Addressing challenges in palladium-catalyzed cross-couplings of aryl mesylates: Monoarylation of ketones and primary alkyl amines

Article abstract of DOI:10.1002/anie.201303305

Mor(DalPhos) for Me(sylates): Described are the first examples of ketone mono-α-arylation and primary aliphatic amine monoarylation employing aryl methanesulfonate coupling partners. A range of functionalized aryl mesylates were employed with dialkyl ketones, and also with primary and secondary amines as well as the otherwise challenging coupling partners acetone and methylamine. Ad=adamantyl. Copyright

Full text of DOI:10.1002/anie.201303305

Angewandte
Chemie
Communications
Synthetic Methods
P. G. Alsabeh,
M. Stradiotto*
&&&& — &&&&
Addressing Challenges in Palladium-
Catalyzed Cross-Couplings of Aryl
Mesylates: Monoarylation of Ketones and
Primary Alkyl Amines
Mor(DalPhos) for Me(sylates): Described
are the first examples of ketone mono-a-
arylation and primary aliphatic amine
monoarylation employing aryl methane-
sulfonate coupling partners. A range of
functionalized aryl mesylates were
employed with dialkyl ketones, and also
with primary and secondary amines as
well as the otherwise challenging cou-
pling partners acetone and methylamine.
Ad=adamantyl.
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DOI: 10.1002/anie.201303305
Synthetic Methods
Addressing Challenges in Palladium-Catalyzed Cross-Couplings of
Aryl Mesylates: Monoarylation of Ketones and Primary Alkyl
Amines**
Pamela G. Alsabeh and Mark Stradiotto*
The development of palladium-catalyzed bond-forming pro-
cesses has revolutionized modern organic synthesis.[1] The
Nobel Prize winning developments of Heck, Negishi, and
wald–Hartwig amination have appeared, these are limited to
the arylation of anilines, amides, pyrroles, and secondary alkyl
amines. Cross-couplings of primary aliphatic amines and aryl
mesylates have not been reported (Scheme 1). Given that
palladium-catalyzed enolate a-arylation and Buchwald–Hart-
À
Suzuki in palladium-catalyzed C C cross-coupling chemistry
À
have led to a diversity of alternative and effective C C and
[2]
À
À
C X (X = N, O, S, etc.) bond-forming protocols. In this
wig amination are among the most widely utilized C C and
À
process, the optimization of reaction conditions, including the
palladium source and ligand has enabled otherwise challeng-
ing electrophilic coupling partners to be accommodated,[3]
including aryl chlorides and pseudohalides. Despite this
significant progress, comparatively few catalyst systems
applicable to aryl methanesulfonates (mesylates) have been
reported. The identification of suitable catalytic conditions
that facilitate turnover of the aryl mesylate while circum-
venting phenol formation has proven to be a daunting
challenge. Nonetheless, significant interest in the use of aryl
mesylates as reaction partners persists owing to their low cost,
high stability, and greater atom economy in comparison to
related aryl tosylates and triflates.[4] Furthermore, the derived
byproduct, methanesulfonic acid, from the cross-coupling is
naturally occurring and undergoes biodegradation in waste-
water processing.[5]
C N bond-forming methods, the identification of catalysts
capable of accommodating aryl mesylates in such processes
represents a desirable target to further expand the scope of
these protocols.
Herein we report the first examples of enolate mono-a-
arylation chemistry, wherein aryl mesylate coupling partners
are employed in combination with cyclic and acyclic dialkyl
ketones. We also present the first Buchwald–Hartwig amina-
tion reactions involving primary aliphatic amine and aryl
mesylate coupling partners.
The mono-a-arylation of carbonyl compounds with (het-
À
ero)aryl (pseudo)halides represents a useful C C bond-
forming reaction which has been applied to a range of
[11]
À
substrates having acidic a C H moieties.
