Unnatural Amino Acid Synthesis Enabled by the Regioselective Cobalt(III)-Catalyzed Intermolecular Carboamination of Alkenes

Article abstract of DOI:10.1002/anie.201608729

Herein, we report an unprecedented regioselective and entirely atom-economic cobalt(III)-catalyzed method for the non-annulative, intermolecular carboamination of alkenes. The methodology enables the direct synthesis of unnatural amino acid derivatives an

Full text of DOI:10.1002/anie.201608729

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Communications
Chemie
International Edition: DOI: 10.1002/anie.201608729
German Edition: DOI: 10.1002/ange.201608729
Alkene Difunctionalization
Unnatural Amino Acid Synthesis Enabled by the Regioselective
Cobalt(III)-Catalyzed Intermolecular Carboamination of Alkenes
Andreas Lerchen+, Tobias Knecht+, Constantin G. Daniliuc, and Frank Glorius*
Abstract: Herein, we report an unprecedented regioselective
and entirely atom-economic cobalt(III)-catalyzed method for
the non-annulative, intermolecular carboamination of alkenes.
The methodology enables the direct synthesis of unnatural
amino acid derivatives and proceeds under redox-neutral
intramolecular[8] as well as annulative intermolecular[9] car-
boamination reactions of alkenes have been examined, the
non-annulative intermolecular carboamination of alkenes
have been far less investigated.[10] Our particular focus was
to explore the regioselective, non-annulative intermolecular
carboamination of alkenes, since this reaction can provide
highly valuable unnatural amino acid derivatives. To our
knowledge no report on any non-annulative Cp*CoIII-cata-
lyzed carboamination reaction has been reported to date.
Additionally, given the generally higher propensity for b-H-
elimination with rhodium, this reaction offers an opportunity
to demonstrate the inherently divergent mechanistic behavior
of the Cp*CoIII catalyst and its Cp*RhIII counterpart, with the
result that both catalysts give completely different product
selectivity.
À
À
conditions with a completely regioselective C C bond and C
N bond formation. Furthermore, this reaction exemplifies the
inherently different mechanistic behavior of the Cp*CoIII
catalyst and its Cp*RhIII counterpart, especially towards b-H-
elimination.
À
T
ransition-metal catalyzed C H bond functionalization has
proven to be a powerful and straightforward strategy for the
synthesis of a variety of complex core structures that are
present in natural products as well as pharmaceuticals.[1]
Besides the widely established transition-metal catalysts
(palladium, rhodium, iridium, ruthenium) that are associated
with low abundance and high costs, the utilization of earth-
abundant metal catalysts, such as cobalt has received consid-
erable attention.[2] Inspired by the seminal reports of Kanai
and Matsunaga,[3] several groups showed that the Cp*CoIII
catalyst (Cp* = C5Me5) is comparable to its Cp*RhIII counter-
part considering its analogous reactivity.[4] Nevertheless, only
a few reports have appeared to date describing a complemen-
tary reactivity of the Cp*CoIII catalyst to its Cp*RhIII
congener.[5] Reactivity differences have, however, been
exploited in the case of other first- and second-row transition
metals.[6] It therefore seems promising to further investigate
the complementary reactivity of Cp*CoIII to Cp*RhIII to
address the limitations found with its heavier counterpart.
Alkenes are amongst the most readily available and
cheapest chemical feedstocks. Despite their great synthetic
potential, the metal-catalyzed difunctionalization of alkenes
is still a formidable and rarely explored challenge because
1) the rate of difunctionalization versus b-H-elimination of
the resulting C(sp3)–metal-species is competitive and 2) the
selective addition needs to be carefully controlled.[7] Consid-
ering the potential as well as the limitations of several alkene
difunctionalizations, we became interested in the selective
carboamination of alkenes. Although a variety of annulative
Recently the Rovis group published a Cp*RhIII-catalyzed
route for the intermolecular carboamination of alkenes.[10a]
They reported that the b-H-elimination could be inhibited by
coordinatively saturating the C(sp3)-rhodium-intermediate
with an in situ generated bidentate directing group (Sche-
me 1a). Subsequently, a similar approach was reported by Liu
and co-workers using a bidentate coupling partner instead of
a bidentate directing group.[10b] However, both concepts
essentially require the coordinative saturation of the metal
center to achieve the carboamination,[11] which brings signifi-
[*] A. Lerchen,[+] T. Knecht,[+] Dr. C. G. Daniliuc, Prof. Dr. F. Glorius
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Organisch-Chemisches Institut
Corrensstrasse 40, 48149 Mꢁnster (Germany)
E-mail: glorius@uni-muenster.de
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under http://dx.doi.org/10.
