Catalytic and Atom-Economic Csp3 ?Csp3 Bond Formation: Alkyl Tantalum Ureates for Hydroaminoalkylation

Article abstract of DOI:10.1002/anie.201712668

Atom-economic and regioselective C_sp3 ?C_sp3 bond formation has been achieved by rapid C?H alkylation of unprotected secondary arylamines with unactivated alkenes. The combination of Ta(CH₂SiMe₃)₃Cl

Full text of DOI:10.1002/anie.201712668

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: Catalytic and Atom Economic Csp3 - Csp3 Bond Formation α-to
Nitrogen. Alkyl Tantalum Ureates for Hydroaminoalkylation
Authors: Rebecca C. DiPucchio, Sorin-Claudiu Rosca, and Laurel
Schafer
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201712668
Angew. Chem. 10.1002/ange.201712668
Link to VoR: http://dx.doi.org/10.1002/anie.201712668
http://dx.doi.org/10.1002/ange.201712668

Angewandte Chemie International Edition
10.1002/anie.201712668
COMMUNICATION
Catalytic and Atom Economic Csp3 – Csp3 Bond Formation α-to
Nitrogen. Alkyl Tantalum Ureates for Hydroaminoalkylation
‡
‡
Rebecca C. DiPucchio, Sorin-Claudiu Roşca, and Laurel. L. Schafer*
3
3
phosphoramidate ligand, can yield room temperature reactivity.8h
Unfortunately, such Ta methyl complexes readily decompose
resulting in low TONs (<20). Finally, all these systems require
excess alkene substrate and isolation of products by column
chromatography.
Abstract: Atom-economic and regioselective Csp -Csp bond
formation has been achieved by rapid C-H alkylation of unprotected
secondary arylamines with unactivated alkenes. The combination of
2 3 3 2
Ta(CH SiMe ) Cl , and a ureate N,O-chelating ligand salt gives an in
situ prepared catalytic system that can realize high yields of β-
alkylated aniline derivatives using either terminal or internal alkene
substrates. These new catalyst systems realize C-H alkylation in as
little as one hour and for the first time a 1:1 stoichiometry of alkene
and amine substrates results in high yielding syntheses of isolated
amine products by simple filtration and concentration.
Previous Work:
R
R
a.3b
10
mol
%
Ir(I)
Catalyst
3
Steps
S
DG
R
DG
H
DG:
N
N
N
O
R
PhCl, 80 °C
n
n
n
Terminal alkenes only
8 Eq. alkene substrate
10 mol %
Linear product only
b.3d
R
R
R'
R
R
R
N
Co(dppp)Br
2
N
+
0.5 mol % Ir PC, hv
The catalytic functionalization of alkenes with amines
represents a sustainable and efficient method for generating
small molecules relevant to the pharmaceutical, agrochemical
and fine chemical industries. Catalytic alkene functionalization is
attractive as valuable building blocks can be prepared with 100%
atom efficiency from commercially available starting materials.1
Furthermore, the direct C–H alkylation of amines by
R"
R'
R
CsOPiv, 25 °C
R"
Tertiary amines only
2 Eq. amine substrate
Linear product only
This Work:
c.
R'
R'
H
5
mol %
[Ta] Cat.
H
N
N
R''
+
R
R''
R
1
10-130 °C
1
:1 amine:alkene substrates Branched product only
Internal or terminal alkenes
2
hydroaminoalkylation, allows for the synthesis of α (Scheme 1, a
b)2f,3 and/or β-alkylated amines (Scheme 1, c).2a-e Notably, early
Scheme 1. Hydroaminoalkylation for catalytic Csp -Csp3 bond formation α-to
nitrogen using late transition metals catalysts with directing groups (a) and
photocatalysts (PC; b) or early transition metals catalysts (c).
