An α-selective, visible light photocatalytic glycosylation of alcohols with selenoglycosides

Article abstract of DOI:10.1016/j.carres.2013.01.004

Exceptionally mild procedures for the visible light photocatalytic activation of selenoglycoside donors in the presence of alcohol acceptors have been developed. This process is demonstrated with both 1-phenylselenyl-2,3,4,6- tetra-O-benzyl glucoside (1) and 1-phenylselenyl-2,3,4,6-tetra-O-benzyl galactoside (2). Catalysis is effected with both metal (Ru(bpy)₃) and organocatalysts (diphenyldiselenide). Reactions afford, in all cases, primarily the α-anomers with selectivities that vary with solvent. This represents the first example of a visible light-promoted O-glycosylation.

Full text of DOI:10.1016/j.carres.2013.01.004

Carbohydrate Research 369 (2013) 42–47
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
An
a-selective, visible light photocatalytic glycosylation of alcohols
with selenoglycosides
⇑
Mark Spell, Xiaoping Wang, Amir E. Wahba, Elizabeth Conner, Justin Ragains
Department of Chemistry, Louisiana State University, 232 Choppin Hall, Baton Rouge, LA 70803, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Exceptionally mild procedures for the visible light photocatalytic activation of selenoglycoside donors in
the presence of alcohol acceptors have been developed. This process is demonstrated with both 1-phe-
nylselenyl-2,3,4,6-tetra-O-benzyl glucoside (1) and 1-phenylselenyl-2,3,4,6-tetra-O-benzyl galactoside
Received 25 November 2012
Received in revised form 7 January 2013
Accepted 9 January 2013
(
2). Catalysis is effected with both metal (Ru(bpy)
afford, in all cases, primarily the -anomers with selectivities that vary with solvent. This represents the
first example of a visible light-promoted O-glycosylation.
3
) and organocatalysts (diphenyldiselenide). Reactions
Available online 16 January 2013
a
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Chemical O-glycosylation
Photoredox catalysis
Visible light photocatalysis
Selenoglycosides
Chalcogenoglycosides such as thioglycosides and selenoglyco-
sides have been used widely in the synthesis of oligosaccharides
due to their stability and orthogonality to conditions bringing
about the activation of other glycosyl donors.1 However, it is this
same stability that necessitates the often harsh conditions (e.g.,
toxic, heavy metal ions and highly reactive and sensitive thio-
and selenophilic electrophiles) that are used to engender the acti-
vation of thioglycosides and selenoglycosides for O-glycosyla-
should be noted that processes similar to this have been demon-
9
strated electrochemically (Ru(III) is replaced by an anode), photo-
1
0
chemically (with various UV-absorbing photosensitizers), and
,2
2b,11
chemically.
To establish a proof of concept, we pursued the conversion of
9
c
selenoglycoside 1 (Eox,(Ag/AgCl) = +1.31 V) with methanol as glyco-
syl acceptor (Table 1, entry 1). Structures of selenoglycoside do-
nors, alcohol acceptors, and glycosidic products are indicated in
Figure 1. Blue LED irradiation of 1 in the presence of 5 mol % Ru(b-
1
,2
tion.
With the goal of developing a high-yielding, easily
4
c
performed glycosylation that uses stable and inexpensive reagents
and chalcogenoglycoside donors under mild conditions, we have
initiated a research program aimed at the development of a visible
light photoredox catalytic O-glycosylation.
py)
thane,
(DTBMP) as base and 3 equiv MeOH in CH
consumption of 1 and a 75% yield of glycosylation product 4 (2.5:1
3
(PF
6
)
2
,
1.1 equiv of the electron acceptor tetrabromome-
and 1.2 equiv of 2,6-di-tert-butyl-4-methylpyridine
CN resulted in complete
5
h
3
Since 2008, visible light photoredox catalysis has enjoyed an
a
/b) after 5 h of irradiation.
Subsequent experiments indicated that this method was effec-
3
4
increasing popularity with the contributions of MacMillan, Yoon,
5
6
7
Stephenson, Sanford, and several others. Our initial interests in
developing a visible light-promoted glycosylation were turned to-
ward visible light photoredox catalysis and the employment of
polypyridyl transition metal catalysts due to mildness, ease of
operation, and use of visible light that these transformations allow.
We envisioned (Scheme 1) a process where oxidative quenching
tive for 1-octanol, cyclohexanol, and glucosyl acceptor 3 (Table 1,
entries 2–4). As in the case of methanol, these experiments favored
the formation of the
absence of alcohol acceptor (Table 1, entry 5) results in the forma-
tion of a-glucosyl bromide 7 and glycal 8 (1.4:1, respectively)
as determined with H NMR of the crude reaction mixture. Con-
a-anomer. Performance of this reaction in the
1
2
13
1
of a photoexcited Ru(II) species such as that derived by the visible
trols indicated that this process is not viable in the absence of
either light or CBr when no conversion of 1 was observed (Table 1,
4
entries 6 and 7). While these reactions characteristically reached a
temperature of 40 °C under irradiation, it was found that heating
these same reactions to 50 °C in the dark resulted in much slower
conversion of 1, suggesting that thermal processes are trivial
0
light irradiation of tris(2,2 -bipyridyl)ruthenium (II) (Ru(bpy)
3
,
8
Scheme 1) would precede the 1-electron oxidation of selenoglyco-
sides. The resulting selenoglycoside radical cations are unstable
and disproportionate to the requisite glycosyl cations that inter-
9
a
cept glycosyl acceptors en route to glycosylated products. It
(
Table 1, entry 8). Despite this, the thermal conversion (Table 1, en-
8
try 8) is intriguing and suggests that an enthalpically unfavorable
but irreversible electron transfer from ground state Ru(bpy) to
⇑
Corresponding author. Tel.: +1 225 578 3238; fax: +1 225 578 3458.