Regarding the
parent ketone, acetone, mono-a-arylation has posed a partic-
The use of aryl mesylates in palladium-
À
catalyzed C C cross-couplings, including
but not restricted to Suzuki–Miyaura,
Stille, and Sonogashira reactions, has been
described.[4] Conversely, the successful ap-
plication of aryl mesylates in an analogous
enolate a-arylation, a powerful and comple-
mentary reaction class developed by the
groups of Buchwald,[6] Hartwig[7] and
others,[8] has yet to be reported (Scheme 1).
Moreover, while a small number of publica-
tions by Kwong and co-workers[9] and Buch-
wald and co-workers[10] detailing the use of
aryl mesylates in the now-ubiquitous Buch-
À
À
Scheme 1. Scope of C C and C N cross-couplings of aryl mesylates, and reactions
featured in this report.
[*] P. G. Alsabeh, Prof. Dr. M. Stradiotto
Department of Chemistry, Dalhousie University
Halifax, Nova Scotia B3H 4R2 (Canada)
E-mail: mark.stradiotto@dal.ca
ular challenge, and has been addressed only recently. The first
examples of acetone mono-a-arylation were reported by our
group[12] and employ the [{Pd(cinnamyl)Cl}2]/Mor-DalPhos
[**] We are grateful to the NSERC of Canada, the Killam Trusts, and
Dalhousie University for their generous support of this work. Dr.
Michael Lumsden (NMR-3, Dalhousie) is thanked for assistance in
the acquisition of NMR spectroscopic data and Mr. Xiao Feng
(Maritime Mass Spectrometry Laboratories, Dalhousie) is thanked
for assistance in the acquisition of spectrometric data.
(see Scheme 2 for structure) catalyst system in combination
with both (hetero)aryl halides and tosylates. Subsequently,
Ackermann and Mehta[13] reported the use of a Pd/XantPhos
catalyst for the coupling of aryl imidazolylsulfonates with
acetone and other ketones.[14] Encouraged by the desirable
performance of [{Pd(cinnamyl)Cl}2]/Mor-DalPhos in this
context,[12,15] we initially directed our efforts towards the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201303305.
2
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Table 1: Optimization of the palladium-catalyzed mono-a-arylation of
50% conversion of 1a, with no formation of 2a observed.
acetone with phenyl mesylate.[a]
Alternative bases were also tested under these optimal
solvent conditions (Table 1, entries 9 and 10) but were
shown to give poor conversion of 1a or low yield of 2a,
thereby establishing K3PO4 as the optimal base for this
transformation.
Entry Solvent (xm)
Base
Conv. Yield
In an effort to assess the influence of the ancillary ligand
on the course of reaction, a judiciously selected range of
mono- and bisphosphines, which have proven effective in the
palladium-catalyzed a-arylation of carbonyl compounds, in
Buchwald–Hartwig amination, and in alternative cross-cou-
pling applications employing aryl mesylates, were tested
under the optimized reaction conditions (Scheme 2). Both
Me-DalPhos and P(o-tol)2-DalPhos afforded minimal con-
[%]
[%]
1
2
3
4
acetone (0.5m)
acetone (0.5m)
1,4-dioxane (0.5m)
tBuOH (0.5m)
tBuOH (0.5m)
tBuOH (0.125m)
tBuOH/1,4-dioxane (1:1; 0.125m) K3PO4
tBuOH/1,4-dioxane (1:1; 0.125m) K3PO4
tBuOH/1,4-dioxane (1:1; 0.125m) CsF
Cs2CO3
K3PO4
Cs2CO3
Cs2CO3
K3PO4
>99
95
81
>99
>99
>99
>99
>99
38
54
43
33
14
78, 56
87, 84
79, 79
85, 85
24
5[b]
6[b]
7[b]
8[b]
9
K3PO4
10[c]
tBuOH/1,4-dioxane (1:1; 0.125m) NaOtBu >99
4
[a] Reaction conditions: 0.2–0.4 mmol 1a ([1a]=x M), 10 equiv acetone
except for entries 1 and 2, [Pd]/L ratio=2:3. Conversions and yields
determined on the basis of calibrated GC data of 1a and 2a using
dodecane as an internal standard. [b] Yields of duplicate reactions
provided. [c] Phenol observed as the major side product.
