Air-Stable Manganese(I)-Catalyzed C?H Activation for Decarboxylative C?H/C?O Cleavages in Water

Article abstract of DOI:10.1002/anie.201702193

The decarboxylative C?H/C?O functionalization was accomplished by air- and water-tolerant manganese(I) catalysis. The versatile C?H allylation occurred by facile organometallic C?H metalation on indoles, arenes, amino acids and synthetically meaningful ar

Full text of DOI:10.1002/anie.201702193

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Communications
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International Edition: DOI: 10.1002/anie.201702193
German Edition: DOI: 10.1002/ange.201702193
Manganese(I) Catalysis
À
Air-Stable Manganese(I)-Catalyzed C H Activation for
Decarboxylative C H/C O Cleavages in Water
À
À
Hui Wang+, Mꢀlanie M. Lorion+, and Lutz Ackermann*
À
À
Abstract: The decarboxylative C H/C O functionalization
was accomplished by air- and water-tolerant manganese(I)
À
catalysis. The versatile C H allylation occurred by facile
À
organometallic C H metalation on indoles, arenes, amino
acids and synthetically meaningful aryl ketimines with ample
substrate scope and high levels of chemo-, site- and regio-
selectivity.
À
C
H functionalization technology has emerged as an
increasingly powerful tool for molecular syntheses,[1] with
enabling applications to material sciences,[2] crop protection[3]
and drug development.[4] While significant advances have
been achieved with the aid of precious 4d and 5d transition
metal complexes,[5] recent focus has shifted towards the use of
earth-abundant base metals.[6] In particular, manganese
catalysts are highly attractive because of their inexpensive
and non-toxic nature. Thus, recent years have witnessed the
À
À
Figure 1. Air- and H2O-tolerant manganese(I)-catalyzed C H/C O acti-
vation.
À
À
Table 1: Optimization of decarboxylative C H/C O activation.
À
emergence of organometallic C H activation by user-friendly
manganese(I) catalysts,[7] with key contributions by inter alia
Kuninobu,[8] Wang,[9] Ackermann,[10] and Fairlamb,[11] among
others.[12] Despite these major advances, the manganese(I)-
Entry
Catalyst
Additive
Solvent
Yield [%][a]
E/Z
À
catalyzed C H transformations were thus far largely limited
1
2
3
4
5
6
7
8
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
–
NaOAc
NaOAc
—
Et2O
nBu2O
nBu2O
MeCN
CH2Cl2
1,4-dioxane
TFE
DCE
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
92[b]
85[b]
21[b]
21[b]
77[b]
90[b]
92[b]
84[b]
93[b]
5.5
1.8
3.5
1.9
2.4
1.4
5.1
2.8
6.4
–
–
–
–
5.9
–
to simple hydroarylation-based manifolds, while decarboxy-
lative transformations have thus far proven elusive. Consid-
ering the remarkable recent advances in decarboxylative
catalysis,[13] we became attracted to devising unprecedented
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
K2CO3
Cy2NH
Piv-Val-OH
NaOAc
NaOAc
NaOAc
À
À
manganese-catalyzed decarboxylative C H/C O transforma-
tions, on which we report herein. Notable features of our
findings include 1) manganese(I)-catalyzed decarboxylative
À
À
9
C H functionalizations, 2) robust organometallic C H acti-
[b]
10
11
12
13
14
15
16
17
18
19
20
–
À
vation in H2O and air, and 3) expedient C H allylations on
[b]
MnCl2
MnBr2
–
indoles, arenes and amino acids as well as synthetically
meaningful ketimines (Figure 1).
[b]
–
Mn2(CO)10
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
MnBr(CO)5
<5[b,c,d]
95
We initiated our studies by probing various solvents for
<10[d]
24
À
À
the envisioned decarboxylative C H/C O activation with
dioxolanone 2a (Table 1, and Table S-1 in the Supporting
6.4
5.7
5.7
5.9
5.9
46
À
Information). Thus, the C H functionalization proved viable
79[c,e]
84[f]
in apolar as well as polar protic reaction media, with best
diastereo-selectivities being achieved in TFE or H2O
H2O
80[g]
[a] Reaction conditions: 1a (0.25 mmol), 2a (0.75 mmol), additive
(20 mol%), solvent (1.0 mL), under air, 1008C, 16 h, isolated yield.
[b] Under N2. [c] NaOAc (10 mol%). [d] GC-conversion. [e] MnBr(CO)5
[*] H. Wang,[+] Dr. M. M. Lorion,[+] Prof. Dr. L. Ackermann
Institut fꢀr Organische und Biomolekulare Chemie
Georg-August-Universitꢁt Gçttingen
(5 mol%). [f] 808C. [g] 608C. py(m)=pyri(mi)dyl.
Tammannstraße 2, 37077 Gottingen (Germany)
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Homepage: http://www.org.chemie.uni-goettingen.de/ackermann/
(entries 1–9). The successful use of H2O clearly illustrates
À
[+] These authors contributed equally to this work.
the outstanding chemo-selectivity of the C H activation.
Control experiments verified the essential role of the
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.201702193.
MnBr(CO)5 catalyst (entries 9–13). The manganese(I)-cata-
À
À
lyzed C H/C O functionalization was not only tolerant to
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À
H2O, but occurred efficiently in an atmosphere of ambient air
as well (entry 14). The use of additives other than NaOAc
proved to be detrimental to the catalytic efficacy (entries 15–
