Palladium-catalyzed reaction of olefins with PhI(OAc)TBAB system: An efficient and highly selective bisfunctionalization strategy

Article abstract of DOI:10.1055/s-0030-1259519

The palladium-catalyzed reaction of olefins with PhI(OAc)TBAB system provides a novel, efficient, and highly selective bisfunctionalization strategy to introduce bromo and oxygen groups simultaneously. The substituents on the C=C bond control the regiosel

Full text of DOI:10.1055/s-0030-1259519

LETTER
579
Palladium-Catalyzed Reaction of Olefins with PhI(OAc)2–TBAB System:
An Efficient and Highly Selective Bisfunctionalization Strategy
P
d-Catalyze
d
R
e
eaction of
O
i
lefins
w
ithP
Y
hI(OAc) –TBA
B
u,* Lingfeng Ren, Rong Yi, Yulan Wu, Tian Chen, Rong Guo
2
School of Chemistry and Chemical Engineering, Yangzhou University, Shouxihu Campus, Yangzhou 225002, P. R. of China
Fax +86(514)87975244; E-mail: yulei@yzu.edu.cn
Received 14 October 2010
Table 1 Reaction of MCB 1a with PhI(OAc)2–TBAB Systema
Abstract: The palladium-catalyzed reaction of olefins with
PhI(OAc)2–TBAB system provides a novel, efficient, and highly
selective bisfunctionalization strategy to introduce bromo and oxy-
gen groups simultaneously. The substituents on the C=C bond con-
trol the regioselectivity of this reaction, which could be an effective
supplement of bromohydroxylation in organic synthesis.
Ph
OAc
Br
[Pd]
+ PhI(OAc)2 + TBAB
Ph
Ph
Ph
1a
2a
Entry Solvent
Catalyst
Time (°C) Time (h) Yield of 2a
Key words: bisfunctionalization reactions, olefins, palladium-cata-
lyzed reactions, selective
(%)b
1
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
none
r.t.
r.t.
40
60
60
60
60
60
60
60
60
3
0
Pd2dba3
Pd2dba3
Pd2dba3
Pd(PPh3)4
PdCl2
5
trace
34
53
62
60
74
0c
During the last decade, highly activated olefins have at-
tracted the interest of chemists, and their novel reactions
have been widely investigated. These include methyle-
necyclopropanes (MCP),1 vinylidenecyclopropanes
(VCP),2 allenes,3 cyclopropyl allenes (CPA),4 and recent-
ly methylenecyclobutanes (MCB).5 Due to their high ring
strain or cumulated C=C bonding character, these olefins
have high reactivity and can undergo a series of interest-
ing reactions under mild conditions, providing convenient
methods for the construction of many useful organic
structures. Therefore, they are useful building blocks in
organic synthesis.
3
3
4
2
5
4
6
5
7
Pd(OAc)2
none
1.5
10
2
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
47
40
63
10
11
toluene
DCE
4
Being able to introduce two different functional groups si-
multaneously, bisfunctionalization reactions are highly
effective in organic synthesis. Halohydroxylation of ole-
fins is one of those bisfunctional strategies. Since the two
functional groups, that is, X and OH, could be introduced
into the substrate at the same time, halohydroxylations of
olefins provide a direct access to b-halogen-substituted al-
cohols, which are useful intermediates in medicinal chem-
istry.6 In recent years, halo-hydroxylation reactions of
highly activated olefins (e.g., allenes,7 MCP,8 CPA,9
MCB10) have been investigated systemically. Rearrange-
ments in the reaction routes may provide some unexpect-
ed particular products with high selectivity when highly
activated olefins were employed.
6
a Reaction conditions: 1a (0.3 mol), PhI(OAc)2 (0.6 mol), TBAB (0.3
mol), and solvent (2 mL) were employed. The catalyst dosage was 10
mol% based on 1a.
b Isolated yields based on 1a.
c Traces of unidentified complexes were observed.
