Catalytic 1,2-Regioselective Dearomatization of N-Heteroaromatics via a Hydroboration

Article abstract of DOI:10.1021/acscatal.8b00074

The thorium methyl and hydride complex (C₅Me₅)₂ThMe₂ and [(C₅Me₅)₂Th(H)(μ-H)]₂ catalyzed highly 1,2-regioselective dearomatization of pyridines via a hydroboration pro

Full text of DOI:10.1021/acscatal.8b00074

Subscriber access provided by UNIV OF MISSOURI ST LOUIS
Catalytic 1,2-Regioselective Dearomatization
of N-Heteroaromatics Via a Hydroboration
Heng Liu, Maxim Khononov, and Moris S. Eisen
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b00074 • Publication Date (Web): 19 Mar 2018
Downloaded from http://pubs.acs.org on March 19, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
ACS Catalysis
1
2
3
4
5
6
7
8
9
Catalytic 1,2-Regioselective Dearomatization of N-Heteroaromatics
Via a Hydroboration
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
a
a
Heng Liu, Maxim Khononov, Moris S. Eisen*
a
Schulich Faculty of Chemistry, Technion – Israel Institute of Technology. Haifa City, 32000, Israel.
2
Me ThMe and [(C Me Th(H)(μ-H)] catalyzed highly 1,2-
ABSTRACT: The thorium-methyl and -hydride complexes (C
5
5
)
2
2
5
5
)
2
regioselective dearomatization of pyridines via a hydroboration process is reported herein. Twelve different kinds of meta- and para-
substituted pyridines are applicable to this reaction, giving the corresponding N-boryl-1,2-dihydropyridine products in high yields.
Other N-heteroaromatic compounds, such as benzofused N-heterocycles, pyrazines, pyrimidines, 1,3,5-triazine and benzothiazole,
were also found to be hydroborated with high chemoselectivity. Kinetics including isotope effect studies revealed a first-order de-
pendence on the concentration of catalyst, pyridine, and pinacolborane, with releasing the dearomatized final product as the rate
determining step. A plausible mechanism is proposed based on stoichiometric reaction and kinetic studies.
Keywords: Thorium, dearomatization, pyridine, N-heteroaromatic, 1,2-regioselective
Table 1. Hydroboration of pyridine under different condi-
tions.
INTRODUCTION
The 1,2-regioselective dearomatizing of pyridines is a challeng-
ing task. It represents an important strategy to prepare valuable
H
1,2-dihydropyridines intermediates, which are frequently used
as an important structural motif in the synthesis of alkaloids and
pharmaceutically molecules, such as anticancer drug lepadin B
O
O
H
B
+
Cat.
70o
N
N
H
N
C, 24h
Bpin
1
-6
Bpin
and the antiviral drug oseltamivir (Tamiflu). Different from
7a'
7
-14
5a
6 (HBpin)
7a
other N-heteroaromatics,
pyridine compounds are much
not observed
more difficult to be dearomatized due to their high resonance
15-18
Temp.
(oC)
stabilization energy,
and up to date, only a handful of meth-
Entry[a]
Yield[b]
Cat.
5a/6
Sol.
odologies are available. Hydrogenation is the simplest way to
reduce pyridine aromatic rings, whereas the harsh conditions
and the over-reduction reaction to afford piperidine often make
1
none
Th1
Th2
Th3
Th4
Th4
Th4
Th4
Th4
Th4
1/1
1/1
1/1
1/1
1/1
C
C
C
6
6
6
D
D
D
6
6
6
6
6
6
6
6
6
6
70
70
70
70
70
70
70
70
50
25
--
1
9-21
2
--
this strategy difficult.
Alternatively, catalytic hydrosilyla-
3
--
tion has emerged as a recent method to prepare dihydro-
pyridines in recent years, however, it should be noted that most
of the hydrosilylation reactions give rise to the 1,4-dihydro-
4
6
C D
58
87
83
5
C
C
C
C
C
C
6
6
6
6
6
6
D
D
D
D
D
D
2
2-25
pyridine,
and this methodology sometimes also have en-
2
6
27-28
6
1/1.5
1/2
countered low selectivities, over-reactions,
substrate scope.
and a narrow
Therefore, developing a facile, atom-effi-
2
5, 29
7
80
89[c]
cient and highly 1,2-regioselective method to dearomatize pyr-
idine compounds is highly demanding.
