NaBH3CN: A janus substitute for tin-free radical-based reactions

Article abstract of DOI:10.1002/ejoc.201402441

Beside showing that thermal radical reactions (reduction, Giese reaction) are efficient if bromo-/iodosugars are treated with NaBH₃CN and 2,2″-azobisisobutyronitrile, we explored new initiation conditions on the basis of Cu^I salts (≤0.5 equiv.) supposed to produce radicals from organobromides through a set. This was confirmed, as at about 50 C under an inert atmosphere acetobromoglucose was reduced to the rearranged 2-deoxyglucose and as N-allyl α-bromoamides reacted, depending on the conditions, either by reductive cyclization or atom-transfer radical cyclization. A related cyclization occurred upon using Cu(OAc)₂. This and other assays showed the reduction by NaBH₃CN of Cu^II salts, either added or formed in situ. Having both ionic and radical reactivity, NaBH ₃CN appears as a Janus reagent that may be useful for tin-free radical chemistry under mild and very simple conditions. Copyright

Full text of DOI:10.1002/ejoc.201402441

Job/Unit: O42441
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SHORT COMMUNICATION
DOI: 10.1002/ejoc.201402441
NaBH3CN: A Janus Substitute for Tin-Free Radical-Based Reactions
Julie Guiard,[a] Yaniss Rahali,[a] and Jean-Pierre Praly*[a]
Keywords: Synthetic methods / Reduction / Radicals / Rearrangement / Cyclization / Copper
Beside showing that thermal radical reactions (reduction,
Giese reaction) are efficient if bromo-/iodosugars are treated
with NaBH3CN and 2,2ЈЈ-azobisisobutyronitrile, we explored
new initiation conditions on the basis of CuI salts
amides reacted, depending on the conditions, either by re-
ductive cyclization or atom-transfer radical cyclization. A re-
lated cyclization occurred upon using Cu(OAc)2. This and
other assays showed the reduction by NaBH3CN of CuII salts,
(Յ0.5 equiv.) supposed to produce radicals from organobrom- either added or formed in situ. Having both ionic and radical
ides through a set. This was confirmed, as at about 50 °C
under an inert atmosphere acetobromoglucose was reduced
to the rearranged 2-deoxyglucose and as N-allyl α-bromo-
reactivity, NaBH3CN appears as a Janus reagent that may be
useful for tin-free radical chemistry under mild and very sim-
ple conditions.
reduction of 1 by UV-light irradiation in the presence of
Et3N, and other assays,[8] suggested anomeric radical for-
mation through photoinduced electron transfer.[9] Electron
transfer plays a major role in nucleophilic substitution reac-
tions[10] and also in transition-metal-promoted free-radical
reactions,[11] a field in continued growth. Atom-transfer
radical methods[12] are also extensively developed through
addition, cyclization,[13] and polymerization[14] (ATRA,
ATRC, and ATRP respectively), which in many cases oper-
ate through CuI–CuII redox cycles. Safe and cheap reducing
agents added to minimize the copper catalyst loading for
ATRP emerged from studies inspired by sustainable chemis-
try.[15] As both light irradiation and metallic species can ini-
tiate free-radical pathways, merging these approaches ap-
pears attractive. Visible-light-induced ATRA of benzyl hal-
ides to olefins has been reported.[16] A recent review focuses
on visible-light-induced photoredox catalysis by using Ru
and Ir complexes.[17]
Introduction
NaBH3CN is an off-the-shelf, easily handled boro-
hydride with mild reactivity. As for other common hydrides,
for example, LiAlH4 and NaBH4, NaBH3CN is usually per-
ceived as a source of hydride anions.[1] The use of an excess
amount of NaBH3CN with small amounts of a tin deriva-
tive maintains the tin hydride concentration needed for rad-
ical reactions.[2] We reported that UV-light irradiation of
tBuOH solutions containing acetobromoglucose 1 and
NaBH3CN afforded selectively acetylated 2-deoxyhexopyr-
anose 3, whereas the use of NaBH3CN and PhSH (10 mol-
%) delivered 1,5-anhydro-d-glucitol 4, both isolated in high
yield and purity (Scheme 1).[3] Under such conditions,
chloride 2 was unreactive, but acyclic ω-iodoalkylacrylates[4]
were cyclized to macrocyclic lactones. The conversion of 1
into 3 implied a Surzur–Tanner rearrangement, known to
occur under poorly reducing conditions [e.g., low tin
hydride concentration or use of the less reactive silane
(Me3Si)3SiH][5] as well studied in the sugar series.[6] With
catalytic amounts of PhXH (X = S, Se) added, the fast re-
duction by PhXH of the anomeric radical to 4 blocks the
rearrangement pathway.[7] We also reported other data col-
lected while applying various photoinduced reductive con-
ditions to different glycosyl bromides (d-gluco, d-galacto, d-
manno, etc.).[8] In some cases, the Surzur–Tanner rearrange-
ment occurred, but the selectivity level was lower than that
initially observed (Scheme 1).[3] The NaBH3CN-mediated
Scheme 1. High selectivity control in photoreductions of 1 with
[a] Institut de Chimie et Biochimie Moléculaires et
Supramoléculaires (ICBMS) – CNRS, Université
Claude-Bernard Lyon 1,
NaBH3CN[3,8] and our work hypothesis.