1002/anie.201608729.
Scheme 1. Cp*RhIII- and Cp*CoIII-catalyzed carboamination strategies.
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cant limitations in the reaction scope and further ligand-
modifications as well as inconvenient multi-step substrate
syntheses are necessary.
Inspired by these reports we designed the first regiose-
lective intermolecular Cp*CoIII-catalyzed carboamination of
alkenes. The unique properties of the catalyst system obviate
the need for either a bidentate directing group or a bidentate
coupling partner (Scheme 1b). In this conceptually and
mechanistically distinct reaction, the Cp*CoIII-catalyst led to
a different product than its Cp*RhIII-counterpart. For the
rhodium catalyst, if the saturation of the nascent C(sp3)–metal
center is not achieved, b-H-elimination predominates and the
oxidative Heck product is formed. In the case of cobalt, no
saturation of the C(sp3)–metal center is required and the
carboamination is inherently favored over the b-H-elimina-
tion.
We began our studies using phenoxyacetamide (1) as it
features a redox-active directing group and n-butylacrylate
(2) as coupling partner. After an extensive screening, (see the
Supporting Information) we could achieve a completely
regioselective addition to the double bond and isolate the
desired product 3a in 82% yield using stoichiometric amounts
of 1 and 2 in the presence of catalytic amounts of [Cp*Co-
(CO)I2], AgSbF6, CsOAc, and K3PO4 (Scheme 2 and see the
Supporting information). When the same conditions were
applied with the [(Cp*RhCl2)2] catalyst instead of the
[Cp*Co(CO)I2] catalyst, the oxidative Heck product was
isolated in 53% yield and only trace amounts of the
carboamination product could be detected in the crude
reaction mixture by ESI-MS (see the Supporting Informa-
tion).
With the optimized reaction conditions in hand, we
investigated the scope of the carboamination reaction
(Scheme 2). Para-substituted phenoxyacetamides with elec-
tron-withdrawing functional groups, such as halogens (3b–
3d), esters (3e), or even the CF3 substituent (3 f), delivered
the desired amino acid derivatives in good to excellent yields.
Similar results could be obtained for para-substituted phe-
noxyacetamides bearing electron-donating functional groups
(3g, 3h). Using the disubstituted 3,4-dimethylphenoxyaceta-
mide, the corresponding product could be isolated in good
yield (60%) and excellent regioselectivity (3l). Furthermore,
2-N-(naphthalen-2-yloxy)acetamide could deliver the desired
amino acid derivative in a moderate yield of 47% (3i). Meta-
substituted electron-withdrawing (m-Br) as well as electron-
donating (m-Me) phenoxyacetamides delivered the corre-
sponding products in good yields and a single regioisomer was
obtained (3j, 3k). The absolute molecule structures for 3j and
3c were confirmed by X-ray crystallography (see Scheme 2
and the Supporting Information).[12] For the meta-methoxy-
and the meta-fluorophenoxyacetamides excellent yields could
be obtained, although a mixture of regioisomers was observed
(3n, 3o). The ortho-methylphenoxyacetamide delivered the
corresponding product in 30% yield (3m). The poor reac-
tivity is attributed to the great steric demand of the Cp*CoIII
catalyst, which results in sensitivity to steric bulk on the
substrates. No product formation was observed in the absence
of the Cp*CoIII catalyst. We further investigated the scope of
the N-protecting group. However, benzyloxycarbonyl- (Cbz),
Scheme 2. Variation of the phenoxyacetamide and acrylate. Isolated
yields are given. 1 (0.2 mmol), 2 (1.0 equiv), [Cp*Co(CO)I2]
(10 mol%), AgSbF6 (20 mol%), CsOAc (25 mol%), K3PO4 (25 mol%),
3 ꢂ MS (40 mg) in TFE (1 mL) at 408C for 22 h; [a] 0.4 mmol of 2 was
used. For crystallographic data see: Ref. [12].
benzoyl- (Bz), tosyl- (Ts), and pivaloyl- (Piv) protected
substrates were unsuccessful under the optimized reaction
conditions (see Supporting Information).
