A Cooperative Strategy for the Highly Selective Intermolecular Oxycarbonylation Reaction of Alkenes using a Palladium Catalyst

Article abstract of DOI:10.1002/anie.201607248

A novel method for intermolecular functionalization of terminal and internal alkenes has been designed. The electrophilic reagent, hypervalent iodine, plays a key role in this process by activating the alkene C=C bond for nucleophilic addition of the palladium catalyst. This process generates an iodonium-containing palladium species which undergoes CO insertion. The new approach, intermolecular oxycarbonylaton reactions of alkenes, has been achieved and carried out under mild reaction conditions to produce the corresponding β-oxycarbonylic acids with excellent efficiencies and levels of regio- and diastereoselectivity.

Full text of DOI:10.1002/anie.201607248

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201607248
German Edition: DOI: 10.1002/ange.201607248
Carbonylation
Cooperative Strategy for the Highly Selective Intermolecular
Oxycarbonylation Reaction of Alkenes using Palladium Catalyst
Ming Li, Feng Yu, Xiaoxu Qi, Pinhong Chen, and Guosheng Liu*
Dedicated to Prof. Qilin Zhou on the occasion of his 60th birthday
Abstract: A novel method for intermolecular functionalization
of terminal and internal alkenes has been designed. The
electrophilic reagent, hypervalent iodine, plays a key role in
=
this process by activating the alkene C C bond for nucleophilic
addition of the palladium catalyst. This process generates an
iodonium-containing palladium species which undergoes CO
insertion. The new approach, intermolecular oxycarbonylaton
reactions of alkenes, has been achieved and carried out under
mild reaction conditions to produce the corresponding b-
oxycarbonylic acids with excellent efficiencies and levels of
regio- and diastereoselectivity.
T
he development of methods to carry out highly selective
functionalization reactions of alkenes is important in the
context of organic synthesis.[1] Owing to their high level of
step economy, difunctionalization reactions of alkenes
(DFAs) are synthetically attractive.[2] In the last decade,
numerous high-valent palladium catalyzed processes, in which
hypervalent iodine reagents are commonly used as oxidants,
have been developed as efficient approaches to carry out
DFAs (Scheme 1a).[3,4] However, in contrast to the highly
efficient intramolecular versions, the intermolecular counter-
parts of these DFAs are often not as effective. Furthermore,
as a result of their sterically hindered nature, internal alkenes
are difficult to activate by palladium catalysts and, conse-
quently, they are much less reactive and/or undergo undesired
alkene isomerization reactions.[5] For instance, we recently
described a palladium-catalyzed intermolecular aminocarbo-
nylation reaction of terminal alkenes and it serves as one of
most efficient approaches to the synthesis of b-aminoacids.
However, internal alkenes are completely inert under the
reaction conditions employed for reactions of their terminal
counterparts.[6] Thus, studies aimed at uncovering new
methods to promote intermolecular DFAs have a synthetic
significance.
Scheme 1. Palladium-catalyzed difunctionalization reaction of alkenes.
FG=functional group.
complexes of alkenes, iodine(III)-mediated reactions are thus
far limited to nucleophilic substitution processes. We sur-
mised that a strategy, which utilizes transition-metal (TM)
=
catalysts to promote nucleophile addition to activated C C
bonds, would be a key component in the design of new
DFAs.[8,9] In processes promoted in this manner, a new type of
organometallic species would serve as a key intermediate.
Thus, it should be possible to use this strategy to design new
transformations. To our knowledge, reactions of this type
have not been explored previously. One unique feature of
organometallic complex is their ability to participate in rapid
CO insertion reactions which generate carbonyl com-
pounds.[10] Importantly, this process does not occur in typical
iodine(III)-mediated/catalyzed reactions when TM catalysts
are absent or in alkene reactions promoted by TM catalysts
alone.[7] In studies designed to test the feasibility of the new
strategy, we uncovered a novel cooperative transition-metal
and iodine(III)-mediated activation mode which serves as the
basis for efficient and selective intermolecular b-oxycarbony-
lation of both terminal and internal alkenes (Scheme 1b).
