
O
AcO
X
11
NHC–BH2
•
X
Et
–
14
16
O
AcO
Me
desired
N
18
BH3
O
N
NHC–BH2
I
AcO
X
Me
12
15
H
O
AcO
X
17
undesired
19 (and other products)
Yieldb
Entry
by-product
Deviation from Standard Conditions
1
2
3
4
None, with 9 used as precursor (Standard Conditions)
Use 8 instead of 9
23 (< 5%)
24 (16%)
25 (60%)
23 (23%)
94%
59%
n.d.
Use 10 instead of 9
21 (1.5 eq.), Et3B (1.5 equiv.), air, DCM
39%
Ir(ppy)3 (0.05 eq.), 455 nm LED, 21 (1.0 eq.)
DIPEA (3.0 eq.), CH3CN, rt
23 (17%)
5
61%
12 (1.5 eq.), AIBN (0.2 eq.), CH3CN, 80 o
THF instead of DCM
C
Table 2. Initial substrate scope survey.
26 (5%)
23 (23%)
23 (22%)
26 (2%)
6
7
44%
67%
61%
82%
I
O
S
O
Standard Conditions
O
Toluene instead of DCM
CH3CN instead of DCM
Acetone instead of DCM
DMSO instead of DCM
8
AcO
AcO
EWG
+
9
EWG
10
11
12
13
61%
85%
66%
70%
27
28
29
26 (4%)
MeOH instead of DCM
23 (16%) / 26 (4%)
23 (26%) / 26 (6%)
Alkene scope
1,4-dioxane instead of DCM
OAc
O
O
Ph
O
Glycosyl Radical
Major Byproducts
S
AcO
AcO
CN
29b, 60%
O
O
OAc
OPh
OAc
OAc
OAc
AcO
SiMe3
EWG
O
O
O
AcO
AcO
X
AcO
AcO
AcO
AcO
29c, 65%
29a, 88%
Me3Si Si
H
O
S
AcO
AcO
AcO
OAc
SiMe3
OAc
OAc
Y
O
O
O
P
21
24 (X = Y = lone pair electrons)
25 (X = Y = O)
22
23
26
iPr
Ph
Me
N
N
H
N
H
OEt
OEt
Me
a Reactions in this Table were performed at 0.05 mmol scale. Yields were determined by 1H NMR with 1,3,5
-trimethoxybenzene used as internal standard. DCM, dichloromethane; LED, light-emitting diode; DIPEA,
N,N-diisopropylethylamine; AIBN, azobisisobutyronitrile; THF, tetrahydrofuran; DMSO, dimethyl sulfoxide.
29d, 58%
29e, 78%
29g, 70%
29f, 75%
Carbohydrate scope
We commenced our study by using 8-10 as the model
substrates (Table 1). Compounds 8-10 could be readily prepared
from peracetylated glucose in 1-2 steps (see SI). Through
optimization, we established that in the presence of Et3B/O2, a
borane-carbene[18] complex 12 (1.5 equiv), sulfoxide 9 (1.0 equiv)
as radical precursor, and CH2Cl2 as solvent, product 13 could be
formed cleanly with almost exclusive a-selectivity[1] (Table 1, entry
1). Notably, a diastereomeric (RS:SS = ca. 1:2) mixture of sulfoxide
9 were used directly in this reaction. A plausible pathway was
proposed for this transformation. Ethyl radical[19] generated from
Et3B and O2 abstracts a hydrogen atom from 12 to afford boryl
radical[20] 14. This boryl radical attacks the iodine atom[21] in 16 to
OAc
OAc
AcO
AcO
AcO
O
H3
AcO
C
O
O
O
AcO
AcO
AcO
O
OAc
AcO
OAc
OMe
29h, 82%
29i, 84%
29j, 67%
OAc
OAc
O
AcO
AcO
O
OAc
OAc
AcO
AcO
OAc
H3
C
O
O
O
AcO
AcO
O
OAc
AcO
O
AcO
O
OAc
AcHN
AcO
AcO
AcO
AcO
AcO
29k, 76%
29l, 82%
29m, 60%
29n, 82%
a Reactions were performed with carbohydrate donor (0.15 mmol, 1.0 equiv.), alkenes (2.0 equiv.), 12
(1.5 equiv.), and Et3B (1.5 equiv.); Isolated yields are reported. EWG, electron withdrawing group.
