Synthesis of 6-Adamantyl-2-pyridone and Reversible Hydrogen Activation by the Corresponding Bis(perfluorophenyl)borane Complex

Article abstract of DOI:10.1055/s-0040-1705970

We herein describe the two-step synthesis of 6-Adamantyl-2-pyridone from 1-Acetyladamantane. The borane complex derived from 6-Adamantyl-2-pyridone and the Piers borane liberates dihydrogen at 60 °C. The reverse reaction, hydrogen activation by the formed pyridonate borane is accomplished under mild conditions. The mechanism of the hydrogen activation is studied by DFT computations.

Full text of DOI:10.1055/s-0040-1705970

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2
020, 52, A–G
feature
A
en
Synthesis
F. Wech et al.
Feature
Synthesis of 6-Adamantyl-2-pyridone and Reversible Hydrogen
Activation by the Corresponding Bis(perfluorophenyl)borane
Complex
Felix Wecha
O
2
steps
Tizian Müllera
Jonathan Beckerb
N
H
O
Urs Gellrich*a
0
0
0
0
-
0
0
0
2
-
8
1
1
9
-
9
6
2
6
44% yield
a
reversible hydrogen
activation
Institut für Organische Chemie, Justus-Liebig-Universität
Gießen, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
urs.gellrich@org.chemie.uni-giessen.de
Institut für Anorganische und Analytische Chemie, Justus-Liebig-
Universität Gießen, Heinrich-Buff-Ring 17, 35392 Gießen,
Germany
N
O
B
catalytic alkyne
hydrogenation
b
H
H
C6F5
C6F5
gem dimerization of
terminal alkynes
UIe nMr ss ta iGitClueoutl rlr frrsüie.cgrshepOlolr rngi dac hni n@i gs co Ahr gue .tcChhhoeermm i iee . ,u Jnu i s- tg ui es -s Ls ie enb . di ge -Universität Gießen, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
Received: 27.08.2020
Accepted after revision: 05.10.2020
Published online: 10.11.2020
activations with terminal alkynes.5 Likewise, pyridonate
borane 1a reacts with terminal alkynes to give a pyridone
alkynyl borane complex 5.
DOI: 10.1055/s-0040-1705970; Art ID: ss-2020-z0457-fa
Abstract We herein describe the two-step synthesis of 6-adamantyl-
(A) previous work
2
-pyridone from 1-acetyladamantane. The borane complex derived
from 6-adamantyl-2-pyridone and the Piers borane liberates dihydro-
gen at 60 °C. The reverse reaction, hydrogen activation by the formed
pyridonate borane is accomplished under mild conditions. The mecha-
nism of the hydrogen activation is studied by DFT computations.
H2 (2 bar), r.t.
tBu
N
H
O
B
tBu
N
O
B
60 °C, – H2
H
C6F5
C6F5
C6F5
C6F5
1
a
2a
Key words frustrated Lewis Pair, hydrogen activation, pyridones,
boron-ligand cooperation, DFT
(
B) this work
O
Ad
N
H
O
Ad
Ad
N
O
In 2006, Stephan and co-workers reported the seminal
B
H
4
H
C6F5
C6F5
finding that specific combinations of sterically encumbered
Lewis bases and highly Lewis acidic boranes are able to ac-
tivate dihydrogen.1 The unique reactivity of these Lewis
pairs was attributed to the fact that they do not form classic
3b
2
b
Scheme 1 (A) Reversible hydrogen activation by a 6-tert-butyl-2-pyr-
idonate borane 1a described previously. (B) A working hypothesis of the
research project described herein: Synthesis of 6-adamantyl-2-pyridone
borane complex and reversible hydrogen activation by a corresponding
pyridonate borane (Ad = adamantyl).