The b-oxycarboxylic acid motif is an important core
structure in natural products, pharmaceuticals, and biomate-
rials.[11] At the outset of the current effort, we speculated that
Iodine(III) reagents have been employed broadly to
activate both terminal and internal alkenes.[7] Unfortunately,
compared to the diverse reactivity profiles of organometallic
[*] M. Li, Dr. F. Yu, X. Qi, Dr. P. Chen, Prof. Dr. G. Liu
State Key Laboratory of Organometallic Chemistry, Shanghai Insti-
tute of Organic Chemistry, University of Chinese Academy of
Sciences, Chinese Academy of Sciences
345 Lingling Road, Shanghai, 200032 (China)
E-mail: gliu@mail.sioc.ac.cn
Homepage: http://guoshengliu.sioc.ac.cn/
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201607248.
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a three-membered-ring iodonium intermediate, formed from
PhI(OAc)2 and alkenes, might react with a TM catalyst in the
presence of CO to produce oxycarboxylic acids. To test this
proposal, the terminal alkene, phthalimido-pentene 1a (see
Table1), was subjected to a reaction promoted by a palladium
catalyst and PhI(OAc)2. The results show that intermolecular
acetoxycarbonylation of the alkene occurs to form the b-
oxycarboxylic acid 2a. An extensive screen of reaction
parameters (Table 1) led to optimized reaction conditions
necessary for the success of the transformation, likely because
this nitrile stabilizes and/or increases the nucleophilicity of
the palladium species. Finally, it is possible to lower the
palladium catalyst loading and still maintain the efficiency of
the reaction (e.g., 90% yield with 2 mol% Pd catalyst, and
71% yield with 1 mol%; entry 1).
With the optimized reaction conditions in hand, our
attention turned to an exploration of the substrate scope with
respect to the alkene. The results (Table 2) show that aliphatic
terminal alkenes react efficiently to yield the corresponding
acids 2a–q. A number of functional groups, including ethers,
esters, carboxylic acids, imides, halides, and indoles, remain
unchanged under the reaction conditions. Noteworthy, excel-
lent levels of regioselectivity, corresponding to addition of the
acetoxy and carboxylate groups to the respective internal and
terminal alkene carbon atoms, result from these reactions.
Exceptions to this trend are seen when substrates containing
chelating allylic ester and amide groups are used, as
exemplified by reactions that form 2b, 2n, and 2o with poor
levels of regioselectivity (1–3:1). Interestingly, the regiose-
lectivities for formation of these adducts are dramatically
improved when PhI(OAc)2 is replaced by PhI(phth) (> 20:1
for 2b and 2o, and 13:1 for 2n). Also, reaction of the t-butyl-
diphenylsilyl-protected allylic alcohol forms 2p in 52% yield
with greater than 20:1 regioselectivity and 7:1 diastereoselec-
tivity for the anti isomer. Furthermore, reactions of styrene
derivatives bearing functional groups on the arene ring were
also surveyed. Under the optimized reaction conditions with
Pd(OAc)2 (10 mol%), PhI(OAc)2 (2.5 equiv), BF3·OEt2
(20 mol%), and toluene and acetonitrile (v/v = 9:1) as the
solvent, these reactions generate the desired products 2r–3b
in high yields and excellent regioselectivities (> 20:1). Ethyl-
ene gas also reacts to form the expected product 3c in 79%
yield. Selected 1,1-disubstituted alkenes also serve as good
substrates for the acetoxycarbonylation reaction, thus pro-
ducing 3d–f as single isomers in good yields. Interestingly,
nonconjugated dienes react under the optimized reaction
conditions to form the bis-acetoxycarbonylation products
3g,h, processes that differ from previously explored carbon-
ylation reactions of dienes.[12] Importantly, the reaction can be
extended to a 5 mmol scale by using 2 mol% Pd(OAc)2, as
exemplified by the generation of 2h in high yield (90%). In
the large-scale reaction, the side product PhI can be
recovered in over 95% yield and readily reoxidized by
H2O2 to produce PhI(OAc)2 in quantitative yield.