2
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10.1002/anie.202009828
Angewandte Chemie International Edition
COMMUNICATION
With the optimal reactions conditions established, we briefly
examined the scope of both reaction partners (27+28 to 29, Table
2). With 9 employed as the precursor, we found a number of
electron-deficient alkenes could participate in this reaction. Those
bearing substituents such as phenoxylcarbonyl (29a), cyano
(29b), sulfonyl (29c), phosphoryl (29d), and carbamoyl (29e-g)
groups were tolerated, with the corresponding products formed in
good yields and with excellent α-selectivity. The scope of radical
precursors was examined as well (Table 2, bottom). Glycosyl
sulfoxides derived from various monosaccharides, including
mannose (29h), galactose (29i), rhamnose (29j), fucose (29k),
and glu-NAc (29l) could participate in this reaction smoothly.
Those prepared from disaccharides such as lactose (29m) and
maltose (29n) are also competent substrates.
the unprotected glycosyl sulfoxides 30 (Table 3) from 27 by ester
hydrolysis. We found sulfoxides 30 are bench stable and water
soluble. With the water-soluble borane complex 32 used as
radical mediator, these unprotected precursors react smoothly
with various amino acid/peptide derivatives in H2O-CH3CN (Table
3). Sulfoxides prepared from glucose (33a-c), mannose (33d-f),
and galactose (33g-i) could all serve as effective substrates, and
the corresponding carbohydrate-peptide conjugates were formed
with good efficiency. To highlight the generality of this method, we
showed that a disaccharide unit couple efficiently with a tripeptide
derivative under our conditions, to furnish 33j in good yield. The
utility of this method was further demonstrated in the modification
of commercial drugs. For example, our radical precursor coupled
smoothly with the anti-cancer agent Ibrutinib to afford conjugate
34. The above results established that glycosyl radicals undergo
efficient addition to C=C bond in aqueous media. Moreover, the
carbohydrate moieties installed are fully unprotected, an
important feature of our reaction since the deprotection step on
such complex products—if required—could be rather inefficient
and challenging.
Table 3. Synthesis of glycopeptidomimetics and carbohydrate-drug conjugates.
Me
N
N
BH3
N
Me
O
HO
O
32
I
O
S
O
O
+
Peptide
HO
Peptide
N
H
Et3B, air
CH3CN-H2O, rt
N
H
bench stable, 1 step from 27
30 (2.0 equiv)
31 (1.0 equiv)
33
Table 4. Synthesis of carbohydrate-DNA conjugates.
From glucose
I
O
S
O
OH
OH
HO
OH
O
O
HO
HO
HO
HO
O
O
O
HO
HO
Ph
H
N
OH
OH
O
Ph
30
CO2Et
Ph
NH
Me
O
OH
N
H
(60 equiv.)
H
N
O
N
H
CO2Et
32 (90 equiv.)
O
HO
N
H
CO2Et
O
+
O
Me
Et3B (90 equiv.), air
H2O-DMSO (1:1)
N
H
O
N
H
36
From mannose
35
OH
OH
OH
OH
(10 nmol, 1 equiv.)
OH
OH
O
O
HO
HO
HO
HO
O
O
O
HO
HO
Ph
H
N
O
Ph
CO2Et
Ph
NH
Me
O
N
H
OH
O
H
N
N
H
CO2Et
O
N
H
CO2Et
OH
OH
AcNH
HO
Me
HO
HO
O
OH
Me
O
O
O
HO
HO
HO
HO
HO
O
HO
O
HO
HO
HO
OH
From galactose
OH
OH
36a, 58%
36b, 38%
36c, 28%
36d, 12%
OH
OH
OH
OH
O
O
HO
HO
O
O
O
Ph
H
N
OH
OH
HO
a Yields were determined by HPLC-MS. See SI for details.