Lewis adducts. Therefore, the term frustrated Lewis pairs
2
(
FLP) was coined to describe these reactive Lewis pairs. Re-
cently, we reported the reversible activation of dihydrogen
by the pyridonate borane 1a, that can be described as an in-
3
tramolecular FLP (Scheme 1). A characteristic aspect of hy-
However, we were able to show that C –H activation of
sp
drogen activation by 1a is that the covalently bound pyrido-
nate substituent becomes a datively bound pyridone ligand
upon bond activation. This change in the coordination
sphere of the borane is reminiscent of metal-ligand cooper-
ation and was therefore referred to as boron-ligand cooper-
terminal alkynes by 1a is reversible and thus competes with
dihydrogen activation. Therefore, we were able to realize
the first metal-free semi-hydrogenation of terminal alkynes
6
(Scheme 2, bottom). In the absence of H , the alkynyl bo-
2
rane complex formed upon C –H activation reacts at ele-
sp
4
ation. This mode of action allows 2a to dissociate into 6-
vated temperatures with a second equivalent of the alkyne
to yield the gem-dimerization product of the terminal
alkyne (Scheme 2, top). This reaction regenerates 1a
tert-butyl-2-pyridone and HB(C F ) (Piers’ borane). This
6
5 2
dissociation enables the hydroboration of an alkyne. A sub-
sequent protodeborylation yields the corresponding cis
alkene and regenerates the pyridonate borane 1a. In this
7
(Scheme 2). Thus, we were able to devise a protocol for the
metal-free dimerization of terminal alkynes catalyzed by
1a. The tert-butyl group at the 6-position of the pyridine
ring is required to suppress the dimerization of 1a. Thus we
way, the catalytic semi-hydrogenation of alkynes was real-
4
ized (Scheme 2). Classic FLPs undergo irreversible C –H
sp
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synthesis
F. Wech et al.
Feature
became interested in how the replacement of this tert-butyl
group by a sterically more demanding and electron-rich
adamantyl group would affect the properties of the pyrido-
nate borane (Scheme 1).
enolate 6 was used to generate a phosphonium ylide in situ
from the phosphonium salt 7 to initiate a Wittig olefina-
tion. The addition of acetic acid enabled the condensation
that furnished the adamantyl pyridone 3b in 52% yield
(Scheme 3). Single-crystal X-ray diffraction (SCXRD) analy-
sis revealed that 3b crystallizes as a lactam dimer in the
space group P1 (Figure 1).
To synthesize the required 6-adamantyl-2-pyridone 3b,
we followed a procedure of Hintermann and co-workers
8
that we had successfully applied for the synthesis of 1a.
We first prepared the sodium enolate 6 from commercially
available 1-acetyladamantane (4) (Scheme 3). Next, the
Biographical Sketches
Felix Wech studied chemistry
for an internship in 2019 and
obtained his M.Sc. in 2020 for
his work on the pyridone-bo-
rane-catalyzed hydrogenations
of alkynes. Currently, he is a
doctoral student in the group of
Urs Gellrich, investigating the
application of pyridine-borane
complexes for metal-free cataly-
sis.
at
Gießen and obtained his B.Sc. in
017. He then joined the re-
Justus-Liebig-Universität
2
search group of Dr. Urs Gellrich
Tizian Müller studied chemis-
try at Justus-Liebig-Universität
Gießen and received his B.Sc. in
group of Dr. Urs Gellrich in 2018
and obtained his M.Sc. in 2019.
Currently, he is working on the
activation of molecular hydro-
gen through self-association of
frustrated Lewis pairs, both ex-
perimentally and computation-
ally.
2016. He joined the research
Jonathan Becker studied
chemistry at Justus-Liebig-Uni-
versität Gießen and received a
postdoctoral fellow with Dr. Pe-
ter Müller at the Massachusetts
Institute of Technology (USA).
After returning to Germany and
Justus-Liebig-Universität Gießen,
he now works on crystallo-
graphic problems in the group
of Professor Müller-Buschbaum
at the Institute of Inorganic and
Analytical Chemistry.
‘Dr. rer. Nat’ degree working in
the group of Professor Siegfried
Schindler. He then worked as a
Urs Gellrich studied chemistry
at the University of Freiburg in
Germany where he obtained his
doctorate in 2013 for his work
on supramolecular ligands un-
der the guidance of Prof. Bern-
hard Breit. In 2014, he moved to
Israel and joined the group of
Prof. David Milstein at the
Weizmann Institute of Science
as a postdoctoral researcher. In
2017, Urs started his indepen-
dent career as a Liebig Fellow of
the Fonds der Chemischen Indus-
trie (FCI) at Justus-Liebig-Univer-
sität Gießen, where he is
currently an Emmy Noether
Group Leader. His research fo-
cuses on the in silico design of
novel metal-free systems for
bond activation and catalysis.