Table 1: Optimization of the reaction conditions for reaction of 1a to
form 2a.[a]
Entry
Reaction conditions
Yield [%][b]
1
“Standard conditions”
95 (90,[c] 71[d])
2
3
4
[Pd(dba)2] instead of Pd(OAc)2
[Pd(PPh3)4] instead of Pd(OAc)2
no Pd catalyst
86
0
0[e]
5
6
7
8
Cu(OAc)2 instead of PhI(OAc)2
no BF3·Et2O
0
0[e]
N2 atmosphere (without CO)
Zn(OTf)2 instead of BF3·Et2O
Mg(ClO4)2 instead of BF3·Et2O
Yb(OTf)3 instead of BF3·Et2O
HOTf instead of BF3·Et2O
PhI(O2CCF3)2 instead of PhI(OAc)2/BF3·Et2O
0[e]
72
68
44
9
10
11
12
79
74[f] (79)[f,g]
[a] Reaction conditions: all reactions were run at 0.2 mmol scale.
1
[b] Yield as determined by H NMR spectroscopy using CF3-DMA as an
internal standard. Regioselectivities in all case are above 20:1. [c] Pd-
(OAc)2 (2 mol%). [d] Pd(OAc)2 (1 mol%). [e] Olefin 1a was recovered
nearly quantitatively. [f] b-trifluoroacetoxyl carboxylic acid as product.
[g] Pd(O2CCF3)2 (5 mol%) was used as catalyst. dba=dibenzylidene-
acetone, DMA=dimethylacetamide, HOTf=trifluoromethanesulfonic
acid.
for this process, and involves the use of Pd(OAc)2 (5 mol%),
PhI(OAc)2 (1.5 equiv), BF3·OEt2 (10 mol%), toluene and
acetonitrile (v/v = 1:1) as the solvent and under a CO
atmosphere (1 atm) at room temperature. Under these
reaction conditions, 1a forms 2a in an excellent yield (95%)
and regioselectivity (entry 1). Moreover, the use of [Pd(dba)2]
in place of Pd(OAc)2 to promote this process gives similar
results (entry 2), but 2a is not generated when [Pd(PPh3)4] is
utilized as the catalyst (entry 3). The results of control
experiments revealed that the palladium catalyst, PhI(OAc)2,
BF3·OEt2, and CO gas are all required for this reaction to
occur (entries 4–7).
We reasoned that the role played by BF3·OEt2 in this
DFAs is to activate loss of acetate from PhI(OAc)2, thus
producing the cationic PhI(OAc)+ species which reacts with
the alkene to form the three-membered iodonium ion
intermediate. Although reaction takes place when other
Lewis and Brønsted acids are utilized, the highest yield is
obtained when BF3·OEt2 serves as the promoting agent
(Table 1, entries 8–11). However, BF3·OEt2 is not required
when PhI(O2CCF3)2 is employed to promote this reaction
(entry 12). In addition, use of acetonitrile as a co-solvent is
Our attention next turned to assessing the reactivities of
internal alkenes (Table 3). The results of a preliminary study
showed that the reactivity of (E)-4-octene [(E)-4a] is
significantly lower than those of terminal alkenes. However,
this substance undergoes the reaction to form anti-5a in high
yield (86%) and with an excellent level of diastereoselectivity
(> 20:1) when a palladium catalyst loading of 10 mol% is
utilized. Interestingly, the opposite diastereoisomer, syn-5a, is
selectively generated in 72% yield when (Z)-4-octene [(Z)-
4a] is employed as the substrate. Other symmetric alkenes,
such as 4b–d, exhibit the same level of reactivity and undergo
the process to form the corresponding products 5b–d
efficiently with excellent diastereoselectivities. Reactions of
asymmetric alkenes also give the corresponding products 5e–
2
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Table 2: Substrate scope with respect to alkenes.[a,b]
[a] Reaction conditions: substrate 1 (0.2 mmol), Pd(OAc)2 (5 mol %), BF3 Et2O (10 mol %), PhI(OAc)2 (1.5 equiv) in CH3CN/toluene (1 mL, v/v = 1:1)
at room temperature under CO balloon. [b] Yield of isolated product. The value within parentheses is that of the regioselectivity. [c] PhI(phth) instead
of PhI(OAc)2, product 2b’, 2n’, and 2o’: OAc replaced by O2CAr (Ar = o-C6H4CO2H). [d] Pd(OAc)2 (2 mol%). [e] Run on a 5 mmol scale with 95% PhI
recovered. [f] d.r.= 7:1. [g] Pd(OAc)2 (10 mol%). [h] Pd(OAc)2 (10 mol%), BF3 Et2O (20 mol%), PhI(OAc)2 (2.5 equiv) in CH3CN/toluene (1 mL, v/v =
1:9). [i] PhI(OAc)2 as a limiting reagent. [j] PhI(OAc)2 (3 equiv). [k] d.r.= 1:1. TBDPS=tert-butyldiphenylsilyl, Ts=4-toluenesulfonyl.