Ms=methanesulfonyl.
identification of suitable reaction conditions employing this
catalyst system for the hitherto unknown mono-a-arylation of
acetone with phenyl mesylate (1a) to form phenylacetone
(2a; Table 1). Central to this effort was the quest to identify
a base/catalyst pairing which would promote the desired
acetone mono-a-arylation reaction while avoiding phenol
formation.
In adapting our previously optimized reaction conditions
established for the mono-a-arylation of acetone with aryl
halides and tosylates,[12] the use of 1 mol% [{Pd-
(cinnamyl)Cl}2], 3 mol% Mor-DalPhos, and Cs2CO3 as
a base in acetone (Table 1, entry 1) resulted in full conversion
of 1a, thus affording the target product 2a in 54% (GC yield).
Substituting K3PO4 as the base resulted in high conversion but
a slightly lower yield of 2a (Table 1, entry 2). At a relatively
high concentration of 1a (0.5m), high conversions but low
yields resulted from either the use of 1,4-dioxane or tert-
butanol with 10 equivalents of acetone. (Table 1, entries 3 and
4). Replacing Cs2CO3 with K3PO4 in tert-butanol allowed both
full conversion and a significant increase in the GC yield of 2a
(Table 1, entry 5). However, performing this reaction in
duplicate gave inconsistent yields (78 versus 56%), which
we believe to be a result of the reactions forming very viscous,
nonuniform mixtures upon heating. To circumvent these
issues, the reaction concentration was decreased to 0.125m
using tert-butanol (Table 1, entry 6), thus resulting in high and
reproducible yields of 2a. However, the reaction mixtures
continued to become viscous, thereby preventing uniform
stirring. Employing 1,4-dioxane under these dilute conditions
allowed more uniform stirring but gave a slightly lower, albeit
reproducible yield for 2a (Table 1, entry 7). Thus we elected
to employ these two solvents together in a 1:1 ratio. Under
these reaction conditions 2a was obtained in reproducible GC
yields of 85% (Table 1, entry 8). Performing the reaction in
the absence of ligand or palladium resulted in approximately
Scheme 2. Ligand comparisons in the mono-a-arylation of acetone
with phenyl mesylate. Reaction conditions: 0.4 mmol 1a, 10 equiv
acetone, [Pd]/L ratio=2:3. Yields (conversions in parentheses) deter-
mined on the basis of calibrated GC data of 1a and 2a using
dodecane as an internal standard. Phenol is the major side product in
most cases. [a] Used 5 mol% Pd(OAc)2, 10 mol% XantPhos, 14 equiv
acetone, 2 equiv Cs2CO3, 1,4-dioxane (0.25m), 808C. [b] Used 2 mol%
palladacycle, 2 mol% ligand. [c] Significant polyarylation observed.
Ad=adamantlyl.
version and none of the desired product 2a. Similarly poor
results were obtained with XantPhos (under the optimized
reaction conditions described herein or under previously
reported conditions[13]), BippyPhos, and a palladacycle/
X-Phos catalyst. Furthermore, the use of the JosiPhos variant
À
CyPFtBu, or ligands used to facilitate C N cross-coupling
reactions of aryl mesylates (CM-Phos and BrettPhos),
afforded 2a (29–42% yield), but the yields were inferior to
those obtained when using the Mor-DalPhos-based catalyst.
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Having established the suitability of the [{Pd-
(cinnamyl)Cl}2]/Mor-DalPhos catalyst system as well as
optimal reaction conditions for the coupling of acetone and
phenyl mesylate, the scope of aryl mesylates was then
explored in the mono-a-arylation of acetone (Scheme 3).
Electron-neutral and electron-rich aryl mesylates were well
tolerated in the reaction, thus affording greater than 80%
yields of the benzyl methyl ketone products 2a–f. Fused-aryl
mesylate substrates also proved to be good reaction partners
(2g and 2h), including a quinoline derivative. Substituted
(hetero)biaryl benzyl ketone derivatives were also prepared
in this manner (2i–l), thus demonstrating the tolerance of
pyrrole (2i), 4-trifluoromethylphenyl (2k), and 4-benzonitrile
(2l) substituents within the mesylate reagent. A 4-phenoxy-
phenyl-derived product (2m) was also obtained in high yield
upon isolation (83%; compare to the more electron-rich 4-
methoxy analogue 2c, 84%).