For his work on the concept of
boron-ligand cooperation, he
was awarded the ADUC Prize in
2020.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

C
Synthesis
F. Wech et al.
Feature
R
+
–
H
H
R
R
H
R
–
+
H2
H2
tBu
N
H
O
B
H
H
tBu
N
H
O
B
tBu
N
O
B
1a
C6F5
R
H
C6F5
F5C6
C6F5
2
a
C6F5
R
C6F5
1
a
5
H/R'
R
H
H/R'
R
H
1a
Scheme 2 Using pyridonate borane complex 1a as a catalyst for the semi-hydrogenation of alkynes and the gem-dimerization of terminal alkynes
Na
O
O
O
demonstrated that the pyridonate borane 1b is indeed ca-
O
NaH
+
pable of H activation. Although 2b is formed as the major
MTBE, r.t., 20 h
2
OEt
83%
product upon mixing of 3b and Piers’ borane, a minor im-
purity was observed by NMR analysis (Figure 2, signals
marked with asterisks). It is known that upon formation of
pyridonate borane 1a in the presence of free 6-tert-butyl-2-
pyridone (3a) a bispyridone complex is formed that con-
4
6
O
Ph3P
Cl
NH2
7
N
H
3b
O
1
2
) EtOH, 80 °C, 3 h
) AcOH, 110 °C, 18 h
2%
3
tains a second equivalent of the pyridone 3a. As described
5
for the tert-butyl analogue, the adamantyl-derived bispyri-
done complex 8b was prepared from addition of two equiv-
Scheme 3 Synthesis of 6-adamantyl-2-pyridone 3b from 1-acetyl-
adamantane (4)
11
alents of 3b to the Piers’ borane at r.t. (Scheme 5). After
crystallization from n-hexane and DCM, 8b was isolated as
colorless crystals in 84% yield. As expected, the NMR signals
of 8b matched the signals of the impurity that had been ob-
served during the hydrogen activation experiments. Crys-
tallization of 8b enabled us to further investigate its molec-
ular structure by SCXRD (Figure 3). Compound 8b crystal-
lizes in the space group P2 /c. The molecular structure of 8b
1
was then compared with the structure of the 6-tert-butyl-
2
-pyridone-derived bispyridone complex 8a that was de-
1
1
scribed previously.
F5C6
C6F5
Figure 1 Molecular structure of 3b (CCDC 2024101) derived from
Ad
N
H
3b
O
+
B
H
SCXRD (50% probability ellipsoids, all hydrogens attached to carbons
9
are omitted). Selected bond lengths and angles: N–C2: 1.3788(10) Å,
C2–O: 1.2509(10) Å, N–O: 2.8021(10) Å, N–H–O: 175.7(12)°, N–C2–
O: 119.91(7)°.
benzene-d6
r.t.
6
0 °C, – H2
Ad
N
H
O
B
Ad
N
O
B
H2 (2 bar), r.t.
The N–O distance is 2.8021(10) Å and thus elongated
compared to that in a non-substituted 2-pyridone (2.76
Å). At the next stage, we added 3b to a solution of Piers’
H
C6F5
C6F5
C6F5
C6F5
1
0
2b
1b
borane in benzene-d (Scheme 4). As expected, the imme-
6
Scheme 4 Synthesis of 2b and reversible hydrogen activation by 2b
diate formation of the pyridone borane complex 2b was ob-
served (Figure 2). The H NMR spectrum shows that hydro-
(Ad = adamantyl)
1
gen loss already occurs at room temperature (Figure 2, bot-
tom). When heating the sample at 60 °C for 20 hours, full
conversion of 2b into the pyridonate borane 1b was ob-
served (Figure 2, middle). When pressurizing the reaction
mixture with 2 bar of hydrogen, re-formation of 2b was ob-
served at r.t. within 24 hours (Figure 2, top). Thus, we
Compound 8a crystallized in the space group Cc and
contains two independent molecules in the unit cell. There-
fore, the averaged structural parameters of 8a are displayed
(Table 1). The bispyridone complexes 8a and 8b show relat-
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

D
Synthesis
F. Wech et al.
Feature
ed structural features. The bond lengths associated with the
pyridone that serves as a hydrogen bond donor show little
difference when comparing both structures. Interestingly,
the N–O distance associated with the hydrogen bond is
slightly contracted for the adamantyl derivative 8b com-
pared to the tert-butyl derivative 8a. Furthermore, the O–B–O
bond angle for the tert-butyl system is widened.
Table 1 Selected Bond Lengths and Angles of 8a and 8b Derived from
SCXRD
tert-Butyl bispyridone 8aa Adamantyl bispyridone 8b
N1–O21
2.718 Å
1.471 Å
1.522 Å
1.292 Å
1.362 Å
113.5°
137°
2.697(2) Å
1.475(2) Å
1.524(2) Å
1.292(2) Å
1.366(2) Å
112.8(1)°
136(1)°
B1–O21
B1–O1
1
C1–O1
Figure 2 H NMR spectrum obtained after mixing Piers’ borane with
1
3
b at r.t. Traces of 1b are already observable (bottom). H NMR spec-
C21–O21
O1–B1–O21
O21–H1–N1
trum after heating at 60 °C under a passive vacuum for 20 hours (mid-
1
dle). H NMR spectrum after pressurizing the NMR tube with 2 bar of
hydrogen and keeping the mixture at r.t. overnight (400 MHz, benzene-
d6, top).