Table 3: Substrate scope with respect to internal alkenes.[a,b]
[a] Reaction conditions: Substrate 4 (0.2 mmol), Pd(OAc)2 (10 mol%), BF3 Et2O (20 mol%), PhI(OAc)2 (2.5 equiv) in CH3CN/toluene (v/v = 1:9,
1 mL) at room temperature with CO balloon. [b] Yield of isolated product. The d.r. value is over 20:1 in all cases, and the value within parentheses is
that of the regioselectivity. [c] [Pd(CH3CN)4](OTf)2 as the catalyst. [c] PhI(OAc)2 was used as a limiting reagent. [e] With Pd(O2CCF3)2/PhI(O2CCF3)2
system. [f] p-MeC6H4I(OAc)2 (2.5 equiv) instead of PhI(OAc)2. [g] 3,5-Me2C6H3I(OAc)2 (2.5 equiv) instead of PhI(OAc)2. [h] The d.r. ratio for 1,3
positions. TFA=trifluoroacetyl.
i with excellent levels of diastereoselectivity (> 20:1) but poor
(1–2:1) regioselectivities. Interestingly, the substrate (Z,Z)-
4g, bearing both electron-rich and electron-deficient internal
alkene moieties, undergoes the acetoxycarboxylation reaction
(65%) at only the electron-rich alkene center to form syn-5g.
In addition, commercially available ethyl (E)-3-nonenate and
(Z)-oleic acid, both of which contain long alkyl chains, react
when treated with the PhI(OCCF3)2/Pd(O2CCF3)2 system to
form the respective products anti-5h and syn-5i in good
yields.
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It was interesting to find that introduction of a chelating
group enables control of the regioselectivity of this process.
For example, the homoallylic phthalimide and acetate groups
in the alkenes (Z)-4j and (Z)-4k direct the acetoxycarbox-
ylation reaction to form the products syn-5j and syn-5k,
respectively, predominantly (ca. 4:1), wherein carboxylate
moiety is vicinal to the directing groups. Moreover, these
allylic directing groups in alkenes (E)/(Z)-4l and (E)/(Z)-4m
enhance the regioselectivity (11:1 and > 20:1, respectively) of
reactions that generate anti/syn-5l and anti/syn-5m, respec-
tively. Cyclohexenes 4n and 4o also serve as good substrates
for this process and form anti-5n (95%) and anti-5o (82%),
respectively. Surprisingly, reaction of 4p, where the imide
group in 5o is replaced by a carboxylic acid moiety, takes
place efficiently (63%) to give 5p with excellent levels of
regio- and diastereoselectivity. This observation suggests that
coordination of a carboxylic acid group with palladium in the
catalyst enhances the step in the process in which it serves as
a nucleophile. Notably, being distinctly different from pre-
vious TM catalyzed functionalization reactions of internal
alkenes,[5] the reaction developed in the current study
generates only trace amounts of alkene isomerization prod-
ucts.
forming cyanobacterium Leptolyngbya crossbyana, and dis-
plays anti-inflammatory and quorum-sensing inhibitory prop-
erties.[13] The plan we employed to prepare honaucin C begins
with 3-butenoic acid, which is transformed into the allylic
ester 10 by sequential chlorination and esterification. Impor-
tantly, oxycarbonylation reaction of 10 occurs exclusively at
the terminal alkene center, even though allylic chlorides like
those present at the other center are reactive in palladium(0)-
catalyzed processes.[14] The high chemoselectivity of the
reaction of 10, a substance containing an array of sensitive
functional groups, demonstrates the synthetic power of the
new process. Finally, methylation using methanol and
TMSCHN2 produces racemic honaucin C in four linear
steps and an overall 60% yield. Importantly, enantiomerically
pure (+)-honaucin C can be generated from the racemate
using enzymatic kinetic resolution with Amano AK.