43 boulevard du 11 Novembre 1918, 69622 Villeurbanne,
France
Results and Discussion
With glycosyl bromides, photoreductive generation of the
glucosyl radical has been studied[18] and applied to prepare
E-mail: jean-pierre.praly@univ-lyon1.fr
http://www.univ-lyon1.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402441.
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J. Guiard, Y. Rahali, J.-P. Praly
SHORT COMMUNICATION
C-glycosyl compounds through Ni-[19] and Ru-catalyzed[20] Table 1. Reduction of acetobromoglucose 1 with sodium boro-
hydrides in the presence of CuI halides.[a]
couplings. Glycosyl radicals have also been invoked in vari-
ous studies with the use of other metallic species based on
Co (visible irradiation),[21] Cr,[22] Ti,[23] and SmI2[24] and for
the Co-catalyzed cross-coupling of Grignard reagents with
glycosyl bromides.[25] We thought that under mild thermal
conditions halogenated precursors might lead to carbon-
centered radicals and in particular to anomeric radicals by
a set induced by metal salts. If a redox cycle could operate
in the presence of NaBH3CN (Scheme 1), this would result
in new and very simple tin-free conditions for radical chem-
istry. From the information above, free-radical initiation
with Cu salts appeared feasible, as shown by our assays
reported below.
Reduction of 1 with NaBH3CN was attempted upon
mild heating of tBuOH solutions containing various copper
halides (CuI, CuBr, CuCl) by using, in most cases, recently
Entry CuIX,[b]
equiv.
T
Time
[h]
Conver- Yield 3+4[c]
sion
of 1 [%] [%] (3/4 ratio)
purchased samples (Table 1), as CuI salts are oxidatively un-
stable. In the absence of a Cu salt, 1 was partially converted
into 4 (Table 1, entry 1). With CuI, preliminary assays led
to multicomponent mixtures owing to reduction by ionic
pathways and glycosidation by tBuOH (Table 1, entry 2).
Trials performed with CuCl showed different outcomes: the
clean reduction of 1 at 40 °C with rearrangement (Table 1,
entry 3) to form 2-deoxy product 3 preferentially was
achieved with 1 equiv. “old” CuCl (Table 1, see note [b]).