8
2/1
9
1/1
33
4
Our research interest is mainly focused on organoactinide
precatalysts, due to the unique characteristics of actinide metals,
such as their large ionic radii and the presence of the 5f-orbitals,
which generally enable them to display complementary cata-
lytic behaviors as compared to early or late transition metals,
10
1/1
[a]Conditions unless specified otherwise: pyridine (0.25 mmol),
HBpin (0.25 mmol), thorium precatalysts (5 μmol), 600 μL
[
b]
1
6 6
C D , 24 h. The yield was determined by H NMR spectros-
[
c]
3
0-43
copy of the crude based on pyridine. The yield was calculated
based on HBpin.
and lanthanide catalysts.
N''
N
N
N''
Dipp
Dipp
H
Recently, we introduced a series of imidazolin-2-iminato acti-
nide complexes that were found active in promoting the hydro-
elementation reaction, in which a catalytic addition of unsatu-
Th
N
N
CH3
CH3
H
H
Th
Th
Th
Si
Th
N''
H
Me Si
N''
3
N''
Th2
rated bonds into a large scope of E-H (E = N, O, P, C, S, Si)
Th1
3
2
N'' = N(SiMe ) )
Th4
44-50
Th3
moieties were observed.
Encouraged by these results, we,
therefore, entered the idea that these actinide complexes might
be also active for the hydroboration of the pyridine C=N bond,
(
Figure 1. Structures of the thorium precatalysts Th1 - Th4.
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 6
which would be a quite meaningful subject for actinide chem-
istry. It is of note that previously reported hydroboration of pyr-
in the reaction of 4-trifluoromethyl pyridine (5h) and HBpin, a
much higher yield of 7h is obtained, even with shorter reaction
times, as compared to substrate 5i.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
5
1
52
53
54
idines by Mg, Fe, Rh, La, and recently a Zr-MOF system
5
5
have been disclosed. In some of these systems, a good 1,2-
Table 2. Thorium complex Th4 catalyzed 1,2-hydroboration
of substituted pyridines.
regioselectivities were observed. Herein we disclose the rapid
and selective hydroboration of pyridines and other N-heterocy-
clic systems.
R2
R2
R3
R4
R1
H
O
O
R3
R1
We commenced the pyridine hydroboration studies by examin-
ing four different types of thorium precatalysts (Figure 1) under
different conditions, and pinacolborane was chosen as the hy-
droboration reagent (Table 1). Initial evaluation revealed that
the thorium amido complexes, Th1 and Th2, were not effective
for the hydroboration process and no reduced product 7a was
detected within 24 hours. We subsequently shifted to study the
thorium methyl complex Th3 and the thorium hydride complex
Th4, and we were pleased to observe that the latter both systems
catalyzed the reaction effectively, giving the N-borylated 1,2-
dihydropyridine product 7a in 58% and 87% yields, respec-
tively. Increasing the amount of HBpin showed little influence
on the yield of 7a. Increasing the amount of pyridine, however,
resulted in a slight decrease in the yield. Attempts to carry out
the reactions at even milder conditions with the complex Th4,
i.e. lower temperatures, proved less efficient, affording only 4%
H
B
Cat.
+
N
o
R4
N
-
70 C, 24h
Bpin
5p
- 7p
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
5b
)
6
(HBpin)
7b
(
)
Yield
product
of
En-
try
R
1
R
2
R
3
R
4
[a]
[b]
(
%)
88 (7b)
90 (7c/7c’)
93/7)
3 (7d/7d’)
92/8)
1
F
H
H
H
H
H
H
5b
5c
2[c]
Cl
I
(
9
(
3[c]
H
H
H
5d
4
5
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Br
5e
5f
95 (7e)
67 (7f)
99 (7g)
96 (7h)
72 (7i)
73 (7j)
60 (7k)
0 (7l)
OMe
H
o
o
and 33% yields at 25 C and 50 C, respectively. It is important
6
7[d]
Ph
5g
5h
5i
5
1, 56
53
to point out, and different from the Mg
tems, for all the Th-based reactions, the regioisomeric N-boryl-
,4-dihydropyridine 7a’ was not detected all through the hy-
and Rh based sys-
H
CF
3
8
H
Me
Et
1
9
H
5j
droboration process. This result indicates the high 1,2-regiose-
lectivities of the thorium precatalysts.