Finally, some experiments were conducted to gain infor-
mation about the mechanism. The steric and electronic effects
of the iodine(III) reagent were initially explored. The results
show that less sterically hindered and electron-rich iodine(III)
reagent exhibited faster reaction rate than more sterically
crowded and electron-deficient iodine(III) reagent (Sche-
me 3a).[15] Secondly, reaction of the allylimide 1b, which
Because the new DFAs is highly efficient, we believed it
would be worthwhile to explore and utilize reactions of the
generated b-oxycarboxylic acid products. As shown by the
examples displayed in Scheme 2a, these substances are
readily converted into 1,3-diols (anti-6), b-lactones (syn-7),
b-azido esters (anti-8), and a,b-unsaturated alkenes (trans-9)
with excellent levels stereoselectivity and in good yields.
A specific example demonstrating the preparative poten-
tial of the new b-oxycarboxylation method is its use in the
preparation of (+)-honaucin C (Scheme 2b). To our knowl-
edge, no approach has yet been described for the synthesis of
this natural product, which is isolated from the bloom-
Scheme 3. Preliminary mechanistic investigation.
contains a chelating group, provided 2b predominantly with
various iodine(III) reagents (Scheme 3b). The observations
summarized above suggest that the b-oxycarboxylation pro-
cess is possibly initiated by formation of a three-membered
iodonium ion, which is stabilized by electron-rich substituents
on the positively charged iodine center, and the nucleophilic
attack of iodonium by palladium is retarded by the stereic
hindrance of aryl ring (Scheme 3c, left). For the alternative
oxypalladation and sequential CO insertion pathway (Sche-
me 3c, middle), several observations suggest that it is less
likely: 1) the iodine(III) reagent in this mechanistic route
would merely serve as an oxidant to regenerate PdII from Pd0.
Thus, owing to their stronger oxidizing ability, electron-
withdrawing-substituted iodine(III) reagents would favor PdII
regeneration and perhaps accelerate the process. This pre-
Scheme 2. Selected transformations and synthetic applications. Reac-
tion conditions: a) LiAlH4, THF, reflux. b) K2CO3, MeOH, RT; c) PPh3,
DIAD, Ph2P(O)N3, THF, 0oC–RT. d) PPh3, DIAD, THF, 0oC–RT.
e) PhSO2Cl, pyridine, 0oC–RT. f) PhSeCl, NCS. g) Allylic alcohol, DCC.
4
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S. S. Stahl, J. Am. Chem. Soc. 2006, 128, 7179 – 7181; d) L. V.
diction is opposite to the observation; 2) the typical chelating
effect on the nucleopalladation reaction of 1b causes it to
favor the C1 position, as proposed by Feringa (Scheme 3c,
right),[16] and result in predominant formation of the opposite
regioisomer to 2b; 3) oxypalladation processes typically favor
electron-deficient alkenes,[17] whereas the iodine(III)-medi-
ated reactions take place selectively at electron-rich alkene
centers.[7] The selective formation of syn-5g (Table 3) and
honausin C (Scheme 2b) exemplifies this significant differ-
ence.
In summary, we have developed a novel synergestic,
transition-metal-catalyzed and iodine(III)-mediated, DFAs
for b-oxycarboxylation, and both terminal and internal
alkenes participate. The process, which is conducted under
very mild reaction conditions, has good functional-group
compatibility, broad substrate scope, and high levels of regio-
and diastereoselectivity. The new oxycarbonylation process
serves as an efficient method for bis-functionalization of
alkenes. Given the importance of the b-hydroxycarboxylic
acid core structure in nature products, pharmaceuticals and
biomaterials, this method should find wide applications in
organic synthesis.
Desai, M. S. Sanford, Angew. Chem. Int. Ed. 2007, 46, 5737 –
5740; Angew. Chem. 2007, 119, 5839 – 5842; e) T. Wu, G. Yin, G.
Liu, J. Am. Chem. Soc. 2009, 131, 16354 – 16355; f) X. Mu, T. Wu,
H.-Y. Wang, Y. Guo, G. Liu, J. Am. Chem. Soc. 2012, 134, 878 –
881; g) R. Alam, L. T. Pilarski, E. Pershagen, K. J. Szabꢁ, J. Am.
Chem. Soc. 2012, 134, 8778 – 8781; h) C. Chen, P. Chen, G. Liu, J.
Am. Chem. Soc. 2015, 137, 15648 – 15651.
[5] a) J. F. Hartwig, Organotransition Metal Chemistry, from Bond-
ing to Catalysis, University Science Books, 2010; b) A. Vasseur, J.