E-mail address: jragains@lsu.edu (J. Ragains).
3
0
008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.01.004

M. Spell et al. / Carbohydrate Research 369 (2013) 42–47
43
ACCEPTORS
DONORS
R1 OBn
MeOH
OH
O
R2
BnO
Se
OH
OH
OBn
O
BnO
BnO
OH
-)-menthol
1
: R =H, R =OBn
1 2
BnO
OMe
2
: R =OBn, R =H
1
2
3
(
GLYCOSIDIC PRODUCTS
OBn
OBn
O
OBn
O
O
BnO
BnO
BnO
BnO
BnO
BnO
n-octyl
OMe
Br
O
O
O
4
OBn
OBn
5 OBn
OBn
O
6 OBn
OBn
O
BnO
O
BnO
BnO
BnO
BnO
BnO
BnO
7
8 BnO
9
OBn
OBn
O
BnO
BnO
OBn
BnO
BnO
O
O
OBn
O
n-octyl
BnO
O
O
1
1
OBn
BnO
OBn
BnO
BnO
1
0 BnO OMe
O
OBn
BnO
BnO
O
OBn
BnO
O
O
1
3 OBn
BnO
1
2
BnO OMe
Figure 1. Glycosyl donors, acceptors, and glycosidic products.
Table 1
Visible light-promoted, ru(bpy)
3
-catalyzed glucosylation
blue LEDs
OBn
Ru(bpy) (PF ) (5 mol%)
3
6 2
OBn
O
"
ROH" (3 equiv.)
BnO
BnO
O
SePh
BnO
BnO
DTBMP(1.2 equiv.),
OBn
CBr (1.1 equiv.), 4ÅMS,
OR
4
OBn
1
CH CN
3
Entry
‘ROH’ (3 equiv)
Irradiation time
Product, yield (%)
Anomeric ratio (a/b)
1
2
3
4
5
MeOH
5 h
3 h
5 h
13 h
5 h
24 h
24 h
2.5 days
18 h
5 h
4, 75
5, 81
6, 53
10, 43
2.5:1
4:1
8.5:1
2:1
n/a
n/a
n/a
2.5:1
4:1
1-Octanol
Cyclohexanol
3
None
7 and 8 (1.4:1, not isolated)
5, 0
5, 0
5, 76
5, 30
5, 59
a
6
1-Octanol
1-Octanol
1-Octanol
1-Octanol
1-Octanol
b
7
c
8
d
9
e
1
0
4:1
All experiments were performed in 5 mL Pyrex reactor vials with blue LED irradiation from the side (see Section 1 for details). We employed 0.147 mmol donor 1 with 3 equiv
alcohol acceptor, and 1.1 equiv CBr with 1.2 equiv DTBMP in 2 mL CH CN. Powdered 4 Å MS (400 mg) was employed with acceptors other than MeOH. Reaction mixtures
4
3
1
characteristically reached a temperature of 40 °C. Anomeric ratios were determined with H NMR analysis of purified product mixtures.
a
Performed in the absence of light.
Performed in the absence of CBr .
4
Performed at 50 °C in the absence of light.
Performed in the absence of Ru(bpy)
b
c
d
e
3
(PF
6
)
)
2
2
.
Performed in the absence of Ru(bpy)
3
(PF
6
with 10 mol % diphenyldiselenide.
CBr
4
(resulting in fragmentation to bromide anion and tribromom-
are not without precedent and have been demonstrated with
thioglycosides and selenoglycosides using the radical cationic
oxidant tris-(4-bromophenyl)-ammoniumyl hexachloroantimonate
3+
11
2b
ethyl radical) to generate the necessary Ru species may be oper-
ative. Thermal, single electron transfer-mediated glycosylations

4
4
M. Spell et al. / Carbohydrate Research 369 (2013) 42–47
OBn
OBn
[Ru(bpy)3]2+
O
BnO
BnO
Se
Se
Ph
Ph
OBn
hν
(λmax=452 nm)
O
BnO
BnO
E0[Ru(II)/Ru(III)]=
1.29 V (SCE)
OBn
+
0
*
3+
[Ru(bpy)3]2+*
oxidant
E [Ru(II )/Ru(III)]=
-0.81 V (SCE)
selenoglycoside 1
donor)
[
Ru(bpy)3]
(
2+
1
e-- reduced oxidant
N
N
N
N
N
Ru
OBn
'
OBn
OBn
rapid, irreversible
fragmentation
ROH
N
O
O
O
BnO
(acceptor) BnO
BnO
BnO
OR'
Se
Ph
BnO
BnO
-
1/2 (PhSe)
2
base
OBn
OBn
OBn
Ru(bpy)3
Scheme 1. Original concept for photocatalytic glycosylation.
