Highly active metal-free catalysts for hydrogenation of unsaturated nitrogen-containing compounds

Article abstract of DOI:10.1002/adsc.201100206

New highly active ansa-ammonium borate catalysts for the direct metal-free hydrogenation of imines were prepared by tuning of the basicity and steric bulkiness of their amine moieties. The highest catalytic activity among previously reported organocatalytic systems was shown for a wide range of nitrogen-containing substrates. The first example of asymmetric imine hydrogenation based on the ansa-ammonium borate concept was demonstrated. Furthermore, effective catalyst recovery by extraction of the acidic solution with an organic solvent followed by dehydration with TMSBr was elaborated. The initial findings highlight the development of more effective chiral ansa-ammonium borates for enantioselective hydrogenation. Therefore, the progress achieved in the ansa-ammonium borate concept makes it very promising for further elaboration with the aim to obtain industrially applicable catalysts. Copyright

Full text of DOI:10.1002/adsc.201100206

FULL PAPERS
DOI: 10.1002/adsc.201100206
Highly Active Metal-Free Catalysts for Hydrogenation of
Unsaturated Nitrogen-Containing Compounds
Victor Sumerin,a Konstantin Chernichenko,a Martin Nieger,a Markku Leskelꢀ,a
Bernhard Rieger,b and Timo Repoa,*
a
Department of Chemistry, University of Helsinki, P.O. Box 55, FIN-00014 Helsinki, Finland
Fax : (+358)-9-191-50198; phone: (+358)-9-191-50194; e-mail: timo.repo@helsinki.fi
WACKER-Lehrstuhl fꢁr Makromolekulare Chemie, Technische Universitꢀt Mꢁnchen, Lichtenbergstrasse 4,
b
D-85747 Garching bei Mꢁnchen, Germany
Received: March 22, 2011; Revised: April 27, 2011; Published online: August 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100206.
Abstract: New highly active ansa-ammonium borate by dehydration with TMSBr was elaborated. The ini-
catalysts for the direct metal-free hydrogenation of tial findings highlight the development of more ef-
imines were prepared by tuning of the basicity and fective chiral ansa-ammonium borates for enantiose-
steric bulkiness of their amine moieties. The highest lective hydrogenation. Therefore, the progress
catalytic activity among previously reported organo- achieved in the ansa-ammonium borate concept
catalytic systems was shown for a wide range of ni- makes it very promising for further elaboration with
trogen-containing substrates. The first example of the aim to obtain industrially applicable catalysts.
asymmetric imine hydrogenation based on the ansa-
ammonium borate concept was demonstrated. Fur-
thermore, effective catalyst recovery by extraction of Keywords: amines; boranes; homogeneous catalysis;
the acidic solution with an organic solvent followed hydrogenation; organocatalysis
Introduction
quire the use of at least a stoichiometric amount of a
hydrogen source as a reducing agent.
During the past century, hydrogen activation and cat-
An alternative atom-economical metal-free enan-
alytic hydrogenation of unsaturated nitrogen-contain- tioselective imine hydrogenation is less developed. To
ing compounds under mild conditions was an exclu- date, there are only two non-metal systems based on
sive prerogative of transition metal catalysts.[1] De- the bis(perfluorophenyl)boranyl [B
ACTHNUTRGNEG(UN C6F5)2] moiety
spite the undeniable achievements obtained in this substituted with a chiral alkyl chain able to catalyze
area in recent decades, there is still a considerable asymmetric N-arylketimine hydrogenation. In an
amount of unresolved challenges related to catalyst early experiment, hydrogenation of N-(1-phenyleth-
selectivity, functional group tolerance, environmental
sustainability, cost-efficiency and fine purification of
ACHTUNGTRENyNGNU lidene)aniline with 10 mol% of 3-pinanylbis(per-
AHCTUNGTREYNGNUN fluorophenyl)borane at 658C under 20 atm of H2
the reaction products.[2] Among the various alterna- pressure showed complete conversion of the imine
tive methods, the fast growing area of enantioselective but with only 13% ee (Scheme 1).[9]
organocatalytic reduction of imines, enamines and ni-
trogen-containing heterocycles is attracting increasing
attention.[3,4,5] Presently, there are essentially two well-
established asymmetric organocatalytic approaches
for this transformation. The first method is a Lewis
base-catalyzed hydrosilylation with trichlorosilane
with the second being a Brønsted acid-catalyzed re-
duction with Hantzsch esters or benzothiazolines.[6,7,8]
Both of these methods give the corresponding amines
Scheme 1. Chiral alkyl-bis(perfluorophenyl)borane-based cata-
in high yields and high enantioselectivities, but re- lysts.[9,10]
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Scheme 2. Proposed mechanism for the catalytic hydrogenation of imines by ansa-ammonium borates.
More
recently,
tris(tert-butyl)phosphonium/ borate-catalyzed hydrogenation of nitrogen-contain-
[2.2.1]- ing compounds are reported.
[(1R,2R,3R,4S)-4,7,7-trimethyl-3-phenylbicycloAHCTUNGTRENNUNG
heptan-2-yl bis(perfluorophenyl)hydroborate pre-
pared from (1R)-(+)-camphor catalyzed (5 mol%)
the reduction of different N-arylketimines at 658C Results and Discussion
under 25 atm pressure of H2 to give the corresponding
amines in high yields and good ees (up to 83%).[10] In Synthesis of ansa-Ammonium Borate Catalysts
contrast to achiral systems based on triarylboranes,[11]
a higher pressure of hydrogen is required in the case One disadvantage of the previously developed
of chiral-alkyldiarylboranes.[12] Moreover, such non- CATH2 is the sensitivity to steric factors around the
metal catalysts cannot be recovered and/or reused, nitrogen atom of the imine. Non-bulky amines or/and
which is an important requirement for large-scale ap- corresponding imines inhibit the catalyst by coordina-
plications.
We recently showed that the ansa-aminoborane N- versions in these cases did not exceed the ansa-ammo-
TMP-CH2C6H4B(C6F5)2 (where TMP is 2,2,6,6-tetra- nium borate loading. Another is CATH2ꢃs low ability
tion to its Lewis acidic boron centre. As a result con-
ACHTUNGTRENNUNG
methylpiperidinyl) can rapidly activate hydrogen at to reduce less basic N-arylketimines in comparison
208C and 1 atm pressure to give the ansa-ammonium with other more basic N-alkyl- and N-benzylket-
borate CATH2, which can release dihydrogen upon
ACHTUNGTRENiNGNU mines. Thus the reduction of N-(4-methoxy)phenyl-1-
heating at 1108C.[13] Besides providing reversible H2 phenylethylideneamine 1d with 4 mol% of CATH2 af-
activation, CATH2 was also found to be an efficient forded only 37% yield of the desired amine in 12 h
catalyst for the reduction of imines and enamines (toluene, 1108C) (Table 1, entry 13). These observa-
(Scheme 2). However, much like other organocatalyt- tions support a proposed mechanism in which any
ic systems with the bis(perfluorophenyl)boranyl one or more steps may be rate-determining depending
moiety, it has significant drawbacks and limitations on the substrate and catalyst structures (Scheme 2).
with respect to the reactivity.
The proton transfer (Scheme 2, stage II) seems to be
Herein we report new efficient catalysts for the a primary and rate-controlling step for the reaction of
metal-free hydrogenation of a broad palette of unsa- bulky imines. For instance, the reduction of N-aryl-a-
turated nitrogen-containing compounds. By tuning imino ester 1e which has the lowest basicity in the
the basicity of the amine moiety a 100-fold increase in series of imines proceeded with a low conversion per-
activity was achieved.[14] Also a simple procedure for centage (Table 2, entry 5). The fact that the conver-
the recovery of the highly moisture-sensitive catalysts sion of non-bulky imines does not exceed the catalyst
after quenching the reaction with aqueous acidic solu- loading highlights another important step in the hy-
tion is described. Furthermore, the first results on the drogenation mechanism: the inhibition of the catalytic
enantioselective ansa-aminoborane/ansa-ammonium
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Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
Table 1. Catalytic hydrogenation of imines.[a] Table 2. Catalytic hydrogenation of imines.[a]
Entry Substrate
Catalyst
[mol%]
Time Conv.
[h]
Entry Substrate
Catalyst
[mol%]
Time Conv.
[h]
[%][b]
[%][b]
1
2
3
4
5
6
7
8
CATH2
4 20
100[c]
100
15
1
2
3
4
5
6
7
8
CATH2
MCATH2
QCATH2
iPrICATH2 4 12
CATH2
MCATH2
QCATH2
iPrICATH2 4 12
iPrQCATH2 4 12
CATH2
4 12
4 12
4 40
4
4
21
15
4
4
4
4
82
4
MCATH2 1 12
QCATH2 1 12
iPrICATH2 1 12
CATH2 4 6
MCATH2 1 12
QCATH2 1 5
iPrICATH2 2 12
CATH2 4 12
MCATH2 2 12
QCATH2 2 12
iPrICATH2 2 12
CATH2 4 12
MCATH2 1 40
QCATH2 1 3
iPrICATH2 2 12
100
100[c]
100
100
100
100[c]
100
100
100
4 12
4 12
4 12
9
9
10
11
12
13
14
15
16
10
11
12
13
14
15
16
4 12
4 12
4 40
MCATH2
QCATH2
4
80
100
100[c]
94[c]
80[d]
iPrICATH2 4 12
QCATH2 4 6
iPrICATH2 4 6
(C6F5)3 5 4
37
70
100[d]
100
BACHTUNGTRENNUNG
[a]
ansa-Ammonium borate catalyst (0.01 mmol, 4%), sub-
strate (0.25 mmol) in toluene (5.0 mL) were refluxed
(1108C) under 2 atm of H2 pressure (56 mL, 2.5 mmol).
[a]
ansa-Ammonium borate catalyst (0.01 mmol, 1–4%),
substrate (0.25–1.0 mmol) in toluene (5.0 mL) were re-
fluxed (1108C) under 2 atm of H2 pressure (56 mL,
2.5 mmol).
[b]
[c]
[d]
1
Determined by H NMR spectroscopy.
In Et2O (3 mL) at room temperature.
[b]
[c]
[d]
1
At 258C, 4 atm H2, ref.[11e]
Determined by H NMR spectroscopy.