Efforts to optimize the established conditions to allow the
accommodation of electron-poor and ortho-substituted aryl
mesylates were unsuccessful, mainly resulting in decomposi-
tion of the starting materials to the corresponding aryl
alcohol. Nevertheless, the scope was extended to the use of
other linear and cyclic aliphatic ketones. 2-Heptanone and
cyclohexanone were found to be suitable coupling partners,
thus affording the desired benzyl ketones in high isolated
yields (2n–s). For the products formed from 2-heptanone
(2n–p), a mixture of regioisomers was obtained in each case,
where the major product corresponded to monoarylation at
the a-methyl position and the minor at the a-CH2-C4H9 of the
1
ketone (determined on the basis of H NMR data). These
products could not be easily separated by use of column
chromatography. Changing the base to K2CO3 at 1108C (0.5m
[ArOMs] in tert-butanol) allowed cyclohexanone mono-a-
arylation (2q–s). Additionally, 4-heptanone was accommo-
dated in this chemistry under more forcing reaction con-
ditions, thus providing 2t in 66% yield upon isolation.
Attempts to a-arylate acetophenone were successful to
a certain extent, that is, employing CsF as the base afforded
68% yield of a mixture of mono- and diarylation products in
a 7.6:1 ratio favoring mono-a-arylation. Thus, further opti-
mization is required to promote the selective mono-a-
arylation of aryl ketone coupling partners.
Encouraged by our success in developing the first
examples of enolate a-arylation employing aryl mesylate
coupling partners, we turned our attention to expanding the
scope of Buchwald–Hartwig amination chemistry involving
such challenging electrophiles using [{Pd(cinnamyl)Cl}2]/
Mor-DalPhos.[16] Although a vast combination of (hetero)aryl
(pseudo)halides and amines can be cross-coupled by using
established Buchwald–Hartwig amination methods, the scope
of phenol-derived (hetero)aryl electrophiles, which have been
successfully employed thus far, is limited almost exclusively to
benzenesulfonates, tosylates, triflates, and nonaflates.[4a,b,17]
À
Only two research groups have achieved C N cross-coupling
reactions of aryl mesylates.[9,10] Kwong and co-workers first
reported the coupling of anilines and secondary amines with
aryl mesylates employing a Pd/CM-Phos catalyst system,[9]
and the scope of the amine reaction partner was limited
primarily to anilines and pyrrolic amines, with only three
examples of secondary aliphatic amines, and no examples
involving primary alkyl amines. Soon after, Buchwald and co-
workers reported the use of the Pd/BrettPhos catalyst system
for the coupling of aryl mesylates with anilines, in which six
examples in total were presented.[10a] More recently, the Pd/X-
Phos catalyst system has been shown to effectively couple
amides with a variety of aryl mesylate partners.[10b] Given the
absence of literature reports of the cross-coupling of primary
aliphatic amines and aryl mesylates, as well as the limited
number of transformations involving secondary dialkyl
amines, we sought to address these substrate scope limitations
by applying our optimized aryl mesylate coupling conditions
(Scheme 4).
Scheme 3. Scope of the palladium-catalyzed a-arylation of ketones
with aryl mesylates. Reaction conditions: 0.6–0.8 mmol ArOMs, 5–
10 equiv ketone, [Pd]/L=2:3, [ArOMs]=0.5–0.125m. See the Support-
ing Information. Yields are of isolated material, and mol% [{Pd-
(cinnamyl)Cl}2] is indicated within parentheses. [a] Yield determined
on the basis of calibrated GC data of 2a and 2d using dodecane as an
internal standard. [b] Mixture of regioisomers. Ratio indicated within
brackets, with major product shown. [c] Used tert-butanol solvent,
K2CO3, 1108C.