B1–O1–C1–N1
3.3°
0.4(2)°
a
Values are the average of the two independent molecules in the unit cell.
Hydrogen activation by 1b was further investigated
F5C6
C6F5
R
N
H
O
B
B
H
DCM, 2 h, r.t.
computationally at the rev-DSD-PBEP86-D4/def2-QZ-
R
N
H
O
+
C6F5
C6F5
12,13
O
VPP//PBEh-3c level (Figure 4).
The SMD model for ben-
1
equiv
3
a,b
N
zene was used to implicitly account for solvent effects (Fig-
2
equiv
14
ure 4). The activation barrier for hydrogen activation is
R
–
1
8
8
a: R = tBu; 73%a
b: R = Ad; 84%
19.3 kcal mol for the adamantyl derivative and thus 0.5
–1
kcal mol lower in Gibbs free energy compared to the 6-
tert-butyl pyridonate borane system. This is expected be-
cause of the more electron-rich pyridine ring of the ada-
mantyl derivative that leads to a higher Lewis basicity. The
hydrogen activation is exergonic for both derivatives by 1.4
Scheme 5 Synthesis of bispyridone complex 8b derived from 6-ad-
mantyl-2-pyridone 3b and Piers’ borane. The 6-tert-butyl-2-pyridone-
derived bispyridone complex 8a was characterized in previous work (Ad
a
=
adamantyl). From reference 3.
–
1
and 1.5 kcal mol , respectively. The dissociation of the pyr-
idone borane complexes into pyridone and Piers’ borane is
–
1
endergonic by 18.0 kcal mol for the adamantyl-substitut-
–1
ed system and 18.1 kcal mol for the tert-butyl-substituted
system, respectively. The formation of the bispyridone com-
plex is exergonic for both systems. For the adamantyl-
substituted system the gain in Gibbs free energy is almost 1
–
1
kcal mol higher compared to the tert-butyl pyridone sys-
tem. This might be due to the shorter and thus stronger hy-
drogen bond.
To gain first insights regarding the catalytic activity of
2
b, we tested it as a catalyst for the gem-selective dimeriza-
tion of terminal alkynes and the hydrogenation of internal
and terminal alkynes (see Scheme 2). The results for a pro-
totypical substrate are compared to those obtained with 2a
5
,7
as the catalyst. The adamantyl pyridone borane complex
2b indeed catalyzed the gem dimerization of phenylacety-
lene. However, the activity of 2b was inferior compared to
that of 2a (Scheme 6). The pyridone borane system 2a was
Figure 3 Molecular structure of bispyridone complex 8b (CCDC
2
024102) derived from SCXRD (50% probability ellipsoids, all hydro-
9
gens attached to carbons are omitted)
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

E
Synthesis
F. Wech et al.
Feature
Figure 4 Gibbs free energy profile for the hydrogen activation by tert-butyl- and adamantyl-substituted pyridonate borane complexes 1a and 1b and
formation of bispyridone complexes 7a and 7b computed at the revDSD-PBEP86/def2-QZVPP//PBEh-3c level of theory. Bulk solvation was considered
implicitly using the SMD model for benzene.
able to hydrogenate terminal alkynes in the presence of hy-
cat. (10 mol%)
H2 (5 bar)
H
H
H
cat. 2a: 61%a
cat. 2b: 52%
drogen due to reversible C –H activation which competes
sp
Ph
H
n-hexane
5
Ph
with hydrogen activation. Therefore, we attempted the hy-
8
0 °C, 20 h
drogenation of phenylacetylene using 2b as the catalyst,
which gave styrene as the product in a slightly lower yield
than that reported when using 2a (Scheme 7, top). In addi-
tion, we used 2b as the catalyst for the hydrogenation of 2-
methyl-3-pentyne (Scheme 7, bottom). The reaction gave
the corresponding cis alkene exclusively after a reaction
time of 16 hours in a slightly higher yield compared to that
obtained with 2a.
cat. (5 mol%)
H2 (5 bar)
H
H
cat. 2a: 83%a
n-hexane
cat. 2b: 88%
8
0 °C, 16 h
Scheme 7 Hydrogenation of phenylacetylene and 2-methyl-3-pentyne
using the pyridone borane complexes 2a and 2b under previously re-
5
ported optimized conditions. Note that for the formation of the respec-
tive pyridone borane complex, a slight excess of Piers’ borane was used
1.3 equiv). The reported yields are the average of two runs. From ref-
a
(
Ph
erence 5.