Ref.[13a]
At 808C.
Interestingly, lowering the basicity of the starting
amines had no significant effect on the hydrogen
activity of ansa-aminoboranes by Lewis acid-Lewis cleavage process by ansa-aminoboranes MCAT,
base adduct formation (Scheme 2, stage IV). QCAT and iPrICAT. However, reduced basicity dra-
On the basis of the above results, two general ap- matically decreased the temperature and the time re-
proaches for further modification of the ansa-ammo- quired for hydrogen liberation (Scheme 5).
nium borate organocatalysts were considered: (i) de-
While ansa-ammonium borate CATH2 released H2
creasing the basicity of the amine moiety to shift the quantitatively in toluene after 18 h at 1108C, less
proton transfer equilibrium to the right and (ii) in- basic MCATH2 liberated hydrogen in 30 min under
creasing the steric hindrance of the active boron the same conditions. Even the less basic QCATH2
centre by introducing a more bulky amine moiety and PrICATH2 either slowly decomposed in CDCl3
(Scheme 3).
solution at room temperature or gave starting ansa-
The air- and moisture-stable ansa-ammonium bo- aminoboranes QCAT and iPrICAT after 5–10 min at
rates MCATH2, QCATH2, iPrQCATH2 and iPrI- 1108C in toluene.[20] Accordingly, the less basic ansa-
CATH2 were synthesized on a gram scale by a simple ammonium borates lost hydrogen much faster than
four-step procedure from readily or commercially the original CATH2, mainly due to the lower energy
1
+
available starting materials (Scheme 4).[15] The H, 11B needed to cleave the weaker N H bonds to form hy-
and 19F NMR spectroscopic data of the final com- drogen gas. Therefore, QCAT and iPrICAT exhibited
pounds were in agreement with the proposed struc- excellent kinetics (a few minutes) in both activation
tures and showed the presence of ammonium and a and liberation of hydrogen.[21]
four-coordinated borohydride species (1H NMR: NH
À
broad singlets at 8.53, 8.93, 8.24 or 8.42[16] and
9.68 ppm; BH broad quartets at 3.72, 3.74, 3.70 and Catalytic Hydrogenation by ansa-Ammonium Borate
1
3.85 ppm, JB,H =65–76 Hz; 11B NMR: À20.74, À21.16, Catalysts
À20.75 and À20.63 ppm, JB,H =65–76 Hz; 19F NMR:
1
+
Ddm,p =3.75, 3.39-3.91, 3.70–3.84 and 3.54-3.58 ppm[17] Because of weaker N H interactions the catalytic
À
for MCATH2, QCATH2, iPrQCATH2 and iPrI- activity of the new MCATH2, QCATH2 and iPrI-
CATH2, respectively). Additionally, the structures of CATH2 in the hydrogenation of imines also increased
all new ansa-ammonium borates were confirmed by dramatically (Table 1 and Table 2). Full conversions
X-ray diffraction experiments.[18,19]
were achieved with either lower catalyst loading and/
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Scheme 3. Rational design of the new ansa-ammonium borate catalysts.[14]
Scheme 4. Synthesis of the new ansa-ammonium borate catalysts.
or shorter reaction time and/or lower temperature were performed under standard conditions, optimiza-
than with CATH2 (Table 1). Thus, the proton transfer tion of which can lead to further increases of catalytic
seems to be a rate-controlling step for the reaction of activity (Table 2 and Table 3).
imines 1a–d. One should note that these experiments
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Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
Scheme 5. Reversible H2 activation by ansa-aminoboranes.
Table 3. Catalytic hydrogenation of imine 1d by ansa-ammo-
nium borate QCATH2.[a]
Entry Solvent Time
[h]
Temperature Conv.
[8C]
TOF
[hÀ1]
[%][b]
Figure 1. X-ray structure of ansa-ammonium borate iPrQ-
CATH2.[18] Hydrogen atoms were omitted for clarity, except
those of the NHHB fragment. Atoms of the ansa fragment
are labelled and coloured with black. The structural disorder
of the C-11 and C-23 atoms is caused by the presence of dia-
stereomers.
1
2
3
4
CH2Cl2
CH2Cl2 2.5
CDCl3
CDCl3 2.5
hexane
1
25
60
25
80
25
80
25
80
25
60
25
80
50
50
10
51
22
92
2
100
31
99
17
100
2
10
20.4
22
36.8
2
1
5
1
6
7
hexane 2.5
toluene 1
ꢀ40
31
8
toluene 2.5
39.6
17
To overcome this obstacle a special catalyst iPrQ-
CATH2 based on the more bulky 8-isopropyl-2,2,4-tri-
methyl-1,2,3,4-tetrahydroquinoline moiety was used
(Figure 1). Although iPrQCATH2 exhibited a catalyt-
ic activity lower than those of MCATH2, QCATH2
and iPrICATH2 for most of the substrates, hydroge-
nation of imine 1f was performed in 82% yield under
the standard conditions.
Inspired by the high activity of QCATH2, we fo-
cused on the reduction of imine 1d in different sol-
vents and temperatures with 1 mol% of catalyst
(Table 3). Overall, the best results were obtained
9
Et2O
Et2O
THF
THF
toluene 1
Et2O
1
2.5
1
10
11
12
13
14
ꢀ40
2
2.5
42
89
97
16.8
89
97
1
[a]
Catalyst QCATH2 (0.01 mmol, 1%) and 1d (1.0 mmol)
were stirred in solvent (5.0 mL) under 2 atm of H2 pres-
sure (56 mL, 2.5 mmol).
[b]
1
Determined by H NMR spectroscopy.
The most expressive example is N-aryl-a-imino using a solvent such as toluene and hexane at 808C
ester 1e which has the lowest basicity in the series of (2.5 h) or Et2O at 508C (1 h).
imines proceeded. Whilst CATH2 and generally more
Thus the rational design of highly active MCATH2,
active MCATH2 provided only stoichiometric reduc- QCATH2, iPrICATH2 and iPrQCATH2 catalysts was
tion, hydrogenation with QCATH2 and iPrICATH2 achieved simply by fine tuning of the electronic and
led to low, but over-stoichiometric conversions steric properties of the amine moiety. To date report-
(Table 2, entries 3 and 4). Additionally QCATH2 and ed substrates for FLP-catalyzed hydrogenation can be
iPrICATH2 were able to hydrogenate 2-phenylquino- divided with small exceptions on two main groups:
line catalytically to give 2-phenyl-1,2,3,4-tetrahydro- sterically hindered (N-t-Bu-,[11a,b,c] N-Dipp-,[11b] N-
quinoline in an almost quantitative yield (Table 2, en- benzhydryl[11a,b,c] imines and enamines[11d]) and low-
tries 10–15).
basic (N-aryl,[9] N-arylsulfonyl[9,11a,b] imines and qui-
unsaturated nitrogen-containing com-
As we have mentioned above the dissociation of a nolines[11e]
)
Lewis acid-Lewis base adduct between the ansa-ami- pounds. Both of these aforementioned factors facili-
noboranes and product amine is the rate-determining tate dissociation of the Lewis adducts between cata-
step in the case of sterically benign substrates lyst and substrates or fully prevent formation of those
(Scheme 2, Stage IV). Therefore, the generally more providing catalytic activity of triarylboranes. In this
active non-metal systems MCATH2, QCATH2 and respect new ansa-ammonium borates substantially
iPrICATH2 (4 mol%) could provide only a stoichio- extend the substrate scope of non-metal catalytic hy-
metric reduction of non-bulky imine 1f (Table 2, en- drogenation. A striking example is hydrogenation of
tries 6–8) evidently due to catalyst inhibition by the 1f with the particularly effective catalyst iPrQCATH2.
substrate.
For substrates hydrogenated by both ansa- and other
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systems, the first provide superior (1a[11a,f] and 1d[10]
or comparable catalytic activity (1g[11e]).
)
After the optimized conditions were determined,
we then investigated the possibility of recovering the
catalyst. It is a well known fact that the free forms of
the catalytic systems based on the frustrated Lewis
acid-Lewis base concept are very sensitive towards
water.[22] Thus, in spite of the fact that most of ansa-
ammonium borates are air- and moisture-stable, the
corresponding ansa-aminoboranes easily react with
H2O from the air affording water activation products.
This indicates that the presence of accidental traces of
water in the reaction system not only inhibits the cat-
alyst activity in the hydrogenation reaction, but also
suggests that water activation products would form
during the quenching of the reaction mixture. Thus,
the dehydration of such compounds is a key transfor-
mation in the catalyst recovery process. Surprisingly,
after the solution of water-activated ansa-ammonium
Figure 3. X-ray structure of ansa-ammonium borate iPrI-
CATH2.[18] Hydrogen atoms were omitted for clarity, except
those of the NHHB fragment. Atoms of the ansa fragment
are labelled and coloured with black. A distinct p-p stacking
borate in benzene had been refluxed with excess of between phenyl and perfluorophenyl groups is noticeable.
TMSBr (5 equiv.) for 5 min. and then evaporated
under vacuum, the starting ansa-aminoborane QCAT
was obtained in almost quantitative yield.[18] Finally,
ACHTUNGTRENNUNG
methoxy)phenyl-1-phenylethylideneamine 1d (ꢄ25
Additionally, due to the fixed conformation of
times, 5.632 g) by ansa-ammonium borate QCATH2 ansa-ammonium borates,[23] nitrogen atoms present in
(1 mol%) was scaled up, with the corresponding these compounds are stereogenic as well. According
amine being isolated in 97% yield. Furthermore, 80% to NMR and X-ray diffraction studies, QCATH2 and
of the catalyst was recovered by extraction of the iPrICATH2 exist as a mixture of diastereomers (5.7:1)
acidic solution with toluene followed by dehydration and a single diastereomer, respectively (Figure 2 and
with TMSBr at 808C. This procedure was successful Figure 3). Thus the stereochemistry of the tertiary
due to the high hydrophobic effect of the perfluoro- carbon in these systems has a strong influence on the
phenyls of the catalyst.
configuration of the tertiary ammonium nitrogen
centre.