10
H
OMe
NMe
Me
H
5k
5l
1
1
H
2
Substituted pyridines (5b - 5p) were subjected to the hydrobo-
ration reaction in the presence of an equimolar of HBpin to
study the substrate scope capabilities (Table 2). It is observed
that a wide range of pyridine compounds with different elec-
tron-donating and electron-withdrawing groups are capable to
undergo the 1,2-regioselective hydroboration to afford the cor-
responding dearomatized products in moderate to high yields.
For meta-substituted pyridines, electron deficient 3-ha-
lopyridines generally performed better reactivities with HBpin
than electron rich counterparts. Hence, the reactions of HBpin
with 3-fluoropyridine (5b), 3-chloropyridine (5c), and 3-io-
dopyridine (5d) proceeded efficiently to give the corresponding
12
Me
H
5m
5n
5o
68 (7m)
0 (7n)
1
1
3
4
H
H
0 (7o)
15
H
H
Me 5p
0 (7p)
[a]Conditions unless specified otherwise: substituted pyridine
(
0.25 mmol), HBpin (0.25 mmol), thorium precatalyst Th4 (5
o
[b]
μmol), 600 μL C
by H NMR spectroscopy of the crude based on pyridines.
Two isomer products were detected, and the ratio was shown in
6
D
6
, 70 C, 24 h. The yield was determined
1
[c]
[
d]
the bracket. In 12 h.
1
,2-dihydroboration products 7b – 7d in 88%, 90% and 93%
For reactions of pyridines having electron-donating groups at
the para- position with HBpin, gradual decreasing yields in the
order of Me~Et>OMe>NMe have been observed, and due to
2
the strong electron donating ability of the dimethylamino group,
overall yields, respectively. Whereas for the substrate 3-meth-
oxy pyridine (5f) a remarkably lower yield of 67% was ob-
tained. Due to the asymmetric nature of the meta-substituted
pyridines, two different hydroboration isomers, namely 3- and
5- substituted-1,2-dihydropyridines, are possible to be obtained.
For the thorium complex, Th4, we obtained excellent regiose-
lectivities to yield preferentially the 3-substituted-1,2-dihydro-
pyridine, as the final product. Interestingly complex Th4, show
a much higher regioselectivity as comparing to the literature
completely inactive substrate 5l was observed.
H
O
Cat.
O
Bpin
+
H
Bpin
o
N
70 C, 24h
N
N
7q
(>99%,
)
5
4
Bpin
values. For some of the substrates, such as 3-fluoropyridine,
-methylpyridine, and 3-methoxy pyridine, 3-substituted-1,2-
Cat.
N
Bpin
3
N
N + 2 H Bpin
o
70 C, 24h
dihydropyridines were detected as the sole dearomatization
products. Until now, it is still unclear what factors influence the
product regioselectivity, however, in a similar study of La-cat-
alyzed hydroboration of 3-halopyridines, Marks et al. rational-
ized that bonding interactions between C3-halogen atoms and
H
H
7r
)
(>99%,
O
O
Bpin
Cat.
+
2 H Bpin
N
N
o
70 C, 24h
H
OMe
7s
)
H
(>99%,
Scheme 1. Hydroboration of pyridines having other unsaturated
functional groups.
newly emerged C2-CH
2
might influence the regioselectivity of
5
4
3
-substituted pyridine dearomatization. For para- substituted
5
1,
pyridines, electron-withdrawing groups are also found to be fa-
vorable to facilitate the hydroboration rate significantly. Hence,
Different from the reported pyridine hydroboration systems,
5
3-54, 57
the thorium hydride complex Th4, displayed no activity
ACS Paragon Plus Environment

Page 3 of 6
ACS Catalysis
in hydroboration of ortho-substituted pyridine compounds,
present reaction, affording the hydroborated products 15 in
moderate yields. Other types of N-heteroaromatics, including
benzoxazole and benzimidazole, were also attempted for the
hydroboration reaction, and no corresponding hydroborated
products were detected.
1
2
3
4
5
6
7
8
9
probably due to the steric encumbrance of these substrates.
The substrate scope was also expanded into pyridines bearing
other unsaturated functionalities such as aldehyde, cyano- and
ester functionalities (Scheme 1). Interestingly the thorium com-
plex Th4 was able to induce the quantitative hydroboration of
the aldehyde, cyano, and the ester moieties to give the corre-
sponding products 7q - 7s. Addition of another equivalent of
HBpin did not induce the hydroboration of the pyridine even
after extended reaction times.