3
&
transition metal catalysts, like tantalum, require no added
protecting/directing groups or photoredox catalysts/co-catalysts.2c
Thus, early transition metal hydroaminoalkylation complements
late transition metal variants and provides an alternative
disconnection to C-H cross-coupling protocols for the synthesis of
Ureate ligands are an electron withdrawing N,O-chelating
ligand that has been used to generate early transition metal
hydrofunctionalization catalysts. 10 For example, a zirconium
ureate complex, with its very electrophilic metal center, has
remarkable C-N bond forming reactivity in hydroamination.10,11 To
date, ureate N,O-chelating ligands have not been explored for
hydroaminoalkylation. Furthermore, known Ta organometallic
reagents that are less susceptible to decomposition than
Csp -Csp bonds α3, 4 to amines. However, limitations due to
3
3
modest activity decomposition remain.
5
6
7
Early transition metal complexes using Sc, Ti, Zr, , and
have been under development for intermolecular
8
Ta
9
hydroaminoalkylation catalysis since the early 1980’s. Recent
advances have expanded reactivity to include tertiary5 or
1
2
2 3 3
and Ta(CH CMe )
Cl2,13
TaMe
3
Cl
2
, such as Ta(CH
2
SiMe
3
)
3
Cl
2
6
,7,8
6i,l
have not been evaluated in hydroaminoalkylation. Here, we show
that in situ prepared catalyst systems assembled from tunable
ureate salts and Ta alkyl reagents can realize improved TOFs (up
to 17/h) and TONs (up to 100) in hydroaminoalkylation. The easily
varied ureate auxiliary ligand can be modified to optimize
reactivity. Finally, this catalyst system requires only a 1:1
stoichiometry of amine:alkene reagents to give uniquely the β-
alkylated amine product that can be isolated using a simple
filtration protocol.
secondary amines and terminal alkene
or diene or internal
8
l
alkenes to give α and/or β-alkylated products. Our group has
shown that N,O-chelated Ta amido complexes offer a tunable
framework for developing enhanced catalysis with improved
substrate scope.2c However, the reactive amido ligands result in
complicating equilibria and byproduct formation that reduces
TOFs (<4/h) and complicates product isolation.8o,p Alternatively
3 2
we have shown that the organometallic precursor, TaMe Cl
,8k
when combined with the electron withdrawing, N,O-chelating
First, known Ta organometallic reagents8k,12,13 and
established Ta amido reagents8a,b were screened for reactivity
using a standard benchmark reaction between N-methylaniline
[*]
Rebecca C. DiPucchio, Dr. Sorin-Claudiu Roşca, Prof. Laurel. L.
Schafer
and 1-octene (Table 1). Ta(CH
TOFs within the first hour of reaction. In contrast
Ta(CH CMe Cl showed no reaction within 1 h, but over 24 h,
1% conversion was observed. The previously explored
2 3 3 2
SiMe ) Cl provides promising
Department of Chemistry
University of British Columbia
2036 Main Mall, Vancouver, B.C, Canada, V6T 1Z1
2
3
)
3
2
E-mail: schaferl@mail.ubc.ca
These authors contributed equally to this work
2
‡
3 2
TaMe Cl showed good reactivity within the first hour, but this
Supporting information for this article is given via a link at the end
of the document.
promising reactivity degraded within
5
h. Importantly,
14
[
Ta(NMe
2
)
3
Cl
2
]
2
,
showed no reaction at this lower temperature
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201712668
COMMUNICATION
Table 2. Study of ligand effects on hydroaminoalkylationa
and time. Thus, Ta(CH
experiments.
2 3 3 2
SiMe ) Cl was chosen for further catalytic
R1
R2
SiMe ) Cl
2
, 5 mol%
Ta(CH -
H
2
3 3
H
R1
+
N
N
mol%
L Na , 5
+
Table 1. Screening of tantalum based precursors
110 or 130 °C, d -toluene
R2
8
H
H
N
N
5 mol% [Ta]
+
5
5
1
h,110 °C, d -toluene
8
Ligand salt
5
iPr
O
L1
tB
u
N
Ta(CH
2 3 3
SiMe ) Cl
2
Ta(CH
2 3 3
CMe ) Cl
2
3
TaMe Cl
2
2 3
[Ta(NMe ) Cl
]
2 2
N
a
1 h, n.r.b
20 h, n.r.
iPr
TOF 8/h
1 h, n.r.b
TOF 6/h
1 h, n.r.b
a
Reaction conditions: amine (0.5 mmol), 1-octene (0.5 mmol), Ta precursor
O
1
L2
(0.025 mmol), d
8
-toluene (0.5 g). TOF determined by H NMR spectroscopy.