(
BAHA). Further, we found that removal of Ru(bpy)
3
resulted in the
Because of the low cost of diphenyldiselenide relative to Ru(b-
py) (PF
range of solvents and unprecedented reactivity as a visible light
photocatalyst, we sought the development of the diphenyldisele-
nide-catalyzed reaction as an inexpensive and perhaps more versa-
tile alternative to the Ru(bpy) -catalyzed reaction. To explore the
3
scope of this ‘organocatalytic’ glycosylation, we performed a
number of preparative experiments (Table 2) with 10 mol %
complete consumption of 1 and formation of a 30% yield of glycos-
ylated product 5 (Table 1, entry 9) with an increased irradiation
time. In addition, 10 mol % of diphenyldiselenide, a byproduct of
3
6
)
2
(ꢀ$4/g and $111/g, respectively), solubility in a wider
both the Ru(bpy)
stored the reactivity afforded with Ru(bpy)
under the same conditions employed for previous experiments in
h (Table 1, entry 10).
3
-catalyzed and uncatalyzed reactions, nearly re-
3
when 1 was consumed
5
Table 2
Visible light-promoted, diphenyldiselenide-catalyzed glucosylation/galactosylation
blue LEDs
OBn
OBn
BnO
diphenyldiselenide (10 mol.%)
BnO
BnO
O
"
ROH" (3 equiv.)
O
SePh
BnO
DTBMP (1.2 equiv.),
OR
OBn
,2
OBn
CBr (1.1 equiv.),
1
4
CH CN, 4ÅMS
3
OR
CH Cl (with or without 4ÅMS)
2
2
Entry
Donor
‘ROH’ (3 equiv)
Solvent
Irradiation time
Product, yield (%)
Anomeric ratio (a/b)
1
2
3
4
5
1
1
1
2
2
1
1
1
1
1
1
2
2
2
Cyclohexanol
(ꢁ)-Menthol
3
1-Octanol
3
1-Octanol
1-Octanol
1-Octanol
Cyclohexanol
(ꢁ)-Menthol
3
1-Octanol
(ꢁ)-Menthol
3
CH
3
3
3
3
3
3
2
2
2
2
2
2
2
2
CN, 4 ÅMS
CN, 4 ÅMS
CN, 4 ÅMS
CN, 4 ÅMS
CN, 4 ÅMS
CN, 4 ÅMS
5 h
10 h
8 h
6, 65
9, 57
10, 33
11, 65
12, 50
5, 0
5, 53
5, 72
6, 71
9, 66
1.5:1
4:1
2:1
2:1
3:1
n/a
20:1
8:1
6:1
10:1
4:1
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
6.5 h
10.5 h
3 days
36 h
12 h
12 h
50 h
76 h
21 h
39 h
70 h
a
6
7
8
9
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
, 4 ÅMS
10
11
12
13
14
10, 20
11, 71
13, 55
12, 49
4:1
8:1
5.5:1
All experiments (unless otherwise stated) were performed in 5 mL Pyrex reactor vials with blue LED irradiation from the side. We employed 0.147 mmol donors 1 and 2 with
equiv of acceptor in the presence of 1.1 equiv CBr and 1.2 equiv DTBMP in 2 mL of the indicated solvent. Powdered 4 Å MS (400 mg) was used in all cases with CH CN as
solvent and in one case with CH Cl as solvent. Anomeric ratios were determined by H NMR analysis of purified product mixtures.
Performed in the absence of light at a temperature of 50 °C.
3
4
3
1
2
2
a

M. Spell et al. / Carbohydrate Research 369 (2013) 42–47
45
hν
CBr4
PhSeSePh
2 PhSe
PhSeBr + unidentified species
O
O
PhSeBr
O
Ph
Se
ROH, base
SePh
Ph
Se
OR
1
4
+
PhSeSePh
Scheme 2. Proposed mechanism.
diphenyldiselenide, 1.1 equiv of CBr
4
, and 1.2 equiv of DTBMP on
non-hazardous light sources. Glycosylation of both simple and
complex 1° and 2° alcohol acceptors with glucosyl and galactosyl
donors 1 and 2 has been demonstrated. Our method is selective
the scale reported for previous preparative experiments
0.147 mmol donor). The use of 3 equiv of cyclohexanol, (ꢁ)-men-
thol, and glucosyl acceptor 3 with donor 1 resulted in low to mod-
erate yields of glycosidic products and a preponderance of
(
for the
a-anomer with benzyl-protected glucosyl and galactosyl
a
-
donors. We have observed that choice of solvent can have a
anomers in all cases (Table 2, entries 1–3). We further demon-
strated the efficacy of this method when galactoside 2 (Fig. 1)
underwent conversion in the presence of both 1-octanol and 3 to
marked effect on stereoselectivity. Further studies of the scope
and mechanism of both the Ru(bpy) and diphenyldiselenide-cata-
3
lyzed glycosylations and related visible light-promoted, selenium-
mediated transformations are currently underway in our
laboratory.