Several acrylates also led to the formation of the
corresponding amino acid derivatives. tert-Butylacrylate and
ethylacrylate delivered the desired products in reasonable
yields (3p, 3q). Moreover, using benzylacrylate the carboa-
minated product (3r) was formed in a synthetically useful
yield of 51%.
Further experiments were carried out to elucidate a pos-
sible reaction mechanism (Scheme 3). First, the kinetic
isotope effect was studied in competition and parallel experi-
ments (Scheme 3a). A KIE of 2.1 (competition experiment)
and kH/kD = 1.5 (parallel experiment) were observed. Based
À
on these results, we propose that the C H activation step is
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Scheme 4. Proposed reaction mechanism.
Scheme 3. Mechanistic experiments.
À
wards, the O N bond undergoes an oxidative addition to the
cobalt(I) species to form the 7-membered CoIII intermediate
E. Finally, intermediate E delivers the desired amino acid
derivative and regenerates the active catalyst species A
through a proto-demetallation.
partly rate determining in the reaction.[13] Second, we inves-
tigated the reaction process after the C H activation event for
the distinction between an intermolecular and an intra-
molecular reaction pathway for the C N bond formation
À
In conclusion, we have developed the first non-annulative
Cp*CoIII-catalyzed carboamination approach for the direct
difunctionalization of alkenes. The reaction proceeds in an
À
(Scheme 3b). Towards this goal we first synthesized the
À
compounds 1d and 1a-D3 and treated them in a cross-over
intermolecular fashion with a completely regioselective C C
À
À
experiment. The results indicate that the C N bond forma-
bond and then an intramolecular C N bond formation.
tion proceeds via an intramolecular pathway. The products
3d-D3 and 3a that would result from an intermolecular cross-
over were not detected by ESI-MS of the crude reaction
mixture, whereas only the products resulting from the intra-
molecular cross-over reaction 3d and 3a-D3 were detected.
Next, we investigated whether the reaction mechanism
could proceed in a stepwise manner. Towards this end
compound 4 was synthesized and treated with acetamide
(5). The reaction was performed under the standard reaction
conditions and only traces of the amino acid derivative were
detected in the crude reaction mixture by ESI-MS (see the
Supporting Information). This result is in accordance with the
mechanistic cross-over experiment. Based on these results we
Additionally, we could demonstrate for the first time that this
reaction proceeds in the absence of a bidentate directing
group or a bidentate coupling partner and that the reaction
outcome is solely attributed to the unique reactivity of the
Cp*CoIII catalyst. The results show the complementary nature
of the Cp*CoIII catalyst and its Cp*RhIII counterpart, since
two completely different products are formed under other-
wise identical conditions. Moreover, this methodology ena-
bles the direct synthesis of unnatural amino acid derivatives
that are highly valuable for industrial research as well as for
academia.
À
propose that after the intermolecular formation of the C C
bond, the reaction proceeds via an intramolecular pathway to
Acknowledgements
À
form the C N bond.
Based on these experimental results we propose a reaction
mechanism (Scheme 4). After the formation of the catalyti-
We gratefully thank A. Rꢀhling, T. Gensch, J. B. Ernst, L.
Rakers, M. Wiesenfeldt, Dr. E. A. Standley, Dr. K. M.
Chepiga, and Dr. M. van Gemmeren for fruitful discussions
and K. Gottschalk for technical assistance (all WWU). We
gratefully acknowledge generous financial support by the
Deutsche Forschungsgemeinschaft (Leibniz award).
À
cally active species A, the C H activation occurs under
elimination of HOAc and formation of intermediate B.
Intermediate B can then undergo an olefin-coordination
followed by an olefin-insertion leading to the 7-membered
intermediate C. The C(sp3)–metal-species
C
undergoes
À
Keywords: alkene difunctionalization · carboamination ·
Cp*Co(III) catalysis · redox-neutral conditions ·
unnatural amino acids
reductive elimination thus forming the desired C N bond
under the concomitant generation of CoI (species D). After-
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[5] For selected examples, see: a) H. Ikemoto, T. Yoshino, K.
Sakata, S. Matsunaga, M. Kanai, J. Am. Chem. Soc. 2014, 136,
5424; b) Y. Suzuki, B. Sun, K. Sakata, T. Yoshino, S. Matsunaga,
M. Kanai, Angew. Chem. Int. Ed. 2015, 54, 9944; Angew. Chem.
2015, 127, 10082; c) B. Sun, T. Yoshino, M. Kanai, S. Matsunaga,
Angew. Chem. Int. Ed. 2015, 54, 12968; Angew. Chem. 2015, 127,
13160; d) D. Zhao, J. H. Kim, L. Stegemann, C. A. Strassert, F.