Whatever the origin of the batch, CuBr afforded essentially
similar results, which confirmed the preferred reduction of
1 with rearrangement, as observed with “old” CuCl. Con-
sistently good results (3 + 4 ≈80%, 3/4 = 80:20) were re-
corded with typically 0.5 equiv. CuBr (and even 0.2 equiv.;
Table 1, entry 6), whereas no reaction took place if
0.1 equiv. was used (Table 1, entry 7). We later used only
recently purchased batches of CuBr. Adding about
0.15 equiv. PhSH changed the outcome of the reduction, as
4 was formed preferentially (Table 1, entries 8 and 9). Oxy-
gen exclusion by securing an inert atmosphere (argon, nitro-
gen) was crucial, as no reaction occurred upon stirring the
mixture in air (Table 1, entry 10). Usually, the medium, ini-
tially greenish (CuBr and CuCl are white), turned brown
if the temperature reached 45–50 °C. At that point, TLC
monitoring showed the reaction onset. With a sufficient
amount of NaBH3CN (≈3 equiv.) and recrystallized 1, com-
pletion was generally reached within 45/60 min on the 50
[°C]
1
–
45
45
40
45
45
45
45
50
55
50
60
18
3
1
0.75
1
0.75
24
1
47
50
80
100
100
100
0
25 (0:100)
9 (0:100)
57 (80:20)
83 (80:20)
79 (80:20)
85 (82:18)
0
2
CuI, 1
3[d]
4
CuCl, 1
CuBr, 0.5
CuBr, 0.5
CuBr, 0.2
CuBr, 0.1
CuBr, 0.5
CuBr, 0.5
CuBr, 0.5
CuBr, 0.5
5[e]
6
7
8[f]
9[f]
10[g]
11[h]
100
100
0
45 (36:64)
37 (0:100)
0
48
24
20
95
Ͻ5 (0:100)
[a] The reducing agent was NaBH3CN (3 equiv.); NaBH4 (3 equiv.)
was used once (entry 11). Typically, a 0.06 m solution of 1 (50 mg)
in distilled tBuOH containing a reducing agent and a CuI halide
was heated with an oil bath and stirred under an inert atmosphere,
unless noted otherwise. For further details, see the Supporting In-
formation. [b] Copper halides were taken from recently purchased
batches, except for entries 3 and 4, which were taken from batches
available in house. [c] The yield is based on the homogeneous mix-
ture obtained after column chromatography, but for entries 1 and
2, the product distribution was estimated by analysis of the crude
mixture by 1H NMR spectroscopy; for entries 7 and 10, no reaction
occurred (TLC). [d] A reduced amount of NaBH3CN (2 equiv.) was
used. [e] The reduction of 1 was performed on a 100 mg scale.
[f] PhSH ≈ 0.15 equiv. was added to the reaction mixture. [g] The
medium was under a normal atmosphere. [h] NaBH4 (3 equiv.) was
the reducing agent.
or 100 mg scale (Table 1, entry 5), whereas chloro analogue yield; 3/4 Ͼ 95:5), the selectivity was lower under these new
2 was found to be stable.[8] Because of identical mobility Cu-initiated conditions, for which the direct reduction of 1
(TLC), 3 and 4 were obtained as homogeneous fractions might occur by other pathways. We next studied the re-
1
analyzed by H NMR spectroscopy. Characteristic signals duction of other mono- and dihalogenated sugars (brom-
seen in the 1H NMR spectra of crude reaction mixtures ides 11, 13; iodides 12, 14), and as expected, reductive cleav-
served to identify and quantify the byproducts formed age of the halogen atoms bound to a secondary position
(Table 1, see also Table 1S in the Supporting Information). was easier (Table 2). Interestingly, these thermal reductions
With NaBH4, the reduction of 1 to 4 (no rearrangement; with NaBH3CN were found to be more efficient if initiation
Table 1, entry 11) was sluggish.[8]
was due to 2,2ЈЈ-azobisisobutyronitrile (AIBN; 15: 70%, 16:
The reduction outcome depended on the applied condi- 75%, 21: 90%) rather than CuI salts (15: 30%, 16: 20%, 20:
tions (rearranged 2-deoxyproduct 3 formed in the presence 50%); the latter conditions resulted in clean but incomplete
of Cu salts, whereas 4 predominated in their absence or if reactions (at the selected temperature). The reactivity order
PhSH was added). Compared to the results observed if the was as expected for radical routes (iodideϾbromide; sec-
reduction was promoted by UV-light irradiation (82% ondaryϾprimary).
2
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Tin-Free Radical-Based Reactions
Table 2. Selected conditions for the thermal reduction of halosugars 11–14 with NaBH3CN (A) in the presence of AIBN (B) or CuBr
(C).[a]
Entry
Substrate
Conditions,
equiv.
