Intermolecular mizoroki-heck reaction of aliphatic olefins with high selectivity for substitution at the internal position

Article abstract of DOI:10.1002/anie.201201806

New ligand for old reaction: The title reaction of aryltriflates with aliphatic olefins leads to substitution at the internal position with high selectivity. The ratio of the desired isomer (shown in the scheme) to the sum of all other isomers is generall

Full text of DOI:10.1002/anie.201201806

Angewandte
Chemie
DOI: 10.1002/anie.201201806
Heck Reaction
Intermolecular Mizoroki–Heck Reaction of Aliphatic Olefins with
High Selectivity for Substitution at the Internal Position**
Liena Qin, Xinfeng Ren, Yunpeng Lu, Yongxin Li, and Jianrong (Steve) Zhou*
The Mizoroki–Heck reaction generally refers to Pd-catalyzed
À
C C bond formation between organic (pseudo)halides and
olefins. Today, it has become a powerful tool to prepare
substituted olefins.[1] A key issue in intermolecular Heck
reactions is the control of the site where aryl groups insert into
olefins. High regioselectivity can be easily achieved for olefins
carrying substituents with a significant electronic difference at
the two olefinic sites,[2] such as acrylates[3] and vinyl ethers.[4]
Aliphatic olefins, however, generally lack intrinsic elec-
tronic differentiation between two olefinic positions and it has
been challenging to achieve good regiocontrol [Eq. (1),
Scheme 1].[5,6] To induce terminal insertion, coordinating
groups are often present on olefins to serve as chelates.[7]
The chelation strategy was also used in oxidative[8] and
decarboxylative[9] Heck reactions to achieve regioselectivity.
Recently, Sigman and Werner reported high terminal selec-
tivity even for olefins without chelating groups.[10] For
aliphatic olefins, high internal selectivity also proved very
difficult to achieve, except a few special cases.[11] For example,
Scheme 1. Intermolecular Heck reactions of aliphatic olefins.
TMEDA=N,N,N’,N’-tetramethylethylenediamine, Tf=trifluorometh-
anesulfonyl, dppp=1,3-bis(diphenylphosphino)propan, dba=dibenzyl-
ideneacetone, DMA=dimethylaceamide.
Cabri et al. reported that olefin insertion into cationic aryl–Pd
intermediates can be biased toward the internal position, but
the selectivity was too low to be synthetically useful.[12] As
a special case, allylic alcohol gave excellent internal selectiv-
ity, because owing to the inductive effect of its hydroxy group
the electronic density on the internal carbon atom is
decreased [Eq. (2), Scheme 1]. The inductive effect quickly
diminishes over several bonds. Thus, for homoallylic alcohol
the selectivity dropped drastically [Eq. (3), Scheme 1].
Herein, we report a general method for Heck reactions of
aliphatic olefins in high internal selectivity, by using a set of
ferrocene-based bisphosphine ligands [Eq. (4), Scheme 1].
The Heck products, a-alkylstyrenes can be readily con-
verted to various chiral building blocks by asymmetric
catalytic processes.[13] They are also intermediates in the
synthesis of bioactive natural products[14] and drug candi-
dates.[15] The a-alkylstyrenes used to be prepared by cross-
couplings of 2-alkenyl electrophiles or 2-alkenyl metallic
reagents. Our new method directly uses simple olefins and
does not require preactivation of olefin substrates.