Stoichiometric reactions were studied in order to gain insights
into the mechanism of this hydroboration reaction. The reaction
of complex Th4 with pyridine rapidly gave the Cp* Th(dihy-
2
dropyridine) intermediate via a Th-H 1,2-addition across the
1
pyridine C=N bonds, which was identified from in situ H NMR
Table 3. Thorium complex Th4 catalyzed hydroboration of
spectra by the disappearance of a characteristic hydride singlet
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
[
a]
different kinds of N-heteroaromatics.
(Th-H) at δ = 19.08 ppm and simultaneous appearance of the
2
2
Y'
1,2-dihydropyridine anion signals. Subsequent addition of
HBpin to the above reaction mixture yields the dearomatized N-
boryl-1,2-dihydropyridine product. Based on these studies, a
plausible hydroboration mechanism is proposed in Scheme 2.
The activation of the reaction cycle is firstly achieved by the
insertion of Th-H moiety (A) into the C=N bond of the coordi-
nated pyridine molecule, which gave rise to the thorium-dihy-
dropyridine intermediate C (For Th3 mediated system, the Th-
Me bond undergoes protonolysis with HBpin to afford the Th-
X'
Z'
Y
O
O
X
Z
Cat.
H
B
N
H
+
o
70 C
N
Bpin
(X, Y, Z = C or N)
(X', Y', Z' = C or N-Bpin)
6
8 - 16
( )
(HBpin)
Bpin
N
H
H
5
8
H moieties firstly ). In the presence of HBpin, a subsequent
Th-N/H-B σ-bond metathesis through the transition state D pro-
duces the target N-boryl-1,2-dihydropyridine products, and
simultaneously regenerate the active species A to complete the
catalytic cycle. Kinetic studies of pyridine/HBpin/Th3 system
revealed a first-order dependence on pyridine, HBpin, and Th3,
giving rise to the rate equation (1):
N
H
N
H
N
Bpin
Cl
Bpin
Bpin
(> 99%, 24 h, 8)
(> 99%,12 h, 9)
(> 99%, 6 h, 10)
H
H
H
Bpin
N
Br
Bpin
H
Bpin
N
N
N
H
N
H
N
ꢀ
ꢁ
Bpin
Bpin
Bpin
= ꢃꢄꢅꢆ ∙ [ꢇꢈꢉ][Pyridine][HBpin]
(1)
ꢀ
ꢂ
(> 99%, 12 h, 11) (> 99%, 12 h, 12)
(90%, 12 h, 13)
H
Bpin
H
Bpin
H
N
N
Bpin
N
N
H
Bpin
S
(96%, 6 h, 14)
(55%, 24 h, 15)
[a]Conditions unless specified otherwise: thorium precatalyst
Th4 (5 μmol), 0.25 mmol HBpin, [C=N]/[HBpin] = 1/1 (0.25
mmol of heteroaromatics in case of compound 8, 9, 15, 0.12
mmol of heteroaromatics in case of compound 10, 11, 12, 13,
0
C
.08 mmol of heteroaromatics in case of compound 14), 600 μL
D , 70 C. The yield was determined by H NMR spectros-
6 6
o
1
copy of the crude based on heteroaromatics.
Based on the aforementioned hydroboration of pyridines, the
present thorium hydride complex Th4 was next applied to ad-
ditional types of N-heteroaromatics (Table 3). Quinoline and 8-
chloroquinoline rapidly reacted with equimolar of HBpin to af-
ford the reduced products 8 and 9 almost quantitatively. In ad-
dition, we were also pleased to observe that pyrazine, pyrimi-
dine and substituted pyrimidine compounds were able to un-
dergo the double hydroboration to afford the corresponding
dearomatized products in high yields. It is notable that the
carbon-carbon double bonds in products 10, 11 and 13 success-
fully survived during the hydroboration reaction, indicating a
highly chemoselective fashion of the precatalyst. Interestingly,
Scheme 2. Proposed mechanism for the pyridine hydroboration
*
*
reaction. In Th3 [Th] = Cp
Deuterium labeling studies with DBpin afforded a kinetic iso-
topic effect (KIE) of K /K = 2.75, corroborating that the rate
2 2
ThMe; in A-D, [Th] = Cp ThH.