Bruffaerts, I. Marek, Nat. Chem. 2016, 8, 209 – 219; c) C.
Martꢂnez, K. MuÇiz, Angew. Chem. Int. Ed. 2012, 51, 7031 –
7034; Angew. Chem. 2012, 124, 7138 – 7141; d) C. Martꢂnez, K.
MuÇiz, Chem. Eur. J. 2016, 22, 7367 – 7370; e) C. Martꢂnez, Y.
Wu, A. B. Weinstein, S. S. Stahl, G. Liu, K. MuÇiz, J. Org. Chem.
2013, 78, 6309 – 6315.
[6] J. Cheng, X. Qi, M. Li, P. Chen, G. Liu, J. Am. Chem. Soc. 2015,
137, 2480 – 2483.
[7] For reviews, see: a) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008,
108, 5299 – 5358; b) Hypervalent Iodine in Organic Chemistry:
Chemical Transformation (Eds.: R. M. Moriatry, O. Prakash,
Wiley-Interscience, New York, 2008. For recent examples on the
iodine(III)-mediated intermolecular reaction of alkenes, see:
c) J. A. Souto, D. Zian, K. MuÇiz, J. Am. Chem. Soc. 2012, 134,
7242 – 7245; d) C. Martꢂnez, K. MuÇiz, Angew. Chem. Int. Ed.
2015, 54, 8287 – 8291; Angew. Chem. 2015, 127, 8405 – 8409; e) S.
Haubenreisser, T. H. Wçste, C. Martꢂnez, K. Ishihara, K. MuÇiz,
Angew. Chem. Int. Ed. 2016, 55, 413 – 417; Angew. Chem. 2016,
128, 422 – 426.
Acknowledgements
[8] Palladium catalysts have been extensively studied as nucleophile
in the organometallic chemistry. For example, Pd0 has been
extensively applied in oxidative addition arylhalides and related
cross coupling reaction. Meanwhile, PdII could be used as
nucleophile to achieve high-valent palladium species formation.
For the pioneering study, see: A. J. Canty, Acc. Chem. Res. 1992,
25, 83 – 90.
[9] The iodine(III) group exhibited higher leaving capacity, as
established by Ochiai. For details, see: a) T. Okuyama, T. Takino,
T. Sueda, M. Ochiai, J. Am. Chem. Soc. 1995, 117, 3360 – 3367.
The ring-opening of iodonium species was reported by Gade,
see: b) Y.-B. Kang, L. H. Gade, J. Am. Chem. Soc. 2011, 133,
3658 – 3667.
[10] For reviews, see: a) “Carbonylation of alkenes”: M. L. Clarke,
J. A. Fuentes in Science of Synthesis, Vol. 1 (Eds.: Z. Van Leeu-
wen, W. N. M. Piet), Thieme, Stuttgart, 2014, pp. 229 – 258;
b) X.-F. Wu, X. Fang, L. Wu, R. Jackstell, H. Neumann, M.
Beller, Acc. Chem. Res. 2014, 47, 1041 – 1053. For selective
examples on the transition metal-catalyzed intermolecular
carbonylation of alkenes, see: c) K. Dong, X. Fang, R. Jackstell,
G. Laurenczy, Y. Li, M. Beller, J. Am. Chem. Soc. 2015, 137,
6053 – 6058; d) G. Zhang, B. Gao, H. Huang, Angew. Chem. Int.
Ed. 2015, 54, 7657 – 7661; Angew. Chem. 2015, 127, 7767 – 7771;
and reference [6]. However, the internal alkenes were ineffec-
tive under these conditions.
[11] A. Parenty, X. Moreau, J.-M. Campagne, Chem. Rev. 2006, 106,
911 – 939, and updated in Chem. Rev. 2013, 113, PR1 – PR35.
[12] Treatment of 3h with Pd(OAc)2/CuCl2/CO/MeOH leads to
formation of a cyclization product in 68% yield. Notably, this
catalytic system is ineffective for promoting reactions of internal
alkenes. For details, see the Supporting Information.
We are grateful for financial support from the National Basic
Research Program of China (973-2015CB856600) and the
National Nature Science Foundation of China (Nos.
21225210, 21421091, 21532009 and 21672236).
Keywords: alkenes · carbonylation · iodine · palladium ·
total synthesis
[1] a) M. Beller, J. Seayad, A. Tillack, H. Jiao, Angew. Chem. Int.