generate a preponderance of the a-anomers of 11 and 12 (Table 2,
entries 4 and 5). Finally, while irradiation with blue LEDs resulted
in the warming of reaction mixtures to a temperature of 39–40 °C,
we also observed that warming at a temperature of 50 °C in the
dark did not result in any detected consumption of starting mate-
rial 1 over the course of 3 days, demonstrating that the diphenyldi-
selenide-catalyzed process is light-dependent and not the result of
adventitious heating (Table 2, entry 6). This effect is likely the re-
sult of inefficient Se–Se bond homolysis (vide infra) in the dark
at 50 °C.
1. Experimental
1.1. General methods
Tris(bipyridyl)ruthenium(II)
bis(hexafluorophosphate)
4
c
(Ru(bpy) (PF6) ), 1-phenylselenyl-2,3,4,6-tetra-O-benzyl gluco-
3
2
2
e
pyranoside, and 1-phenylselenyl-2,3,4,6-tetra-O-benzyl galacto-
1
0a
Hypothesizing that CH
ways that we believed to be a cause for the low stereoselectivity,
we conducted a number of experiments in CH Cl . In all cases
with donors 1 and 2, we observed increased selectivity for the
-anomeric products. Reaction of glucosyl donor 1 with 1-octa-
nol in CH Cl in the presence of 4 Å molecular sieves resulted
3
CN might facilitate ionization path-
pyranoside were prepared as previously described. Flash column
1
chromatography was performed using 60 Å silica gel. H NMR and
C NMR spectroscopy were performed on a Bruker AV-400, DPX
1
3
2
2
400, or DPX 250 spectrometer. Mass spectra were obtained using
an Agilent 6210 electrospray time-of-flight mass spectrometer.
Optical rotation measurements were obtained using a JASCO P-
2000 polarimeter. Unless otherwise noted, all materials were ob-
tained from commercial suppliers and used without further purifi-
cation. TLC analysis was conducted on aluminum sheets (Merck,
silica gel 60, F254). Compounds were visualized by UV absorption
(254 nm) and staining with anisaldehyde. Pyrex micro reaction
vessels (5 mL, Supelco) were used in the glycosylation reactions.
All glassware was flame-dried under vacuum and backfilled with
dry nitrogen prior to use. Deuterated solvents were obtained from
Cambridge Isotope Labs. All solvents were purified according to the
a
2
2
in a 53% yield of 5 (Table 2, entry 7) whereas reaction of gluco-
syl donor 1 with 1-octanol, cyclohexanol, (ꢁ)-menthol, and
acceptor 3 in the absence of 4 Å molecular sieves resulted in
7
2%, 71%, 66%, and 20% yields of glucosides (respectively, Table 2,
entries 8–11). Galactosyl donor 2 underwent reaction with 1-oct-
anol, (ꢁ)-menthol, and acceptor 3 to generate 71%, 55%, and 49%
yields of products (Table 2, entries 12–14). All of these reactions
showed higher selectivity for
ation time to bring about consumption of 1 and 2 relative to
reactions in CH CN.
2 2 4
Irradiation of both CH CN and CH Cl solutions of CBr and
a-anomer but an increased irradi-
1
6
3
method of Grubbs.
3
diphenyldiselenide in the absence of 1 and 2 results in the for-
1.2. General procedure for the visible light-mediated
glycosylation
mation of phenylselenyl bromide (PhSeBr) as observed with
7
7
Se NMR (Section 1). We propose a mechanism where visible
light-promoted homolysis of the Se–Se bond1 of diphenyldisele-
4
1.2.1. Ru(bpy) (PF ) -catalyzed reactions
3
6 2
nide (Scheme 2) results in the formation of phenylselenyl radi-
cals that react with CBr to generate PhSeBr. The fate of CBr
4 4
A flame dried 5 mL Pyrex reactor vial was charged with the gly-
cosyl donor (1 equiv, 0.147 mmol), Ru(bpy) (PF ) (5 mol %,
3
6 2
in these reactions is not clear at this time. The reaction of
PhSeBr with the Se atom in donors 1 and 2 results in the forma-
tion of onium species 14.15 Whether the intermediates 14 pro-
ceed directly to glycosylated products or via glycosyl bromides
or oxocarbenium ions (or some combination of these pathways)
to glycosylated products will be the subject of ongoing mecha-
nistic investigation.
4
7.4 lmol), CBr (1.1 equiv, 0.161 mmol), 2,6-di-tert-butyl-4-meth-
ylpyridine (DTBMP, 1.2 equiv, 0.176 mmol), the glycosyl acceptor
(3 equiv, 0.441 mmol), 400 mg of freshly activated 4 Å molecular
sieves, and 2 mL of dry acetonitrile under nitrogen atmosphere.