H
D
determining step (r.d.s) of the catalytic cycle is Th-N/H-B σ-
bond metathesis. The thermodynamic activation parameters
were experimentally calculated from the Erying and Arrhenius
plots (Supporting Information), affording an activation barrier
1
,3,5-triazine underwent a triple hydroboration reaction with
-
1
≠
(
(
a
E ) of 20.3(1) kcal mol , and the enthalpy (ΔH ) and entropy
three equivalents of HBpin to give a saturated product 14 in ex-
cellent yield within 6h. Moreover, five-membered aromatic N-
heterocycles, such as benzothiazole, was also subjected to the
≠
-1
ΔS ) of activation of 19.6(5) kcal mol and -23.5(1) e.u. re-
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 6
≠
≠
spectively. The ΔH and ΔS data are consistent with a concur-
rent bond-cleavage and -formation events and the four-mem-
bered ring, respectively.
catalyzed direct asymmetric dearomative amination of tryptamines. Angew.
Chem. Int. Ed. 2016, 55, 751-754.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1. Repka, L. M.; Ni, J.; Reisman, S. E. Enantioselective synthesis of
pyrroloindolines by a formal [3+2] cycloaddition reaction. J. Am. Chem.
Soc. 2010, 132, 14418-14420.
12. Lian, Y.; Davies, H. M. L. Rhodium-catalyzed [3+2] annulation of
indoles. J. Am. Chem. Soc. 2010, 132, 440-441.
In conclusion, we have established an efficient method for the
dearomatization of pyridine compounds using a thorium-cata-
lyzed hydroboration reaction. Highly 1,2-regioselective for-
mation of N-boryl-1,2-dihydropyridine products was achieved
when using meta- and para-substituted pyridine substrates.
Various N-heteroaromatics are also applicable to this reaction,
giving the hydroborated products in high yields. Studies to ex-
pand the substrate scope by using other types of actinide precat-
alysts are currently ongoing in our lab.
1
3. Ding, Q.; Zhou, X.; Fan, R. Recent advances in dearomatization of
heteroaromatic compounds. Org. Biomol. Chem. 2014, 12, 4807-4815.
4. Schröder, F.; Sharma, U. K.; Mertens, M.; Devred, F.; Debecker, D. P.;
1
Luque, R.; Eycken, E. V. V. d. Silver-nanoparticle-catalyzed
dearomatization of indoles toward 3-spiroindolenines via a 5-exo-dig
spirocyclization. ACS Catal. 2016, 6, 8156-8161.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
5. Balaban, A. T.; Oniciu, D. C.; Katritzky, A. R. Aromaticity as a
cornerstone of heterocyclic chemistry. Chem. Rev. 2004, 104, 2777-2812.
6. Krygowski, T. M.; Cyrański, M. K. Structural sspects of aromaticity.
Chem. Rev. 2001, 101, 1385-1420.
7. Edraki, N.; Mehdipour, A. R.; Khoshneviszadeh, M.; Miri, R.
1
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
1
Dihydropyridines: evaluation of their current and future pharmacological
applications. Drug Discov. Today 2009, 14, 1058-1066.
18. Chong, C. C.; Kinjo, R. Catalytic hydroboration of carbonyl
derivatives, imines, and carbon dioxide. ACS Catal. 2015, 5, 3238-3259.
Experimental details, characterization data.
1
9. Chen, Q.-A.; Chen, M.-W.; Yu, C.-B.; Shi, L.; Wang, D.-S.; Yang, Y.;
Zhou, Y.-G. Biomimetic asymmetric hydrogenation: in situ regenerable
hantzsch esters for asymmetric hydrogenation of benzoxazinones. J. Am.
Chem. Soc. 2011, 133, 16432-16435.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chmoris@tx.technion.ac.il. Phone: +972-4-8292680
2
0. Guo, Q.-S.; Du, D.-M.; Xu, J. The development of double axially chiral
phosphoric acids and their catalytic transfer hydrogenation of quinolines.
Angew. Chem. Int. Ed. 2008, 47, 759-762.
(
M.S.E.).
2
1. Wang, C.; Li, C.; Wu, X.; Pettman, A.; Xiao, J. pH-Regulated
Notes
asymmetric transfer hydrogenation of quinolines in water. Angew. Chem.
2009, 121, 6646-6650.
The authors declare no competing financial interests.