T
[°C]
Products (yield [%])
1
2
3
4
5
6
7
8
11
11
12
12
12
13
13
13
14
14
14
14
14
A, 3; B, 1
A, 5; C, 0.5
A, 1; B, 1
A, 3; C, 0.5
A, 3; C, 0.5
A, 3; B, 1
A, 5; B, 1
A, 5; C, 0.5
A, 5; B, 1
A, 3; B, 0.5
A, 2; B, 0.5
A, 5; C, 0.5
A, 5; C, 1
80
60
80
15 (70)[b]
15 (30)[b,c]
16 (75)[b]
60
16 (0)[d]
80[e]
80
16 (20)[e]
17 (44), 18 (12), 19 (25)[b]
17 (50), 18 (0), 19 (50)[f]
17 (35), 19 (30)[b]
21 (90)[b]
80
45
80
80
80
45
45/60
9
10
11
12
13
21 (60), 20 (40)[f]
21 (25), 20 (75)[f]
20 (37)[f,g]
20 (50)[b,h]
[a] Upon heating tBuOH solutions under an inert atmosphere, compounds 11–14 were reduced with NaBH3CN and with AIBN or CuBr
as the initiator (quantities indicated in equiv.; for full details, see the Supporting Information). [b] The yield is based on the material
purified by chromatography. [c] The reaction was incomplete, and unreacted 11 (29%) was recovered. [d] The reaction was incomplete,
and unreacted 12 (≈70% by NMR spectroscopy) remained in the reaction mixture. [e] The reaction was performed under microwave
irradiation, and unreacted 12 (80% by NMR spectroscopy) remained in the reaction mixture. [f] The composition of the reaction mixture
was estimated by NMR spectroscopy. [g] The reaction was incomplete, and unreacted 14 (≈63%) remained in the reaction mixture.
[h] Incomplete reaction with unreacted 14 (25%) recovered.
These approaches with iodosugars 12 or 14, NaBH3CN
In contrast to the efficient reductions and C–C bond-
as the hydrogen source, and either AIBN or CuBr as the forming reactions involving halosugars 11–14 with AIBN
radical initiator were extended to the synthesis of C-glyc- initiation, these processes were sluggish if initiated with
osyl compounds by radical addition to acrylonitrile or CuBr. This was puzzling on the basis of the data that indi-
methyl acrylate (5 equiv.; Table 3). Although in our hands cated that ATRA and ATRC (mediated by complexes of
both conditions proved ineffective if applied to 1, the copper[13a] and other metals in catalytic amounts)[13b] take
AIBN-based conditions worked well, as seen from the place at mild temperatures in usual solvents (e.g., CH2Cl2,
yields recorded for isolated 22 (79%), 23 (70%), and 26 CH3CN). These reactions often use activated substrates of
(40%) (Table 3, entries 3, 4, 9). With isobutyl vinyl ether the α-halo carbonyl type, whereas nitrogen-based ligands
and styrene as electron-rich radical acceptors, 24 and 25 enhance the catalyst efficiency, which thus reduces the load-
were isolated in low to moderate yields (Table 3, entries 5 ing of copper salt required. So, we selected non-osidic α-
and 6), owing to the nucleophilic character of the glucosyl bromoamides as substrates to test the reduction and intra-
radical. Coupling of 12 to acrylonitrile with CuBr as the or intermolecular coupling reactions. The NaBH3CN-medi-
initiator was incomplete but clean and afforded, in our ated reduction of 28 did not work without AIBN (Table 4),
hands, coupled compound 22 in modest yield (Table 3, en- but it was equally successful with AIBN and 0.5 equiv.
tries 7 and 8), plus reduced compound 16 [upon using CuBr (Table 4, entries 2–4). Moreover, it performed well
0.1 equiv. CuBr and tris(2-pyridylmethyl)amine (TPMA); with only 0.1 equiv. each of CuBr and TPMA at 45 °C
Table 3, entry 8]. These AIBN-initiated reactions of halides within 1 h (Table 4, entry 5). Attempted couplings with
11–14 with NaBH3CN further exemplify Ryu’s recent stud- AIBN initiation afforded desired product 30 in 53% yield
ies on C–C bond-forming reactions under related condi- besides reduced product 29 in 18% yield, if using 2 equiv.
tions.[26]
NaBH3CN (Table 4, entries 6 and 7).