The reactor vial was placed 1–2 cm away from the light source
(blue LEDs, 2 strips, Sapphire Blue LED Flex Strips from Creative
Lighting Solutions, were wrapped around
a 250 mL beaker,
We have demonstrated that visible light promotion with Ru(b-
py) and diphenyldiselenide catalysis provides an effective means
3
for O-glycosylation with phenylselenoglycosides and various alco-
hol acceptors. This method employs inexpensive reagents and
exceptionally mild conditions using commercially available and
Fig. S1) and irradiated from the side. Reaction progress was moni-
tored by TLC. After consumption of the glycosyl donor, the reaction
mixture was filtered through a silica gel pad to remove molecular
sieves and the crude products were concentrated and then purified
by gradient silica gel chromatography.

4
6
M. Spell et al. / Carbohydrate Research 369 (2013) 42–47
1
.2.2. PhSeSePh catalyzed reactions
A flame dried 5 mL Pyrex reactor vial was charged with the gly-
cosyl donor (1 equiv, 0.147 mmol), PhSeSePh (0.1 equiv,
.014 mmol), CBr (1.1 equiv, 0.161 mmol), 2,6-di-tert-butyl-4-
1.7. Cyclohexyl 2,3,4,6-tetra-O-benzyl-
a-D
-glucopyranoside (6)19
1H NMR (400 MHz, CDCl
3
) d 1.12–1.57 (6H, m), 1.67–1.94 (4H,
0
4
m), 3.55 (2H, m), 3.63 (2H, m), 3.73 (1H, dd, J = 10.6, 3.7 Hz), 3.88
(1H, dd, J = 10.0, 3.0 Hz), 4.00 (1H, t, J = 9.3 Hz), 4.47, (2H, m),
4.61 (1H, d, J = 12.2 Hz), 4.65 (1H, d, J = 12.0 Hz), 4.73 (1H, d,
J = 12.0 Hz), 4.82 (2H, m), 4.95 (1H, d, J = 2.8 Hz), 4.99 (1H, d,
methylpyridine (DTBMP) (1.2 equiv, 0.176 mmol), the glycosyl
acceptor (3 equiv, 0.441 mmol), 400 mg of freshly activated 4 Å
molecular sieves (with acetonitrile as solvent and in one case with
13
CH
2
Cl
2
as solvent), and 2 mL of dry solvent (acetonitrile or CH
2
Cl
2
)
J = 10.8 Hz), 7.09–7.18 (2H, m), 7.22–7.40 (18, m);
C NMR
under nitrogen atmosphere. The reactor vial was placed 1–2 cm
away from the blue LEDs (2 strips, vide supra for details, were
wrapped around a 250 mL beaker, Fig. S1) and irradiated from
the side. Reaction progress was monitored by TLC. After consump-
tion of the glycosyl donor, the reaction mixture was filtered
through a silica gel pad to remove molecular sieves and the crude
products were concentrated and then purified by silica gel
chromatography.
(100 MHz, CDCl ) d 24.2, 24.4, 25.6, 31.4, 33.3, 68.6. 70.1, 73.0,
73.4, 75.1, 75.3, 75.6, 77.9, 80.0, 82.1, 94.7, 127.6, 127.8, 127.8,
127.9, 128.0, 128.1, 128.1, 128.2, 128.5, 128.5, 138.0, 138.3,
3
+
138.3, 139.0; HRMS m/z Calcd for C40
H
46NaO
6
(M+Na) 645.3187,
2
5
found 645.3179; ½
1.8. Menthyl 2,3,4,6-tetra-O-benzyl-
1H NMR (400 MHz, CDCl
aꢂ
+52.7 (c 0.63, DCM).
D
a-D
-glucopyranoside (9)19
3
) d 0.70 (3H, d, J = 6.9 Hz), 0.75–1.12
1
.3. Determination of anomeric ratios
(9H, m), 1.20–1.40 (2H, m), 1.56–1.65 (2H, m), 2.13 (1H, d,
J = 12.0 Hz), 2.37–2.46 (1H, m), 3.35 (1H, dt, J = 10.6, 4.3 Hz), 3.54
(1H, dd, J = 9.8, 3.6 Hz), 3.58–3.69 (2H, m), 3.75 (1H, dd, J = 10.5,
3.8 Hz), 3.92–3.98 (1H, m), 4.01 (1H, t, J = 9.3 Hz), 4.46 (1H, d,
J = 10.8 Hz), 4.47 (1H, d, J = 12.0 Hz), 4.61–4.73 (3H, m), 4.82 (1H,
In all cases, the major product (
a-anomer) was purified by silica
gel chromatography or preparative TLC. The anomeric ratio (
a/b)
was determined based on the integration of key resonances identi-
fied with the assistance of published NMR data (references pro-
vided for each compound, vide infra) in the 1H NMR of the
purified anomeric mixtures.
d, J = 10.8 Hz), 4.83 (1H, d, J = 10.8 Hz), 4.97 (1H, d, J = 11.0 Hz),
13
5.02 (1H, d, J = 3.6 Hz), 7.09–7.17 (2H, m), 7.21–7.37 (18H, m)
NMR (100 MHz, CDCl
3.0, 48.8, 68.7, 70.3, 73.2, 73.4, 75.0, 75.5, 78.1, 80.6, 81.0, 82.0,
98.6, 127.6, 127.6, 127.7, 128.0, 128.3, 128.4, 138.0, 138.3, 138.4,
C
3
) d 16.0, 21.1, 22.3, 23.1, 24.6, 31.7, 34.3,
4
1
.4. Formation of PhSeBr from PhSeSePh and CBr
4
under
+
irradiation
138.9; HRMS m/z Calcd for C44
H
54NaO
Cl ).