Initially, we used a model reaction of 1-naphthyl triflate
and 1-octene and dppf as supporting ligand for the palladium
catalyst (Figure 1). To our surprise, a dramatic effect of bases
was observed (Figure 1). In particular, when trialkylamines,
such as triethylamine and Hꢀnigꢁs base, were used, significant
reduction of aryl triflate was observed, and the corresponding
reduction product was obtained in up to 50% yield.[16] In
contrast, when urotropine was used, no reduction byproduct
was detected and Heck products were formed in almost
quantitative yield. The ratio of the desired isomer, 2-aryl-1-
octene versus all other isomers was 13:1, determined by
GC.[17] It is worth pointing out that this ratio is not equivalent
to regioselectivity. Urotropine is a relatively weak Lewis
base,[18] and it does not compete strongly for the vacant site on
a cationic (dppf)Pd(Ar) intermediate. Furthermore, its b-
hydrogen atom cannot eliminate to donate a hydride to
palladium, according to Bredtꢁs rule. In comparison, when the
more basic and donating bases DBU and DABCO were used,
only small amounts of Heck products were formed. Other
bases such as 2,6-lutidine, proton sponge, and Li2CO3 gave
much lower yields than urotropine.
[*] L. Qin, Dr. X. Ren, Dr. Y. Lu, Dr. Y. Li, Prof. Dr. J. Zhou
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University, 21 Nanyang Link 637371
(Singapore)
E-mail: jrzhou@ntu.edu.sg
[**] We thank Singapore National Research Foundation (NRF-RF2008-
10) and Nanyang Technological University for financial support and
Johnson-Matthey for a gift of palladium.
In the model reaction of 1-naphthyl triflate and 1-octene,
we have screened many bisphosphine ligands to improve the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201201806.
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Figure 1. Effect of bases on the formation of different products of the
model reaction. In addition to the formation of the Heck product
(black bars) and isomers (light gray), reduction of the aryl triflate (dark
gray) was also observed. DIPEA=diisopropylethylamine, Cy=cyclo-
hexyl, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DABCO=1,4-
diazabicyclo[2.2.2]octane.
Figure 3. Effect of ligands in the Heck reaction of phenyl triflate. dppe,
dppb, dpppent, and dppbz are typical bisphosphine ligands.[19]
selectivity. To our delight, ferrocene-derived 1,1’-bisphos-
phine ligands were particularly selective in delivering the
branched product (Figure 2). For example, when the ligand
dippf was used, the selectivity was improved to 57:1 in the
presence of 2 mol% palladium catalyst (for details, see the
Supporting Information).
Figure 2. Interplay between ligands and aryl triflates on selectivity. The
ratios of the branched Heck product to all other isomers are shown.
[a] 5 mol% [Pd(dba)2] and 10 mol% ligand were used.
Scheme 2. Scope of organic triflates in the Heck reaction of 1-octene.
The ratios of the Heck product shown in the scheme to all other
isomers are given in brackets.
Later, we found that the selectivity was highly dependent
on the aryl electrophiles. For example, if the aryl triflate
contained a large ortho-tert-butyl group, the ligand dppf was
very selective and gave a selectivity of 50:1 (Figure 2). In
general, we found it very difficult to achieve high selectivity
for aryl triflates without an ortho group. In model reactions
with phenyl triflate, the ligand dppf only afforded 4:1
selectivity, and the ligand dippf gave a complex mixture of
product isomers. After examination of a dozen of bisphos-
phine ligands, we found that the new ligand 1,1’-bis[di(1-
naphthyl)phosphino]ferrocene (dnpf) can give a good selec-
tivity of 11:1 (Figure 3; dnpf = d(1-naph)pf in Figure 3).[19]
After establishing suitable conditions for each subclass of
aryl triflates, we examined the scope of aryl triflates with 1-
octene as model olefin (Scheme 2). Some observations are
noteworthy. a) For aryl electrophiles without ortho groups,
the ligand dnpf gave a selectivity above 10:1 for most
substrates. For aryl triflates substituted with either electron-
donating or electron-withdrawing groups at the para position,
the selectivity dropped slightly. Some heteroaryl triflates,
derived from indole and quinoline, worked well. One example
of a vinyl electrophile is also included. b) For aryl electro-
philes carrying small ortho substituents, the dippf ligand
afforded 2-aryl-1-octenes almost exclusively in most cases.