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J. Guiard, Y. Rahali, J.-P. Praly
Table 3. Couplings of iodosugars 12 or 14 and radical acceptors in the presence of NaBH3CN (A) and AIBN (B) or CuBr (C).[a]
SHORT COMMUNICATION
Entry
Iodosugar
Radical acceptor, equiv.
Conditions, equiv.
Products (yield [%])
1
2
3
4
5
6
7
8
9
12
12
12
12
12
12
12
12
14
acrylonitrile, 5
acrylonitrile, 5 + 5
acrylonitrile, 5
A, 1; B, 1
A, 1; B, 2 + 1
A, 2; B, 1
A, 2; B, 1
A, 2; B, 1
12 (23), 22 (53)[b]
12 (40), 22 (60)[c]
22 (79)[b,d]
methyl acrylate, 5
vinyl isobutyl ether, 5
styrene, 5
23 (70)[b,d]
16 (40), 24 (25)[b]
25 (56)[b]
A, 2; B, 1
acrylonitrile, 15[e,f]
acrylonitrile, 5[g]
acrylonitrile, 5
A, 3; C, 0.5
A, 3; C, 0.1[h]
A, 3; B, 0.5
12 (78), 22 (13)[b]
12 (60), 16 (20), 22 (20)[c]
20 (15), 26 (40), 27 (6)[b]
[a] Assays were typically performed under an argon atmosphere by heating a 0.1 m solution of 12 or 14 in tBuOH to 80 °C with the
additives specified (quantities indicated in equiv.; for full detail, see the Supporting Information). [b] The yield is based on the material
purified by chromatography. [c] The composition of the mixture was estimated by NMR spectroscopy. [d] Reduced product 16 was not
detected. [e] A 0.06 m solution of 12 in tBuOH was used. [f] The reaction was performed under microwave irradiation. [g] The reaction
was performed at 90 °C under microwave irradiation. [h] TPMA (0.1 equiv.) was added as a ligand.
Table 4. Reduction and intermolecular coupling of 28 with NaBH3CN and AIBN or copper salts.[a]
Entry
NaBH3CN
equiv.
Initiator,
equiv.
T
[°C]
Time
[h]
Products (yield [%])
28
29
30
31
Reduction
1
2
3
4
5
3
2
3
5
3
AIBN, 0
AIBN, 1
CuBr, 0.5
45
80
45
60
45
7.5
2.5
7.5
4
100
0
24
5
0[b]
Ͼ90[b]
76[b]
CuBr, 0.5
87[c]
CuBr/TPMA, 0.1
1
Ͻ5
95[b]/66[c]
Coupling with acrylonitrile (5 equiv.)
[d]
6
7
1
2
AIBN, 1
AIBN, 1
80
80
4
3.5
60[b]
Ͻ10
0
18
30[b,c]
53[c]
[a] Experiments were performed at a substrate concentration of 0.1 m in tBuOH (except for entry 4, 0.05 m) under an argon atmosphere.
[b] Product distribution was determined by analysis of the crude mixture by 1H NMR spectroscopy. [c] Yield based on the isolated
product. [d] Compound 31 present in low amounts in the crude mixture, as shown by MS.
Finally, N-tosyl-N-allyl-α-bromamide (32)[27] was chosen 1H NMR spectroscopy), from which reduced product 33,
to test the intramolecular cyclization with Cu salts and once cyclized in a 5-exo-trig mode, was isolated in 60% yield
with AIBN (Table 5). After prolonged heating to 45 °C (Table 5, entry 3). If CuBr was used with TPMA (each
without additive, 32 was partially reduced to allylamine 36 0.1 equiv., 45 °C), bromide 34 (≈75%) was predominantly
(Table 5, entry 1). Similar heating of 32 and CuBr without formed through ATRA, independent of the reaction time
NaBH3CN brought about no reaction (Table 5, entry 2). (Table 5, entries 4 and 5) besides minor amounts of 33 and
An assay with 3 equiv. NaBH3CN afforded a mixture of 36. As CuII salts (considered oxidatively more stable)[15,27]
33, 34, and 35 within 4 h (75:20:5 ratio, as determined by appear to be reduced by NaBH3CN, a test was performed
4
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Tin-Free Radical-Based Reactions
Table 5. Reduction of bromides 32 and 34 with NaBH3CN and additives: products distribution.[a]
Entry
NaBH3CN, Initiator,
T
[°C]
Time
[h]
Products (yield [%])
equiv.
equiv.