We initially examined the reaction of MCB, and MCB 1a
was chosen as the model substrate. When 1a, PhI(OAc)2,
and TBAB were stirred in MeCN at room temperature, no
desired product was observed (Table 1, entry 1). Further
investigations demonstrated that when the reaction could
take place in the presence of palladium catalyst, and a bi-
functional product 2a was obtained. The yield of 2a could
be enhanced to 74% at a higher temperature in MeCN and
in the presence of Pd(OAc)2 (Table 1, entry 7). To con-
firm that catalyst palladium is necessary in this reaction,
we examined the blank reaction, and only traces of uni-
dentified complexes were observed (Table 1, entry 8).
When other solvents, such as THF, toluene and DCE were
employed, the yields of 2a decreased (Table 1, entries 9–
11).
Encouraged by these works, we are interested in the bis-
functionalization reactions of olefins. Herein, we wish to
report that palladium complex could catalyze the reaction
of olefins with PhI(OAc)2–TBAB (tetrabutylammonium
bromide) system11 and introduced halogen and oxygen
groups simultaneously.
SYNLETT 2011, No. 4, pp 0579–0581
x
x.
x
x.
2
0
1
1
Advanced online publication: 27.01.2011
DOI: 10.1055/s-0030-1259519; Art ID: W16510ST
© Georg Thieme Verlag Stuttgart · New York
With the optimized conditions, a series of MCB was em-
ployed to examine the reaction’s application scope. Both

580
L. Yu et al.
LETTER
disubstituted and monosubstituted MCB led to the bifunc-
tional products 2 smoothly (Table 2).12 It is interesting
that, when monosubstituted MCB 1e was employed, the
regioselectivity was reversed (Table 2, entry 5).
Table 3 Difunctional Reactions of a Series of Simple Olefins
Pd(OAc)2
(10 mol%)
R1 OAc
R3
R1
R2
R3
R4
R2
+ PhI(OAc)2 + TBAB
MeCN
60 °C
Br R4
2
Table 2 Difunctional Reactions of a Series of MCBs
Entry R1, R2, R3, R4
Time Yield of 2
OAc
Br
(h) (%)a
R2 R1
2a–d
1
2
1f Ph, Ph, H, H
7
9
2f 63
2g 67
Pd(OAc)2
R1
R2
(10 mol%)
or
+ PhI(OAc)2 + TBAB
1g Ph, 4-MeC6H4, H, H
1h Ph, 2-MeC6H4, H, H
1i Ph, 1-C10H7, H, H
1j Ph, 4-ClC6H4, H, H
1k Ph, H, H, Ph
MeCN, 60 °C
Br
3
10 2h 62
12 2i 51
14 2j 56
OAc
H
4
5
2e
6
9
7
2k 50
2l 58
Entry R1, R2
Time (h) Yield of 2 (%)a
7
1l C7H15, H, H, Ph
1m H, H, H, Ph
1
2
3
4
5
1a Ph, Ph
1.5
2.5
3
2a 74
2b 63
2c 68
2d 55
2e 70
8
10 2m 52
12 traceb
1b 4-ClC6H4, 4-ClC6H4
1c 4-FC6H4, 4-FC6H4
1d 4-MeC6H4, Me
1e 4-MeC6H4, H
9
1n Ph, Ph, Ph, H
10
11
1o Bn, H, H, Pr
6
7
0b
0b
1p R1–R2 = -(CH2CH2CHPhCH2CH2)-,
3
R3 = H, R4 = Pr
1
a Isolated yields.
b A series of unidentified compounds were observed.
a Isolated yields.