P
EtO
EtO
b
N
1 h, n.r.
20 h, n.r.
n.r.: no reaction.
Na
Next, ligand effects on hydroaminoalkylation reactivity were
investigated using precatalysts generated in situ (Table 2).15 Note
O
N
N
a
L3
that the present state-of-the-art reaction conditions use an
isolated Ta precatalyst at 145 °C. This in situ catalyst preparation
1
h, 31%
20 h, 33%
8
l
protocol featured ligands previously used as isolated precatalysts;
amidate (L1),8c phosphoramidate (L2),8h and pyridonate (L3).8l
O
L4
L5
Ph
For the first time, a variety of ureate (L4–6) ligand salts were also
N
N
N
a
1 h, 83%
1 h, 12%
1 h, 5%
20 h, 19%
20 h, 83%
20 h, 6%
explored.
Ph
Catalytic screening of in situ prepared complexes with
amidate L1 and phosphoramidate L2 resulted in no conversion,
regardless of the alkene substrate. In contrast, using the less
sterically encumbered pyridonate ligand salt L3 proved to be more
successful, as 31% and 33% conversions were observed for both
terminal and internal alkenes. Next ureate salts L4–6 were tested.
These ligands were expected to generate a more electrophilic
metal center to give improved reactivity. Gratifyingly, the in situ
catalyst system with L4 was excellent, affording 83% conversion
in only 1 h for the reaction between 1-octene and N-methylaniline;
a TOF of more than 16/h. However, when the more challenging
cyclohexene substrate was evaluated, only a modest 19%
conversion was observed after 20 h. Remarkably, the mixed
aryl/alkyl substituted ureate ligand L5, resulted in a reversed
trend; this system realized higher conversion of the internal
alkene substrate (20 h, 83%) but was less effective for the
terminal alkene substrate (1 h, 12%). These results are surprising
considering that the only change is one N-Ph group of L4 to an N-
O
r
Ph
N
N
Na
iP
O
r
L6
iP
r
N
N
N
a
iP
a
Reaction conditions: amine (0.5 mmol), alkene (0.5 mmol), Ta(CH
0.025 mmol), ligand salt (0.025 mmol), -toluene (0.5 g). Conversion
NMR spectroscopy. All reactions with 1-octene were
2 3 3 2
SiMe ) Cl
(
d
8
1
determined by
H
performed at 110 °C, while those with cyclohexene were performed at 130 °C.
b
n.r. = no reactivity
i
Pr moiety in L5. With this empirical observation in hand, we
i
thought to exchange the remaining Ph group of L5 with an Pr
Next we sought to explore the amine substrate scope of
catalysts prepared with L4 for terminal alkenes (1-octene) and L5
for internal alkenes (cyclooctene; Table 3). Reaction times were
adapted to favor full conversion of substrate and facilitate product
isolation i.e. 2 h for 1-octene and 6 h for cyclooctene. The desired
products were isolated by filtration in >95% purity,17 and typically
column chromatography could be avoided (eg. Entry 1).
Furthermore, only 1 mol% of catalyst gave complete conversion
TON = 100), as measured over 30 h by H NMR spectroscopy.
group (L6). Unfortunately, this change in ligand design did not
improve the catalytic system, as only poor conversions were
obtained for both alkenes. We propose that the known hemilability
of N,O-chelating ligands,16 coupled with the variable coordination
modes of ureate ligands would result in a flexible coordination
environment about the reactive metal center, thereby promoting
reactivity.
