Nickel-catalyzed C-H coupling with allyl phosphates: A site-selective synthetic route to linear allylarenes

Article abstract of DOI:10.1021/ol501707z

It is reported that a nickel/phosphine catalyst allows the C-H allylation to occur effectively with the allyl site selectivity predominantly governed by steric effects. This reaction provides a facile and predictable route for the selective preparation of linear allylarenes from readily available benzamides and allyl phosphates.

Full text of DOI:10.1021/ol501707z

Letter
pubs.acs.org/OrgLett
Nickel-Catalyzed C−H Coupling with Allyl Phosphates: A Site-
Selective Synthetic Route to Linear Allylarenes
Xuefeng Cong, Yuexuan Li, Yu Wei, and Xiaoming Zeng*
Center for Organic Chemistry, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710054, P. R.
China
S
* Supporting Information
ABSTRACT: It is reported that a nickel/phosphine catalyst
allows the C−H allylation to occur effectively with the allyl site
selectivity predominantly governed by steric effects. This
reaction provides a facile and predictable route for the selective
preparation of linear allylarenes from readily available
benzamides and allyl phosphates.
he use of first-row transition metals such as nickel in
developing sustainable catalytic strategies to construct
C−H allylation by use of allyl oxygen electrophiles, which
largely expands the scope from electron-rich and -deficient
arenes16 to directing-group-containing substrates (Scheme
2a).17 Note that these transformations are typically dominant
T
appealing structural motifs has attracted much attention in the
synthetic community.1 In particular, the functionalization of
C−H bonds provides a powerful method toward diversely
functionalized molecule synthesis.2 The pioneering investiga-
tion by Chatani demonstrates that cost-attractive nickel salts
enable improving the transformation of inert C−H bonds in
the assistance of an 8-aminoquinoline auxiliary.3−6 More
recently, the groups of Chatani,7 Ge,8 Akermann,9 and You10
greatly broadened the reaction scope (Scheme 1a). Unfortu-
Scheme 2. Chelation-Assisted C−H Allylation
Scheme 1. Ni-Promoted C−H Functionalization
in γ-regioselectivity. Compared with this olefin insertion
pathway, we hypothesized that, after the cleavage of the o-C−
H bond, an π-(allyl)nickel cyclometalated species can be
formed regardless of whether linear or branched allyl oxygens
were utilized, which may undergo a facile reductive elimination
at a position of less steric hindrance to give a linear α- or γ-
selective allylated product (Scheme 2b).18 To the best of our
knowledge, such a selectivity-predictable approach involving
chelation-assisted C−H activation remains an elusive but
efficient strategy to buildup target-oriented allylarene frame-
works.
nately, successful examples in the field are still scarce and
currently studies are limited to couplings with C−X (X = I, Br)
bonds. Inspired by a recent achievement on nickel-promoted
C−H couplings with unactivated aryl C−O bonds,4a,e,11 herein,
we demonstrate a nickel-catalyzed allylation via chelation-
assisted C−H activation, allowing for the incorporation of allyl
scaffolds into the ortho position of benzamides, leading to
linear allylarene derivatives in high selectivity (Scheme 1b).12
Owing to the advantage of easy functionalization of allyl
moieties by numerous methods, the exploration of an efficient
strategy to introduce these attractive structural motifs has
inspired broad interests.13 However, a long-standing challenge
in the reaction is the control of allyl regioselectivity. Glorius14
and Nakamura15 elegantly demonstrated a chelation-assisted
Received: June 12, 2014
Published: July 21, 2014
© 2014 American Chemical Society
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Letter
We started our investigation by treating cinnamyl alcohol and
its derivatives with 8-aminoquinoline-containing benzamides. In
the presence of 10 mol % of Ni(COD)2, 20 mol % of PCy3, and
2 equiv of Na2CO3, the use of cinnamyl alcohol, ether, acetate,
and carbonate as allyl partners did not give the desired
allylarene (see the Supporting Information for parameter
optimization). In contrast, it was found that cinnamyl
phosphate allows the formation of the allylated product 3a in
excellent yield (Scheme 3). Meanwhile, the Ni(II) salt of
regioisomer 3o and 3o′ in the transformation, which may be
generated from two distinctive SE2 and SE2′ reaction pathways.