2
2. Intemann, J.; Bauer, H.; Pahl, J.; Maron, L.; Harder, S. Calcium hydride
catalyzed highly 1,2-selective pyridine hydrosilylation. Chem. Eur. J. 2015,
1, 11452-11461.
ACKNOWLEDGMENT
2
This work was supported by the Israel Science Foundation admin-
istered by the Israel Academy of Science and Humanities under
Contract No. 78/14, and by the PAZY Foundation Fund (2015) ad-
ministered by the Israel Atomic Energy Commission. H.L. thanks
the Technion-Guangdong Fellowship Program.
23. Lee, S.-H.; Gutsulyak, D. V.; Nikonov, G. I. Chemo- and regioselective
catalytic reduction of N-heterocycles by silane. Organometallics 2013, 32,
4
2
457-4464.
4. Königs, C. D. F.; Klare, H. F. T.; Oestreich, M. Catalytic 1,4-selective
hydrosilylation of pyridines and benzannulated congeners. Angew. Chem.
Int. Ed. 2013, 52, 10076-10079.
25. Gutsulyak, D. V.; van der Est, A.; Nikonov, G. I. Facile catalytic
hydrosilylation of pyridines. Angew. Chem. 2011, 123, 1420-1423.
REFERENCES
REFERENCES
2
6. Cook, N. C.; Lyons, J. E. Dihydropyridines from silylation of pyridines.
J. Am. Chem. Soc. 1966, 88, 3396-3403.
1
. Ruiz-Sanchis, P.; Savina, S. A.; Albericio, F.; Álvarez, M. Structure,
27. Hao, L.; Harrod, J. F.; Lebuis, A.-M.; Mu, Y.; Shu, R.; Samuel, E.;
Woo, H.-G. Homogeneous catalytic hydrosilylation of pyridines. Angew.
Chem. Int. Ed. 1998, 37, 3126-3129.
28. Harrod, J. F.; Shu, R.; Woo, H.-G.; Samuel, E. Titanocene(III)
catalyzed homogeneous hydrosilation-hydrogenation of pyridines. Can. J.
Chem. 2001, 79, 1075-1085.
29. Lortie, J. L.; Dudding, T.; Gabidullin, B. M.; Nikonov, G. I. Zinc-
catalyzed hydrosilylation and hydroboration of N-heterocycles. ACS Catal.
2017, 7, 8454-8459.
30. Fox, A. R.; Bart, S. C.; Meyer, K.; Cummins, C. C. Towards uranium
catalysts. Nature 2008, 455, 341-349.
31. Arnold, P. L.; Turner, Z. R. Carbon oxygenate transformations by
actinide compounds and catalysts. Nat. Rev. Chem. 2017, 1, 0002.
32. Matson, E. M.; Forrest, W. P.; Fanwick, P. E.; Bart, S. C.
Functionalization of carbon dioxide and carbon disulfide using a stable
uranium(III) alkyl complex. J. Am. Chem. Soc. 2011, 133, 4948-4954.
33. Kosog, B.; Kefalidis, C. E.; Heinemann, F. W.; Maron, L.; Meyer, K.
Uranium(III)-Mediated C-C coupling of terminal alkynes: formation of
dinuclear uranium(IV) vinyl complexes. J. Am. Chem. Soc. 2012, 134,
12792-12797.
34. Mansell, S. M.; Bonnet, F.; Visseaux, M.; Arnold, P. L. Uranium(iv)
amido-borohydrides as highly active diene polymerisation catalysts. Dalton
Trans. 2013, 42 , 9033-9039.
35. Gardner, B. M.; Stewart, J. C.; Davis, A. L.; McMaster, J.; Lewis, W.;
Blake, A. J.; Liddle, S. T. Homologation and functionalization of carbon
monoxide by a recyclable uranium complex. Proc. Nat. Acad. Sci. 2012,
109, 9265-9270.
Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3-
b]indole. Chem. Eur. J. 2011, 17, 1388-1408.
2. Yang, Z.-P.; Wu, Q.-F.; Shao, W.; You, S.-L. Iridium-catalyzed
intramolecular asymmetric allylic dearomatization reaction of pyridines,
pyrazines, quinolines, and isoquinolines. J. Am. Chem. Soc. 2015, 137,
1
5899-15906.