1
(
In Entry 2, cyclooctene was fully converted within 6 h, offering an
excellent isolated yield of product (83%). Consistent with previous
work, para-substituted N-methylaniline derivatives (Entries 3-12)
are well tolerated, including the para-methoxyphenyl substituent
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201712668
COMMUNICATION
(
Entries 3 & 4) can be oxidatively cleaved to access primary
substrates, giving product in 75% yield in only 2 h (1). Such
aminosilylether products are valuable precursors to β-alkylated
heterocycles.8j,q Compounds 2 and 3 show that aryl or alkyl
groups can be incorporated into the alkene substrates. A gem-
disubstituted alkene can be used to install a β-quaternary center
in high yield (4). Products 5 and 6, prepared from dienes, illustrate
the outstanding chemoselectivity of the in situ catalyst system with
L4; only the terminal alkene undergoes hydroaminoalkylation,
leaving the internal alkene available for further functionalization.
However, when L5 is used, a mixture of products results from
unselective hydroaminoalkylation. Halide substituted styrene
derivatives are also compatible with this d0 metal system (7),
including an example with the halide in the sterically hindered
ortho–position (8). This result contrasts with the observation that
sterically demanding 2-methylstyrene does not react under these
conditions. Notably, 8 is a known intermediate en route to the β-
methylated indoline product obtained after subsequent Buchwald-
Hartwig coupling.8k
1
8
amine products.
(
Halide substituents on the aromatic ring
0
Entries 5 - 10) are completely compatible with this d metal that
does not engage in oxidative addition/reductive elimination
chemistry. Such aryl halides can then be used in further cross-
coupling reactions.8k These Lewis acidic tantalum catalysts are
compatible with the pharmaceutically relevant trifluoromethoxy
groups (Entries 11 & 12) and catechol (Entry 13). As shown, the
aniline derivatives are all compatible with both L4 and L5.
However, more challenging dialkyl substituted amines do not
react.
a
Table 3. Substrate scope in amine
H
a
N
SiMe
Ta(CH -
Cl 5 mol%
L Na 5 mol%
5
2
)
3 3
2,
R
H
N
5
or
+
or
+
,
R
or 130 °C d8 toluene
,
-
H
N
110
b
R
Having obtained such promising results with terminal alkenes,
we next investigated the substrate scope with more challenging
internal alkenes. Tables 2, 3 and 9 - 11, show that cyclic alkenes
are all viable substrates for hydroaminoalkylation. Due to ring-
strain, cycloheptene is the most reactive cyclic alkene, requiring
only 2 h to reach full conversion. Linear internal alkenes have
reduced reactivity. The reaction with cis-3-hexene (12) takes 20
h to reach 77% conversion (65% isolated yield). For comparison,
the only other reported catalyst for the hydroaminoalkylation of
internal alkenes requires 44 h at 145 °C to obtain 69% yield of
Entry
Amine
Alkene
Isolated Yield
(
%)
H
N
1
2
a
b
88
83
H
N
3
4
a
b
77
70
O
8
l
12. The stereochemistry of the internal alkene affects reactivity,
H
N
as trans-3-hexene results in only 15% conversion.
Chart 1. Substrate scope in alkenea
SiMe Cl , 5 mol %
5
6
a
b
86
95
Br
Cl
R1
R2
H
R1
Ta(CH -
2
3
)
3
2
H
N
+
H
N
N
L Na , 5
mol
%
+
°
R2
110 or 130
d8-toluene
7
8
a
b
90
93
C,
OTBDMS
H
H
N
H
N
N
H
N
1b,c, 75%
2
b,d, 86%
3
b,c, 86%
9
a
b
85
88
10
F
H
N
H
H
N
N
H
N
b,d, 86%
5b,c, 99%
6b,c, 86%
4
1
1
2
a
b
92
85
Br
H
N
1
H
N
H
N
F3CO
H
Cl
7b,c, 98%
8
b,c, 65%
e,f, 70%
9
N
O
O
13
a
85
H
N
H
N
H
N
1
0e,f, 75%
11e,c, 95%
12e,f, 65%
a
Reaction conditions: amine (0.5 mmol), alkene (0.5 mmol),
SiMe Cl (0.025 mmol), ligand salt (0.025 mmol), d -toluene (0.5 g). L4
a
Ta(CH
2
)
3 3
2
8
Reaction conditions: amine (0.5 mmol), alkene (0.5 mmol), Ta(CH
2 3 3 2
SiMe ) Cl
b
was used for all terminal alkene substrates at 110 °C over 2 h and L5 was used
for internal alkene substrates at 130 °C over 6 h.