Both aromatic chloride and nitrile were tolerated under the
catalytic condition. For o-anisyl triflate, the ligand dnpf was
found to be more selective than dippf. c) For aryl electro-
philes carrying large ortho groups, the dppf ligand gave good
to excellent selectivity. Even sterically demanding 2-mesityl
triflate can give high selectivity at 1008C. Some polar ortho
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subtituents such as nitro, ester, and dimethylamino substitu-
ents did not interfere with the catalytic cycle.
Next, we studied the scope of terminal olefins with each
subclass of aryl triflates (Scheme 3). Many polar groups on
olefins are compatible, such as ester, nitrile, phthalimide,
Scheme 4. a Arylation of acrolein diethyl acetal [Eqs.(5) and (6)] and
treatment of the [(dnpf)Pd(Ph)Br] complex with 1-octene [Eq. (7)].
presence of AgOTf gave the Heck product in 68% yield and
10:1 selectivity [Eq. (7), Scheme 4].[24] The selectivity is very
similar to that observed under catalytic conditions. Single-
crystal X-ray diffraction analysis of the complex showed some
unusual structural features.[25] First, the backbone of dnpf
adopts an almost eclipsed ferrocene conformation, unlike
staggered ones in related dppf complexes.[26] Edge-to-edge
interactions between two neighboring P-naphthyl groups
were identified to enforce this unusual conformation. Second,
the coordination geometry is significantly distorted from
square planarity. For example, the bond angles ]P2-Pd-
C(phenyl) and ]P1-Pd-Br are deviated from linearity by
more than 10degrees (Figure 4). Furthermore, both the Pd-
phenyl group and bromine atom are forced substantially out
of the plane defined by P1-Pd-P2; this kind of distorted
geometry is absent in dppf complexes.[26] The distortion is
caused by steric repulsion with neighboring P-naphthyl
groups of the ligand. In the terminal insertion mode, the
olefinic substituent will experience severe steric repulsion
with the ligand. Thus, terminal insertion is greatly disfavored.
We have also conducted DFT calculations (PBE1PBE) on
the insertion step using propene as model olefin. The purpose
is to understand the effect of both ligands and ortho groups on
Pd-phenyl groups on regioselectivity. Assuming fast equilib-
rium among olefin conformers of each complex, regioselec-
tivity will be dictated by relative energy (DE) of transition
Scheme 3. Scope of olefins in Heck reactions of model aryl triflates.
The ratios of the Heck product shown in the scheme to all other
isomers are given in brackets. Phth=phthaloyl, Ts=p-toluenesulfonyl.
sulfonamide, and even alcohol groups. Most reactions pro-
vided good internal selectivity. For example, homoallylic and
bishomoallylic alcohols coupled with aryl triflates carrying no
ortho substituents in more than 10:1 selectivity, which is
unprecedented.[12] Some very hindered olefins can also be
used. In a reaction of tert-butylethylene, the aryl group added
preferentially to the more hindered internal position in 9:1
selectivity, in the presence of the dppf ligand. Furthermore,
allylbenzene reacted smoothly, although it is prone to
undergo facile olefin isomerization catalyzed by palladium
hydride.[20] One example, with 5-hydroxy-1-pentene as olefin
substrate, was scaled up to produce 1.2 g of the Heck product
without loss of selectivity (12:1). The desired isomer can be
separated from other isomers by flash chromatography.
In Heck reactions of a,b-unsaturated carbonyl com-
pounds, there is a strong bias for aryl groups to insert at the
electron-poor b position.[21] Thus, to introduce aryl groups at
the a position, cross-couplings of a-halogenated or a-metal-
lated acrylates are often employed.[22] Interestingly, our Heck
condition can be applied to perform selective a arylation of
acrolein diethyl acetal [Eqs. (5)–(6), Scheme 4].[23]
Figure 4. ORTEP representation of the [(dnpf)Pd(Ph)Br] complex with
50% thermal ellipsoid probability. Important bond angles: ]Br-Pd-
C(phenyl)=848; ]P1-Pd-P2=1038; ]P2-Pd-C(phenyl)=1688; ]P1-
Pd-Br=1668.