Ed. 2004, 43, 3368 – 3398; Angew. Chem. 2004, 116, 3448 – 3479;
b) Catalytic Heterofunctionalization (Eds.: A. Togni, H. Grꢀtz-
macher), Wiley-VCH, Weinheim, 2001.
[2] a) L. M. Surhone, M. T. Tennoe, S. F. Henssonow, Vicinal
Difunctionalization, Betascript Publishing, Saarbrꢀcken, 2010;
b) R. M. Romero, T. H. Woeste, K. Muniz, Chem. Asian J. 2014,
9, 972 – 983; c) J. P. Wolfe, Top. Heterocycl. Chem. 2013, 32, 1 –
38; d) Y. Shimizu, M. Kanai, Tetrahedron Lett. 2014, 55, 3727 –
3737; e) S. R. Chemler, M. T. Bovino, ACS Catal. 2013, 3, 1076 –
1091; f) K. H. Jensen, M. S. Sigman, Org. Biomol. Chem. 2008, 6,
4083 – 4088.
[3] For some reviews, see: a) K. MuÇiz, Angew. Chem. Int. Ed. 2009,
48, 9412 – 9423; Angew. Chem. 2009, 121, 9576 – 9588; b) L.-M.
Xu, B.-J. Li, Z. Yang, Z.-J. Shi, Chem. Soc. Rev. 2010, 39, 712 –
733; c) K. M. Engle, T.-S. Mei, X. Wang, J.-Q. Yu, Angew. Chem.
Int. Ed. 2011, 50, 1478 – 1491; Angew. Chem. 2011, 123, 1514 –
1528; d) A. J. Hickman, M. S. Sanford, Nature 2012, 484, 177 –
185; e) “Organometallic Complexes of Palladium”: P. Chen, G.
Liu, K. M. Engle J.-Q. Yu in Science of Synthesis, Vol. 1 (Ed.:
B. M. Stoltz), Thieme, Stuttgart, 2013, p. 63.
[4] For some recent examples with iodine(III) reagents, see: a) E. J.
Alexanian, C. Lee, E. J. Sorensen, J. Am. Chem. Soc. 2005, 127,
7690 – 7691; b) J. Streuff, C. H. Hçvelmann, M. Nieger, K.
MuÇiz, J. Am. Chem. Soc. 2005, 127, 14586 – 14587; c) G. Liu,
[13] H. Choi, S. J. Mascuch, F. A. Villa, T. Byrum, M. E. Teasdale,
J. E. Smith, L. B. Preskitt, D. C. Rowley, L. Gerwick, W. H.
Gerwick, Chem. Biol. 2012, 19, 589 – 598.
[14] V. P. Baillargeon, J. K. Stille, J. Am. Chem. Soc. 1986, 108, 452 –
461.
[15] For details see the Supporting Information.
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[16] Feringa and co-workers demonstrates that the Wacker reaction
of 1b occurs in the terminal carbon atom. See: a) B. Weiner, A.
Baeza, T. Jerphagnon, B. L. Feringa, J. Am. Chem. Soc. 2009,
131, 9473 – 9474; b) J.-J. Dong, E. C. Harvey, M. FaÇanas-
Mastral, W. R. Browne, B. L. Feringa, J. Am. Chem. Soc. 2014,
136, 17302 – 17307.
[17] a) S. S. Stahl, Angew. Chem. Int. Ed. 2004, 43, 3400 – 3420;
Angew. Chem. 2004, 116, 3480 – 3501; b) V. Kotov, C. C. Scar-
borough, S. S. Stahl, Inorg. Chem. 2007, 46, 1910 – 1923.
Received: July 26, 2016
Published online: && &&, &&&&
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Communications
Carbonylation
M. Li, F. Yu, X. Qi, P. Chen,
G. Liu*
&&&& — &&&&
Cooperative Strategy for the Highly
Selective Intermolecular
Oxycarbonylation Reaction of Alkenes
using Palladium Catalyst
‘Kene activation: A novel method for
intermolecular oxycarbonylation of ter-
minal and internal alkenes has been
designed. The electrophilic reagent,
hypervalent iodine, plays a key role in this
process by activating the alkene bond for
nucleophilic addition of the palladium
catalyst.
Angew. Chem. Int. Ed. 2016, 55, 1 – 7
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!