2
a: 54%a
cat. (20 mol%)
toluene
H
H
2
Ph
H
2b: 33%
100 °C, 6 h
Ph
at room temperature under 2 bar of hydrogen. We were also
able to synthesize a bispyridone complex 8b that is an ad-
duct of pyridonate borane complex 1b with another equiva-
lent of pyridone. The molecular structure of 8b, derived
from SCXRD, revealed a shortened hydrogen bond com-
pared to the tert-butyl-derived bispyridone complex that
was described previously. Additionally, we have shown
that 3b in conjunction with Piers’ borane is a suitable cata-
lyst for the gem dimerization of terminal alkynes and the
hydrogenation of terminal and internal alkynes.
Scheme 6 Dimerization of phenylacetylene using the pyridone borane
complexes 2a and 2b as catalysts under previously reported optimized
conditions. The reported yields are the average of two runs. From ref-
erence 7.
7
a
In summary, we have synthesized the novel 6-adaman-
tyl-2-pyridone 3b from commercially available 1-acetyl-
adamantane in 44% yield over two steps. This pyridone deriv-
ative can form pyridonate borane complex 1b on loss of hy-
drogen. The pyridonate borane 1b can reactivate hydrogen
11
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

F
Synthesis
F. Wech et al.
Feature
Rf = 0.24; mp 219.5 °C
All manipulations involving air- or moisture-sensitive compounds
were performed using standard Schlenk or glovebox techniques. All
dry, non-deuterated solvents were, if commercially available, pur-
chased from Acros Organics or Sigma-Aldrich in sealed bottles with a
septum. Deuterated solvents were distilled under inert conditions
and kept in a glovebox over 4 Å molecular sieves or were degassed us-
ing the freeze/pump/thaw method and stored over 4 Å molecular
sieves for at least one day prior to use. B(C F ) was synthesized from
1
H NMR (400 MHz, CDCl ):  = 11.1 (s, 1 H, NH), 7.36 (dd, J = 9.1 Hz,
3
7.1 Hz 1 H, PyrH), 6.38 (dd, J = 9.1 Hz, 0.8 Hz, 1 H, PyrH), 6.03 (dd, J =
7.0 Hz, 0.7 Hz, 1 H, PyrH), 2.13–2.08 (m, 3 H), 1.96–1.88 (m, 6 H),
1.79–1.71 (m, 6 H).
13
C NMR (100 MHz, CDCl ):  = 164.9 (C ), 157.1 (C ), 141.6 (Pyr-CH),
3
q
q
1
2
17.6 (Pyr-CH), 101.6 (Pyr-CH), 40.6 (3 CH ), 36.6 (C ), 36.4 (3 CH ),
8.2 (3 CH).
2 q 2
6
5 3
boron trifluoride–diethyl etherate according to a literature proce-
HRMS (ESI): m/z [M + Na]+ calcd for C15
H19NONa: 252.1358; found:
252.1360.
dure.15 Piers’ borane was synthesized from B(C F ) according to a
6
5 3
1
6
modified literature procedure: B(C F ) (2.0 g, 3.9 mmol) and Et SiH
6
5
3
3
(
623 L, 3.9 mmol) were dissolved in benzene (20 mL) in a pressure
Anal. Calcd for C15H19NO: C, 78.56; H, 8.35; N, 6.11. Found: C, 78.18;
H, 8.08; N 6.11.
tube and stirred for 4–5 d at 60 °C. The reaction mixture was cooled
to r.t., causing precipitation of the product. The supernatant was re-
moved, and the residue was washed with benzene (3 × 3 mL) and n-
pentane (2 × 2–3 mL). 2-Triphenylphosphonium-acetamide chloride
was synthesized according to a literature procedure. Flash column
chromatography was performed using Macherey-Nagel silica gel
6
-Adamantyl-2-pyridone Borane Complex 2b
In a nitrogen-filled glovebox, 6-adamantyl-2-pyridone (3b) (6.8 mg,
.03 mmol) and Piers’ borane (10.6 mg, 0.031 mmol) were dissolved
8
0
in benzene-d6 (0.3 mL) in a vial. The solution was transferred to an
NMR tube via a J. Young valve and the vial was washed with benzene-
d6 (0.1 mL). NMR spectra were recorded immediately, showing the
formation of pyridone borane complex 2b and bispyridone complex
(0.04–0.063 mm). TLC analyses were performed using standard silica
TLC plates purchased from Macherey-Nagel. Melting points were
measured on an A. Krüss Optotronics melting point meter. IR spectra
were recorded on a Bruker Optics VERTEX70 Platinum ATR spectrom-
eter. NMR spectra were recorded on Bruker Avance II 200 MHz,
Bruker Avance III HD 400 MHz, Bruker Avance II 400 MHz or Bruker
Avance III HD 600 MHz spectrometers. H and C NMR chemical
shifts are referenced to residual solvent resonance signals. Mass spec-
tra were recorded on an ESI-MS Bruker Micro-TOF mass spectrome-
ter. Samples were dissolved in methanol. In positive ion detection
mode the capillary current was set to 4500 V with an end plate offset
of –500 V, and in negative mode the capillary current was set to 3000
V with an end plate offset of 500 V. Elemental analysis was performed
with a Thermo FlashEA 1112 instrument.