To determine the origin of high selectivity from the dnpf
ligand, we have prepared its oxidative addition complex with
PhBr. Treatment of [(dnpf)Pd(Ph)Br] with 1-octene in the
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[2] Reviews: a) W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2;
b) G. D. Daves, A. Hallberg, Chem. Rev. 1989, 89, 1433; c) P.
Nilsson, K. Olofsson, M. Larhed, The Mizoroki-Heck Reaction
(Ed.: M. Oestreich), Wiley, New York, 2009, pp. 133.
[3] Examples: a) A. F. Littke, G. C. Fu, J. Am. Chem. Soc. 2001, 123,
6989; b) B. P. Carrow, J. F. Hartwig, J. Am. Chem. Soc. 2010, 132,
79.
states (TSs). From the cationic (dppf)Pd(Ph)(propene), DE
between the predominant TS(terminal) and TS(internal) was
calculated to be 2 kcalmolÀ1. From the corresponding ortho-
tert-butylphenyl complex, DE increased to 4.5 kcalmolÀ1. The
reason is that the TS of terminal insertion is more sensitive to
steric influence than that of internal insertion. Moreover,
when the ligand was switched from dppf to dnpf in the
cationic (ligand)Pd(Ph)(propene) complex, DE was raised to
2.3 kcalmolÀ1, which is in agreement with observed trends of
selectivity.
In summary, we have realized a general method for Heck
reaction of terminal aliphatic olefins with high internal
selectivity. The ratio of the desired products, 2-aryl-1-alkenes
versus the sum of all other isomers is generally higher than
10:1. When aryl triflates contain ortho substituents, the
selectivity is even higher, up to 100:0. The synthetic usefulness
of the method was further augmented by the fact that trace
amounts of minor isomers can be readily removed from the
desired isomers by flash chromatography in most cases. Our
experimental and computational studies indicate that the
dnpf ligand improved selectivity by inhibiting the minor
pathway of terminal insertion owing to steric effects. Fur-
thermore, the (dnpf)Pd catalyst was successfully applied to
a regioselective Heck reaction of aromatic olefins by us
recently.[27] Application of the catalyst to similar Heck
reactions of aryl halides is ongoing.
[4] Examples: a) W. Cabri, I. Candiani, A. Bedeschi, R. Santi, J.
Org. Chem. 1990, 55, 3654; b) K. S. A. Vallin, M. Larhed, A.
Hallberg, J. Org. Chem. 2001, 66, 4340; c) T. M. Gøgsig, A. T.
Lindhardt, M. Dekhane, J. Grouleff, T. Skrydstrup, Chem. Eur. J.
2009, 15, 5950; d) J. Ruan, J. Xiao, Acc. Chem. Res. 2011, 44, 614.
[5] Examples: a) H. A. Dieck, R. F. Heck, J. Am. Chem. Soc. 1974,
96, 1133; b) S. Brꢂse, M. Schroen, Angew. Chem. 1999, 111, 1139;
Angew. Chem. Int. Ed. 1999, 38, 1071; c) A. C. Albꢃniz, P.
Espinet, B. Martꢄn-Ruiz, D. Milstein, J. Am. Chem. Soc. 2001,
123, 11504; d) S. P. Mabic, L. Vaysse, C. Benezra, J.-P. Lepoitte-
vin, Synthesis 1999, 1127; e) Y. Fall, F. Berthiol, H. Doucet, M.
Santelli, Synthesis 2007, 1683; f) In the reaction of PhBr and
vinylcyclohexane under the ligand-free condition, we deter-
mined selectivity to be 5:1 favoring terminal insertion: Q. Yao,
E. P. Kinney, Z. Yang, J. Org. Chem. 2003, 68, 7528; g) V. Calꢅ,
A. Nacci, A. Monopoli, P. Cotugno, Angew. Chem. 2009, 121,
6217; Angew. Chem. Int. Ed. 2009, 48, 6101.