3. Roche, S. P.; Porco, J. A. Dearomatization strategies in the synthesis of
complex natural products. Angew. Chem. Int. Ed. 2011, 50, 4068-4093.
4
.
Southgate, E. H.; Pospech, J.; Fu, J.; Holycross, D. R.; Sarlah, D.
Dearomative dihydroxylation with arenophiles. Nat. Chem. 2016, 8, 922-
28.
9
5. Wan, J.-P.; Liu, Y. Recent advances in new multicomponent synthesis
of structurally diversified 1,4-dihydropyridines. RSC Adv. 2012, 2, 9763-
9
6
777.
. Eisner, U.; Kuthan, J. Chemistry of dihydropyridines. Chem. Rev. 1972,
72, 1-42.
. DiPoto, M. C.; Hughes, R. P.; Wu, J. Dearomative indole (3+2) reactions
7
with azaoxyallyl cations - new method for the synthesis of pyrroloindolines.
J. Am. Chem. Soc. 2015, 137, 14861-14864.
8.
Zhuo, C.-X.; Zhou, Y.; Cheng, Q.; Huang, L.; You, S.-L.
Enantioselective construction of spiroindolines with three contiguous
stereogenic centers and chiral tryptamine derivatives via reactive
spiroindolenine intermediates. Angew. Chem. Int. Ed. 2015, 54, 14146-
14149.
9
.
Acharya, A.; Anumandla, D.; Jeffrey, C. S. Dearomative indole
cycloaddition reactions of aza-oxyallyl cationic intermediates: modular
access to pyrroloindolines. J. Am. Chem. Soc. 2015, 137, 14858-14860.
36. Gardner, B. M.; Liddle, S. T. Uranium triamidoamine chemistry. Chem.
Commun. 2015, 51, 10589-10607.
1
0. Liu, C.; Yi, J.-C.; Zheng, Z.-B.; Tang, Y.; Dai, L.-X.; You, S.-L.
Enantioselective synthesis of 3a-amino-pyrroloindolines by copper-
ACS Paragon Plus Environment

Page 5 of 6
ACS Catalysis
3
7. Siladke, N. A.; Meihaus, K. R.; Ziller, J. W.; Fang, M.; Furche, F.;
Long, J. R.; Evans, W. J. Synthesis, structure, and magnetism of an f
element nitrosyl complex, (C Me H) UNO. J. Am. Chem. Soc. 2012, 134,
243-1249.
38. Evans, W. J.; Mueller, T. J.; Ziller, J. W. Reactivity of (C
complexes: synthesis of a tris(pentamethylcyclopentadienyl) complex with
two additional ligands, (C Me La(NCCMe . J. Am. Chem. Soc. 2009,
48. Batrice, R. J.; Kefalidis, C. E.; Maron, L.; Eisen, M. S. Actinide-
catalyzed intermolecular addition of alcohols to carbodiimides. J. Am.
Chem. Soc. 2016, 138, 2114-2117.
49. Liu, H.; Fridman, N.; Tamm, M.; Eisen, M. S. Addition of E-H (E = N,
P, C, O, S) bonds to heterocumulenes catalyzed by benzimidazolin-2-
iminato actinide complexes. Organometallics 2017, 36 , 3896-3903.
50. Liu, H.; Ghatak, T.; Eisen, M. S. Organoactinides in catalytic
transformations: scope, mechanisms and quo vadis. Chem. Commun. 2017,
53, 11278-11297.
51. Arrowsmith, M.; Hill, M. S.; Hadlington, T.; Kociok-Köhn, G.;
Weetman, C. Magnesium-catalyzed hydroboration of pyridines.
Organometallics 2011, 30, 5556-5559.
52. Zhang, F.; Song, H.; Zhuang, X.; Tung, C.-H.; Wang, W. Iron-catalyzed
1,2-selective hydroboration of N-heteroarenes. J. Am. Chem. Soc. 2017, 139
, 17775-17778.
1
2
3
4
5
6
7
8
9
5
4
3
1
5
5 3 x
Me ) LaL
5
5
)
3
3 2
)
1
3
31 , 2678-2686.
9. Weiss, C. J.; Wobser, S. D.; Marks, T. J. Organoactinide-mediated
hydrothiolation of terminal alkynes with aliphatic, aromatic, and benzylic
thiols. J. Am. Chem. Soc. 2009, 131 , 2062-2063.