8
b.
1
H NMR (400 MHz, benzene-d ):  = 10.33 (s, 1 H, NH), 6.69 (dd, J =
6
1
13
8.9 Hz, 7.5 Hz, 1 H, Pyr-H), 6.53 (ddd, J = 8.9 Hz, 2.2 Hz, 0.9 Hz, 1 H,
Pyr-H), 5.70 (ddd, J = 7.5 Hz, 1.9 Hz, 1.0 Hz, 1 H, Pyr-H), 5.01 (br s, 1 H,
BH), 1.66–1.59 (m, 3 H, CH), 1.43–1.35 (m, 3 H, CH ), 1.30–1.21 (m, 3
2
H, CH ), 1.15–1.09 (m, 6 H, CH ).
2
2
1
3
C NMR (100 MHz, benzene-d ):  = 161.9 (C ), 156.9 (C ), 145.8 (Pyr-
6
q
q
CH), 114.3 (Pyr-CH), 109.4 (Pyr-CH), 40.1 (CH ), 36.7 (C ), 35.7 (CH ),
2
q
2
28.0 (CH).
11
B NMR (128 MHz, benzene-d ):  = –7.1.
6
1
9
F NMR (377 MHz, benzene-d ):  = –134.4 (dd, J = 22.1 Hz, 7.7 Hz),
6
Sodium Enolate 6
–
158.6 (t, J = 20.5 Hz), –164.3 (ddd, J = 24.3 Hz, 19.8 Hz, 9.4 Hz)
Sodium hydride (60% dispersion, 0.84 g, 21 mmol) was suspended in
MTBE (15 mL). EtOH (0.1 mL) was added slowly with gas evolution at
r.t. Next, a solution of ethyl formate (1.37 g, 18.5 mmol) and 1-acetyl-
adamantane (4) (2.99 g, 16.8 mmol) in MTBE (5.0 mL) was added
dropwise over 2 h. The resulting yellow slurry was diluted with MTBE
(
F integration 2:1:2).
6
-Adamantyl-2-pyridonate Borane Complex 1b
In a nitrogen-filled glovebox, 6-adamantyl-2-pyridone (3b) (6.8 mg,
.03 mmol) and Piers’ borane (10.8 mg, 0.031 mmol) were dissolved
0
(
5 mL) and the suspension was stirred overnight at r.t. The mixture
in benzene-d6 (0.4 mL) in a vial. The solution was transferred to an
NMR tube via a J. Young valve and the vial was washed with benzene-
d6 (0.1 mL). The NMR tube was degassed three times using the
freeze/pump/thaw technique and placed in a 60 °C oil bath for 20 h.
Afterwards, it was again degassed via freeze/pump/thaw and NMR
spectra were recorded. The formation of pyridonate borane 1b and
bispyridone complex 8b were observed.
was filtered, and the yellow residue was washed multiple times with
n-pentane. After drying in vacuo, the product was obtained as a pale
yellow solid (3.2 g, 83%). No NMR data were obtained because of the
insolubility of the product. The product was used without further pu-
rification.
IR (ATR): 2892, 2850, 1698, 1586, 1446, 1360, 1224, 774 cm–1
HRMS (ESI): m/z [M – Na]– calcd for C13H17O : 205.1234; found:
.
2
1
H NMR (400 MHz, benzene-d ):  = 7.01 (t, J = 8.0 Hz, 1 H, Pyr-H),
6
205.1233.
6
.43 (dd, J = 7.7 Hz, 0.4 Hz, 1 H, Pyr-H), 6.40 (dd, J = 8.2 Hz, 0.6 Hz, 1 H,
Pyr-H) 1.85–1.78 (m, 3 H, CH), 1.60–1.44 (m, 12 H, CH2).