palladium species A.1h Coordination of A with olefins
then gave the palladium intermediate B. Further transfor-
mation of which led to the intermediate C. To reduce the
steric hinderance, the larger palladium atom tended to add
to the less sterically hindered position when bisaryl-sub-
stituted olefins were employed. This also determined the
reaction regioselectivity. Oxidation of C with PhI(OAc)2
generated intermediate D,1h and reductive elimination of
which led to the final product 2 in an anti-Markovnikov
fashion and generated palladium species E. Reaction of
E with TBAB regenerate the palladium species A
(Scheme 2). However, when monoaryl-substituted olefins
were employed, the regioselectivity changed (Table 2, en-
try 5; Table 3, entries 7 and 8). Although the aryl-substi-
tuted carbon might have larger (in 1m) or similar (in 1e
and 1l) steric hindrance, the acetoxy group tended to add
to the aryl carbon and gave 2e, 2l, and 2m in high regiose-
lectivity. For the monoaryl-substituted substrates, the
steric hindrance of the aryl-substituted carbon decreased
considerably and could accommodate the larger palladi-
um group. Hence, steric hindrance was no longer an im-
portant factor in the regioselectivity-deciding step.
Therefore, the palladium groups tended to add to the aryl-
substituted carbon to generate the intermediate F, which
led to the Markovnikov adducts (Scheme 2).
In order to gain more hints in mechanism studies, we ex-
amined the similar reactions on simple olefins. The exper-
imental results showed that the reaction could also happen
when simple olefins were employed. The reaction had
high selectivity, and in the cases of the bisaryl substituted
olefins, the oxygen group tended to add to the less steric
hindrance site while the bromide added at the more hin-
dered position (Table 3, entries 1–5). This is very differ-
ent from traditional bromohydroxylations, which
proceeded under Markovnikov rules (Scheme 1).13 When
monoaryl-substituted olefins were employed the regiose-
lectivity changed, and acetyoxy group tended to add to the
more sterically hindered carbon atom (Table 3, entries 7
and 8). Triphenylethene 1n gave only trace of the desired
product, probably due to the its steric hindrance (Table 3,
entry 9). It was also found that the substrate should have
at least one aryl group on the C=C bond. Otherwise, no
desired product could be obtained (Table 3, entries 10 and
11).
acetone–H2O
Ph
Ph
Ph
Ph
Br
(5:1)
Ph OH
+ NBS
Br
r.t., 3 h
Ph
3 (76%)
H2O
Scheme 1
In conclusion, we have developed a novel bisfunctional-
ization reaction of olefins. In this reaction, oxygen and
bromide groups could be introduced simultaneously. The
regioselectivity of this reaction was controllable, depend-
Based on the above experimental results as well as litera-
ture references, we supposed a possible mechanism. Re-
action of Pd(OAc)2 with TBAB would generate the
Synlett 2011, No. 4, 579–581 © Thieme Stuttgart · New York

LETTER
Pd-Catalyzed Reaction of Olefins with PhI(OAc)2–TBAB
581
(5) Selected recent articles about MCB, please see: (a) Jiang,
M.; Shi, M. J. Org. Chem. 2009, 74, 2516. (b) Jiang, M.;
Shi, M. Org. Lett. 2008, 10, 2239. (c) Jiang, M.; Liu, L.-P.;
Shi, M. Tetrahedron Lett. 2007, 63, 9599. (d) Li, W.; Shi,
M. Tetrahedron 2007, 63, 11016. (e) Jiang, M.; Shi, M.
Tetrahedron 2008, 64, 10140. (f) Jiang, M.; Shi, M.
Tetrahedron 2009, 65, 798.
Bu4NBr + Pd(OAc)2
R1
R2
R3
R4
AcO–
R1 = Ar,
2 = H
(Bu4N)2Pd3Br8
Br
Pd
R3
R4
R
4
A
H
R1
R3
(6) (a) Cabanal-Duvillard, I.; Berrien, J.; Royer, J.; Husson, H.