32
33
34
35
36
1
2
3
4
5
6
7
3
0
3
3
3
3
1
3
none
CuBr, 0.5
CuBr, 0.5
45
45
45
45
45
60
80
80
20
20
4
0.33
5.5
20
2.5
1
20[b]
–
–
–
–
–
–
60[c]
–
100[d]
0
0
0
0
0
–
60[c]
13[c]
8[c]
13[c]
74[c]
77[c]
10[b]
22[b]
35[b]
5[d]
–
–
CuBr/TPMA 0.1
CuBr/TPMA 0.1
5[c]
5[c]
–
–
Cu(OAc)2,[e]
AIBN, 1
1
10[b]
60[b]
65[b]
80[b]
–
18[b]
8 (34Ǟ33)
CuBr, 0.5
[a] Experiments were performed in tBuOH at a substrate concentration of 0.05 m (entries 1–3, 6, 8) or 0.1 m (entries 4, 5, 7) under an
argon atmosphere. [b] Product distribution as indicated by analysis of the crude mixture by 1H NMR spectroscopy. [c] Yield based on
the isolated product. [d] TLC indicated no transformation. [e] Batch purchased at an undetermined time.
with Cu(OAc)2 from an in-house batch. In this case, 32 led aims at improving copper-mediated ATR reactions, with
predominantly to cyclized hydroxylated product 35, as evi- lower catalyst loadings.[27,32] As noted[1] and also seen upon
denced by analysis of the reaction mixture by 1H NMR reducing reactive benzyl halides (Supporting Information,
spectroscopy (Table 5, entry 6). With AIBN initiation Table 6S), NaBH3CN may react through ionic pathways.
(Table 5, entry 7), predominant reductive cyclization oc- With its emerging radical reactivity, NaBH3CN is a Janus
curred under our conditions[27] to yield 33, 34, and 36 reagent with double-faced reactivity. It might contribute to
(60:22:18 ratio). Finally, cyclic primary bromide 34 was par- the continuing search for mild, cheap, selective, and green
tially reduced to 33 in the presence of CuBr (80 °C, 1 h; synthetic methods, as its potential for tin-free radical meth-
Table 5, entry 8).
ods is emerging. Beside AIBN, and as disclosed herein for
the first time, Cu salts can be used as initiators with
NaBH3CN, and this might open further developments.[33,34]
Conclusions
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details; general procedures, complete lists of at-
tempted assays, characterization of new products 15, 18, 20, 22,
23, 24, 25, 26, 27, 30, 31, and 35; as well as additional relevant
references.
With NaBH3CN and halosugars 11–14, reduction and
C–C bond-forming reactions worked best with AIBN. The
clean CuBr-mediated reduction of 1 with rearrangement,
and the reactions observed with α-bromamides 28 and 32
highlighted their reactivity in the presence of CuI salts,
probably because (1) copper ions interact with the oxygen
atoms in the sugar ring or in the carbonyl group, and the
nearby bromine atom; (2) the electronegativity of oxygen
favors the set; (3) structural features resulting in stabilized
radicals. Our data confirmed again that NaBH3CN can
carry free-radical chain reactions, as suggested earlier from
ESR studies[28] and from bond dissociation energy (BDE)
calculations.[29] A number of reaction pathways have been
proposed for photoinitiated reactions by using boro-
hydrides[26,30] for photoredox processes[18,20] and for cop-
per-catalyzed ATRA, ATRC,[13] and ATRP.[15] A related
mechanism can be assumed for the heat-promoted reactions
Acknowledgments
Financial support by Centre National de la Recherche Scientifique
(CNRS), is thankfully acknowledged. Isabelle Bruyère (see ref.[3,8]
is thanked for dedicated initial studies with NaBH3CN.
)
[1] C. F. Lane, Synthesis 1975, 135–146.
[2] G. Stork, P. M. Sher, J. Am. Chem. Soc. 1986, 108, 303–304.
[3] J.-P. Praly, A. S. Ardakani, I. Bruyère, C. Marie-Luce, B. B.
Qin, Carbohydr. Res. 2002, 337, 1623–1632.