6
-Adamantyl-2-pyridone (3b)
13
C NMR (100 MHz, benzene-d ):  = 166.6 (C ), 163.4 (C ), 142.4 (Pyr-
6
q
q
Sodium enolate 6 (1.07 g, 5.00 mmol) was suspended in EtOH (25
mL). 2-Triphenylphosphonium-acetamide chloride (7) (1.78 g, 5.00
mmol) was added and the mixture was heated at 80 °C for 3 h. Acetic
acid (10 mL) was then added and the mixture was refluxed at 110 °C
for 18 h. The solvent was then removed and the residual acetic acid
was co-evaporated with toluene. The product was purified by column
chromatography on silica gel using n-hexane/EtOAc/AcOH (3:1:0.01).
The product was isolated as a white crystalline solid (600 mg, 52%).
C), 114.5 (Pyr-C), 108.2 (Pyr-C), 41.2 (CH ), 38.7 (C ), 36.6 (CH ), 28.7
2
q
2
(CH).
1
1
B NMR (128 MHz, benzene-d ):  = 29.7.
6
1
9
F NMR (377 MHz, benzene-d ):  = –132.3 (dd, J = 24.0, 9.2 Hz),
6
–
150.8 (s), –162.0 to –162.1 (m) (F integration 2:1:2).
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

G
Synthesis
F. Wech et al.
Feature
Adamantyl Bispyridone Complex 8b
Supporting Information
In a nitrogen-filled glovebox, 6-adamantyl-2-pyridone (3b) (22.9 mg,
Supporting information for this article is available online at
0.1 mmol) and Piers’ borane (17.3 mg, 0.05 mol) were suspended in
https://doi.org/10.1055/s-0040-1705970. Su
p
p
ortingI
n
form atio
n
S
u
p
p
ortingInform ati
o
n
DCM (0.7 mL). The solution was stirred for 2 h at r.t. and then n-hex-
ane (5 mL) was added. Upon evaporation of the DCM, the product
crystallized as colorless crystals (33.7 mg, 84%).
1
References
H NMR (400 MHz, benzene-d ):  = 12.8 (s, 1 H, NH), 6.93 (dd, J = 8.4
6
Hz, 7.6 Hz, 2 H, PyrH), 6.65 (d, J = 8.4 Hz, 2 H, PyrH), 6.14 (d, J = 7.5 Hz,
(1) Welch, G. C.; San Juan, R. R.; Masuda, J. D.; Stephan, D. W.
Science 2006, 314, 1124.
2
H, PyrH), 1.83 (s, 6 H, 6 CH), 1.58–1.49 (m, 24 H, 12 CH2).
1
3
(2) (a) Stephan, D. W. J. Am. Chem. Soc. 2015, 137, 10018.
C NMR (100 MHz, benzene-d ):  = 162.6 (C ), 162.5 (C ), 142.2 (Pyr-
6
q
q
(b) Stephan, D. W.; Erker, G. Angew. Chem. Int. Ed. 2015, 54,
CH), 113.6 (Pyr-CH), 110.9 (Pyr-CH), 40.9 (CH ), 37.9 (C ), 36.5 (CH )
2
2
q
2
6400.
8.6 (CH).
1
(3) Gellrich, U. Angew. Chem. Int. Ed. 2018, 57, 4779.
1
B NMR (128 MHz, benzene-d ):  = 4.93.
6
(
4) (a) Gunanathan, C.; Milstein, D. Acc. Chem. Res. 2011, 44, 588.
(b) Khusnutdinova, J. R.; Milstein, D. Angew. Chem. Int. Ed. 2015,
1
9
F NMR (377 MHz, benzene-d ):  = –137.1 (dd, J = 24.4, 9.3 Hz),
6
–
158.1 (t, J = 20.6 Hz), –164.5 to –164.7 (m) (F integration 2:1:2).
5
4, 12236. (c) Gellrich, U.; Diskin-Posner, Y.; Shimon, L. J. W.;
Milstein, D. J. Am. Chem. Soc. 2016, 138, 13307.
(5) Wech, F.; Hasenbeck, M.; Gellrich, U. Chem. Eur. J. 2020, 26,
3445.
