A Mn(iii)/TEMPO-co-mediated tandem azidation-1,2-carbon migration reaction of allylic silyl ethers

Article abstract of DOI:10.1039/c4cc04707a

A novel Mn(iii)/TEMPO-co-mediated tandem azidation-1,2-carbon migration reaction of allylic silyl ethers with an unactivated CC bond has been explored, generating α-aryl-alkyl β-azido ketones with an α-quaternary stereocenter. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc04707a

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A Mn(III)/TEMPO-co-mediated tandem
azidation–1,2-carbon migration reaction
of allylic silyl ethers†
Cite this: Chem. Commun., 2014,
0, 10805
5
Received 20th June 2014,
Accepted 22nd July 2014
a
a
ac
a
a
Zhi-Min Chen, Zhen Zhang, Yong-Qiang Tu,* Ming-Hui Xu, Fu-Min Zhang,
a
ab
Chen-Chen Li and Shao-Hua Wang*
DOI: 10.1039/c4cc04707a
www.rsc.org/chemcomm
A novel Mn(III)/TEMPO-co-mediated tandem azidation–1,2-carbon
migration reaction of allylic silyl ethers with an unactivated CQC
bond has been explored, generating a-aryl–alkyl b-azido ketones
with an a-quaternary stereocenter.
Organic azides are an important class of organic compounds
because of their remarkable properties for functional materials
1
and broad synthetic utilities for bioactive molecules. Accordingly,
other than the S 2 type azido-substitution, more and more
N
progresses have been made on the direct azidation of the carbon
framework due to its high efficiency in introducing the azido Scheme 1 Design of a tandem azidation–1,2-migration reaction.
2
group. Among them, strategies via difunctionalization of alkenes,
which could be trapped or initiated with an azide radical, have
attracted broad attention of the chemistry community in recent through the proper use of electrophilic reagents.
7
,8
In our
years. For example, the carboazidation and hydroazidation of previous studies, a wide range of electrophiles such as halonium
olefins by trapping with azidyl radicals have been intensively ions and even carbon-electrophiles with relatively low reactivity
3,4
9
reported. In contrast, for procedures initiated with an azidyl have been used to initiate this type of reaction. In 2013, the
radical, although transition metal-catalyzed or metal-free radical electrophile scope was further expanded to CF radicals by Wu,
3
1
0
azidations of olefins leading to carbon-heteroatom bond for- Sodeoka and our group (Scheme 1a). Inspired by this result
5
mation have been documented, there is still a lack of straight- and recent progress in azidyl radical related reactions, we
3
forward and efficient approaches to C–N and C–C bonds within envisioned that under certain conditions such a 1,2-migration
one step. To the best of our knowledge, only a few examples of reaction of allylic alcohols might be triggered by an azidyl
6
azidoarylation of activated alkenes have been developed, and radical to deliver b-azidyl carbonyl derivatives (Scheme 1b).
there is no such an example of difunctionalization of unactivated Herein, we describe the first Mn(III)/TEMPO-co-mediated tandem
alkenes, which is triggered by azidyl radicals and terminated by a azidation–1,2-carbon migration reaction of allylic silyl ethers
1
,2-migration step. Thus, further investigation toward this type with an unactivated CQC bond.
of tandem reaction is still highly desirable. Since manganese(III) acetate has shown huge potential in
,2-Migration reactions have been considered as one of the various oxidative free-radical procedures, we firstly chose
most significant methods for constructing a-quaternary carbonyls 3.0 equiv. of Mn(OAc) O as an oxidant and allylic silyl ether
1
1
1
3
ꢀ2H
2
and have found widespread applications in organic synthesis 1a as a model substrate to test the feasibility of the designed
azidation–1,2-migration reaction in the presence of 5.0 equiv. of
a
3 3
NaN as an azide source in CH CN at ambient temperature.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou,
P. R. China
Disappointingly, no reaction occurred after 24 h (Table 1, entry 1).
b
c
11a
School of Pharmacy, Lanzhou University, Lanzhou, P. R. China
Collaborative Innovation Center of Chemical Science and Engineering, Tianjin,
P. R. China. E-mail: tuyq@lzu.edu.cn, wangshh@lzu.edu.cn
Electronic supplementary information (ESI) available. CCDC 997264–997266.