2
6
(M+Na) 701.3813, found
2
5
7
01.3821; ½
aꢂ
+92.5 (c 0.25, CH
2
D
To a reaction vial containing 30.8 mg (0.0987 mmol) diphenyl
diselenide and 349.5 mg (1.054 mmol) CBr was added 3.0 mL sol-
vent of choice (CH Cl or CH CN) at once. The capped reaction vial
was placed in a beaker surrounded by blue LEDs (setup similar to
Fig. S1) and was allowed to stir under N . At the indicated time
intervals, an aliquot of the reaction mixture was concentrated
and redissolved in CDCl
. The 77Se NMR spectrum of these aliquots
4
1.9. Methyl-O-(2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl)-
2
0
2
2
3
(1?6)-2,3,4-tri-O-benzyl- -glucopyranoside (10)
a-D
1H NMR (400 MHz, CDCl
) d 3.32 (3H, s), 3.40 (1H, dd, J = 9.6,
3
2
3.6 Hz), 3.50 (2H, m), 3.58 (1H, t, J = 9.0 Hz), 3.69–3.82 (3H, m),
3.87–3.99 (4H, m), 4.02 (1H, dd, J = 9.3, 3.5 Hz), 4.36 (1H, d,
J = 11.8 Hz), 4.43 (1H, d, J = 11.9 Hz), 4.51–4.60 (4H, m), 4.65–
4.75 (4H, m), 4.75–4.82 (2H, m), 4.84 (1H, d, J = 11.0 Hz), 4.93
3
indicated the presence of diphenyl diselenide at d 464 and forma-
tion of phenylselenyl bromide at d 867.
(
1H, d, J = 11.5 Hz), 4.95 (1H, d, J = 10.9 Hz), 4.99 (1H, d,
1
.5. Methyl 2,3,4,6-tetra-O-benzyl-
a-D
-glucopyranoside (4)17
J = 3.6 Hz), 7.18–7.36 (35H, m); C NMR (100 MHz, CDCl
13
3
) d 55.0,
6
6.4, 68.9, 69.4, 70.3, 72.5, 72.8, 73.3, 74.7, 75.0, 75.1, 75.7, 76.5,
1H NMR (400 MHz, CDCl
) d 3.37 (3H, s), 3.56 (1H, dd, J = 9.6,
.6 Hz), 3.62 (2H, m), 3.68–3.77 (2H, m), 3.98 (1H, t,
77.2, 78.0, 78.3, 80.2, 82.1, 97.9, 97.9, 127.3, 127.4, 127.5, 127.6,
127.6, 127.7, 127.8, 127.9, 128.0, 128.2, 128.2, 128.2, 128.3,
3
3
J = 9.3 Hz),4.44–4.50 (2H, m), 4.57–4.69 (3H, m), 4.76–4.85 (3H,
m), 4.97 (1H, d, J = 10.9 Hz), 7.13 (2H, m), 7.23–7.38 (18H, m);
128.3, 128.4, 128.4, 138.1, 138.2, 138.4, 138.7, 138.8, 138.9,
+
138.9; HRMS m/z Calcd for C62
H
66NaO11 (M+Na) 1009.4497, found
1
3
25
C NMR (100 MHz, CDCl
3
) d 55.2, 68.5, 70.1, 73.4, 73.5, 75.0,
1009.4490; ½
aꢂ
D
2 2
+87.2 (c 0.55, CH Cl ).
7
1
5.7, 77.2, 77.7, 82.1, 98.2, 127.6, 127.7, 127.8, 127.9, 128.1,
28.3, 128.4, 128.5, 137.9, 138.2, 138.3, 138.8; HRMS m/z Calcd
1.10. n-Octyl 2,3,4,6-tetra-O-benzyl-a-D-galactopyranoside
(M+K)+ 593.2300, found 593.2316; ½
a
ꢂ
25
D
+43.1 (c
(11)
21
for C35
H38KO
6
0
2 2
.24, CH Cl ).