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minimal formation of the desired aniline derivative because
of the competing background reactions involving sulfonyl
transfer.[18] However, methylamine, which can be a challeng-
ing substrate in its own right in Buchwald–Hartwig amination
chemistry,[10a,16c,19] was employed without difficulty in cross-
coupling reactions involving aryl mesylates featuring ortho
substitutents and electron-withdrawing groups. The standard
reaction of methylamine with phenyl mesylate proceeded
cleanly, thus affording the target aniline 3k in high yield, as
did the analogous reaction leading to the naphthyl derivative
3l. The 8-quinolinyl mesylate was also tolerated in this
chemistry (3m). The acetophenone derivatives 3n and 3p
were synthesized in good yields, thereby establishing the
À
ability to conduct N H arylation reactions chemoselectively
in the presence of functionality featuring enolizable protons
as well as electron-withdrawing, base-sensitive functional
groups. Additional functional-group tolerance was estab-
lished in the synthesis of the ethyl ester 3o (82%). Finally,
substrates containing two potentially reactive NH sites were
selectively monoarylated at the primary amine sites (3q and
3r), thereby further demonstrating the chemoselective capa-
bilities of this transformation.
In summary, we have disclosed the first examples of
ketone mono-a-arylation using aryl mesylates and have also
successfully demonstrated for the first time the amination of
these inexpensive phenol derivatives with primary aliphatic
amines. The [{Pd(cinnamyl)Cl}2]/Mor-DalPhos catalyst
system allowed a range of substituted aryl mesylates to be
coupled with both cyclic and acyclic dialkyl ketones, including
acetone, which is normally a challenging reagent in mono-a-
arylation chemistry. Applying these optimized ketone a-
arylation conditions to Buchwald–Hartwig amination enabled
the mono-N-arylation of primary and secondary aliphatic
amines, including methylamine, by employing aryl mesylates
featuring electron-donating or electron-withdrawing func-
tionality, ortho-substitution, as well as base-sensitive groups.
Furthermore, the amination protocol displayed chemoselec-
tivity, thus favoring cross-coupling of the primary amine in
each case. We are continuing to examine the role of catalyst
design in expanding the scope of nucleophilic reaction
partners with challenging nonhalide aryl electrophiles in
cross-coupling chemistry, and will disclose our progress in
future reports.
Scheme 4. Scope of the palladium-catalyzed amination of aryl mesy-
lates. Reaction conditions: 0.6–1.0 mmol ArOMs, 1.1–5 equiv amine,
[Pd]/L=2:3, [ArOMs]=0.25–0.1m. See the Supporting Information.
Yields are of isolated material, and mol% [{Pd(cinnamyl)Cl}2] indicated
within parentheses. [a] Yield determined on the basis of calibrated GC
data of 3a, 3d, 3 f, and 3k using dodecane as an internal standard.
We were pleased to find that cyclic dialkyl amines such as
morpholine (3a and 3b) and piperidine (3c) afforded the
corresponding aryl amines in excellent yields. Dimethylamine
performed similarly well both with phenyl mesylate produc-
ing 3d (98%), as well as with a xylyl mesylate where the
derived volatile aryl amine 3e was obtained in high yield upon
isolation (80%). Notably, octylamine was well tolerated in
reactions employing either the parent aryl mesylate 1a (98%
yield of 3 f) or the more sterically hindered o-tolyl mesylate
(62% yield of 3g). Aniline, serving as a representative
example of primary aromatic amines, proved to be a favorable
reaction partner in this system, thus requiring low catalyst
loading (1 mol% Pd) and achieving nearly quantitative yield
of diphenylamine (3h). Both cyclohexylamine and the
hydrazine derivative 1-amino-4-methylpiperazine, were also
mono-N-arylated successfully, each in greater than 80% yield
upon isolation (3i and 3j).