(0.025 mmol), ligand salt (0.025 mmol), d -toluene (0.5 g). Reaction was run
8
using ligand L4 at 110 °C. c 2 h reaction time. d 3 h reaction time. e Reaction
was run using ligand L5 at 130 °C. f from cis-3-hexene, 20 h reaction time.
We next switched our attention to exploring the alkene
substrate scope with the aforementioned systems; using L4 for
terminal alkenes and L5 for internal alkenes (Chart 1). 19
Gratifyingly, alkenes containing silyl protected alcohols are good
In summary, modified ureate auxiliary ligands in combination
with Ta(CH SiMe ) Cl have been shown to deliver superior TOFs
and TONs for the atom- and step-economic hydroaminoalkylation
2
3
3
2
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201712668
COMMUNICATION
reaction. By leveraging the variable ureate framework excellent Acknowledgements
activity with either terminal or challenging internal alkenes has
been realized. This approach is operationally simple in that no
amine protecting groups, directing groups or additives are
required and products can be isolated by filtration. Furthermore,
this new family of easily prepared catalysts is the only class that
uses a 1:1 combination of alkene and amine substrates. These
new systems address acknowledged problems in catalyst activity.
On-going work focuses on mechanistic investigations to
understand and optimize ligand substituent effects. Future work
aims to enhance substrate scope and selectively modify regio-
and stereoselectivity in hydroaminoalkylation.
RCD and SCR thank NSERC CREATE Sustainable Synthesis
and RCD thanks UBC for a graduate fellowship. LLS thanks
NSERC for financial support of this work. This research was
undertaken, in part, thanks to funding from the Canada Research
Chairs program.
Keywords: amines • C-H activation • hydroaminoalkylation •
tantalum alkyls • ureates
[
1]
2]
Dong, Z. Ren, S. J. Thompson, Y. Xu, G. Dong, Chem. Rev. 2017, 117,
333-9403.
[8]
For Ta and Nb catalysts see: a) S. B. Herzon, J. F. Hartwig, J. Am. Chem.
Soc. 2007, 129, 6690-6691. b) S. B. Herzon, J. F. Hartwig, J. Am. Chem.
Soc. 2008, 130, 14940-14941. c) P. Eisenberger, R. O. Ayinla, J. M. P.
Lauzon, L. L. Schafer, Angew. Chem. Int. Ed. 2009, 48, 8361-8365. d)
G. Zi, F. Zhang, H. Song, Chem. Comm. 2010, 46, 6296-6298. e) A. L.
Reznichenko, T. J. Emge, S. Audörsch, E. G. Klauber, K. C. Hultzsch, B.
Schmidt, Organometallics 2011, 30, 921-924. f) F. Zhang, H. Song, G.
Zi, Dalton Trans. 2011, 40, 1547-1566. g) A. L. Reznichenko, K. C.
Hultzsch, J. Am. Chem. Soc. 2012, 134, 3300-3311. h) P. Garcia, Y. Y.
Lau, M. R. Perry, L. L. Schafer, Angew. Chem. Int. Ed. 2013, 52, 9144-
9148. i) P. Garcia, P. R. Payne, E. Chong, R. L. Webster, B. J. Barron,
A. C. Behrle, J. A. R. Schmidt, L. L. Schafer, Tetrahedron 2013, 69, 5737-
5743. j) P. R. Payne, P. Garcia, P. Eisenberger, J. C. H. Yim, L. L.
Schafer, Org. Lett. 2013, 15, 2182-2185. k) Z. Zhang, J.-D. Hamel, L. L.