O
Ph
CO2Et
Ph
NH
O
OH
N
H
H
N
H
CO2Et
N
O
N
H
CO2Et
To further test the limit of this transformation, we applied it in
the synthesis of carbohydrate–DNA conjugates. These
conjugates found widespread use in antisense biotechnology and
in the studies of sugar or DNA functioning.[28] Our interest in these
conjugates, however, stems from the need to construct novel
DNA-encoded libraries (DEL).[29] Given the stringent requirements
for DEL synthesis such as high dilution and functional group
tolerance,[ 30 ] transformations suitable for constructing DELs
remain rare.[31, 32] We found our reaction could be adapted to
prepare carbohydrate-DNA conjugates. In our study, compound
O
Me
Me
Disaccharide-tripeptide conjugate
Glucose-Ibrutinib conjugate
OH
O
HO
HO
N
OH
OH
O
NH2
HO
O
N
O
HO
HO
HO
O
O
HO
OH
O
N
Ph
N
N
NH
O
H
N
OEt
N
H
O
O
Me
Me
33j, 72%b
34, 80%c
a Reactions were performed with carbohydrate donor (2.0 equiv.), alkenes (0.15 mmol, 1.0 equiv.), 32 (3.0 equiv.), and
35,
a
14-base
DNA
headpiece
[HP-NH2(5’-
see
Et3B (3.0 equiv.). b 1.3 equiv. of carbohydrate donor was used. c NMR yield.
/5Phos/GAGTCA/iSp9/iUniAmM/iSp9/-TGACTCCC-3’),
Figure S1 in SI for exact structure] equipped with an acrylamide
unit was employed as acceptor and as the limiting reagent. As
shown in Table 4, when the reactions were performed in
water/DMSO (1:1), 35 could couple with an excess amount of 30
(60 equiv.) to generate conjugate 36. Various sugar moieties such
as glucosyl (36a), 2-deoxy-2-amino glucosyl (36b), fucosyl (36c),
and maltosyl (36d) group can be introduced.
We next employed density functional theory [UB3LYP/6-
31g(d)] to evaluate the energetics of this process, with substrates
37a-c chosen as the truncated models of our real system
(Scheme 2). We have located transition structures 40a-c for the
Having established proof-of-concept with the above results,
we became interested if our reactions could be applied to prepare
biologically important glycopeptidomimetics[
by linking
27
]
carbohydrate moieties with polypeptides via C–C bonds (Table 3).
Toward this goal, the ability to perform our reactions in the
presence of water is of practical value, since, besides the
environmental considerations, many of these glycoconjugates are
only sparingly soluble in pure organic solvents. However,
methods capable of generating and utilizing glycosyl radicals in
aqueous media remain largely unexplored. Thanks to the stability
of sulfoxide unit to hydrolytic conditions, we could readily access
3
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10.1002/anie.202009828
Angewandte Chemie International Edition
COMMUNICATION
a
Conclusion
‡
Me
MeO
H
H
Me
X
In conclusion, we have developed a class of readily
accessible and bench-stable precursors to glycosyl radicals, and
employed them in the synthesis of various C-glycosides.
Capitalizing on a facile radical substitution reaction on sulfur atom,
our method permits the generation of the valuable glycosyl
radicals from the corresponding sulfoxides. This transformation
proceeds under mild conditions, tolerates a broad array of
functional groups, occurs smoothly in aqueous media, and is
amenable to the preparation of complex glycopeptidomimetics
and carbohydrate-DNA conjugates. Computational studies
provide further insights into the mechanism of this process. We
anticipate this method will be adopted for the preparation of
advanced glycoconjugates that are needed in various fields.
MeO
X
38a/b/c
39a/b/c
Me
X
OMe
Me
X
37a/b/c
Me
MeO
+
Me
O
H
X
42
40a/b/c
41a/b/c
ΔG‡
ΔG‡
ΔGsub
sub
HAT
X
(G40-G37
)
(G38-G37
)
[(G41+G42)-G37]
S
37a
7.3
–28.7
12.7
O–
S+
37bb
37c
5.7
13.1
15.2
–25.6
–24.8
O
O
32.4
S
Acknowledgements
b
This work is supported by funding from National Key Research
and Development Program (2018YFA0903300), National Natural
Science Foundation of China (Nos. 21922106, 21772125, and
81803359), and start-up funding from Sichuan University. We
thank Prof. Yang Li (Chongqing University) for computing
resources.