Received: April 19, 2013
Revised: May 10, 2013
Published online: && &&, &&&&
Keywords: amination · cross-coupling · N,P ligands ·
.
palladium · synthetic methods
[1] a) S. Brꢀse, A. D. Meijere in Metal-Catalyzed Cross-Coupling
Reactions (Eds.: A. d. Meijere, F. Diederich), Wiley-VCH,
Weinheim, 2008, pp. 217 – 315; b) N. Miyaura in Metal-Catalyzed
Cross-Coupling Reactions (Eds.: A. de Meijere, F. Diederich),
Wiley-VCH, Weinheim, 2008, pp. 41 – 123; c) J. F. Hartwig,
Organotransition Metal Chemistry, University Science Books,
Sausalito, CA, 2010; d) C. L. Allen, J. M. J. Williams, Chem. Soc.
Rev. 2011, 40, 3405 – 3415.
In select cases, reactions employing morpholine, dime-
thylamine, or octylamine in combination with sterically
hindered or electron-deficient aryl mesylates resulted in
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
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These are not the final page numbers!

.
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Communications
[2] a) X.-F. Wu, P. Anbarasan, H. Neumann, M. Beller, Angew.
Chem. 2010, 122, 9231 – 9234; Angew. Chem. Int. Ed. 2010, 49,
9047 – 9050; b) C. C. C. Johansson Seechurn, M. O. Kitching,
T. J. Colacot, V. Snieckus, Angew. Chem. 2012, 124, 5150 –
5174; Angew. Chem. Int. Ed. 2012, 51, 5062 – 5085.
122, 686 – 718; Angew. Chem. Int. Ed. 2010, 49, 676 – 707; c) F.
Bellina, R. Rossi, Chem. Rev. 2010, 110, 1082 – 1146; d) P. Novak,
R. Martin, Curr. Org. Chem. 2011, 15, 3233 – 3262.
[12] K. D. Hesp, R. J. Lundgren, M. Stradiotto, J. Am. Chem. Soc.
2011, 133, 5194 – 5197.
[3] a) R. J. Lundgren, M. Stradiotto, Chem. Eur. J. 2012, 18, 9758 –
9769; b) C. Valente, S. C¸ alimsiz, K. H. Hoi, D. Mallik, M. Sayah,
M. G. Organ, Angew. Chem. 2012, 124, 3370 – 3388; Angew.
Chem. Int. Ed. 2012, 51, 3314 – 3332; c) S. M. Wong, C. M. So,
F. Y. Kwong, Synlett 2012, 1132 – 1153.
[4] For selected recent reports and reviews, see: a) C. M. So, F. Y.
Kwong, Chem. Soc. Rev. 2011, 40, 4963 – 4972; b) B.-J. Li, D.-G.
Yu, C.-L. Sun, Z.-J. Shi, Chem. Eur. J. 2011, 17, 1728 – 1759;
c) S. I. Kozhushkov, H. K. Potukuchi, L. Ackermann, Catal. Sci.
Technol. 2013, 3, 562 – 571; d) D. S. Lee, P. Y. Choy, C. M. So, J.
Wang, C. P. Lau, F. Y. Kwong, RSC Adv. 2012, 2, 9179 – 9182;
e) G. A. Molander, I. Shin, Org. Lett. 2012, 14, 3138 – 3141; f) B.
Song, T. Knauber, L. J. Gooßen, Angew. Chem. 2013, 125, 3026 –
3030; Angew. Chem. Int. Ed. 2013, 52, 2954 – 2958.
[5] a) S. C. Baker, D. P. Kelly, J. C. Murrell, Nature 1991, 350, 627 –
628; b) E. S. Venkataramani, A. L. Forman, R. J. Magliette, Jr.,
W. A. Vaughn, R. R. Dauer, PCT Int. Appl. WO 9521135, 1995
(CAN 123:207938); c) A. Commarieu, W. Hoelderich, J. A.
Laffitte, M.-P. Dupont, J. Mol. Catal. A 2002, 182 – 183, 137 – 141;
d) M. C. Wilkinson, Org. Lett. 2011, 13, 2232 – 2235.
[6] a) M. Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1997, 119,
11108 – 11109; b) J. ꢁhman, J. P. Wolfe, M. V. Troutman, M.
Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1998, 120, 1918 –
1919.