Schafer, Chem. Eur. J. 2013, 19, 8751-8754. l) E. Chong, J. W. Brandt,
L. L. Schafer, J. Am. Chem. Soc. 2014, 136, 10898-10901. m) J. Dörfler,
S. Doye, Eur. J. Org. Chem. 2014, 2014, 2790-2797. n) B. Hamzaoui, J.
D. A. Pelletier, E. Abou-Hamad, Y. Chen, M. El Eter, E. Chermak, L.
Cavallo, J.-M. Basset, Chem. Eur. J. 2016, 22, 3000-3008. o) J. M.
Lauzon, P. Eisenberger, S.-C. Roşca, L. L. Schafer, ACS Catalysis 2017,
7, 5921-5931. p) J. W. Brandt, E. Chong, L. L. Schafer, ACS Catalysis
2017, 7, 6323-6330. q) P. M. Edwards, L. L. Schafer, Org. Lett. 2017, 19,
5720-5723.
9
[
For reviews and highlights describing hydroaminoalkylation reactions
see: a) P. W. Roesky, Angew. Chem. Int. Ed. 2009, 48, 4892-4894. b) P.
Eisenberger, L. L. Schafer, Pure Appl. Chem. 2010, 82, 1503-1515. c) E.
Chong, P. Garcia, L. L. Schafer, Synthesis 2014, 46, 2884-2896. d) S. A.
Ryken, L. L. Schafer, Acc. Chem. Res. 2015, 48, 2576-2586. e) J. D. A.
Pelletier, J.-M. Basset, Acc. Chem. Res. 2016, 49, 664-677. f) F. Perez,
S. Oda, L. M. Geary, M. J. Krische, Top. Curr. Chem. 2016, 374, 35.
a) S. Oda, J. Franke, M. J. Krische, Chem. Sci. 2016, 7, 136-141. b) A.
T. Tran, J.-Q. Yu, Angew. Chem. Int. Ed. 2017, 56, 10530-10534. c) D.
Yamauchi, T. Nishimura, H. Yorimitsu, Angew. Chem. Int. Ed. 2017, 56,
[
3]
4]
7200-7204. d) S. M. Thullen, T. Rovis, J. Am. Chem. Soc. 2017, 139,
15504-15508.
[
a) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem. Int. Ed.
2009, 48, 5094-5115. b) L. Ackermann, Chem. Comm. 2010, 46, 4866-
4877. c) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147-1169.
d) D. A. Colby, A. S. Tsai, R. G. Bergman, J. A. Ellman, Acc. Chem. Res.
012, 45, 814-825. e) C. Le, Y. Liang, R. W. Evans, X. Li, D. W. C.
2
MacMillan, Nature 2017, 547, 79-83.
[
5]
6]
a) A. E. Nako, J. Oyamada, M. Nishiura, Z. Hou, Chem. Sci. 2016, 7,
6
429-6434. b) F. Liu, G. Luo, Z. Hou, Y. Luo, Organometallics 2017, 36,
557-1565. c) H. Gao, J. Su, P. Xu, X. Xu, Org. Chem. Front. 2018 in
1
press DOI: 10.1039/C7QO00718C.
[9]
a) M. G. Clerici, F. Maspero, Synthesis 1980, 1980, 305-306. b) W. A.
Nugent, D. W. Ovenall, S. J. Holmes, Organometallics 1983, 2, 161-162.
[
For Ti catalysts see: a) C. Müller, W. Saak, S. Doye, Eur. J. Org. Chem.
2
008, 2008, 2731-2739. b) Kubiak, I. Prochnow, S. Doye, Angew. Chem.
[10] a) D. C. Leitch, P. R. Payne, C. R. Dunbar, L. L. Schafer, J. Am. Chem.
Soc. 2009, 131, 18246-18247. b) D. C. Leitch, C. S. Turner, L. L. Schafer,
Angew. Chem. Int. Ed. 2010, 49, 6382-6386. c) D. C. Leitch, R. H. Platel,
L. L. Schafer, J. Am. Chem. Soc. 2011, 133, 15453-15463. d) P. R.
Payne, J. A. Bexrud, D. C. Leitch, L. L. Schafer, Can. J. Chem. 2011, 89,
1222-1229. e) Lauzon, J. M. P.; Schafer, L. L. Z. Anorg. Allg. Chem. 2015,
641, 128-135.