[4] M. Abe, T. Hayashikoshi, T. Kurata, Chem. Lett. 1994, 1789–
1792.
achieved with NaBH3CN and copper bromide initiation. [5] B. Giese, B. Kopping, C. Chatgilialoglu, Tetrahedron Lett.
1989, 30, 681–684.
Whether copper hydride could be formed in the presence of
NaBH3CN and intervene in the reactions is an open issue.
Finally, an analogy with the innovative chemistry based on
[6] a) A. Koch, C. Lamberth, F. Wetterich, B. Giese, J. Org. Chem.
1993, 58, 1083–1089; b) H.-G. Korth, R. Sustmann, K. S.
Gröninger, M. Leisung, B. Giese, J. Org. Chem. 1988, 53, 4364–
N-heterocyclic carbene (NHC) borane complexes must be
underlined. NHC–boranes have relatively low B–H BDEs,
calculated to be in the 79–88 kcalmol–1 range.[31] These rea-
gents appear by now to have a lower scope than tributyltin
hydride, and this is valid also for our conditions, but in both
cases, the work is still at an early stage. Current research
4369; c) B. Quiclet-Sire, S. Z. Zard, J. Am. Chem. Soc. 1996,
118, 9190–9191; d) J. Boivin, V. T. Nguyen, Beilstein J. Org.
Chem. 2007, 3, n°45; e) D. Crich, F. Brebion, D.-H. Suk, Top.
Curr. Chem. 2006, 263, 1–38.
[7] D. Crich, Q. Yao, J. Org. Chem. 1995, 60, 84–88.
[8] I. Bruyère, Z. Tóth, H. Benyahia, J. L. Xue, J.-P. Praly, Tetrahe-
dron 2013, 69, 9656–9662.
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J. Guiard, Y. Rahali, J.-P. Praly
SHORT COMMUNICATION
[9] a) J. Cossy, V. Bellosta, J.-L. Ranaivosata, B. Gille, Tetrahedron
2001, 57, 5173–5182; b) P. A. Waske, N. T. Tzvetkov, J. Mattay,
Synlett 2013, 24, 669–685.
[10] R. A. Rossi, A. B. Pierini, A. B. Peñéñory, Chem. Rev. 2003,
103, 71–167.
[25] L. Nicolas, P. Angibaud, I. Stansfield, P. Bonnet, L. Meerpoel,
S. Reymond, J. Cossy, Angew. Chem. Int. Ed. 2012, 51, 11101–
11104; Angew. Chem. 2012, 124, 11263–11266.
[26] a) I. Ryu, S. Uehara, H. Hirao, T. Fukuyama, Org. Lett. 2008,
10, 1005–1008; b) S. Kobayashi, T. Kawamoto, S. Uehara, T.
Fukuyama, I. Ryu, Org. Lett. 2010, 12, 1548–1551; c) T. Kawa-
moto, T. Fukuyama, I. Ryu, J. Am. Chem. Soc. 2012, 134, 875–
877; d) T. Fukuyama, T. Kawamoto, M. Kobayashi, I. Ryu,
Beilstein J. Org. Chem. 2013, 9, 1791–1796.
[27] A. J. Clark, P. Wilson, Tetrahedron Lett. 2008, 49, 4848–4850.
[28] a) J. R. M. Giles, B. P. Roberts, J. Chem. Soc. Perkin Trans. 2
1982, 1699–1711; b) J. A. Baban, J. C. Brand, B. P. Roberts, J.
Chem. Soc., Chem. Commun. 1983, 315–316.
[11] J. Iqbal, B. Bhatia, N. K. Nayyar, Chem. Rev. 1994, 94, 519–
564.
[12] D. P. Curran, Synthesis 1988, 489–513.
[13] a) W. T. Eckenhoff, T. Pintauer, Catal. Rev. 2010, 52, 1–59; b)
T. Pintauer, Eur. J. Inorg. Chem. 2010, 2449–2460.
[14] T. Pintauer, K. Matyjaszewski, Top. Organomet. Chem. 2009,
26, 221–251.
[15] K. Matyjaszewski, Macromolecules 2012, 45, 4015–4039.