[6] Computational studies: a) R. J. Deeth, A. Smith, J. M. Brown, J.
Am. Chem. Soc. 2004, 126, 7144; b) H. von Schenck, B. ꢆker-
mark, M. Svensson, J. Am. Chem. Soc. 2003, 125, 3503.
[7] Examples: a) F. Berthiol, H. Doucet, M. Santelli, Synthesis 2006,
1518; b) D. Pan, A. Chen, Y. Su, W. Zhou, S. Li, W. Jia, J. Xiao,
Q. Liu, L. Zhang, N. Jiao, Angew. Chem. 2008, 120, 4807; Angew.
Chem. Int. Ed. 2008, 47, 4729.
[8] a) Terminal-selective oxidative Heck reaction of aliphatic olefins
carrying directing groups: J. H. Delcamp, M. C. White, J. Am.
Chem. Soc. 2006, 128, 15076; b) Y. Su, N. Jiao, Org. Lett. 2009,
11, 2980; c) J. H. Delcamp, A. P. Brucks, M. C. White, J. Am.
Chem. Soc. 2008, 130, 11270; d) E. W. Werner, M. S. Sigman, J.
Am. Chem. Soc. 2010, 132, 13981.
[9] Terminal-selective decarboxylative Heck reaction of aliphatic
olefins carrying directing groups: P. Hu, J. Kan, W. Su, M. Hong,
Org. Lett. 2009, 11, 2341.
[10] E. W. Werner, M. S. Sigman, J. Am. Chem. Soc. 2011, 133, 9692.
[11] Ni-catalyzed internal-selective Heck reactions of benzyl chlor-
ides: R. Matsubara, A. C. Gutierrez, T. F. Jamison, J. Am. Chem.
Soc. 2011, 133, 19020.
[12] A Pd/dppp catalyst gave good internal selectivity (19:1) in
reactions of homoallylic alcohol with 1-naphthyl electrophiles
(special case). The high selectivty was not observed with other
aryl electrophiles; a) W. Cabri, I. Candiani, A. Bedeschi, R.
Santi, J. Org. Chem. 1992, 57, 3558; b) One example of 9:1
selectivity favoring internal insertion was reported for a special
pair of substrates: J. Ruan, J. A. Iggo, N. G. Berry, J. Xiao, J. Am.
Chem. Soc. 2010, 132, 16689; c) J. Mo, L. Xu, J. Ruan, S. Liu, J.
Xiao, Chem. Commun. 2006, 3591.
Experimental Section
In air, a 100 mL dry Schlenk tube containing a magnetic stir bar was
charged with [Pd(dba)2] (172 mg, 0.30 mmol) and 1,1’-bis[di(1-
naphthyl)phosphino]ferrocene, dnpf (453 mg, 0.60 mmol). The
atmosphere was switched to argon after three cycles of evacuation
and refilling. Degassed DMA (30 mL) was then added. After stirring
for 10 min at room temperature, the mixture was treated with p-tert-
butylphenyl triflate (1.69 g, 6.0 mmol), 4-pentene-1-ol (2 equiv, 1.03 g,
12.0 mmol), and urotropine (2 equiv, 1.68 g, 12.0 mmol). The reaction
tube was capped tightly and the mixture was heated with vigorous
stirring in an oil bath at 808C (external temperature). The aryl triflate
was fully consumed after seven hours (monitored by GC). The ratio of
the desired isomer versus all other isomers combined was determined
to be 12:1 by GC. After routine workup and flash chromatography,
the Heck product was obtained as colorless oil (1.20 g, 92% combined
yield). The desired isomer was separated from other minor isomers by
flash chromatography.