Due to the above-mentioned results, we attempted
to prepare enantioenriched catalysts Q*CATH2 and
iPrI*CATH2 containing enantiopure amine moieties
Chiral ansa-Ammonium Borate Catalysts
So far, the ansa-ammonium borates QCATH2 and and test them as catalysts for enantioselective hydro-
iPrICATH2 are the most active catalysts in the hydro- genation. The starting 7-isopropyl-3,3-dimethyl-2-
genation of imines among the previously reported B- phenyl-3H-indole 1i and 2,2,4,7-tetramethyl-1,2-dihy-
droquinoline 1j were prepared according to the stan-
dard procedures.[18,24] The 7-isopropyl-3,3-dimethyl-2-
phenylindoline was synthesized by a similar method
to that recently elaborated by Rueping et al.[7b,25] The
reduction of 3H-indole with Hantzsch ester catalyzed
by enantiopure phosphoric acid (R)-TRIP[26] showed
the same enantioselectivity of 99% as previously re-
ported with 3,3-bis(9-anthracenyl)-substituted phos-
phoric acid (Scheme 6).
To date no direct enantioselective approach to 4-
substituted tetrahydroquinolines from 2,2-substituted-
1,2-dihydroquinolines has been described.[7b,27] More-
over, the only known example of asymmetric reduc-
tion of 4-substituted quinolines by a chiral Brønsted
Figure 2. X-ray structure of ansa-ammonium borate
QCATH2.[18] Hydrogen atoms were omitted for clarity,
except those of the NHHB fragment. Atoms of the ansa
fragment are labelled and coloured with black.
acid with a Hantzsch ester as hydrogen source postu-
lates the first step of the mechanism to be hydride
attack on the 4-position of protonated quinoline with
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Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
Scheme 6. Synthesis of enantiopure amines.
subsequent formation of 1,4-dihydroquinoline.
Whereas such a mechanism cannot be realized in the
case of 2,2-substituted-1,2-dihydroquinolines, the cor-
responding 2,2,4,7-tetramethyl-1,2,3,4-tetrahydroqui-
noline was prepared in high yield and good ee
(86.5%, Scheme 6) by a similar organocatalytic proce-
dure. We believe that prior formation of the ortho-
quinone tautomer followed by 1,4-reduction could be
a possible explanation for this observation. Notably,
>99% ee was achieved after one recrystallization of
the hydrochloride salt. Therefore, our method pro-
vides a simple route to the synthesis of valuable enan-
Scheme 7. Racemization of the enantiopure iPrI*CAT.
tiopure
2,2,4-substituted-1,2,3,4-tetrahydroquino- in Table 4. Under standard conditions (heating for
15 h with 10 mol% of the catalyst at 1108C in tolu-
(C6F5)3 was found to be superior, providing full
lines.[28]
The ansa-ammonium borates Q*CATH2, and iPrI*- ene) B
ACHTUNGTRENNUNG
CATH2 were synthesized by a standard two-step pro- racemization. Among the tested ansa-ammonium bo-
cedure from corresponding enantiopure amines rates, only QCATH2 showed activity comparable to
1
(Scheme 4). The H, 11B, 13C and 19F NMR spectro- that of B
C
scopic data of Q*CATH2 were in agreement with the plained by slow dehydrogenation into the correspond-
proposed structure. However, in contrast to the race- ing ansa-aminoborane which is considered to be the
mic compound Q*CATH2 exist as a mixture of diaste- actual catalyst. The ansa-aminoborane iPrICAT is
reomers at a lower ratio (1.5:1) at the ammonium ni- unable to abstract hydrogen from substrate amine as
trogen atom. This is probably due to the longer time it exists in zwitterionic form (Scheme 7). Interestingly,
needed for crystallization of the enantiopure ansa-am-
monium borate compared to that of the racemic
system and the previously observed slow decomposi-
Table 4. Catalytic racemization of amines.[a]
tion of QCATH2 to QCAT in solution at room tem-
Entry Substrate
Catalyst
Final ee [%][b]
perature even under an atmosphere of hydrogen.
1
The H, 11B, 13C and 19F NMR spectroscopic data of
1
2
3
4
5
6
7
8
9
B
B
U
0
>97[c]
96.8
13
iPrI*CATH2 were identical to those of racemic ansa-
ammonium borate iPrICATH2. Furthermore, the X-
ray crystal structure study of PrI*CATH2 revealed the
same P1 space group.[18] Thus, in spite of the absence
of b-protons[29] in the starting amine and the high
steric hindrance of the iPrI*CAT, the Lewis acidic
boron centre can abstract the a-proton of the amine
fragment to form the intramolecular iminium borohy-
dride species, which is in equilibrium with the starting
ansa-aminoborane (Scheme 7).
CATH2
QCATH2
iPrICATH2 86.6
B
N
<0.8
87.6
42.5
CATH2
QCATH2
iPrICATH2 86.2
[a]
Substrate (0.1 mmol), BAHCNUTTGERG(NNUN C6F5)3 (0.01 mmol, 10% mol)
were heated (1108C) in toluene (2.0 mL) under an argon
atmosphere for 15 h.
Determined by chiral-HPLC.
To evaluate the catalytic activity of BACHTUNRGTNEUNG(C6F5)3 and
ansa-ammonium borates in the racemization of enan-
tioenriched amines, illustrative examples are collected
[b]
[c]
Under 2 atm of hydrogen pressure.
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Victor Sumerin et al.
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enantiopure (2R,4aR)-2-isopropyl-4a-methyl-2,3,4,4a-
tetrahydro-1H-carbazole was prepared according to
the literature procedure.[30] The subsequent addition
of PhLi in toluene gave only the cis isomer
(2R,4aR,9aS)-2-isopropyl-4a-methyl-9a-phenyl-
2,3,4,4a,9,9a-hexahydro-1H-carbazole in high yield.[31]
The final ansa-aminoborane CarCAT was synthesized
by the standard procedure (Scheme 8). Interestingly,
while ansa-ammonium borates QCATH2 and iPrI-
CATH2 slowly decomposed in solution at room tem-
perature, CarCAT did not react with hydrogen even
at À208C. Since the hexahydrocarbazole has the
lowest basicity in the series of investigated amines,
the hydrogen activation equilibrium shifts to the left
and the corresponding ansa-ammonium borate Car-
Scheme 8. Synthesis of CarCAT.
a hydrogen atmosphere (2 atm) fully suppresses race- CATH2 cannot be isolated.
mization with B(C6F5)3 as the catalyst (Table 4,
AHCTUNGTRENNUNG
entry 2). These results provide an important mecha-
nistic datapoint for extending our understanding of Asymmetric Hydrogenation by ansa-Ammonium
hydrogen/hydride exchange between amines/imines Borate Catalysts
and catalysts.
Therefore, only the enantiomeric amines without a- To gain insight into the reactivity of the ansa-ammo-
protons can be applied in the backbone of chiral nium borate Q*CATH2 and ansa-aminoborane
ansa-ammonium borates. Additionally, the steric hin- CarCAT, their catalytic activity in the asymmetric hy-
drance around the nitrogen centre must be sufficient drogenation of nitrogen-containing compounds at dif-
to preclude a Lewis acid-Lewis base adduct forma- ferent temperatures and solvents was investigated
tion. Due to this reason, the less bulky ansa-amino- (Table 5). The reduction of the model imine 1d with
borane ICATH2 without the isopropyl group at the 7- 4 mol% of ansa-ammonium borate Q*CATH2 in tolu-
position forms a stable intramolecular Lewis acid- ene, hexane, diethyl ether or methyl tert-butyl ether
Lewis base adduct, which is totally inactive in hydro- (MTBE) at 20–808C under 2 atm of H2 pressure
gen activation.
(56 mL, 2.5 equiv.) gave N-(4-methoxy)phenyl-1-phe-
Based on the above observations, the 4a,9a-substi- nylethylamine in a quantitative yield in one hour
tuted 2,3,4,4a,9,9a-hexahydro-1H-carbazole skeleton (Table 4, entries 1–5). Thus, the enantiopure ansa-am-
was chosen for the further evaluation. The starting monium borate Q*CATH2 exhibited the same unpre-
Table 5. Asymmetric catalytic hydrogenation.[a]
Entry
Substrate
Catalyst
Solvent
Time [h]
Temp. [8C]
Conv. [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
Q*CATH2
Q*CATH2
Q*CATH2
Q*CATH2
Q*CATH2
Q*CATH2
Q*CATH2
Q*CATH2
toluene
hexane
Et2O
Et2O
MTBE
Et2O
1
1
1
1
1
1
12
12
80
80
60
20
20
60
20
20
100
100
100
100
100
100
100
100
4
1
12
19
26[32]
21
31
35
Et2O
MTBE
9
10
11
Q*CATH2
Q*CATH2
Q*CATH2
Et2O
Et2O
MTBE
1
12
12
60
20
20
100
100
100
18
31
37
12
13
14
CarCAT
CarCAT
CarCAT
Toluene
Hexane
Et2O
20
20
20
80
80
60
70
30
35
8
17
17
[a]
Catalyst (0.01 mmol, 4%) and imine (0.25 mmol) were stirred in solvent (3.0 mL) under 2 atm of H2 pressure.
Determined by H NMR spectroscopy.
Determined by chiral HPLC.
[b]
[c]
1
2100
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Adv. Synth. Catal. 2011, 353, 2093 – 2110

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
0.166 g KI (1 mmol) in 18 mL of dry acetonitrile. The mix-
cedentedly high activity as its racemic version. How-
ever, the enantioselectivities were low. The best ee of
26% was obtained using MTBE as a solvent at 208C
(1 h). Repeating the reduction of N-benzylketimine
1b or 2-phenylquinoline 1g with 4 mol% of ansa-am-
monium borate Q*CATH2 gave the corresponding
amines in quantitative yields (12 h). The best ee
values (35–37%) were also achieved in MTBE at
room temperature (Table 5, entries 6–11).
ture was heated at 958C for 24 h. The Schlenk tube was
cooled and the content filtered. The solvent present in the
filtrate was removed under reduced pressure. The crude
product was purified by flash chromatography (silica gel was
washed with 100 mL of hexane to remove unreacted 2-bro-
mobenzyl bromide and then with 150 mL of CH2Cl2). The
resulting CH2Cl2 fraction was rotovaped to give 4-(2-bromo-
benzyl)-3,3,5,5-tetramethylmorpholine as white crystals;
yield:2.617 g (84%). 1H NMR (CDCl3, 300 MHz): d=7.83
The reduction of the model imine 1d with CarCAT
resulted in low enantioselectivities of 8–17% (Table 5,
entries 12–14), and low to moderate conversions (30–
70%) after 20 h. This observation supports the idea
that the hydrogen activation became the rate-deter-
mining step in the hydrogenation of imines when the
Lewis acidity or Lewis basicity of ansa-aminoborane
is not high enough.[13b] Accordingly, ansa-aminobor-
ane CarCAT showed the low activity, mainly because
of the too low basicity of the active nitrogen centre.