1
ꢀ4:1 (
a
/b) mixture, H NMR (
a
-anomer, 400 MHz, CDCl
3
) d 0.88
1
.6. n-Octyl 2,3,4,6-tetra-O-benzyl-
a-
D
-glucopyranoside (5)18
(3H, m), 1.26 (10H, m), 1.62 (2H, m), 3.43 (1H, dt, J = 9.9, 6.6 Hz),
.48–3.66 (3H, m), 3.91–3.98 (3H, m), 4.03 (1H, dd, J = 9.3, 3.6 Hz),
4.33–4.96 (9H, m), 7.20–7.40 (20H, m); C NMR (
3
1H NMR (250 MHz, CDCl
13
a-anomer,
3
) d 0.88 (3H, t, J = 6.8 Hz), 1.19–1.40
(10H, m), 1.53–1.67 (2H, m), 3.40 (1H, dt, J = 9.9, 6.7 Hz), 3.55
(1H, dd, J = 9.7, 3.5 Hz), 3.55–3.68 (3H, m), 3.72 (1H, m), 3.78
(1H, m), 3.99 (1H, t, J = 9.2 Hz), 4.47 (2H, d, J = 11.5 Hz), 4.61 (1H,
100 MHz, CDCl ) d 14.1, 22.6, 26.2, 29.2, 29.4, 31.8, 68.2, 69.0, 69.2,
73.2, 73.4, 74.7, 75.1, 76.6, 79.1, 97.4, 127.4, 127.5, 127.6, 127.7,
127.7, 127.8, 127.9, 128.1, 128.1, 128.2, 128.2, 128.3, 128.3, 128.4,
3
d, J = 12.2 Hz), 4.64 (1H, d, J = 12.2 Hz), 4.76 (2H, m), 4.81 (1H, d,
J = 10.8 Hz), 4.83 (1H, d, J = 10.8 Hz), 4.99 (1H, d, J = 10.8 Hz),
138.0, 138.5, 138.7, 138.9; HRMS m/z Calcd for C42
H
52NaO
2
)
6
+
25
D
(M+Na) 675.3656, found 675.3660; ½
a
ꢂ
+33.5 (c 1.65, CH
2
Cl
7
.06–7.18 (2H, m), 7.20–7.44 (18H, m); 13C NMR: (100 MHz, CDCl
3
)
d 14.2, 22.8, 26.3, 29.4, 29.5, 29.5, 32.0, 68.4, 68.7, 70.4, 73.2, 73.6,
1.11. Methyl-O-(2,3,4,6-tetra-O-benzyl-
a-D-glucopyranosyl)-
2
2
7
5.2, 75.8, 78.0, 80.3, 82.3, 97.0, 127.6, 127.8, 127.9, 128.0, 128.0,
(1?6)-2,3,4-tri-O-benzyl- -galactopyranoside (12)
a-D
1
28.1, 128.5, 128.5, 138.1, 138.4, 138.5, 139.1; HRMS m/z Calcd
+
25
D
1H NMR (400 MHz, CDCl
3.6 Hz), 3.46–3.55 (2H, m), 3.58 (1H, t, J = 9.1 Hz), 3.63 (1H, m),
for C42
H52NaO
6
(M+Na) 675.3656, found 675.3658; ½
a
ꢂ
+38.6 (c
3
) d 3.29 (3H, s), 3.41 (1H, dd, J = 9.6,
0
.46, DCM).

M. Spell et al. / Carbohydrate Research 369 (2013) 42–47
47
3
4
4
.70–3.82 (3H, m), 3.88–4.00 (3H, m), 4.03 (1H, dd, J = 9.5, 3.5 Hz),
.36 (1H, d, J = 11.8 Hz), 4.43 (1H, d, J = 11.8 Hz), 4.52–4.61 (4H, m),
.67–4.75 (4H, m), 4.77–4.82 (2H, m), 4.85 (1H, d, J = 11.0 Hz), 4.93
R. A. Carbohydr. Res. 2006, 341, 1391–1397; (c) Yamago, S.; Yamada, T.; Hara,
O.; Ito, H.; Mino, Y.; Yoshida, J. Org. Lett. 2001, 3, 3867–3870; (d) Ikeda, K.;
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B. M.; Mehta, S. J. Org. Chem. 1993, 58, 3269–3276; (f) Mehta, S.; Pinto, B. M.
Tetrahedron Lett. 1991, 32, 4435–4438.
(
1H, d, J = 11.2 Hz), 4.95 (1H, d, J = 11.2 Hz), 4.99 (1H, d, J = 3.6 Hz),
.15–7.45 (35H, m); 1 C NMR (100 MHz, CDCl
3
3. (a) Nagib, D. A.; MacMillan, D. W. C. Nature 2011, 480, 224–228; (b) McNally,
A.; Prier, C. K.; MacMillan, D. W. C. Science 2011, 334, 1114–1117; (c) Shih, H.-
W.; Vander Wal, M. N.; Grange, R. L.; MacMillan, D. W. C. J. Am. Chem. Soc. 2010,
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Chem. Soc. 2009, 131, 10875–10877; (e) Nicewicz, D.; MacMillan, D. W. C.
Science 2008, 322, 77–80.
7
6
7
1
1
3
) d 55.0, 66.4, 68.9,
9.7, 70.5, 72.5, 72.8, 73.3, 73.5, 74.7, 75.0, 75.1, 75.7, 76.5, 78.0,
8.2, 80.2, 82.1, 97.9, 97.9, 127.5, 127.6, 127.7, 127.8, 127.8,
27.8, 127.9, 128.1, 128.3, 128.4, 128.4, 128.5, 128.5, 138.0,
38.2, 138.4, 138.7, 138.8, 138.9; HRMS m/z Calcd for C62
H
66NaO11
4.