Based on previous studies, we speculated that the result might be
caused by the low solubility of the azide anion or low Lewis acidity
of Mn(OAc)
3
ꢀ2H
2
O. Therefore, chloroacetic acid and trifluoro-
†
acetic acid (0.2 mL) were examined as acidic additives to generate
For ESI and crystallographic data in CIF or other electronic format see DOI:
0.1039/c4cc04707a
1
the HN
3
in situ. As expected, the reactions proceeded smoothly
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a
a,b,c
Table 1 Optimization of the azidation–1,2-migration reaction
Table 2 Substrate scope of the azidation–1,2-migration reaction
b,c
Entry
1
Temp.
Acid
Additive
Solvent
Yield (%)/d.r.
RT
RT
0
—
4
—
—
—
—
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
—
d
2
36/(410 : 1)
44/(410 : 1)
Trace
3
4
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
e
0
0
0
0
0
0
0
5
6
7
10% Cu(OAc)
2
40/(410 : 1)
47/(410 : 1)
86/(6.3 : 1)
87/(5.0 : 1)
79/(6.1 : 1)
80/(6.5 : 1)
68/(6.5 : 1)
64/(6.0 : 1)
10% Co(OAc)
10% TEMPO
10% 5
5% TEMPO
20% TEMPO
10% TEMPO
10% TEMPO
2
f
8
9
1
1
1
0
1
2
ꢂ10
g
0
a
Reaction conditions: Mn(OAc)
1
1
3
ꢀ2H
2
O (0.6 mmol) was dissolved in
(0.10 mmol). After 10–20 min,
.5 mL of solvent followed by addition of NaN
a (0.2 mmol) in 0.5 mL of solvent was added. Isolated yield. Diastereo-
isomeric ratio was determined by H NMR. 4 = CH ClCO H (9.0 equiv.).
3
b
c
1
d
2 2
e
f
g
TMSN
3 3
was added instead of NaN . 5 = 4-OH-TEMPO. 3.0 equiv. of
NaN was added.
3
to give the corresponding product 2a, and the use of TFA could
lead to a better yield of 44% and high diastereoselectivity at 0 1C
(
3
Table 1, entry 3). Next, changing the azide source to TMSN led
a
b
0
Reaction conditions, please see the ESI. Yields of 2 and 2 . Dia-
1 d
c
1
2
to poor result (entry 4). Inspired by the work of Magnus, we
envisioned that such a radical initiated process might also be weight of the isolated product.
facilitated by using of additives like TEMPO. Accordingly,
stereoisomeric ratio was determined by H NMR. Determined by the
different additives such as Cu(OAc)
2 2
, Co(OAc) , TEMPO and
4-OH-TEMPO were investigated (entries 5–8). The results indicated the stated conditions, albeit with lower diastereoselectivity and
that the additive played a key role in the yield and diastereoselectivity yield. Finally, some acyclic substrates were examined and success-
of this reaction. Especially, when TEMPO was used as an additive, fully afforded 2j, 2k, and 2l in good to excellent yields. It should be
the desired product was obtained in 86% yield with a d.r. value of noted that the relative configuration of 2a–i was assigned by X-ray
14
6.3 : 1. Subsequently, variation of the ratio between TEMPO and crystallography of 2a as a representative.
NaN as well as the reaction temperature showed that these changes
To further expand the scope of this tandem reaction, the
3
would slightly lower either the yield or the diastereoselectivity dihydropyran-type allylic silyl ether 1m was subjected to the
entries 9–12). Thus, entry 7 was chosen as the optimal conditions. standard conditions. Different from the substrates shown in
(
To test the generality of this transformation, we next subjected Table 2, the diazide addition product 3m was obtained in 30%
allylic silyl ethers 1b–l to the optimized conditions. As shown in yield with excellent anti-selectivity. Although no desired b-azidyl
Table 2, all the substrates performed well and the desired b-azidyl ketone was observed, this result also supported a possible azide
carbonyl derivatives were obtained in moderate to excellent yields. radical initiated process, which prompted us to further optimize
Firstly, for the cyclic substrates with five- and seven-membered the conditions for this type of substrates. After some unsuccessful
rings, this reaction was applicable, and the corresponding attempts, we accidentally found that the yield of 3m was notably
products 2b and 2c could be obtained, respectively, in 69% improved to 62% without using TEMPO (Scheme 2). Considering
12,15
and 84% yields with moderate diastereoselectivity. Also, the the valuable synthetic utility of bisazido compounds,
we then
p-OMe-phenyl- and 2-naphthyl-substituted substrates were also applied a variety of activated allylic silyl ethers to this diazidation
suitable for this transformation (2d, 2e). Compared with 1a, reaction (1m–w). All the substrates were well tolerated under
substrates 1f–g with an alkyl and an aryl substituent exhibited the same conditions and produced the corresponding diazide
relatively low reactivities, affording the desired products with addition products 3m–w in moderate to good yields with
1
6
exclusive migration of aryl groups in 67% and 61% yields, excellent diastereoselectivity (35–82%). The relative configu-
1
4
respectively. Furthermore, silyl ether substrate 1h derived from ration of 3m–w was deduced by X-ray crystallography of 3m. It
the corresponding secondary alcohol was also amenable to the is worth mentioning that the reaction of 1p with electron-
0
protocol, furnishing the products 2h and 2h in 64% yield, donating groups at the para-position of the phenyl moiety not
which could provide an alternative strategy for the synthesis of only gave the diazide addition product 3p in 35% yield, but also
1
3
(
ꢁ)-crinane. To our delight, the substrate bearing a cyclo- produced the rearrangement product 2p in 40% yield, which
butanol motif 1i also underwent the reaction smoothly under promoted us to further investigate the possibility of a semipinacol
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Scheme 2 Reaction results of dihydropyran-type allylic silyl ethers 1m
and 1p.