4
0. Cooper, O.; Camp, C.; Pécaut, J.; Kefalidis, C. E.; Maron, L.;
Gambarelli, S.; Mazzanti, M. Multimetallic cooperativity in uranium-
mediated CO activation. J. Am. Chem. Soc. 2014, 136 , 6716-6723.
1. Mougel, V.; Camp, C.; Pécaut, J.; Copéret, C.; Maron, L.; Kefalidis, C.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
4
E.; Mazzanti, M. Siloxides as supporting ligands in uranium(III)-mediated
small-molecule activation. Angew. Chem. 2012, 124 , 12446-12450.
42. Walshe, A.; Fang, J.; Maron, L.; Baker, R. J. New mechanism for the
ring-opening polymerization of lactones? Uranyl aryloxide-induced
intermolecular catalysis. Inorg. Chem. 2013, 52 , 9077-9086.
53. Oshima, K.; Ohmura, T.; Suginome, M. Regioselective synthesis of
1,2-dihydropyridines by rhodium-catalyzed hydroboration of pyridines. J.
Am. Chem. Soc. 2012, 134 , 3699-3702.
54. Dudnik, A. S.; Weidner, V. L.; Motta, A.; Delferro, M.; Marks, T. J.
Atom-efficient regioselective 1,2-dearomatization of functionalized
pyridines by an earth-abundant organolanthanide catalyst. Nat. Chem. 2014,
6 , 1100-1107.
55. Ji, P.; Feng, X.; Veroneau, S. S.; Song, Y.; Lin, W. Trivalent zirconium
and hafnium metal–organic frameworks for catalytic 1,4-dearomative
additions of pyridines and quinolines. J. Am. Chem. Soc. 2017, 139, 15600-
15603.
4
3. Sharma, M.; Eisen, M. S., Metallocene Organoactinide Complexes. In
Organometallic and Coordination Chemistry of the Actinides, Albrecht-
Schmitt, T. E., Ed. Springer Berlin Heidelberg: Berlin, Heidelberg, 2008;
pp 1-85.
4
4. Batrice, R. J.; Eisen, M. S. Catalytic insertion of E-H bonds (E = C, N,
P, S) into heterocumulenes by amido-actinide complexes. Chem. Sci. 2016,
7 , 939-944.
56. Mukherjee, D.; Shirase, S.; Spaniol, T. P.; Mashima, K.; Okuda, J.
4
5. Karmel, I. S. R.; Tamm, M.; Eisen, M. S. Actinide-mediated catalytic
Magnesium hydridotriphenylborate [Mg(thf)
6 3 2
][HBPh ] : a versatile
addition of E-H Bonds (E=N, P, S) to carbodiimides, isocyanates, and
isothiocyanates. Angew. Chem. Int. Ed. 2015, 54 , 12422-12425.
46. Liu, H.; Khononov, M.; Fridman, N.; Tamm, M.; Eisen, M. S. Catalytic
Addition of alcohols into carbodiimides promoted by organoactinide
complexes. Inorg. Chem. 2017, 56, 3153-3157.
hydroboration catalyst. Chem. Commun. 2016, 52 , 13155-13158.
57. Fan, X.; Zheng, J.; Li, Z. H.; Wang, H. Organoborane catalyzed
regioselective 1,4-hydroboration of pyridines. J. Am. Chem. Soc. 2015, 137
, 4916-4919.
58. Liu, H.; Kulbitski, K.; Tamm, M.; Eisen, M. S. Organoactinide
catalyzed monohydroboration of carbodiimides. Chem. Eur. J. 2018, doi:
10.1002/chem.201705987.
4
7. Ghatak, T.; Fridman, N.; Eisen, M. S. Actinide complexes possessing
six-membered N-heterocyclic iminato moieties: synthesis and reactivity.
Organometallics 2017, 36, 1296-1302.
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 6
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Insert Table of Contents artwork here
or
5Me 2ThMe
5
)
2
(
C
5Me5
µ-H)]2
Y'
N
[
(C
)
2
Th(H)(
Y
N
X'
Z'
X
Z
1
.0 equiv. HBpin,
7
0
H
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
C, 24h
Bpin
(
X, Y, Z = C or N)
(X', Y', Z' = C or N-Bpin)
Diverse substrates;
(
substituted pyridines, quinoline,
High activities;
High 1,2-regioselectivity;
pyrimidine, pyrazine, triazine)
ACS Paragon Plus Environment