Received: March 6, 2012
Published online: && &&, &&&&
[13] Asymmetric hydrogenation: a) S. J. Roseblade, A. Pfaltz, Acc.
Chem. Res. 2007, 40, 1402; b) J. Mazuela, P.-O. Norrby, P. G.
Andersson, O. Pamies, M. Dieguez, J. Am. Chem. Soc. 2011, 133,
13634; c) J. Mazuela, J. J. Verendel, M. Coll, B. Schaffner, A.
Borner, P. G. Andersson, O. Pamies, M. Dieguez, J. Am. Chem.
Soc. 2009, 131, 12344; d) Sharpless dihydroxylation: H. C. Kolb,
M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94,
2483; Epoxidation: e) Z. Li, H. Yamamoto, J. Am. Chem. Soc.
2010, 132, 7878; Hydroboration: f) R. Corberꢇn, N. W. Mszar,
A. H. Hoveyda, Angew. Chem. 2011, 123, 7217; Angew. Chem.
Int. Ed. 2011, 50, 7079; g) C. Mazet, D. Gꢃrard, Chem. Commun.
2011, 47, 298; Hydroacylation: h) I. Piel, M. Steinmetz, K.
Hirano, R. Froehlich, S. Grimme, F. Glorius, Angew. Chem. 2011,
123, 5087; Angew. Chem. Int. Ed. 2011, 50, 4983; i) K. Kundu,
Keywords: alkenes · Heck reaction · insertion ·
palladium catalysis · regioselectivity
.
[1] Reviews: a) R. F. Heck, Acc. Chem. Res. 1979, 12, 146; b) I. P.
Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009;
c) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. 2005,
117, 4516; Angew. Chem. Int. Ed. 2005, 44, 4442; d) S. Brꢂse, A.
de Meijere, Metal-Catalyzed Cross-coupling Reactions (Eds.: A.
de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004,
pp. 217 – 316; e) G. Zeni, R. C. Larock, Chem. Rev. 2006, 106,
4644.
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J. V. McCullagh, A. T. Morehead, Jr., J. Am. Chem. Soc. 2005,
127, 16042.
[20] Example: D. Gauthier, A. T. Lindhardt, E. P. K. Olsen, J.
Overgaard, T. Skrydstrup, J. Am. Chem. Soc. 2010, 132, 7998.
[21] A single example of a-selective Heck reaction between PhI and
methyl acrylate was reported, using Pd nanoparticles as catalyst
in supercritical CO2: L. K. Yeung, C. T. Lee, K. P. Johnston,
R. M. Crooks, Chem. Commun. 2001, 2290.
[14] Examples: a) S. P. Cook, A. Polara, S. J. Danishefsky, J. Am.
Chem. Soc. 2006, 128, 16440; b) G. Li, A. Padwa, Org. Lett. 2011,
13, 3767; c) A. Padwa, M. A. Brodney, M. Dimitroff, B. Liu, T.
Wu, J. Org. Chem. 2001, 66, 3119; d) J. R. Vyvyan, C. Loitz, R. E.
Looper, C. S. Mattingly, E. A. Peterson, S. T. Staben, J. Org.
Chem. 2004, 69, 2461.
[15] Examples: a) L. Zhou, C. K. Tan, X. Jiang, F. Chen, Y.-Y. Yeung,
J. Am. Chem. Soc. 2010, 132, 15474; b) L. J. Farmer, L. Zhi, S.
Jeong, W. W. Lamph, D. L. Osburn, G. Croston, K. S. Flatten,
R. A. Heyman, A. M. Nadzan, Bioorg. Med. Chem. Lett. 2003,
13, 261; c) T. Nishi, K. Ishibashi, K. Nakajima, Y. Iio, T.
Fukazawa, Tetrahedron: Asymmetry 1998, 9, 3251; d) A. P.
Truong, et al., Bioorg. Med. Chem. Lett. 2010, 20, 4789; e) N.