(dm, 1H, JH,H =7.7 Hz), 7.46 (dd, 1H, JH,H =7.5 Hz, JH,H
=
1.1 Hz), 7.27 (pseudo t, 1H, JH,H =7.7 Hz,), 7.04 (pseudo t,
1H, JH,H =7.7 Hz), 3.73 (s, 2H), 3.48 (s, 4H), 1.00 (br. s,
12H); 13C NMR (CDCl3, 75 MHz): d=142.69 (s), 131.95 (s),
129.80 (s), 127.43 (s), 126.72 (s), 122.26 (s), 79.13 (s), 53.88
(s), 48.08 (s), 23.96 (br. s); HR-MS (ESI+-TOF): m/z=
312.0946, calcvd. for C15H22NO79Br*H+: 312.0958, m/z=
314.0929, calcd. for C15H22NO81Br*H+: 314.0938.
1-(2-Bromobenzyl)-2,2,4,7-tetramethyl-1,2,3,4-tetra-
hydroquinoline [pKa =4.67 (0.6)]
A dry 25-mL Schlenk tube was charged with 1.893 g
Conclusions
(10 mmol)
2.499 g
1,2,3,4-tetrahydro-2,2,4,7-tetramethylquinoline,
(10 mmol) 2-bromobenzyl bromide, 1.6 g
(11.6 mmol) K2CO3 and 0.166 g KI (1 mmol) in 18 mL of
dry acetonitrile. The mixture was heated at 1108C for 12 h.
The Schlenk tube was cooled and the content filtered. The
solid residue was washed with 100 mL of CH2Cl2 and the
combined organic solution evaporated under reduced pres-
sure. The crude product was dissolved in mixture of hexane
150 mL and CH2Cl2 30 mL, passed through a short column
with silica gel. The solvent was removed under reduced
pressure, and the resulting oil was crystalized from hexane
5 mL to give 1-(2-bromobenzyl)-2,2,4,7-tetramethyl-1,2,3,4-
tetrahydroquinoline as white crystals; yield: 2.52 g (70%).
1H NMR (CDCl3, 300 MHz): d=7.58 (dd, 1H, JH,H =7.6 Hz,
In summary, new catalysts for the direct hydrogena-
tion of nitrogen-containing compounds were designed
based on the ansa-ammonium borate concept previ-
ously reported by our research group.[13] Decreasing
the basicity of the amine moiety causes a growth in
catalytic activity by two orders of magnitude. More-
over, relatively low basicity allowed the elaboration
of a simple and elegant catalyst recovery procedure.
An efficient fine-tuning of the steric surroundings of
the nitrogen catalyst atom allows hydrogentation of a
wide substrate range, including sterically hindered
and benign, N-aryl- and N-alkyl imines, quinolines,
and others. Therefore, the newly designed catalysts
are considered to be promising a toolkit for large-
scale applications. Furthermore, the approach to the
synthesis of enantiopure ansa-ammonium borates
using organocatalytic reduction was elaborated, and
the first example of the enantioselective hydrogena-
tion based on the ansa-ammonium borate concept
was demonstrated. These initial findings provide es-
sential information for the further rational design of
efficient ansa-ammonium borates for asymmetric hy-
drogenation. Further studies on ansa-ammonium
borate concept are ongoing.
J
H,H =1.2 Hz), 7.34 (d, 1H, JH.H =7.7 Hz), 7.23 (pseudo t,
3
1H, JH,H =7.7 Hz), 7.11 (m, 2H), 6.51 (d, 1H, JH,H =7.7 Hz),
6.02 (s, 1H), 4.64 (d, 1H, JH,H =18.4 Hz), 4.21 (d, 1H, JH,H
=
18.4 Hz), 3.06 (m, 1H), 2.14 (s, 3H), 1.81 (m, 2H), 1.39 (d,
3H, JH,H =6.6 Hz), 1.29 (s, 3H), 1.23 (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=144.99 (s), 138.85 (s), 136.56 (s),
132.34 (s), 128.80 (s), 128.01 (s), 127.40 (s), 126.12 (s), 124.29
(s), 122.02 (s), 116.96 (s), 112.84 (s), 54.50 (s), 50.54 (s),
46.94 (s), 29.56 (s), 26.95 (s), 24.10 (s), 21.54 (s), 20.50 (s);
HR-MS
(ESI+-TOF):
m/z=358.1120,
calcd.
for
C20H24N79Br*H+: 358.1165, m/z=360.1095, calcd. for
C20H24N81Br*H+: 360.1146.
8-Isopropyl-2,2,4-trimethyl-1,2,3,4-tetrahydro-
quinoline
Reactions were performed in 20-mL glass vials sealed with
caps. Three Biotage vials were charged with 2.7 g
(20.0 mmol) 2-isopropylaniline, 0.51 g (2 mmol) I2 in 15 mL
of acetone. The mixtures were heated in a microwave at
1508C (40 W) for 1 h. Vials were cooled and the contents
were combined and evaporated under reduced pressure. The
residue was purified by flash chromatography on silica gel
(hexane-CH2Cl2, 1:1). After evaporation of solvent the ob-
tained product was hydrogenated under 1.5 atm of H2 and
Experimental Section
4-(2-Bromobenzyl)-3,3,5,5-tetramethylmorpholine
[pKa =6.61ACHTUNGTRENNUNG
(0.7)][14]
A dry 25-mL Schlenk tube was charged with 1.432 g
(10 mmol) 3,3,5,5-tetramethylmorpholine, 2.499 g (10 mmol)
2-bromobenzyl bromide, 1.6 g (11.6 mmol) K2CO3 and
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2101

Victor Sumerin et al.
FULL PAPERS
room temperature with 0.5 g 5% Pd/C in 80 mL MeOH for
16 h. The content was filtered through silica gel and evapo-
rated under reduced pressure to give 8-isopropyl-2,2,4-tri-
methyl-1,2,3,4-tetrahydroquinoline as an yellow oil; yield:
(s), 128.25 (s), 125.95 (s), 124.43 (s), 118.16 (s), 53.45 (s),
28.92 (s), 24.82 (s), 23.54 (s); HR-MS (ESI+-TOF): m/z=
264.1753, calcd. for C19H21N*H+: 264.1747, m/z=286.1567,
calcd. for C19H21N*Na+: 286.1566.
1
8.47 g (65%). H NMR (CDCl3, 300 MHz): d=7.09 (d, 1H,
J
H,H =7.7 Hz), 7.01 (d, 1H, JH,H =7.4 Hz), 6.69 (t, 1H, JH,H =
7-Isopropyl-3,3-dimethyl-2-phenylindoline
7.6 Hz), 3.62 (br.s, 1H), 2.96 (m, 1H), 2.82 (m, 1H), 1.77
(dd, 1H, JH,H =12.8 Hz, JH,H =5.6 Hz), 1.47 (m, 1H), 1.37 (d,
3H, JH,H =6.9 Hz), 1.30 (s, 3H), 1.27 (d, 3H, JH,H =7.4 Hz),
1.25 (d, 3H, JH,H =7.7 Hz), 1.21 (s, 3H); 13C NMR (CDCl3,
75 MHz): d=140.46 (s), 130.78 (s), 125.25 (s), 124.36 (s),
122.61 (s), 116.24 (s), 49.23 (s), 44.22 (s), 31.95 (s), 28.24 (s),
28.01 (s), 27.09 (s), 22.62 (s), 21.98 (s), 20.63 (s).
7-Isopropyl-3,3-dimethyl-2-phenyl-3H-indole
(3.0 g,
11.4 mmol) was dissolved in 24 mL of an MeOH/AcOH
mixture (5:1), cooled to À208C and then NaBH4 (0.95 g,
25.1 mmol) was added in portions during 1 hour.The result-
ing suspension was warmed to room temperature and stirred
vigorously for 3 h then additional NaBH4 (0.95 g,
25.1 mmol) was added at À208C. The reaction mixture was
stirred overnight at room temperature. The contents were
evaporated under reduced pressure. The obtained solid was
basified to pH 12 with NaOH and extracted with CH2Cl2
(3ꢄ50 mL). The resulting organic layer was dried over
K2CO3, passed through a short column with silica gel and
evaporated to give 7-isopropyl-3,3-dimethyl-2-phenylindo-
line as a colourless oil; yield: 2.91 g (96%). 1H NMR
(CDCl3, 300 MHz): d=7.50 (m, 2H), 7.36 (m, 3H), 7.04 (d,
1H, JH,H =7.7 Hz), 6.95 (dd, 1H, JH,H =7.3 Hz, JH,H =1.2 Hz),
6.82 (t, 6H, JH,H =6.8 Hz), 4.63 (s, 1H), 4.05 (br.s, 1H), 2.90
1-(2-Bromobenzyl)-8-isopropyl-2,2,4-trimethyl-1,2,3,4-
tetrahydroquinoline [pKa =4.96 (0.6)]
A
dry 25-mL Schlenk tube was charged with 2.17 g
(10 mmol) 8-isopropyl-2,2,4-trimethyl-1,2,3,4-tetrahydroqui-
noline, 2.50 g (10 mmol) 2-bromobenzyl bromide, 1.6 g
(11.6 mmol) K2CO3 and 0.166 g KI (1 mmol) in 18 mL of
dry acetonitrile. The mixture was heated at 958C for 12 h,
then 0.5 g (2 mmol) 2-bromobenzyl bromide and 0.5 g
(3.6 mmol) K2CO3 were added and the resulting suspension
was refluxed at 958C for an extra 12 h. The Schlenk tube
was cooled and the content filtered. The solid residue was
washed with 100 mL of CH2Cl2 and the combined organic
solution evaporated under reduced pressure. The crude
product was purified by column chromatography on silica
gel in hexane to give 1-(2-bromobenzyl)-8-isopropyl-2,2,4-
trimethyl-1,2,3,4-tetrahydroquinoline as yellow crystals;
(septet, 1H, JH,H =6.9 Hz), 1.46 (s, 3H), 1.33 (d, 3H, JH,H
=
6.9 Hz), 1. 31 (d, 3H, JH,H =6.9 Hz), 0.77 (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=146.63 (s), 140.28 (s), 137.61 (s),
129.12 (s), 128.04 (s), 127.45 (s), 127.43 (s), 123.55 (s), 119.90
(s), 119.14 (s), 74.36 (s), 45.46 (s), 29.98 (s), 26.76 (s), 24.56
(s), 22.18 (s), 22.10 (s); HR-MS (ESI+-TOF): m/z=
264.1778, calcd. for [C19H23N]ÀHÀ: 264.1747, m/z=266.1937,
calcd. for C19H23N*H+: 266.1903.