40a
40b
40c
a Energies are in kcal•mol-1. Distances are in Å. b The sulfur center in 37b is S-configured. Computation for the R-
configured diastereomer gives qualitatively same results (see SI for details). sub, substitution.
Keywords: radical reactions • C-glycosides • glycoconjugates
Scheme 2. Mechanistic studies.
[1]
(a) B. Giese, J. Dupuis, Angew. Chem., Int. Ed. 1983, 22, 622-623. (b)
R. M. Adlington, J. E. Baldwin, A. Basak, R. P. Kozyrod, J. Chem. Soc.,
Chem. Commun. 1983, 944-945. (c) J. Dupuis, B. Giese, D. Rüegge, H.
Fischer, H.-G. Korth, R. Sustmann, Angew. Chem., Int. Ed. 1984, 23,
896-898. (d) B. Giese, J. Dupuis, Tetrahedron Lett. 1984, 25, 1349-1352.
(e) B. Giese, J. Dupuis, M. Leising, M. Nix, H. J. Lindner, Carbohydr. Res.
1987, 171, 329-341. (f) B. Giese, Pure Appl. Chem. 1988, 60, 1655-1658.
(g) G. E. Keck, E. J. Enholm, D. F. Kachensky. Tetrahedron Lett. 1984,
25, 1867–1870.
radical substitution event. For these substrates, the generation of
alkyl radical 42 (along with 41a-c) is thermodynamically favorable
by similar degrees, but with different activation energies. The
radical substitution step for both sulfide 37a (DG‡ = 7.3 kcal•mol-
1) and sulfoxide 37b (DG‡ = 5.7 kcal•mol-1) is predicted to be very
facile, with the latter slightly more rapid. However, the substitution
on sulfone 37c is significantly more challenging (DG‡ = 32.4
kcal•mol-1). Recall the results shown in Table 1, the use of sulfide
led to the formation of a small amount of deiodinated product 24,
and the use of sulfone gave only 25. It is reasonable to assume
that the slower the intramolecular substitution event is, the more
likelihood the hydrogen transfer to 37a-c would occur. In this
regard, the computed results agree well with our experimental
observations.
Closer scrutiny of the transition structures 40a-c (Scheme
2b) revealed some additional information. The sulfur atoms in
these transition structures adopt (twisted) trigonal bipyramidal
geometries, with the incoming aryl group and the departing alkyl
group occupying the two apical positions. As in a classical SN2
reaction, the formation of new bond and breaking of old bond in
these radical processes are concerted, causing inversion of the
configuration of the sulfur atom.[22] In our case, experimental
results are consistent with this prediction as well (See Figure S2
in SI).
[2]
For glycosyl halides as radical precursors, see: (a) R. S. Andrews, J. J.
Becker, M. R. Gagné, Angew. Chem., Int. Ed. 2010, 49, 7274-7276. (b)
R. S. Andrews, J. J. Becker, M. R. Gagné, Org. Lett. 2011, 13, 2406-
2409. (c) R. S. Andrews, J. J. Becker, M. R. Gagné, Angew. Chem., Int.
Ed. 2012, 51, 4140-4143. (d) L. Nicolas, P. Angibaud, I. Stansfield, P.
Bonnet, L. Meerpoel, S. Reymond, J. Cossy, Angew. Chem., Int. Ed.
2012, 51, 11101-11104. (e) J. Liu, H. Gong, Org. Lett. 2018, 20, 7991-
7995. (f) L. Adak, S. Kawamura, G. Toma, T. Takenaka, K. Isozaki, H.
Takaya, A. Orita, H. C. Li, T. K. M. Shing, M. Nakamura, J. Am. Chem.
Soc. 2017, 139, 10693-10701.
[3]
[4]
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5
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Entry for the Table of Contents
O
H
O
H
O
O
H
O
HO
HO
HO
I
unimolecular
substitution
bimolecular
trapping
S
FG
S
O
O
bench stable precursors
mild conditions
complex glycoconjugates
Glycosyl sulfoxides appended with an aryl iodide moiety were shown to be readily available, air and moisture stable precursors to
glycosyl radicals. The use of these radical precursors enabled the synthesis of various complex C-linked glycoconjugates under mild
conditions.
6
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