Glorius, Angew. Chem. Int. Ed. 2015, 54, 4508; Angew. Chem.
2015, 127, 4591; e) Q. Lu, S. Vꢂsquez-Cꢃspedes, T. Gensch, F.
Glorius, ACS Catal. 2016, 6, 2352; f) J. H. Kim, S. Greßies, F.
Glorius, Angew. Chem. Int. Ed. 2016, 55, 5577; Angew. Chem.
2016, 128, 5667; g) J. Park, S. Chang, Angew. Chem. Int. Ed. 2015,
54, 14103; Angew. Chem. 2015, 127, 14309; h) H. Wang, M. M.
Lorion, L. Ackermann, Angew. Chem. Int. Ed. 2016, 55, 10386;
Angew. Chem. 2016, 128, 10542; i) D. Kalsi, R. A. Laskar, N.
Barsu, J. R. Premkumar, B. Sundararaju, Org. Lett. 2016, 18,
4198; j) J. A. Boerth, J. R. Hummel, J. A. Ellman, Angew. Chem.
Int. Ed. 2016, 55, 12650; Angew. Chem. 2016, 128, 12840.
[6] V. P. Ananikov, ACS Catal. 2015, 5, 1964.
[7] a) K. H. Jensen, M. S. Sigman, Org. Biomol. Chem. 2008, 6, 4083;
b) R. I. McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011, 111,
2981; c) for dihydroxylation, see: H. C. Kolb, M. S. VanNieu-
wenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483; d) for
diamination, see: Y. Zhu, R. G. Cornwall, H. Du, B. Zhao, Y. Shi,
Acc. Chem. Res. 2014, 47, 3665; e) F. Cardona, A. Goti, Nat.
Chem. 2009, 1, 269; f) K. MuÇiz, Chem. Soc. Rev. 2004, 33, 166;
g) for dihalogenation, see; A. J. Cresswell, S. T.-C. Eey, S. E.
Denmark, Angew. Chem. Int. Ed. 2015, 54, 15642; Angew. Chem.
2015, 127, 15866; h) U. Hennecke, Chem. Asian J. 2012, 7, 456;
i) for aminohalogenation, see: S. R. Chemler, M. T. Bovino, ACS
Catal. 2013, 3, 1076; j) for carboamination, see: D. M. Schultz,
J. P. Wolfe, Synthesis 2012, 351.
[8] a) S. R. Chemler, Org. Biomol. Chem. 2009, 7, 3009; for selected
annulative intramolecular carboamination reactions, see: b) A.
Faulkner, J. S. Scott, J. F. Bower, J. Am. Chem. Soc. 2015, 137,
7224; c) B. A. Hopkins, J. P. Wolfe, Chem. Sci. 2014, 5, 4840;
d) B. A. Hopkins, J. P. Wolfe, Angew. Chem. Int. Ed. 2012, 51,
9886; Angew. Chem. 2012, 124, 10024; e) J. D. Neukom, N. S.
Perch, J. P. Wolfe, J. Am. Chem. Soc. 2010, 132, 6276; f) G.
Zhang, L. Cui, Y. Wang, L. Zhang, J. Am. Chem. Soc. 2010, 132,
1474; g) C. F. Rosewall, P. A. Sibbald, D. V. Liskin, F. E.
Michael, J. Am. Chem. Soc. 2009, 131, 9488; h) N. C. Giampietro,
J. P. Wolfe, J. Am. Chem. Soc. 2008, 130, 12907; i) K.-T. Yip, M.
Yang, K.-L. Law, N.-Y. Zhu, D. Yang, J. Am. Chem. Soc. 2006,
128, 3130; j) J. S. Nakhla, J. W. Kampf, J. P. Wolfe, J. Am. Chem.
Soc. 2006, 128, 2893. Intramolecular: the olefin is preinstalled
and the first step of the reaction proceeds in an intramolecular
fashion.
[9] For selected intermolecular annulative carboamination reac-
tions, see: a) D. R. White, J. T. Hutt, J. P. Wolfe, J. Am. Chem.
Soc. 2015, 137, 11246; b) M. K. Manna, A. Hossian, R. Jana, Org.