1
yield: 2.2 g (57%). H NMR (CDCl3, 300 MHz): d=8.02 (d,
1H, JH,H =8.0 Hz), 7.48 (d, 1H, JH,H =8.0 Hz), 7.33 (t, 1H,
J
H,H =7.6 Hz), 7.11 (m, 3H), 7.02 (t, 1H, JH,H =7.4 Hz), 4.32
1-(2-Bromobenzyl)-7-isopropyl-3,3-dimethyl-2-phenyl-
indoline [pKa =4.16 (0.6)]
(d, 1H, JH,H =18.4 Hz), 3.78 (d, 1H, JH,H =18.4 Hz), 3.31
(septet, 1H, JH,H =6.9 Hz), 2.98 (m, 1H), 1.80 (m, 1H), 1.63
(dd, 1H, JH,H =13.7 Hz, JH,H =8.0 Hz), 1.40 (d, 3H, JH,H
6.9 Hz), 1.12 (s, 3H), 1.09 (d, 3H, JH,H =6.6 Hz), 0.99 (s,
3H), 0.96 (d, 3H,
H,H =6.9 Hz); 13C NMR (CDCl3,
75 MHz): d=147.88 (s), 144.64 (s), 141.43 (s), 135.33 (s),
132.23 (s), 129.97 (s), 127.65 (s), 126.51 (s), 124.96 (s), 123.90
(s), 123.13 (s), 122.00 (s), 59.34 (s), 54.46 (s), 38.11 (s), 29.60
(s), 29.25 (s), 27.28 (s), 26.73 (s), 24.95 (s), 22.71 (s), 22.07
(s); HR-MS (ESI+-TOF): m/z=384.1326, calcd. for
[C22H28N79Br]ÀHÀ: 384.1321, m/z=388.1455, calcd. for
C22H28N81Br*H+; 388.1460.
A
dry 25-mL Schlenk tube was charged with 2.91 g
=
(11 mmol) 7-isopropyl-3,3-dimethyl-2-phenylindoline, 2.74 g
(11 mmol) 2-bromobenzyl bromide, 1.8 g (13.0 mmol)
K2CO3 and 0.2 g KI (1.2 mmol) in 18 mL of dry acetonitrile.
The mixture was heated at 958C for 65 h. The Schlenk tube
was cooled and the content filtered. The solid residue was
washed with 100 mL of CH2Cl2 and the combined organic
solution evaporated under reduced pressure. The crude
product was dissolved in mixture of hexane (150 mL) and
CH2Cl2 (30 mL), then passed through a short column with
silica gel. The solvent was removed under reduced pressure,
and the resulting oil was crystallized from hexane (20 mL)
to give 1-(2-bromobenzyl)-7-isopropyl-3,3-dimethyl-2-phe-
J
7-Isopropyl-3,3-dimethyl-2-phenyl-3H-indole
1
A solution of 2-isopropylphenylhydrazine (7.511 g, 50 mmol)
and isopropyl phenyl ketone (7.41 g, 50 mmol) in acetic acid
(50 mL) was heated under reflux (1408C oil bath) for 25 h.
After cooling down to room temperature, the solution was
evaporated. The crude product was dissolved in 100 mL of
CH2Cl2, washed with 1M K2CO3 (3*50 mL). The organic
phase was dried (K2CO3) and concentrated under reduced
pressure. The residue was crystallized from petroleum ether
to give 7-isopropyl-3,3-dimethyl-2-phenyl-3H-indole as
white crystals; yield: 8.5 g (65%). 1H NMR (CDCl3,
300 MHz): d=8.18 (m, 2H), 7.49 (m, 3H), 7.23 (m, 3H),
3.90 (septet, 1H, JH,H =6.9 Hz), 1.59 (s, 6H), 1.43 (d, 6H,
nylindoline as white crystals; yield: 4.14 g (87%). H NMR
(CDCl3, 300 MHz): d=7.58 (pseudo t, 2H, JH,H =7.7 Hz),
7.25 (br.s, 5H), 7.17 (pseudo t, 1H, JH,H =7.4 Hz), 7.10 (dd,
1H, JH,H =7.7 Hz, JH,H =1.4 Hz), 7.06 (pseudo t, 1H, JH,H
=
7.4 Hz), 6.92 (dd, 1H, JH,H =7.1 Hz, JH,H =1.4 Hz), 6.85 (t,
1H, JH,H =7.4 Hz), 4.64 (d, 1H, JH,H =18.1 Hz), 4.41 (d, 1H,
J
H,H =18.1 Hz), 4.34 (s, 1H), 2.97 (septet, 1H, JH,H =6.6 Hz),
1.44 (s, 3H), 1.16 (d, 1H, JH,H =6.9 Hz), 1.14 (d, 1H, JH,H
=
6.9 Hz), 0.80 (s, 3H); 13C NMR (CDCl3, 75 MHz): d=147.20
(s), 139.68 (s), 139.62 (s), 138.85 (s), 132.59 (s), 130.83 (s),
128.63 (s), 128.01 (s), 128.00 (s), 127.99 (s), 127.31 (s), 127.18
(s), 125.55 (s), 122.42 (s), 119.96 (s), 119.74 (s), 81.35 (s),
55.39 (s), 44.55 (s), 30.22 (s), 27.28 (s), 25.50 (s), 24.73 (s),
23.51 (s); HR-MS (ESI+-TOF): m/z=432.1376, calcd. for
J
H,H =6.9 Hz); 13C NMR (CDCl3, 75 MHz): d=181.41 (s),
150.65 (s), 147.58 (s), 141.49 (s), 133.85 (s), 130.06 (s), 128.47
2102
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2093 – 2110

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
[C26H28N79Br]ÀHÀ: 432.1321, m/z=436.1493, calcd. for
MS
(ESI+-TOF):
m/z=432.1376,
432.1321, m/z=436.1493,
calcd.
for
calcd.
C26H28N81Br*H+: 436.1461.
[C26H28N79Br]ÀHÀ:
forC26H28N81Br*H+: 436.1461.
Chiral 7-Isopropyl-3,3-dimethyl-2-phenylindoline
Chiral 2,2,4,7-Tetramethyl-1,2,3,4-tetrahydroquinoline
7-Isopropyl-3,3-dimethyl-2-phenyl-3H-indole
(3.5 g,
13.3 mmol), Hantzsch dihydropyridine (4.2 g, 16.6 mmol,
1.25 equiv.) and 1 mol% of (R)-3,3’-bis(2,4,6-triisopropyl-
phenyl)-1,1’-binaphthyl-2,2’-diyl hydrogen phosphate (R-
TRIP, 0.1 g, 0.133 mmol) were suspended in CHCl3 (25 mL).
The resulting mixture was stirred vigorously at room tem-
perature for 20 h.The solvent was evaporated under reduced
pressure and the crude product was purified by flash chro-
matography on silica gel (hexane-EtOAc, 20:1) to give 7-iso-
propyl-3,3-dimethyl-2-phenylindoline as a colourless oil with
Reactions were performed in 20-mL glass vials sealed with
caps. Three Biotage vials were charged with 3.6 g
(33.6 mmol) 3-methylaniline, 0.75 g (3 mmol) I2 in 15 mL of
acetone. The mixtures were heated in a microwave at 1508C
(40 W) for 4 h. Vials were cooled and the contents were
combined and evaporated under reduced pressure. The resi-
due was distilled under vacuum to afford 2,2,4,7-tetrameth-
yl-1,2-dihydroquinoline; yield: 4.21 g (67%): bp 1008C/1 mm
Hg).
1
99% ee; yield: 3.53 g (100%). H NMR (CDCl3, 300 MHz):
2,2,4,7-Tetramethyl-1,2-dihydroquinoline
(2.154 g,
d=7.50 (m, 2H), 7.36 (m, 3H), 7.04 (d, 1H, JH,H =7.7 Hz),
11.5 mmol), Hantzsch dihydropyridine (8.73 g, 34.5 mmol,
3.0 equiv.) and 1 mol% of (S)-3,3’-bis(2,4,6-triisopropylphen-
yl)-1,1’-binaphthyl-2,2’-diyl hydrogenphosphate (S-TRIP,
0.086 g, 0.115 mmol) were suspended in CHCl3 (50 mL). The
resulting mixture was stirred vigorously at 608C for 20 h.
The solvent was evaporated under reduced pressure and the
crude product was purified by flash chromatography on
silica gel (hexane-CH2Cl2, 2:1) to give chiral-2,2,4,7-tetra-
methyl-1,2,3,4-tetrahydroquinoline with 86.5% ee as a col-
ourless oil; yield: 3.53 g (80%).