Encouraged by these results, we then turned our attention
toward probing various substituents on benzamides. As shown
in Scheme 4, the replacement of ortho-methyl with methoxy or
a
Scheme 4. Synthesis of Monoallylated Products
a
Scheme 3. Scope of Allyl Phosphates
a
Reaction conditions: 1 (0.2 mmol), 2a (0.6 mmol), Ni(COD)2 (0.02
mmol), PCy3 (0.04 mmol), Na2CO3 (0.4 mmol), Toluene (1.0 mL),
b
c
140 °C, 30 h; isolated yields. 160 °C. Ni(OTf)2 (0.02 mmol) was
d
employed.
The ratio of allylarene and the olefin isomer was
1
determined by H NMR.
fluoride on benzamide leads to a low conversion (3p and 3q).
Electron-donating methyl and methoxy groups can be
successfully introduced to the meta position of allylarene
derivatives (3r and 3s). Interestingly, the formation of a
corresponding olefin-migration isomer in small amounts was
observed from 3-bromo or trifluoromethyl-containing sub-
strates (3u and 3v). In contrast, the use of disubstituted
benzamides produces single monoallylation products 3w and 3x
in good yields. Additionally, the reactions of 1- and 2-
naphthamides also take place smoothly under standard
conditions (3y and 3z).
a
Reaction conditions: 1a (0.2 mmol), 2 (0.6 mmol), Ni(COD)2 (0.02
mmol), PCy3 (0.04 mmol), Na2CO3 (0.4 mmol), Toluene (1.0 mL),
140 °C, 30 h; isolated yields. b Ni(OTf)2 (0.02 mmol) was employed. c
The ratio of 3d and the related olefin-migration isomer was
1
d
determined by H NMR. 160 °C.
Compared with forming a monoallylated product from 3,4-
dimethoxy-substituted benzamide, the replacement of 3-
methoxy with fluoride affords mixed mono- and diallylation
products 3aa (Scheme 5). It may be ascribed to the effect of
less steric hindrance of the fluoro substituent, resulting in a high
reaction rate for the diallylation. In particular, simple
benzamide furnishes diallylated arenes as major products in
the conversion (3ab−3ae). 4-Alkyl and chloro-bearing
benzamides proved to be effective, leading to mixed or
diallylated products 3af−3ai in good yields. It was noteworthy
that the C−H allylation of 1a can be conducted on a large scale;
the allylated product 3a was achieved with complete α- and E-
selectivity (eq 1).
Ni(OTf)2 enables the improvement of this transformation,
leading to 3a in 90% yield. In addition to PCy3, other ligands
such as Pt-Bu3·HCl, PPh3, and carbenes also permit the
reaction to occur smoothly, even though slightly lower yields
were obtained. It is worth mentioning that the C−H allylation
proceeds with complete α- and E-selectivity, and the related
olefin-migration isomer was not detected in these cases.
The scope of allyl phosphates was explored by treatment
with benzamide 1a (Scheme 3). The presence of electron-
donating or -withdrawing substituents on the scaffolds of
cinnamyl phosphates has no obvious influence on the
transformation, giving linear allylarenes 3b−3f in good to
excellent yields (84%−96%). In addition to cinnamyl
phosphates, alkyl-substituted partners are also suitable in the
allylation (3g−3j). As expected, the reactions of 2-methyl and
pentyl-bearing allyl phosphates occur effectively giving allylated
products 3k−3n in 83%−98% yields. Notably, a sterically
demanding secondary allyl phosphate furnishes a mixed
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Organic Letters
Letter
a
influence on the conversion, suggesting that the single-electron-
transfer (SET) mechanism may be excluded in the reaction
pathway (Scheme 6d).
Scheme 5. Nickel-Catalyzed Diallylation
Because no related diallylation compound was detected
within 2 h in the reaction of 1b with 2-butenyl phosphate, the
measurement of the intermolecular kinetic isotope effect (KIE)
for the transformation was performed next (Scheme 7a). A low
Scheme 7. Mechanistic Experiments
a
Reaction conditions: 1 (0.2 mmol), 2 (0.6−1.2 mmol), Ni(COD)2
(0.02 mmol), PCy3 (0.04 mmol), Na2CO3 (0.4−0.8 mmol), Toluene
b
(1.0 mL), 140 °C, 30 h; isolated yields. Ni(OTf)2 (0.02 mmol) was
employed.
determined by H NMR. 160 °C.