Table 3 Substrate scope of the deazidation–1,2-carbon migration
Scheme 3 Proposed mechanism for the azidation–1,2-migration reaction.
radical species 6 could directly undergo a 1,2-rearrangement
to give radical intermediate 8, which would be further oxidized
by manganese(III) acetate to produce the desired product 2 after
1
8
eliminating a TMS. In path 2, carbon radical species 6 might
be first oxidized by manganese(III) to a carbon cation inter-
mediate 9, which would subsequently undergo a 1,2-migration
to afford the corresponding product 2. At the moment, it is still
unclear which path is dominant based on our preliminary
experiments, although we hypothesized that the effect of TEMPO
16
is beneficial to accelerate the rate of path 1. Also, since the
difference between conformation 6-a and 6-b was not very signifi-
cant, the corresponding diastereoselectivity was not excellent. In
contrast, the diazidation reaction might proceed through only one
19
possible way. As shown in Scheme 4, the azidyl radical reacted
with activated allylic silyl ether to give carbon radical intermediate 10,
and further oxidation of 10 would produce the cyclic oxonium
intermediate 11, which could go through a sterically favored
anti-addition with an azide anion to give product 3. While in
the presence of BF
upon the release of TMSN
3
ꢀEt
2
O, intermediate 12 would be generated
. Accordingly, a subsequent semi-
3
rearrangement with bisazido compounds 3 to afford a-quaternary pinacol rearrangement would afford product 2 with excellent
b-azidyl ketones (Scheme 2). Fortunately, under the promotion of diastereoselectivity, which could be explained by the clear
BF
3
ꢀEt
2
O, a common Lewis acid, the expected rearrangement difference between conformation 12-a and 12-b.
reaction of 3m–w proceeded smoothly to give the desired b-azidyl
ketones 2m–w in moderate to excellent yields with excellent
diastereoselectivity (Table 3). The relative configuration of 2m–w
14
was confirmed by single crystal X-ray analysis of 2m.
Next, some additional experiments were conducted in order
to get a better understanding of the azidation–1,2-migration
reaction. When 1.0 equiv. of the radical-trapping reagent BHT
(2,6-di-tert-butyl-p-cresol) was added instead of TEMPO, the
reaction was messy and no desired product but BHT–N could
3
1
7
be detected by GC-MS. The result suggested the existence
of an azidyl radical during this transformation. On the basis of
the above experimental results and previous literature, a
proposed reaction mechanism is depicted in Scheme 3. Initi-
ally, an azidyl radical generated from the oxidation of sodium
azide by manganese(III) acetate would add to allylic silyl ether 1
to provide radical intermediate 6. Next, two possible pathways
for the transformation could take place. In path 1, carbon Scheme 4 Proposed mechanism for the deazidation–1,2-migration reaction.
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In summary, we have developed a novel and mild Mn(III)/
TEMPO-co-mediated tandem azidation–1,2-carbon migration
reaction of allylic silyl ethers for the first time. This tandem
transformation enables the difunctionalization of unactivated
alkenes through simultaneous construction of an alkyl azide
and an all-carbon quaternary center and is synthetically valu-
able since a variety of a-quaternary b-azidyl carbonyl derivatives
were obtained in moderate to excellent yields. In addition, the
diazidation reaction of activated allylic silyl ethers has also
been achieved and the 1,2-diazides could further undergo
a novel semipinacol rearrangement to produce a-quaternary
b-azidyl ketones with the loss of an azide leaving group.
This work was supported by the NSFC (No. 21102061,
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17 When 1.0 equiv. of TEMPO was added, TEMPO-N
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3
could also be
4
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4
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