The content was filtered through silica gel and evaporated
under reduced pressure to give 8-isopropyl-2,2,4-trimethyl-
1,2,3,4-tetrahydroquinoline (yield 65%) as an yellow oil;
yield: 8.47 g (65%). 1H NMR (CDCl3, 300 MHz): d=7.09
(d, 1H, JH,H =7.7 Hz), 7.01 (d, 1H, JH,H =7.4 Hz), 6.69 (t,
1H, JH,H =7.6 Hz), 3.62 (br.s, 1H), 2.96 (m, 1H), 2.82 (m,
1H), 1.77 (dd, 1H, JH,H =12.8 Hz, JH,H =5.6 Hz), 1.47 (m,
1H), 1.37 (d, 3H, JH,H =6.9 Hz), 1.30 (s, 3H), 1.27 (d, 3H,
6.95 (dd, 1H, JH,H =7.3 Hz, JH,H =1.2 Hz), 6.82 (t, 6H, JH,H
6.8 Hz), 4.63 (s, 1H), 4.05 (br.s, 1H), 2.90 (septet, 1H, JH,H
=
=
6.9 Hz), 1.46 (s, 3H), 1.33 (d, 3H, JH,H =6.9 Hz), 1. 31 (d,
3H, JH,H =6.9 Hz), 0.77 (s, 3H); 13C NMR (CDCl3, 75 MHz):
d=146.63 (s), 140.28 (s), 137.61 (s), 129.12 (s), 128.04 (s),
127.45 (s), 127.43 (s), 123.55 (s), 119.90 (s), 119.14 (s), 74.36
(s), 45.46 (s), 29.98 (s), 26.76 (s), 24.56 (s), 22.18 (s), 22.10
(s). HPLC (1% 2-propanol in n-hexane, flow rate=
0.7 mLminÀ1): major enantiomer: tR =7.3 min, minor enan-
tiomer: tR =9.4 min (the absolute configuration was not de-
termined); HR-MS (ESI+-TOF): m/z=264.1778, calcd. for
[C19H23N]ÀHÀ: 264.1747, m/z=266.1937, calcd. for
C19H23N*H+: 266.1903.
Chiral 1-(2-Bromobenzyl)-7-isopropyl-3,3-dimethyl-2-
phenylindoline [pKa =4.16 (0.6)]
A
dry 25-mL Schlenk tube was charged with 2.91 g
J
H,H =7.4 Hz), 1.25 (d, 3H, JH,H =7.7 Hz), 1.21 (s, 3H);
13C NMR (CDCl3, 75 MHz): d=140.46 (s), 130.78 (s), 125.25
(s), 124.36 (s), 122.61 (s), 116.24 (s), 49.23 (s), 44.22 (s),
31.95 (s), 28.24 (s), 28.01 (s), 27.09 (s), 22.62 (s), 21.98 (s),
20.63 (s); HPLC (1% 2-propanol in n-hexane, flow rate=
0.4 mLminÀ1): major enantiomer: tR =12.473 min; minor
enantiomer: tR =11.820 min; the absolute configuration of
was not determined.
(11 mmol) (2R)-7-isopropyl-3,3-dimethyl-2-phenylindoline,
2.74 g (11 mmol) 2-bromobenzyl bromide, 1.8 g (13.0 mmol)
K2CO3 and 0.2 g KI (1.2 mmol) in 18 mL of dry acetonitrile.
The mixture was heated at 958C for 65 h. The Schlenk tube
was cooled and the content filtered. The solid residue was
washed with 100 mL of CH2Cl2 and the combined organic
solution evaporated under reduced pressure. The crude
product was dissolved in mixture of hexane (150 mL) and
CH2Cl2 (30 mL), then passed through a short column with
silica gel. The solvent was removed under reduced pressure,
and the resulting oil was crystallized from hexane (20 mL)
to give chiral-1-(2-bromobenzyl)-7-isopropyl-3,3-dimethyl-2-
phenylindoline with >99% ee as white crystals; yield: 4.14 g
Chiral 1-(2-Bromobenzyl)-2,2,4,7-tetramethyl-1,2,3,4-
tetrahydroquinoline
A dry 25-mL Schlenk tube was charged with 1.893 g
(10 mmol)
2.499 g
1,2,3,4-tetrahydro-2,2,4,7-tetramethylquinoline,
(9.6 mmol) 2-bromobenzyl bromide, 1.6 g
1
(87%). H NMR (CDCl3, 300 MHz): d=7.58 (pseudo t, 2H,
J
H,H =7.7 Hz), 7.25 (br.s, 5H), 7.17 (pseudo t, 1H, JH,H
=
(11.6 mmol) K2CO3 and 0.166 g KI (1 mmol) in 18 mL of
dry acetonitrile. The mixture was heated at 1108C for 12 h.
The Schlenk tube was cooled and the content filtered. The
solid residue was washed with 100 mL of CH2Cl2 and the
combined organic solution evaporated under reduced pres-
sure. The crude product was purified by flash chromatogra-
phy on silica gel (hexane-CH2Cl2, 5:1) to give chiral 1-
(2-bromobenzyl)-2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquin-
oline as a colorless oil; yield: 3.05 g (85%). 1H NMR
7.4 Hz), 7.10 (dd, 1H, JH,H =7.7 Hz, JH,H =1.4 Hz), 7.06
(pseudo t, 1H, JH,H =7.4 Hz), 6.92 (dd, 1H, JH,H =7.1 Hz,
J
H,H =1.4 Hz), 6.85 (t, 1H, JH,H =7.4 Hz), 4.64 (d, 1H, JH,H
18.1 Hz), 4.41 (d, 1H, JH,H =18.1 Hz), 4.34 (s, 1H), 2.97
(septet, 1H, JH,H =6.6 Hz), 1.44 (s, 3H), 1.16 (d, 1H, JH,H
=
=
6.9 Hz), 1.14 (d, 1H, JH,H =6.9 Hz), 0.80 (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=147.20 (s), 139.68 (s), 139.62 (s),
138.85 (s), 132.59 (s), 130.83 (s), 128.63 (s), 128.01 (s), 128.00
(s), 127.99 (s), 127.31 (s), 127.18 (s), 125.55 (s), 122.42 (s),
119.96 (s), 119.74 (s),81.35 (s), 55.39 (s), 44.55 (s), 30.22 (s),
27.28 (s), 25.50 (s), 24.73 (s), 23.51 (s); HPLC (0.5% 2-prop-
anol in n-hexane, flow rate=0.7 mLminÀ1): major enantio-
mer: tR =9.036 min; minor enantiomer: tR =9.411 min; HR-
(CDCl3, 300 MHz): d=7.58 (dd, 1H, JH,H =7.6 Hz, JH,H
=
1.2 Hz), 7.34 (d, 1H, JH,H =7.7 Hz), 7.23 (pseudo t, 1H,
3JH,H =7.7 Hz), 7.11 (m, 2H), 6.51 (d, 1H, JH,H =7.7 Hz), 6.02
(s, 1H), 4.64 (d, 1H, JH,H =18.4 Hz), 4.21 (d, 1H, JH,H
=
18.4 Hz), 3.06 (m, 1H), 2.14 (s, 3H), 1.81 (m, 2H), 1.39 (d,
Adv. Synth. Catal. 2011, 353, 2093 – 2110
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2103

Victor Sumerin et al.
FULL PAPERS
3H, JH,H =6.6 Hz), 1.29 (s, 3H), 1.23 (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=144.99 (s), 138.85 (s), 136.56 (s),
132.34 (s), 128.80 (s), 128.01 (s), 127.40 (s), 126.12 (s), 124.29
(s), 122.02 (s), 116.96 (s), 112.84 (s), 54.50 (s), 50.54 (s),
46.94 (s), 29.56 (s), 26.95 (s), 24.10 (s), 21.54 (s), 20.50 (s);
CH2Cl2 and the combined organic solution evaporated
under reduced pressure. The crude product was purified by
column chromatography on silica gel in hexane-CH2Cl2 5:1
to give (2R,4aR,9aS)-9-(2-bromobenzyl)-2-isopropyl-4a-
methyl-9a-phenyl-2,3,4,4a,9,9a-hexahydro-1H-carbazole as
yellow crystals; yield: 3.42 g (72%). 1H NMR (CDCl3,
HR-MS
(ESI+-TOF):
m/z=358.1120,
calcd.
for
C20H24N79Br*H+: 358.1165, m/z=360.1095, calcd. for
300 MHz): d=7.55 (d, 1H, JH,H =8.0 Hz), 7.48 (d, 1H, JH,H
=
C20H24N81Br*H+: 360.1146.
7.7 Hz), 7.27–7.14 (m, 4H), 7.11–7.05 (m, 4H), 6.91 (d, 1H,
J
H,H =7.1 Hz), 6.71 (t, 1H, JH,H =7.3 Hz), 6.26 (d, 1H, JH,H
=
=
7.7 Hz), 4.25 (d, 1H, JH,H =18.1 Hz), 4.14 (d, 1H, JH,H
ACHTUNGTRENNUNG
18.1 Hz), 2.39 (m, 1H), 2.06 (m, 1H), 1.69–1.29 (m, 6H),
1.05 (s, 3H), 0.87 (d, 3H, JH,H =3.0 Hz), 0.84 (d, 3H, JH,H
=
3.0 Hz); 13C NMR (CDCl3, 75 MHz): d=150.38 (s), 142.82
(s), 139.56 (s), 138.03 (s), 132.47 (s), 128.92 (s), 128.11 (s),
127.95 (s), 127.87 (s), 127.38 (s), 127.28 (s), 126.73 (s), 122.49
(s), 120.70 (s), 117.71 (s), 105.51 (s), 77.85 (s), 49.16 (s),
48.39 (s), 45.45 (s), 39.24 (s), 32.41 (s), 29.53 (s), 25.56 (s),
19.67 (s), 19.41 (s); HR-MS (ESI+-TOF): m/z=472.1726,
calcd. for [C29H32N79Br]ÀHÀ: 472.1634, m/z=476.1826,
calcd. for C29H32N81Br*H+: 476.1775.