6) (a) Dureen, M. A.; Stephan, D. W. J. Am. Chem. Soc. 2009, 131,
396. (b) Chen, C.; Eweiner, F.; Wibbeling, B.; Fröhlich, R.;
Catalytic Experiments
1
(
Dimerization of Phenylacetylene
8
The gem dimerization was performed according to a previously re-
ported procedure.7 Under a nitrogen atmosphere, 6-adamantyl-2-
pyridone (3b) (7.0 mg, 0.03 mmol) and Piers’ borane (11.5 mg, 0.033
mmol) were dissolved in toluene (1 mL). The solution was transferred
to a Schlenk tube and phenylacetylene (16.5 L, 0.15 mmol) was add-
ed. The tube was placed in a pre-heated oil bath at 100 °C and the
contents stirred for 6 h. The solvent was removed in vacuo and tri-
methoxybenzene (8.4 mg, 0.05 mmol) was added. The residue was
dissolved in chloroform-d and NMR spectra were recorded (see Fig-
ures SI 29 and SI 30 in the Supporting Information).
Senda, S.; Ohki, Y.; Tatsumi, K.; Grimme, S.; Kehr, G.; Erker, G.
Chem. Asian J. 2010, 5, 2199.
(
(
(
7) Hasenbeck, M.; Müller, T.; Gellrich, U. Catal. Sci. Technol. 2019, 9,
2438.
8) Hintermann, L.; Dang, T. T.; Labonne, A.; Kribber, T.; Xiao, L.;
Naumov, P. Chem. Eur. J. 2009, 15, 7167.
9) CCDC 2024101 and CCDC 2024102 contain the supplementary
crystallographic data for this paper. The data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/getstructures.
(
(
10) Yang, H. W.; Craven, B. M. Acta Crystallogr., Sect. B 1998, 54, 912.
11) Müller, T.; Hasenbeck, M.; Becker, J.; Gellrich, U. Eur. J. Org.
Chem. 2019, 451.
Hydrogenation of Alkynes
The hydrogenations were performed according to a previously re-
ported procedure.5 Under a nitrogen atmosphere, 6-adamantyl-2-
pyridone (3b) (6.9 mg, 0.03 mmol) and Piers’ borane (13.5 mg, 0.039
mmol) were dissolved in n-hexane (5 mL) in a Fisher–Porter type re-
actor bomb. The respective alkyne [phenylacetylene (0.3 mmol) or 2-
methyl-3-pentyne (0.6 mmol] was added and the vessel sealed. It was
(
12) (a) Hellweg, A.; Hättig, C.; Höfener, S.; Klopper, W. Theor. Chem.
Acc. 2007, 117, 587. (b) Caldeweyher, E.; Bannwarth, C.;
Grimme, S. J. Chem. Phys. 2017, 147, 34112. (c) Caldeweyher, E.;
Ehlert, S.; Hansen, A.; Neugebauer, H.; Spicher, S.; Bannwarth,
C.; Grimme, S. J. Chem. Phys. 2019, 150, 154122. (d) Weigend, F.
Phys. Chem. Chem. Phys. 2006, 8, 1057. (e) Santra, G.; Sylvetsky,
N.; Martin, J. M. L. J. Phys. Chem. A 2019, 123, 5129. (f) Weigend,
F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297.
then connected to a H bomb cylinder with a gas hose that had been
2
rinsed several times with hydrogen. The vessel was pressurized with
5
1
bar hydrogen and placed in an 80 °C pre-heated oil bath for 20 h or
6 h. Finally, trimethoxybenzene (8.4 mg, 0.05 mmol) was added and
(13) (a) Kruse, H.; Grimme, S. J. Chem. Phys. 2012, 136, 154101.
NMR spectra were recorded (see Figures SI 25–28 in the Supporting
Information).
(b) Grimme, S.; Brandenburg, J. G.; Bannwarth, C.; Hansen, A.
J. Chem. Phys. 2015, 143, 54107. (c) Grimme, S.; Antony, J.;
Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104.
(d) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32,
Funding Information
1456. (e) Weigend, F. J. Comput. Chem. 2008, 29, 167.
14) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B
2009, 113, 6378.
(
This work was supported by the Deutsche Forschungsgemeinschaft
(DFG; German Research Foundation) (GE 3117/1-1).
D
eutsche Forsch
u
n
gsg
e
meinschaft(G
E
3
1
1
7
/1-1)
(15) Soltani, Y.; Wilkins, L. C.; Melen, R. L. Angew. Chem. Int. Ed. 2017,
6, 11995.
5
(
16) Longobardi, L. E.; Johnstone, T. C.; Falconer, R. L.; Russell, C. A.;
Acknowledgment
Stephan, D. W. Chem. Eur. J. 2016, 22, 12665.
Continued support from Prof. Dr. P. R. Schreiner, Prof. Dr. R. Göttlich,
and Prof. Dr. H. A. Wegner is acknowledged.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G