Lett. 2015, 17, 672; c) C. E. Houlden, C. D. Bailey, J. G. Ford,
M. R. Gagnꢃ, G. C. Lloyd-Jones, K. I. Booker-Milburn, J. Am.
Chem. Soc. 2008, 130, 10066; d) C. C. Scarborough, S. S. Stahl,
Org. Lett. 2006, 8, 3251; e) D. Zhao, S. Vꢂsquez-Cꢃspedes, F.
Glorius, Angew. Chem. Int. Ed. 2015, 54, 1657; Angew. Chem.
2015, 127, 1677. Intermolecular: the first step of the reaction
proceeds in an intermolecular fashion.
[1] Selected Reviews: a) P. B. Arockiam, C. Bruneau, P. H. Dixneuf,
Chem. Rev. 2012, 112, 5879; b) G. Song, X. Li, Acc. Chem. Res.
2015, 48, 1007; c) L. Ackermann, Chem. Rev. 2011, 111, 1315;
d) L. Ackermann, Acc. Chem. Res. 2014, 47, 281; e) T. Gensch,
M. N. Hopkinson, F. Glorius, J. Wencel-Delord, Chem. Soc. Rev.
2016, 45, 2900; f) N. Kuhl, N. Schrçder, F. Glorius, Adv. Synth.
Catal. 2014, 356, 1443; g) T. Satoh, M. Miura, Chem. Eur. J. 2010,
16, 11212; h) D. Zhao, J. You, C. Hu, Chem. Eur. J. 2011, 17,
5466; i) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev.
2010, 110, 624; j) L. McMurray, F. OꢁHara, M. J. Gaunt, Chem.
Soc. Rev. 2011, 40, 1885; k) S. H. Cho, J. Y. Kim, J. Kwak, S.
Chang, Chem. Soc. Rev. 2011, 40, 5068; l) J. Yamaguchi, A. D.
Yamaguchi, K. Itami, Angew. Chem. Int. Ed. 2012, 51, 8960;
Angew. Chem. 2012, 124, 9092; m) X.-S. Zhang, K. Chen, Z.-J.
Shi, Chem. Sci. 2014, 5, 2146; n) T. Cernak, K. D. Dykstra, S.
Tyagarajan, P. Vachal, S. W. Krska, Chem. Soc. Rev. 2016, 45,
546; o) M. Zhang, Y. Zhang, X. Jie, H. Zhao, G. Li, W. Su, Org.
Chem. Front. 2014, 1, 843; p) J. Mo, L. Wang, Y. Liu, X. Cui,
Synthesis 2015, 439; q) H. Huang, X. Ji, W. Wu, H. Jiang, Chem.
Soc. Rev. 2015, 44, 1155.
À
[2] Selected Reviews on earth-abundant metal-catalyzed C H bond
activation: a) M. Moselage, J. Li, L. Ackermann, ACS Catal.
2016, 6, 498; b) K. Gao, N. Yoshikai, Acc. Chem. Res. 2014, 47,
1208; c) W. Liu, L. Ackermann, ACS Catal. 2016, 6, 3743;
d) A. A. Kulkarni, O. Daugulis, Synthesis 2009, 4087; e) S. Z.
Tasker, E. A. Standley, T. F. Jamison, Nature 2014, 509, 299;
f) J. J. Mousseau, A. B. Charette, Acc. Chem. Res. 2013, 46, 412;
g) E. Nakamura, N. Yoshikai, J. Org. Chem. 2010, 75, 6061.
[3] a) T. Yoshino, H. Ikemoto, S. Matsunaga, M. Kanai, Angew.
Chem. Int. Ed. 2013, 52, 2207; Angew. Chem. 2013, 125, 2263;
b) T. Yoshino, H. Ikemoto, S. Matsunaga, M. Kanai, Chem. Eur.
J. 2013, 19, 9142.
[4] For selected examples, see: a) D. Zell, Q. Bu, M. Feldt, L.
Ackermann, Angew. Chem. Int. Ed. 2016, 55, 7408; Angew.
Chem. 2016, 128, 7534; b) J. Li, L. Ackermann, Angew. Chem.
Int. Ed. 2015, 54, 8551; Angew. Chem. 2015, 127, 8671; c) J. Li, L.
Ackermann, Angew. Chem. Int. Ed. 2015, 54, 3635; Angew.
Chem. 2015, 127, 3706; d) H. Wang, J. Koeller, W. Liu, L.