ACHTUNGTRENNUNG(2R,4aR)-2-Isopropyl-4a-methyl-2,3,4,4a-tetrahydro-1H-car-
bazole was prepared according to the reported proce-
dure.[30,31]
(2R,4aR,9aS)-2-Isopropyl-4a-methyl-9a-phenyl-
2,3,4,4a,9,9a-hexahydro-1H-carbazole
To a solution of (2R,4aR)-2-isopropyl-4a-methyl-2,3,4,4a-tet-
rahydro-1H-carbazole (2.273 g, 10 mmol) in toluene (75 mL)
PhLi (10.0 mL, 18.0 mmol, 1.8M solution in cycloxexane-
ether, 70/30) was added dropwise at À108C. The solution
was allowed to warm up to room temperature and stirred
for 5 hours. The solution was recooled to À108C and then
an additional 5.0 mL of PhLi (9.0 mmol, 1.8M solution in
cyclohexane-ether, 70/30) was added dropwise. After stirring
at room temperature for 12 h the reaction mixture was hy-
drolyzed with water (100 mL) and the organic layer was sep-
arated. The water phase was extracted with CH2Cl2 (3ꢄ
30 mL). The combined organic phase was dried with K2CO3,
evaporated to give a residue which was purified by flash
chromatography using hexane:EtOAc 10:1 as eluent. The
HydridoACHTNUTRGNE[UNG bis(pentafluorophenyl)]{2-[(3,3,5,5-tetra-
methylmorpholin-4-ium-4-yl)methyl]phenyl}-
borate(1À) (MCATH2)
To a solution of 4-(2-bromobenzyl)-3,3,5,5-tetramethylmor-
pholine (0.937 g, 3 mmol) in toluene (15 mL) t-BuLi
(3.8 mL, 6.1 mmol, 1.6M solution in pentane) was added
dropwise at À708C. The solution was allowed to warm up to
room temperature in about 30 min and stirred for additional
1 hour. Without further purification the resultant lithium
salt suspension was recooled to À808C and a precooled so-
lution (À708C) of (C6F5)2BCl (1.141 g, 3 mmol) in toluene
(5 mL) was added in one portion. Immediately, an intense
bright yellow colouration indicated formation of the prod-
uct. The reaction mixture was stirred overnight at room
temperature and the contents were filtered. The solvent
present in the filtrate was removed to give the crude prod-
uct 1-{2-[bis(pentafluorophenyl)boryl]benzyl}-2,2,6,6-tetra-
methylpiperidine as an yellow oil; yield: 1.7 g.
Without further purification the product was dissolved in
toluene (10 mL) and the resultant solution was degassed
once with a freeze-pump-thaw cycle and refilled with H2
(1.5 atm). The reaction mixture was stirred at 1000 rpm at
room temperature for 1 hour, a short period (5 min) of in-
tense precipitation was observed. The reaction mixture was
filtered, washed with toluene (3ꢄ3 mL) to give the final
corresponding
(2R,4aR,9aS)-2-isopropyl-4a-methyl-9a-
phenyl-2,3,4,4a,9,9a-hexahydro-1H-carbazole was obtained
as a white solid; yield: 3.05 g (100%). 1H NMR (CDCl3,
300 MHz): d=7.30 (m, 2H), 7.18 (m, 3H), 7.09 (td, 1H,
J
J
J
J
J
J
H,H =7.6 Hz, JH,H =1.4 Hz), 6.84 (dd, 1H, JH,H =7.1 Hz,
H,H =0.8 Hz), 6.76 (d, 1H, JH,H =7.7 Hz), 6.70 (td, 1H,
H,H =7.4 Hz, JH,H =0.8 Hz), 4.07 (br.s, 1H), 2.36 (ddd, 1H,
H,H =4.7 Hz, JH,H =12.6 Hz, JH,H =17.3 Hz), 1.92 (dt, 1H,
H,H =3.3 Hz, JH,H =14.6 Hz), 1.69 (m, 1H), 1.60 (dt, 2H,
H,H =2.2 Hz, JH,H =12.6 Hz), 1.36 (m, 3H), 1.08 (s, 3H), 0.89
(d, 6H, JH,H =6.9 Hz); 13C NMR (CDCl3, 75 MHz): d=
149.00 (s), 146.22 (s), 139.43 (s), 127.66 (s), 127.32 (s), 127.17
(s), 126.41 (s), 121.40 (s), 118.45 (s), 108.19 (s), 72.26 (s),
47.81 (s), 45.05 (s), 39.01 (s), 33.87 (s), 32.44 (s), 25.49 (s),
19.93 (s), 19.83 (s), 19.67 (s).
product {hydridoACHTUNTRGNEUNG[bis(pentafluorophenyl)]{2-[(3,3,5,5-tetra-
methylmorpholin-4-ium-4-yl)methyl]phenyl}borate(1À)} as a
white solid; yield: 0.960 g (55%). 1H NMR (CDCl3,
300 MHz): d=8.53 (br. s, 1H), 7.18 (m, 4H), 4.43 (s, 1H),
4.41 (s, 1H), 3.73 (d, 2H, JH,H =12.9 Hz), 3.72 (br q, 1H,
1JB,H =74 Hz, BH), 3.62 (d, 2H, JH,H =12.9 Hz), 1.62 (s, 6H),
0.97 (s, 6H). 11B NMR (CDCl3, 128 MHz): d=À20.74 (d,
1JB,H =75 Hz); 13C NMR (CDCl3, 75 MHz): d=147.88 (dm,
(2R,4aR,9aS)-9-(2-Bromobenzyl)-2-isopropyl-4a-
methyl-9a-phenyl-2,3,4,4a,9,9a-hexahydro-1H-carb-
azole
A
dry 25-mL Schlenk tube was charged with 3.05 g
(10 mmol) (2R,4aR,9aS)-2-isopropyl-4a-methyl-9a-phenyl-
2,3,4,4a,9,9a-hexahydro-1H-carbazole, 2.50 g (10 mmol) 2-
bromobenzylbromide, 1.6 g (11.6 mmol) K2CO3 and 0.166 g
KI (1 mmol) in 18 mL of dry acetonitrile. The mixture was
heated at 1108C for 5 d, then 2.50 g (10 mmol) 2-bromoben-
zyl bromide together with 1.6 g (11.6 mmol) K2CO3 were
added and the resulting suspension was refluxed at 1108C
for an extra 5 d. The Schlenk tube was cooled and the con-
tent filtered. The solid residue was washed with 100 mL of
J
C,F =236 Hz), 138.30 (dm, JC,F =245 Hz), 136.82 (dm, JC,F =
253 Hz), 136.72 (s), 132.22 (s), 129.96 (s), 129.18 (s), 125.55
(s), 77.63 (s), 64.30 (s), 54.81 (s), 24.18 (s), 20.73 (s), quater-
nary carbons of C6F5 ring and (C6F5)2BC6H4 were not ob-
served; 19F NMR (CDCl3, 282 MHz): d=À132.83 (d, 4F,
J
F,F =22 Hz, ortho-F), À161.62 (t, 2F, JF,F =20 Hz, para-F),
À165.37 (m, 4F, meta-F); HR-MS (ESI+-TOF): m/z=
2104
asc.wiley-vch.de
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2093 – 2110

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
602.1629, calcd. for C27H24BNOF10*Na+: 602.1688, m/z=
stirred for additional 30 min. The resultant lithium salt sus-
1181.3405, calcd. for (C27H24BNOF10)2*Na+: 1181.3475.
pension was recooled to À808C and a precooled solution
(À708C) of (C6F5)2BCl (1.141 g, 3 mmol) in toluene (5 mL)
was added in one portion. The reaction mixture was stirred
overnight at room temperature and the contents were fil-
tered. The solvent present in the filtrate was removed to
give the crude product 1-{2-[ bis(pentafluorophenyl)boryl]-
benzyl}-2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquinoline as a
red oil; yield:1.8 g.
HydridoACHTUNGTRENNUNG[bis(pentafluorophenyl)]{2-[(2,2,4,7-tetra-
methyl-3,4-dihydroquinolinium-1(2H)-yl)methyl]-
phenyl}borate(1À) (QCATH2)
To
a solution of 1-(2-bromobenzyl)-2,2,4,7-tetramethyl-
1,2,3,4-tetrahydroquinoline (1.075 g, 3 mmol) in toluene
(15 mL) t-BuLi (3.8 mL, 6.1 mmol, 1.6M solution in pen-
tane) was added dropwise at À808C. The solution was al-
lowed to warm up to room temperature in about 30 min and
stirred for additional 30 min. The resulted lithium salt sus-
pension was recooled to À808C and a precooled solution
(À708C) of (C6F5)2BCl (1.141 g, 3 mmol) in toluene (5 mL)
was added in one portion. The reaction mixture was stirred
overnight at room temperature and the contents were fil-
tered. The solvent present in the filtrate was removed to
give the crude product 1-{2-[ bis(pentafluorophenyl)boryl]-
benzyl}-2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquinoline as a
red oil; yield: 1.8 g.
Without further purification the product was dissolved in
a mixture of hexane (10 mL) and toluene (10 mL). The re-
sulted solution was degassed once with a freeze-pump-thaw
cycle and refilled with H2 (1.5 atm). The reaction mixture
was stirred at 1000 rpm at room temperature for 1 hour, a
short period (5 min) of intense precipitation was observed.
The reaction mixture was filtered, washed with toluene (3ꢄ
Without further purification the product was dissolved in
mixture of hexane (10 mL) and toluene (10 mL). The resul-
tant solution was degassed once with a freeze-pump-thaw
cycle and refilled with H2 (1.5 atm). The reaction mixture
was stirred at 1000 rpm at room temperature for 24 h. The
reaction mixture was filtered, washed with hexane (3ꢄ
3 mL) to give the final product chiral {hydrido-
AHCTUNGERTG[NNUN bis(pentafluorophenyl)]{2-[(2,2,4,7-tetramethyl-3,4-dihydro-
quinolinium-1(2H)-yl)methyl]phenyl}borate(1À)} as a white
solid; (yield: 0.815 of 43%). 1H NMR (CDCl3, 300 MHz)
major isomer: d=8.93 (br. s, 1H), 7.09–7.32 (m, 4H), 6.81
(pseudo t, 1H, JH,H =7.4 Hz), 6.17 (d, 1H, JH,H =7.4 Hz),
5.81 (s, 1H), 5.18 (d, 1H, JH.H =11.0 Hz), 3.74 (br q, 1H,
1JB,H =74 Hz, BH), 3.64 (dd, 1H, JH,H =10.7 Hz, J=9.1 Hz),
3.11 (m, 1H), 2.10 (m, 2H), 1.89 (s, 3H), 1.70 (s, 3H), 1.50
(d, 3H, JH,H =6.9 Hz), 1.42 (s, 3H); 1H NMR (CDCl3,
300 MHz) minor trans-isomer: d=9.05 (br. s, 1H), 7.09–7.32
(m, 4H), 6.75 (pseudo t, 1H, JH,H =7.4 Hz), 6.11 (d, 1H,
J
H,H =7.4 Hz), 5.98 (s, 1H), 5.09 (d, 1H, JH,H =11.5 Hz), 3.74
1
(br q, 1H, JB,H =74 Hz, BH), 3.69 (dd, 1H, JH,H =11.0 Hz,
J=9.1 Hz), 3.24 (m, 1H), 2.59 (m, 1H), 2.10 (m, 1H), 1.93
(s, 3H), 1.70 (s, 3H), 1.47 (d, 3H, JH,H =6.9 Hz), 1.42 (s,
3 mL)
to
give
the
final
product
(hydrido-
ACHTUNGTRENNUNG[bis(pentafluorophenyl)]{2-[(2,2,4,7-tetramethyl-3,4-dihydro-
quinolinium-1(2H)-yl)methyl]phenyl}borate(1-)) as a white
3H); 19F NMR (CDCl3, 282 MHz): d=À131.80 (d, 2F, JF,F
=
1
solid: yield: 0.775 (41%). H NMR (CDCl3, 300 MHz): d=
21.4 Hz, ortho-F), À134.01 (d, 2F, JF,F =21.4 Hz, ortho-F),
À161.95 (t, 2F, 3JF,F =21.4 Hz, para-F), À165.35 (m, 2F,
meta-F), À165.85 (m, 2F, meta-F); HR-MS (ESI+-TOF):
m/z=624.1944, calcd. for [C32H26BNF10]ÀHÀ: 624.1920; HR-
MS (ESIÀ-TOF): m/z=624.1967, calcd. for [C32H26BNF10]-
H+: 624.1926.