Tetrahedron Lett. 1998, 39, 5181. (b) Rossen, K.; Reamer,
R. A.; Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1996,
37, 6843. (c) Mevellec, L.; Evers, M.; Huet, F. Tetrahedron
1996, 52, 15103. (d) Sawyer, D. T.; Hage, J. P.; Sobkowiak,
A. J. Am. Chem. Soc. 1995, 117, 106.
(7) (a) Ma, S.-M.; Hao, X.-S.; Huang, X. Chem. Commun. 2003,
1082. (b) Ma, S.-M.; Hao, X.-S.; Huang, X. Org. Lett. 2003,
5, 1217. (c) Ma, S.-M.; Ren, H.-J.; Wei, Q. J. Am. Chem.
Soc. 2003, 125, 4817. (d) Ma, S.-M.; Wei, Q.; Wang, H.
Org. Lett. 2000, 2, 3893.
(8) (a) Yang, Y.-W.; Huang, X. J. Org. Chem. 2008, 73, 4702.
(b) Yang, Y.-W.; Su, C.-L.; Huang, X.; Liu, Q.-Y.
Tetrahedron Lett. 2009, 50, 5754.
(9) Yu, L.; Meng, B.; Huang, X. J. Org. Chem. 2008, 73, 6895.
(10) Yu L., Ren L.-F., Xu B., Guo R. Synth. Commun. 2010, 40,
in press.
(11) Selected recent articles on PhI(OAc)2–TBAX system:
(a) Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem.
Int. Ed. 2008, 47, 5215. (b) Fan, R.-H.; Wen, F.-Q.; Qin,
L.-H.; Pu, D.-M.; Wang, B. Tetrahedron Lett. 2007, 48,
7444. (c) Fan, R.-H.; Sun, Y.; Ye, Y. Org. Lett. 2009, 11,
5174. (d) Ye, Y.; Zheng, C.; Fan, R.-H. Org. Lett. 2009, 11,
3156. (e) Fan, R.-H.; Ye, Y.; Li, W.-X.; Wang, L.-F. Adv.
Synth. Catal. 2008, 350, 2488.
R
Pd(OAc)LnBrm–1
R2
R4
PdLnBrm
F
E
B, L = Bu4N
2
R1, R2 ≠ H
Br
2e, 2l
or 2m
R3
R4
PdLnBrm–1
R1
R2
AcO
Br
E
R3
R4
PdLnBrm–1
C, R1, R2 >> R3, R4
PhI(OAc)2
R1
R2
OAc
D
PhI
Scheme 2
ing on the substituted groups on the C=C bond. Therefore,
this strategy could be an effective supplement of bromo-
hydroxylations in organic synthesis.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(12) Typical Procedure for the Preparation of 2
In the presence of Pd(OAc)2 (0.03 mmol, 6.7 mg), olefins
(0.3 mmol), PhI(OAc)2 (0.6 mmol), and TBAB (0.3 mmol)
were heated in MeCN (2 mL) at 60 °C. The reaction was
monitored by TLC. When the reaction terminated, H2O (5
mL) was added, and the liquid was extracted by EtOAc (3 ×
5 mL). The combined organic layer was dried by anhyd
MgSO4, and the solvent was evaporated under vacuum. The
residue was subjected to preparative TLC (eluent: PE–
EtOAc = 8:1) to give the corresponding product 2.
Data for Compound 2a
Acknowledgment
This work was supported by the Natural Scientific Foundation of
Jiangsu Province (NO. BK2010321), University Natural Scientific
Foundation of Jiangsu Province (NO. 09KJB150014), the 45th Post-
doctor foundation of China (NO. 20090451249), and the National
Natural Scientific Foundation of China (NO. 20633010 and
20773106).