Int. Ed. 2009, 48, 1153-1156. c) I. Prochnow, R. Kubiak, O. N. Frey, R.
Beckhaus, S. Doye, ChemCatChem 2009, 1, 162-172. d) R. Kubiak, I.
Prochnow, S. Doye, Angew. Chem. Int. Ed. 2010, 49, 2626-2629. e) I.
Prochnow, P. Zark, T. Müller, S. Doye, Angew. Chem. Int. Ed. 2011, 50,
6
401-6405. f) D. Jaspers, W. Saak, S. Doye, Synlett 2012, 23, 2098-
102. g) E. Chong, L. L. Schafer, Org. Lett. 2013, 15, 6002-6005. h) J.
2
Dörfler, S. Doye, Angew. Chem. Int. Ed. 2013, 52, 1806-1809. i) T.
Preuß, W. Saak, S. Doye, Chem. Eur. J. 2013, 19, 3833-3837. j) J.
Dörfler, T. Preuß, A. Schischko, M. Schmidtmann, S. Doye, Angew.
Chem. Int. Ed. 2014, 53, 7918-7922. k) J. Dörfler, B. Bytyqi, S. Hüller, N.
M. Mann, C. Brahms, M. Schmidtmann, S. Doye, Adv. Synth. Catal.
[11] R. H. Platel, L. L. Schafer, Chem. Comm. 2012, 48, 10609-10611.
[12] S. Moorhouse, G. Wilkinson, J. Chem. Soc., Dalton Trans. 1974, 2187-
2190.
[13] R. R. Schrock, J. D. Fellmann, J. Am. Chem. Soc. 1978, 100, 3359-3370.
[14] M. H. Chisholm, J. C. Huffman, L.-S. Tan, Inorg. Chem. 1981, 20, 1859-
1866.
2015, 357, 2265-2276. l) J. Dorfler, Preu, C. Brahms, D. Scheuer, S.
Doye, Dalton Trans. 2015, 44, 12149-12168. m) L. H. Lühning, C.
Brahms, J. P. Nimoth, M. Schmidtmann, S. Doye, Z. Anorg. Allg. Chem.
[15] In situ reactions were monitored by 1H NMR via the disappearance of
CH2 peaks from the starting material. Please refer to figures S5 and S6
in the Supporting Information.
2
015, 641, 2071-2082. n) M. Manßen, N. Lauterbach, J. Dörfler, M.
Schmidtmann, W. Saak, S. Doye, R. Beckhaus, Angew. Chem. Int. Ed.
015, 54, 4383-4387. o) M. Weers, L. H. Lühning, V. Lührs, C. Brahms,
[16] J. M. Clarkson, L. L. Schafer, Inorg. Chem. 2017, 56, 5553-5566.
[17] Please refer to Figures S7 and S8 in the Supporting Information.
[18] S. Kobayashi, H. Ishitani, M. Ueno, J. Am. Chem. Soc. 1998, 120, 431-
432.
2
S. Doye, Chem. Eur. J. 2017, 23, 1237-1240. p) J. Bielefeld, S. Doye,
Angew. Chem. Int. Ed. 2017, 56, 15155-15158.
[7]
For Zr catalysts see: a) J. A. Bexrud, P. Eisenberger, D. C. Leitch, P. R.
Payne, L. L. Schafer, J. Am. Chem. Soc. 2009, 131, 2116-2118. b) B.
Hamzaoui, J. D. A. Pelletier, M. El Eter, Y. Chen, E. Abou-Hamad, J.-M.
Basset, Adv. Synth. Catal. 2015, 357, 3148-3154.
[19] For a comparison of L4 and L5 among a variety of substrates, refer to
Table S1 in the Supporting Information.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201712668
COMMUNICATION
This article is protected by copyright. All rights reserved.