[16] S. Paria, M. Pirtsch, V. Kais, O. Reiser, Synthesis 2013, 45, [29] P. R. Rablen, J. Am. Chem. Soc. 1997, 119, 8350–8360.
2689–2698.
[30] a) A. N. Abeywickrema, A. L. S. Beckwith, Tetrahedron Lett.
1986, 27, 109–112; b) Q. Liu, B. Han, W. Zhang, L. Yang, Z.-
L. Liu, W. Yu, Synlett 2005, 2248–2250.
[31] D. P. Curran, A. Solovyev, M. M. Brahmi, L. Fensterbank, M.
Malacria, E. Lacôte, Angew. Chem. Int. Ed. 2011, 50, 10294–
10317; Angew. Chem. 2011, 123, 10476–10500.
[17] T. Koike, M. Akita, Synlett 2013, 24, 2492–2505.
[18] R. S. Andrews, J. J. Becker, M. R. Gagné, Org. Lett. 2011, 13,
2406–2409.
[19] H. Gong, R. S. Andrews, J. L. Zuccarello, S. J. Lee, M. R.
Gagné, Org. Lett. 2009, 11, 879–882.
[20] a) R. S. Andrews, J. J. Becker, M. R. Gagné, Angew. Chem. Int.
Ed. 2010, 49, 7274–7276; Angew. Chem. 2010, 122, 7432–7434;
b) R. S. Andrews, J. J. Becker, M. R. Gagné, Angew. Chem. Int.
Ed. 2012, 51, 4140–4143; Angew. Chem. 2012, 124, 4216–4219.
[21] A. Ghosez, T. Göbel, B. Giese, Chem. Ber. 1988, 121, 1807–
1811.
[22] a) J. Augé, R. Gil, S. Kalsey, Tetrahedron Lett. 1999, 40, 67–
70; b) G. Kovács, K. Tóth, Z. Dinya, L. Somsák, K. Micskei,
Tetrahedron 1999, 55, 5253–5264; c) Z. Zuhász, K. Micskei, E.
Gál, L. Somsák, Tetrahedron Lett. 2007, 48, 7351–7353, and
references cited therein.
[32] F. Bellesia, A. J. Clark, F. Felluga, A. Gennaro, A. A. Isse, F.
Roncaglia, F. Ghelfi, Adv. Synth. Catal. 2013, 355, 1649–1660.
[33] For example, whereas propargyl bromamides react by ATRC
to afford mixtures of bromovinylic and vinylic pyrrolidin-2-
ones,[27] the presence of NaBH3CN should favor the reduced
product; the use of NaBH3CN in ATRP reactions with organo-
chlorides seems feasible.
[34] For recent updates of carbohydrates radical chemistry, see:
R. W. Binkley, E. R. Binkley, Radical Reactions of Carbo-
hydrates, vol. 1: Structure and Reactivity of Carbohydrate Radi-
cals, 2013, and vol. II: Radical Reactions in Carbohydrate Syn-
thesis 2014; both are available at no charge on the website
www.carborad.com.
[23] R. P. Spencer, J. Schwartz, J. Org. Chem. 1997, 62, 4204–4205.
[24] a) J.-M. Beau, T. Gallagher, Top. Curr. Chem. 1997, 187, 154;
b) N. Miquel, G. Doisneau, J.-M. Beau, Angew. Chem. Int. Ed.
2000, 39, 4111–4114; Angew. Chem. 2000, 112, 4277–4280.
Received: April 18, 2014
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42441
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Date: 12-06-14 17:04:54
Pages: 7
Tin-Free Radical-Based Reactions
Radical Chemistry
NaBH3CN carries heat-induced free-rad-
ical reactions initiated with either 2,2ЈЈ-
azobisisobutyronitrile (AIBN) or copper
salts. AIBN-initiated reactions further
show the potential of NaBH3CN for simple
and safe radical methods. The NaBH3CN–
copper salts system tested for the first time
might benefit other atom-transfer radical
reactions; Ts = p-tolylsulfonyl.
J. Guiard, Y. Rahali, J.-P. Praly* ..... 1–7
NaBH3CN: A Janus Substitute for Tin-
Free Radical-Based Reactions
Keywords: Synthetic methods / Reduction /
Radicals / Rearrangement / Cyclization /
Copper
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