Ackermann, Chem. Eur. J. 2015, 21, 15525; e) H. Wang, M.
Moselage, M. J. Gonzꢂlez, L. Ackermann, ACS Catal. 2016, 6,
2705; f) N. Sauermann, M. J. Gonzꢂlez, L. Ackermann, Org.
Lett. 2015, 17, 5316; g) A. Lerchen, S. Vꢂsquez-Cꢃspedes, F.
Glorius, Angew. Chem. Int. Ed. 2016, 55, 3208; Angew. Chem.
2016, 128, 3261; h) T. Gensch, F. J. R. Klauck, F. Glorius, Angew.
Chem. Int. Ed. 2016, 55, 11287; Angew. Chem. 2016, 128, 11457;
i) X. Wang, A. Lerchen, F. Glorius, Org. Lett. 2016, 18, 2090;
j) D.-G. Yu, T. Gensch, F. de Azambuja, S. Vꢂsquez-Cꢃspedes, F.
Glorius, J. Am. Chem. Soc. 2014, 136, 17722; k) J. R. Hummel,
J. A. Ellman, J. Am. Chem. Soc. 2015, 137, 490; l) J. R. Hummel,
J. A. Ellman, Org. Lett. 2015, 17, 2400; m) B. Sun, T. Yoshino, S.
Matsunaga, M. Kanai, Adv. Synth. Catal. 2014, 356, 1491; n) M.
Sen, D. Kalsi, B. Sundararaju, Chem. Eur. J. 2015, 21, 15529;
o) M. Sen, B. Emayavaramban, N. Barsu, J. R. Premkumar, B.
Sundararaju, ACS Catal. 2016, 6, 2792; p) S. Prakash, K.
Muralirajan, C.-H. Cheng, Angew. Chem. Int. Ed. 2016, 55,
1844; Angew. Chem. 2016, 128, 1876; q) L. Kong, S. Yu, X. Zhou,
X. Li, Org. Lett. 2016, 18, 588; r) Y. Liang, N. Jiao, Angew. Chem.
Int. Ed. 2016, 55, 4035; Angew. Chem. 2016, 128, 4103; s) X.-G.
Liu, S.-S. Zhang, C.-Y. Jiang, J.-Q. Wu, Q. Li, H. Wang, Org. Lett.
2015, 17, 5404; t) Z.-Z. Zhang, B. Liu, C.-Y. Wang, B.-F. Shi, Org.
Lett. 2015, 17, 4094; u) Z.-Z. Zhang, B. Liu, J.-W. Xu, S.-Y. Yan,
B.-F. Shi, Org. Lett. 2016, 18, 1776.
[10] For intermolecular non-annulative carboamination reactions,
see: a) T. Piou, T. Rovis, Nature 2015, 527, 86; b) Z. Hu, X. Tong,
G. Liu, Org. Lett. 2016, 18, 1702. Intermolecular: the olefin is not
preinstalled and the first step of the reaction proceeds in an
intermolecular fashion.
[11] For results with coordinatively non-saturated Cp*RhIII species,
see: a) for the Rovis work: T. Piou, T. Rovis, J. Am. Chem. Soc.
2014, 136, 11292; b) for the Liu work: Y. Shen, G. Liu, Z. Zhou,
X. Lu, Org. Lett. 2013, 15, 3366.
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[12] CCDC 1501392 and 1501393 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[13] a) E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51,
3066; Angew. Chem. 2012, 124, 3120; b) G. Bellucci, R.
Bianchini, C. Chiappe, D. Lenoir, A. Attar, J. Am. Chem. Soc.
1995, 117, 6243.
Received: September 6, 2016
Published online: && &&, &&&&
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Communications
Alkene Difunctionalization
A. Lerchen, T. Knecht, C. G. Daniliuc,
F. Glorius*
&&&& — &&&&
Unnatural Amino Acid Synthesis Enabled
by the Regioselective Cobalt(III)-
Catalyzed Intermolecular
It’s cobaltastic: An unprecedented regio-
selective and entirely atom-economic
cobalt(III)-catalyzed method for the non-
annulative, intermolecular carboamina-
tion of alkenes enables the direct syn-
thesis of acyclic unnatural amino acid
derivatives in a redox-neutral fashion.
Moreover Cp*CoIII and Cp*RhIII catalysts
gave different products under otherwise
identical conditions.
Carboamination of Alkenes
6
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!