[13] L. Ackermann, V. P. Mehta, Chem. Eur. J. 2012, 18, 10230 –
10233.
[14] While this manuscript was under review, the following report
was published in which an alternative P,N ligand was employed
under reaction conditions identical to those previously reported
by us for the coupling of aryl chlorides and acetone: P. Li, B. Lꢂ,
C. Fu, S. Ma, Adv. Synth. Catal. 2013, 355, 1255 – 1259.
[15] S. M. Crawford, P. G. Alsabeh, M. Stradiotto, Eur. J. Org. Chem.
2012, 6042 – 6050.
[16] For selected reports featuring the [{Pd(cinnamyl)Cl}2]/Mor-
DalPhos catalyst system in challenging Buchwald–Hartwig
aminations, see: a) R. J. Lundgren, B. D. Peters, P. G. Alsabeh,
M. Stradiotto, Angew. Chem. 2010, 122, 4165 – 4168; Angew.
Chem. Int. Ed. 2010, 49, 4071 – 4074; b) R. J. Lundgren, M.
Stradiotto, Angew. Chem. 2010, 122, 8868 – 8872; Angew. Chem.
Int. Ed. 2010, 49, 8686 – 8690; c) B. J. Tardiff, R. McDonald, M. J.
Ferguson, M. Stradiotto, J. Org. Chem. 2012, 77, 1056 – 1071.
[17] For selected lead references and reviews, see: a) J. Louie, M. S.
Driver, B. C. Hamann, J. F. Hartwig, J. Org. Chem. 1997, 62,
1268 – 1273; b) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc.
1998, 120, 7369 – 7370; c) X. Huang, K. W. Anderson, D. Zim, L.
Jiang, A. Klapars, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125,
6653 – 6655; d) K. W. Anderson, M. Mendez-Perez, J. Priego,
S. L. Buchwald, J. Org. Chem. 2003, 68, 9563 – 9573; e) J.
Hçgermeier, H.-U. Reissig, Adv. Synth. Catal. 2009, 351, 2747 –
2763; f) B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang,
A.-M. Resmerita, N. K. Garg, V. Percec, Chem. Rev. 2011, 111,
1346 – 1416.
[7] a) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1997, 119,
12382 – 12383; b) K. H. Shaughnessy, B. C. Hamann, J. F. Hart-
wig, J. Org. Chem. 1998, 63, 6546 – 6553.
[8] T. Satoh, Y. Kawamura, M. Miura, M. Nomura, Angew. Chem.
1997, 109, 1820 – 1822; Angew. Chem. Int. Ed. Engl. 1997, 36,
1740 – 1742.
[18] I. M. Gordon, H. Maskill, M.-F. Ruasse, Chem. Soc. Rev. 1989,
18, 123 – 151.
[9] C. M. So, Z. Zhou, C. P. Lau, F. Y. Kwong, Angew. Chem. 2008,
120, 6502 – 6506; Angew. Chem. Int. Ed. 2008, 47, 6402 – 6406.
[10] a) B. P. Fors, D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am.
Chem. Soc. 2008, 130, 13552 – 13554; b) K. Dooleweerdt, B. P.
Fors, S. L. Buchwald, Org. Lett. 2010, 12, 2350 – 2353.
[19] For selected recent examples, see: a) R. J. Lundgren, A.
Sappong-Kumankumah, M. Stradiotto, Chem. Eur. J. 2010, 16,
1983 – 1991; b) B. P. Fors, S. L. Buchwald, J. Am. Chem. Soc.
2010, 132, 15914 – 15917; c) P. G. Alsabeh, R. J. Lundgren, L. E.
Longobardi, M. Stradiotto, Chem. Commun. 2011, 47, 6936 –
6938; d) C. B. Lavery, R. McDonald, M. Stradiotto, Chem.
Commun. 2012, 48, 7277 – 7279.
[11] a) D. A. Culkin, J. F. Hartwig, Acc. Chem. Res. 2003, 36, 234 –
245; b) C. C. C. Johansson, T. J. Colacot, Angew. Chem. 2010,
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