Charrier, et al., Bioorg. Med. Chem. Lett. 2009, 19, 3664 For
authors of references [15d,e] see the Supporting Information.
[16] Examples of Pd-catalyzed reduction of aryl triflates by trialkyl-
amines: a) J. M. Saa, M. Dopico, G. Martorell, A. Garcia-Raso,
J. Org. Chem. 1990, 55, 991; b) W. Cabri, I. Candiani, S.
DeBernardinis, F. Francalanci, S. Penco, R. Santo, J. Org.
Chem. 1991, 56, 5796.
[22] Examples: a) F. Berthiol, H. Doucet, M. Santelli, Eur. J. Org.
ˇ
ˇ
´
Chem. 2003, 1091; b) B. H. Lipshutz, Z. V. Boskovic, D. H. Aue,
Angew. Chem. 2008, 120, 10337; Angew. Chem. Int. Ed. 2008, 47,
10183; c) L. Jeremy I, Tetrahedron Lett. 1993, 34, 6211; d) Cou-
pling of a-diazocarbonyl compounds: C. Peng, G. Yan, Y. Wang,
Y. Jiang, Y. Zhang, J. Wang, Synthesis 2010, 4154; e) Coupling of
tosylhydrazides: J. Barluenga, M. Tomꢇs-Gamasa, F. Aznar, C.
Valdꢃs, Chem. Eur. J. 2010, 16, 12801.
[23] a-Arylacroleins can be obtained after hydrolysis of the acetals,
but the former are unstable at room temperature: I. Crossland,
Org. Synth. 1981, 60, 6.
[24] The stoichiometric reaction of [(PMe3)2PdPh]+BF4 and 1-
À
octene gave 2:1 selectivity favoring terminal insertion: F.
Kawataka, I. Shimizu, A. Yamamoto, Bull. Chem. Soc. Jpn.
1995, 68, 654.
[25] CCDC 870134 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[26] Examples of [(dppf)Pd(Ar)X] complexes: a) A. G. Sergeev,
G. A. Artamkina, V. N. Khrustalev, M. Y. Antipin, I. P. Belet-
skaya, Mendeleev Commun. 2007, 17, 142; b) C. Czauderna, H.
Wurziger, Y. Sun, W. R. Thiel, Z. Anorg. Allg. Chem. 2008, 634,
2380.
[17] As many as six minor isomers of the Heck product were detected
1
by GC. Integration of the signals in the H NMR spectrum was
not suitable for determination of selectivity in these reactions
owing to low signal intensity of the minor isomers.
[18] The pKa values of conjugate acids in water: urotropine, 5.1;
DBU, 12; DABCO, 8.8; 2,6-lutidine, 6.8; proton sponge, 12.
[19] Ligands d(o-tol)pf, d(o-biph)pf, d(1-naph)pf, and d(2-naph)pf
are 1,1’-ferrocene bisphosphines carrying o-tolyl, o-biphenyl, 1-
naphthyl, and 2-naphthyl groups on the phosphorus atom,
respectively.
[27] Y. Zou, L. Qin, X. Ren, Y. Lu, Y. Li, J. Zhou, unpublished results.
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Angewandte
Communications
Communications
Heck Reaction
L. Qin, X. Ren, Y. Lu, Y. Li,
J. Zhou*
&&&& — &&&&
Intermolecular Mizoroki–Heck Reaction
of Aliphatic Olefins with High Selectivity
for Substitution at the Internal Position
New ligand for old reaction: The title
reaction of aryltriflates with aliphatic
olefins leads to substitution at the inter-
nal position with high selectivity. The
ratio of the desired isomer (shown in the
scheme) to the sum of all other isomers
is generally above 10:1. The key to
success is the use of a ferrocene
bisphosphine ligand (R=1-naphthyl).
The reaction can be easily scaled up, and
minor isomers can be separated by
chromatography.
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
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