c
The ratio of mono- and diallylation products was
1
d
To gain mechanistic insights into the allyl regioselectivity,
branched secondary allylphosphate 4 was chosen to react with
benzamide 1a. As shown in Scheme 6a, only formation of linear
Scheme 6. Mechanistic Insights
KIE value of 1.4 was obtained, implying that the cleavage of the
o-C−H bond of benzamide may not be rate-limiting step in the
catalysis. Meanwhile, a significant H/D exchange between the
NH moiety and ortho-D was observed, suggesting that a
reversible and rapid C−H bond cleavage may be involved in the
conversion (Scheme 7b). Moreover, the competitive experi-
ment shows that an electron-withdrawing substituent on the
benzamide favors the transformation. This result indicates that
a concerted-metalation−deprotonation (CMD) mechanism can
be considered for the cleavage of the ortho-C−H bond (Scheme
7c).
In summary, we have developed a nickel-catalyzed C−H
allylation with allyl phosphates. This reaction enables highly
selective installation of allyl scaffolds into the ortho site of
benzamides with the assistance of an 8-aminoquinoline
auxiliary. Unlike the Rh- and Fe-catalyzed transformations,14,15
the allyl regioselectivity in the reaction was predominantly
governed by the steric hindrance of allyl partners, allowing for
the predictable and scalable preparation of linear allylarene
derivatives by the use of cost-attractive nickel catalysts.
stereoisomeric products with complete γ-site selectivity was
observed. This result suggests that the allyl site selectivity was
heavily influenced by the steric environment around allyl
phosphates, and reaction is favored at a position of less steric
hindrance. Interestingly, the employment of Z-allyl phosphates
affords mixed E/Z stereoisomers in the reaction (Scheme 6b).
Note that the C−H allylation of 1a provides an allylic dimer 5
as a side product (Scheme 6c). In the absence of 1a, the same
compound was also detected under standard conditions. It was
thought to be derived from a disproportionation of the related
π-(allyl)Ni(OR) complex.19 Further study reveals that the
addition of a radical scavenger of 2,4-di-tert-butyl-4-methyl-
phenol (BHT) into the catalytic system has no obvious
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Letter
Tamaru, Y. Angew. Chem., Int. Ed. 2001, 40, 3600. (c) Son, S.; Fu, G.
C. J. Am. Chem. Soc. 2008, 130, 2756.
(13) Carreira, E. M.; Kvaerno, L. Classics in Stereoselective Synthesis;
ASSOCIATED CONTENT
* Supporting Information
■
S
Wiley-VCH: Weinheim, Germany, 2009; pp 153−185.
Detailed optimization data; experimental procedures; character-
ization data of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) Wang, H.; Schroder, N.; Glorius, F. Angew. Chem., Int. Ed. 2013,
̈
52, 5386.
(15) Asako, S.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2013, 135,
17755.
AUTHOR INFORMATION
Corresponding Author
■
(16) (a) Yao, T.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2011, 50, 2990. (b) Makida, Y.; Ohmiya, H.; Sawamura, M. Angew.
Chem., Int. Ed. 2012, 51, 4122. (c) Fan, S.; Chen, F.; Zhang, X. Angew.
Chem., Int. Ed. 2011, 50, 5918. (d) Yu, Y.-B.; Fan, S.; Zhang, X.
Chem.Eur. J. 2012, 18, 14643.
*E-mail: zengxiaoming@mail.xjtu.edu.cn.
Notes
(17) (a) Oi, S.; Tanaka, Y.; Inoue, Y. Organometallics 2006, 25, 4773.
(b) Zeng, R.; Fu, C.; Ma, S. J. Am. Chem. Soc. 2012, 134, 9597. (c) Ye,
B.; Cramer, N. J. Am. Chem. Soc. 2013, 135, 636. (d) Zhang, Y. J.;
Skucas, E.; Krische, M. J. Org. Lett. 2009, 11, 4248.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Support for this work by XJTU from a start-up fund and the
National Natural Science Foundation of China [No. 21202128
(X.Z.)] is gratefully acknowledged.
(18) One single example on Ni-catalyzed C−H allylic alkylation
using allyl bromide was described by Chatani’s group. See ref 7b.
(19) It is known that Ni(COD)2 enables reaction with an allyl
oxygen such as in allyl acetate via a disproportionation to afford
Ni(OR)2 and Ni(allyl)2. See: Yamamoto, T.; Ishizu, J.; Yamamoto, A.
J. Am. Chem. Soc. 1981, 103, 6863.
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