References and Notes
Oil. IR (film): 2952, 1751, 1639, 1494, 1446, 1366, 1218,
1084, 1013, 986, 961, 904, 750, 706 cm–1. 1H NMR (600
MHz, CDCl3): d = 7.52–7.53 (m, 4 H), 7.30–7.32 (m, 6 H),
3.28–3.30 (m, 2 H), 2.40–2.43 (m, 1 H), 2.25–2.28 (m, 2 H),
2.12 (s, 3 H), 1.83–1.85 (m, 1 H) ppm. 13C NMR (150 MHz,
CDCl3): d = 15.8, 22.3, 37.3, 74.4, 88.7, 127.0, 127.8, 129.7,
137.7, 168.0 ppm. MS (EI, 70 eV): m/z (%) = 278 (3) [M+ –
Br], 183 (100). Anal. Calcd for C19H19BrO2: C, 63.52; H,
5.33. Found: C, 63.20; H, 5.14.
(1) For reviews, please see: (a) Brandi, A.; Cicchi, S.; Cordero,
F. M.; Goti, A. Chem. Rev. 2003, 103, 1213. (b) Nakamura,
I.; Yamamoto, Y. Adv. Synth. Catal. 2002, 344, 111. (c)
Selected recent articles about MCP, please see: Nakamura,
E.; Yamago, S. Acc. Chem. Res. 2002, 35, 867. (d) Yu, L.;
Meng, J.-D.; Xia, L.; Guo, R. J. Org. Chem. 2009, 74, 5087.
(e) Miao, M.-Z.; Huang, X. J. Org. Chem. 2009, 74, 5636.
(f) Hu, B.; Zhu, J.-L.; Xing, S.-Y.; Fang, J.; Du, D.; Wang,
Z.-W. Chem. Eur. J. 2009, 15, 324. (g) Tian, G.-Q.; Li, J.;
Shi, M. J. Org. Chem. 2008, 73, 673. (h) Jiang, M.; Shi, M.
Organometallics 2009, 28, 5600.
(2) Selected recent articles about VCP, please see: (a) Li, W.;
Shi, M. J. Org. Chem. 2009, 74, 856. (b) Su, C.-L.; Huang,
X. Adv. Synth. Catal. 2009, 351, 135. (c) Yao, L.-F.; Shi,
M. Eur. J. Org. Chem. 2009, 4036. (d) Lu, J.-M.; Shi, M.
J. Org. Chem. 2008, 73, 2206.
(3) For a monograph on the chemistry of allenes, please see:
Krause, N.; Hashmi, A. S. K. Modern Allene Chemistry;
Wiley-VCH: Weinheim, 2004.
(4) Selected recent articles about cyclopropyl allenes, please
see: (a) Yu, L.; Meng, B.; Huang, X. Synlett 2007, 2919.
(b) Yu, L.; Meng, B.; Huang, X. Synlett 2008, 1331.
(c) Meng, B.; Yu, L.; Huang, X. Tetrahedron Lett. 2009, 50,
1947.
(13) Procedure for the Bromohydroxylation of Compound 1f
Compound 1f (0.3 mmol) and NBS (0.3 mmol) were stirred
in acetone–H2O (2 mL; 5:1) at r.t. The reaction was
monitored by TLC (eluent: PE). When the reaction
terminated, the liquid was subjected to preparative TLC
(eluent: PE–EtOAc = 7:1) to give the adduct 3 in 76% yield.
Data for 3
Oil. IR (film): 3060, 3029, 2971, 1493, 1448, 1425, 1332,
1279, 1226, 1163, 1062, 1032, 993, 913, 843, 750, 699 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.25–7.43 (m, 10 H), 4.09
(s, 2 H), 3.14 (s, 1 H) ppm. 13C NMR (150 MHz, CDCl3):
d = 44.0, 76.9, 126.4, 127.7, 128.4, 143.5. MS (EI, 70 eV):
m/z (%) = 276 (3) [M+], 105 (100). Anal. Calcd for
C14H13BrO: C, 60.67; H, 4.73. Found: C, 60.95; H, 4.88.
Synlett 2011, No. 4, 579–581 © Thieme Stuttgart · New York

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