17). Notably, the catalyst loading and the reaction temper-
ature could be significantly reduced (entries 18–20), with
a high catalytic performance even at 608C when using H2O as
the reaction medium (entry 20).
lyzed C H activation efficiently delivered the secondary and
tertiary allylic alcohols 3ab–3af with high levels of site- and
chemo-selectivity, as for instance reflected by the high-
yielding preparation of the nitro-substituted product 3ae.
À
À
The robustness of the decarboxylative C H/C O func-
tionalization with heteroarenes 1 was illustrated by efficient
manganese(I) catalysis with H2O as the reaction medium,
again efficiently proceeding in an atmosphere of air
(Scheme 3). Here, reactions performed in the presence of
the surfactant PTS/H2O (polyoxyethanyl a-tocopheryl seba-
cate) did not provide improved yields of the products 3.[14,15]
With the optimized manganese(I) catalyst in hand, we
À
À
probed its versatility in the decarboxylative C H/C O
functionalization with heteroarenes 1 in an atmosphere of
ambient air (Scheme 1). Thus, a variety of indoles 1a–1p
À
À
Scheme 1. Scope of manganese(I)-catalyzed C H/ C O activation of
indoles.
À
Scheme 3. Manganese(I)-catalyzed C H allylation on water.
proved to be viable substrates, even when being more
sterically hindered (1c–e,1k). Thereby, a set of synthetically
useful electrophilic functional groups, including chloro,
bromo, iodo, hydroxyl, ester, and enolizable ketone substitu-
ents, was fully tolerated. The manganese(I) catalyst was not
Given the unique features of the manganese(I)-catalyzed
À
À
decarboxylative C H/C O functionalization, we became
attracted to delineating its mode of action. First, intermolec-
ular competition experiments between electronically differ-
entiated arenes revealed a minor preference for electron-
À
limited to heteroaromatic substrates. Indeed, arene C H
activation was also viable to selectively deliver product 3pa.
À
Subsequently, a representative set of vinylated dioxola-
deficient substrates.[14] Second, C H activations in the pres-
À
À
nones 2 was probed in the decarboxylative C H/C O
functionalization (Scheme 2). Hence, the manganese(I)-cata-
ence of isotopically labeled D2O clearly revealed the rever-
sible nature of a water-tolerant organometallic C H activa-
tion elementary step (Scheme 4a). In good agreement with
this observation and third, the independently prepared
organometallic complex 4 proved to be competent in both
À
À
À
catalytic C H/C O functionalization (Scheme 4b) as well as
within its stoichiometric transformation (Scheme 4c).
À
À
Finally, the synthetic utility of the C H/C O functional-
ization was exploited for the direct modification of amino
acids 5,[16,17] notably under racemization-free reaction con-
ditions (Scheme 5a).[14] Furthermore, the C H/C O activa-
tion strategy allowed for the direct functionalization of
synthetically useful ketimines 7 in a diastereo- and posi-
tional-selective manner (Scheme 5b). Thereby, a variety of
ketones 8 was accessed featuring diverse substituents, includ-
ing useful chloro or bromo groups. The site-selectivity was
À
À
À
À
Scheme 2. C H/C O activation with substituted dioxolanones 2.
2
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found tolerant of air and water, which further set the stage for
the direct modification of amino acids under racemization-
free conditions.
Acknowledgements
Generous support by the European Research Council under
the European Communityꢀs Seventh Framework Program
(FP7 2007–2013)/ERC Grant agreement no. 307535, the CSC
(fellowship to H.W.) and the Alexander von Humboldt-
foundation (fellowship to M.M.L.) is gratefully acknowl-
edged.
Conflict of interest
The authors declare no conflict of interest.
À
À
Keywords: amino acids · C H activation · C O cleavage ·
heterocycles · imines · manganese
Scheme 4. Key mechanistic findings.
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Scheme 5. Manganese(I)-catalyzed C H/C O functionalization of
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group exerted a secondary effect to furnish ketone 8i and 8k
as the sole product.
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Manuscript received: February 28, 2017
Final Article published: && &&, &&&&
4
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Communications
Manganese(I) Catalysis
H. Wang, M. M. Lorion,
L. Ackermann*
&&&& — &&&&
À
Manganese-catalyzed C H activation:
Robust organometallic manganese(I)-
and amino acids in air and H2O. Mech-
anistic experiments show the reversibility
À
Air-Stable Manganese(I)-Catalyzed C H
À
À
À
À
À
Activation for Decarboxylative C H/C O
Cleavages in Water
catalyzed C H/C O functionalizations
enabled expedient decarboxylative diver-
sifications of indoles, arenes, ketimines,
of the C H metalation and the interme-
diacy of the metalacycle species.
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
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5
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