(a) Lin, S.; Ischay, M. A.; Fry, C. G.; Yoon, T. P. J. Am. Chem. Soc. 2011, 133, 19350–
19353; (b) Lu, Z.; Shen, M.; Yoon, T. P. J. Am. Chem. Soc. 2011, 133, 1162–1164;
+
25
D
(
M+Na) 1009.4497, found 1009.4490; ½
aꢂ
+71.19 (c 0.83, DCM).
(
c) Ischay, M. A.; Lu, Z.; Yoon, T. P. J. Am. Chem. Soc. 2010, 132, 8572–8574; (d)
Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131, 14604–14605; (e) Ischay, M. A.;
Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2008, 130, 12886–12887.
1
.12. Menthyl 2,3,4,6-tetra-O-benzyl-
a
-
D
-galactopyranoside
2
0
(
13)
5. (a) Wallentin, C. J.; Nguyen, J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem.
Soc. 2012, 134, 8875–8884; (b) Tucker, J. W.; Zhang, Y.; Jamison, T. F.;
Stephenson, C. R. J. Angew. Chem., Int. Ed. 2012, 51, 4144–4147; (c) Furst, L.;
Narayanam, J. M. R.; Stephenson, C. R. J. Angew. Chem., Int. Ed. 2011, 50, 9655–
9659; (d) Nguyen, J. D.; Tucker, J. W.; Konieczynska, M. D.; Stephenson, C. R. J. J.
Am. Chem. Soc. 2011, 133, 4160–4163; (e) Dai, C.; Narayanam, J. M. R.;
Stephenson, C. R. J. Nature Chem. 2011, 3, 140–145; (f) Condie, A. G.; Gonzalez-
Gomez, J.-C.; Stephenson, C. R. J. J. Am. Chem. Soc. 2010, 132, 1464–1465; (g)
Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. J. Am. Chem. Soc. 2009,
131, 8756–8757; (h) Tucker, J. W.; Narayanam, J. M. R.; Shah, P. S.; Stephenson,
C. R. J. Chem. Commun. 2011, 47, 5040–5042.
1H NMR (500 MHz, CDCl
3
) d 0.69 (3H, d, J = 6.9 Hz), 0.81 (3H, d,
J = 6.9 Hz), 0.82 (3H, d, J = 6.0 Hz), 0.75–0.97 (2H, m), 1.02 (1H, q,
J = 12.0 Hz), 1.20–1.40 (2H, m), 1.53–1.63 (2H, m), 2.08 (1H, d,
J = 12.0 Hz), 2.41 (1H, m), 3.33 (1H, td, J = 10.8, 4.5 Hz), 3.54 (2H,
m), 3.96 (1H, dd, J = 10.1, 2.8 Hz), 3.99 (1H, m), 4.02 (1H, dd,
J = 10.1, 3.7 Hz), 4.10 (1H, t, J = 9.3 Hz), 4.42 (1H, d, J = 11.9 Hz),
4
.48 (1H, d, J = 11.9 Hz), 4.57 (1H, d, J = 11.5 Hz), 4.67 (1H, d,
J = 11.7 Hz), 4.74 (1H, d, J = 11.8 Hz), 4.80 (1H, d, J = 11.5 Hz), 4.81
1H, d, J = 12.0 Hz), 4.95 (1H, d, J = 11.5 Hz), 5.02 (1H, d,
6.
(a) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2012, 134, 9034–9037; (b) Kalyani, D.;
McMurtrey, K. B.; Neufeldt, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133,
18566–18569.
(
13
7. For recent reviews, see: (a) Teply, F. Collect. Czech. Chem. Commun. 2011, 76,
59–917; (b) Xuan, J.; Xiao, W.-J. Angew. Chem., Int. Ed. 2012, 51, 2–13; (c)
J = 3.7 Hz), 7.23–7.39 (20H, m); C NMR (125 MHz, CDCl
3
) d
8
1
7
1
C
6.0, 21.1, 22.3, 22.9, 24.5, 31.8, 34.3, 42.9, 48.9, 59.2, 69.3, 72.2,
3.4, 73.6, 74.7, 75.1, 79.3, 80.2, 99.3, 127.4, 127.5, 127.6, 127.7,
Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 1617–1622; (d)
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28.1, 128.3, 128.3, 138.1, 138.8, 138.9; HRMS m/z Calcd for
(M+Na)+ 701.3813, found 701.3832; ½
25
44
H
54NaO
6
a
ꢂ
D
+58.3 (c
8. Kalyanasundaram, K. Coord. Chem. Rev. 1982, 46, 159–244.
0
.15, CH Cl
2
2
).
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Acknowledgments
This work was supported with funds provided by Louisiana
State University. The authors thank Mr. William Sheffield for assis-
tance in the execution of experiments. The authors also thank Dr.
Thomas Weldeghiorghis, Dr. Dale Treleaven, and Mr. Kyle Hollister
for assistance with NMR and Ms. Connie David for assistance with
HRMS.
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Supplementary data
1
1
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2013.
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