8.95 (br. s, 1H), 7.09–7.32 (m, 4H), 6.81 (pseudo t, 1H,
J
H,H =7.4 Hz), 6.17 (d, 1H, JH,H =7.4 Hz), 5.81 (s, 1H), 5.18
1
(d, 1H, JH,H =11.0 Hz), 3.74 (br q, 1H, JB,H =74 Hz, BH),
3.64 (dd, 1H, JH,H =10.7 Hz, J=9.1 Hz), 3.11 (m, 1H), 2.10
(m, 2H), 1.89 (s, 3H), 1.70 (s, 3H), 1.50 (d, 3H, JH,H
=
6.9 Hz), 1.42 (s, 3H); 11B NMR (CDCl3, 128 MHz): d)=
À21.16 (d, 1JB,H =69 Hz); 13C NMR (CDCl3, 75 MHz): d=
148.14 (dm, 1JC,F =247 Hz), 138.36 (dm, 1JC,F =254 Hz),
Hydrido{2-[(8-isopropyl-2,2,4-trimethyl-3,4-dihy-
droquinolinium-1(2H)-yl)methyl]phenyl}
1
137.16 (s), 136.81 (dm, JC,F =240 Hz), 136.24 (s), 132.52 (s),
131.43 (s), 130.88 (s), 130.46 (s), 129.87 (s), 129.21 (s), 128.70
(s), 126.21 (s), 124.75 (s), 63.96 (s), 62.56 (s), 37.51 (s), 27.37
(s), 25.39 (s), 25.32 (s), 22.21 (s), 20.29 (s), quaternary car-
bons of C6F5 ring and (C6F5)2BC6H4 were not observed;
Bis(pentafluorophenyl)borate(1À) (iPrQCATH2)
To
a solution of 1-(2-bromobenzyl)-8-isopropyl-2,2,4-tri-
methyl-1,2,3,4-tetrahydroquinoline (1.159 g, 3 mmol) in tolu-
ene (15 mL) t-BuLi (3.8 mL, 6.1 mmol, 1.6M solution in
pentane) was added dropwise at À808C. The solution was
allowed to warm up to room temperature in about 30 min
and stirred for additional 30 min. The resultant lithium salt
suspension was recooled to À808C and a precooled solution
(À708C) of (C6F5)2BCl (1.141 g, 3 mmol) in toluene (5 mL)
was added in one portion. The reaction mixture was stirred
overnight at room temperature and the contents were fil-
tered. The solvent present in the filtrate was removed to
give the crude product 1-{2-[bis(pentafluorophenyl)boryl]-
benzyl}-8-isopropyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquino-
line as a red oil; yield: 1.8 g.
19F NMR (CDCl3, 282 MHz): d=À131.80 (d, 2F, JF,F
=
21.4 Hz, ortho-F), À134.01 (d, 2F, JF,F =21.4 Hz, ortho-F),
À161.95 (t, 2F, 3JF,F =21.4 Hz, para-F), À165.35 (m, 2F,
meta-F), À165.85 (m, 2F, meta-F); HR-MS (ESI+-TOF):
m/z=624.1944, calcd. for [C32H26BNF10]ÀHÀ: 624.1920; HR-
MS
(ESIÀ-TOF):
m/z=624.1967,
calcd.
for
[C32H26BNF10]ÀH+: 624.1926.
Chiral HydridoACHTUNGTRENNUNG[bis(pentafluorophenyl)](2-{[(2,2,4,7-
tetramethyl-3,4-dihydroquinolinium-1(2H)-yl]-
methyl}phenyl)borate(1-) (Q*CATH2)
To a solution of chiral-1-(2-bromobenzyl)-2,2,4,7-tetrameth-
yl-1,2,3,4-tetrahydroquinoline (1.075 g, 3 mmol) in toluene
(15 mL) t-BuLi (3.8 mL, 6.1 mmol, 1.6M solution in pen-
tane) was added dropwise at À808C. The solution was al-
lowed to warm up to room temperature in about 30 min and
Without further purification the product was dissolved in
mixture of hexane (10 mL) and toluene (10 mL). The resul-
tant solution was degassed once with a freeze-pump-thaw
cycle and refilled with H2 (1.5 atm). The reaction mixture
was stirred at 1000 rpm at room temperature for 1 hour, a
Adv. Synth. Catal. 2011, 353, 2093 – 2110
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2105

Victor Sumerin et al.
FULL PAPERS
short period (5 min) of intense precipitation was observed.
The reaction mixture was filtered, washed with toluene/
hexane mixture (1:1, 3ꢄ3 mL) to give the final product
hydrido{2-[(8-isopropyl-2,2,4-trimethyl-3,4-dihydroquinolini-
The resultant solution was concentrated to 10 mL, degassed
once with a freeze-pump-thaw cycle and refilled with H2
(1.5 atm). The reaction mixture was stirred at 1000 rpm at
room temperature for 12 hour, a short period (5 min) of in-
tense precipitation was observed. The reaction mixture was
filtered, washed with hexane (3ꢄ10 mL) to give the final
product hydrido(2-{[7-isopropyl-3,3-dimethyl-2-phenyl-2,3-
dihydro-1H-indolium-1-yl]methyl}phenyl)bis(pentafluoro-
phenyl)borate(1À) as a white solid; yield: 1.250 g (60%).
1H NMR (C6D6, 300 MHz): d09.68 (br. s, 1H), 7.78 (d, 1H,
um-1(2H)-yl)methyl]phenyl}
bis(pentafluorophenyl)bo-
rate(1À) as a white solid; yield : 0.700 g (36%). According
1
to H NMR and X-ray diffraction studies the product exists
as a mixture of diastereomers at C-4 atom of quinoline ring
(2.1:1, cis/trans). 1H NMR (CDCl3, 300 MHz) major cis-
isomer: d=8.24 (br. s, 1H), 6.98–7.44 (m, 6H), 6.75 (pseudo
t, 1H, JH,H =7.4 Hz), 6.01 (d, 1H, JH,H =7.4 Hz), 5.18 (d, 1H,
J
H,H =7.1 Hz), 7.30 (pseudo t, 1H,
(pseudo t, 1H, JH,H =7.4 Hz), 7.01 (t, 1H, JH,H =7.6 Hz), 6.93
(m, 2H), 6.87 (d, 1H, JH,H =7.4 Hz), 6.72 (t, 2H, JH,H
8.0 Hz), 6.52 (dd, 1H, JH,H =7.4 Hz, JH,H =1.1 Hz), 6.13 (d,
2H, H,H =7.4 Hz), 5.11 (dd, 1H, H,H =12.5 Hz, JH,H =
JH,H =7.4 Hz), 7.17
1
J
H,H =11.0 Hz), 3.70 (br q, 1H, JB,H =76 Hz, BH), 3.65 (m,
1H), 3.24 (m, 1H), 2.56 (m, 1H), 2.13 (m, 1H), 1.69 (s, 3H),
1.60 (d, 3H, JH,H =7.1 Hz), 1.33 (s, 3H), 0.94 (d, 3H, JH,H
6.6 Hz), 0.19 (d, 3H,
H,H =6.3 Hz); 1H NMR (CDCl3,
=
=
J
J
J
1
300 MHz) minor trans-isomer: d=8.42 (br. s, 1H), 6.98–7.44
(m, 6H), 6.73 (pseudo t, 1H, JH,H =7.2 Hz), 6.05 (d, 1H,
3.7 Hz), 4.55 (s, 1H), 3.85 (br q, 1H, JB,H =74 Hz, BH), 3.49
(septet, 1H, JH,H =6.6 Hz), 3.38 (dd, 1H, JH,H =12.4 Hz, J=
9.3 Hz), 1.26 (d, 3H, JH,H =6.6 Hz), 1.13 (s, 3H), 1.07 (d,
3H, JH,H =6.9 Hz), 0.43 (s, 3H); 11B NMR (C6D6, 128 MHz):
J
H,H =8.0 Hz), 5.15 (d, 1H, JH,H =10.7 Hz), 3.70 (br q, 1H,
1JB,H =76 Hz, BH), 3.88 (m, 1H), 3.34 (m, 1H), 2.56 (m,
1H), 2.13 (m, 1H), 1.71 (s, 3H), 1.51(d, 3H, JH,H =6.6 Hz),
d=À20.63 (d, JB,H =65 Hz); 13C NMR (C6D6, 75 MHz): d=
1
1.30 (s, 3H), 1.00 (d, 3H, JH,H =6.6 Hz), 0.14 (d, 3H, JH,H
=
=
148.56 (dm, 1JC,F =238 Hz), 143.27 (s), 141.00 (s), 138.85
1
1
1
6.3 Hz); 11B NMR (CDCl3, 128 MHz): d=À20.75 (d, JB,H
(dm, JC,F =248 Hz), 138.04 (s), 137.27 (dm, JC,F =239 Hz),
137.20 (s), 134.51 (s), 132.38 (s), 131.67 (s), 131.04 (s), 130.16
(s), 129.94 (s), 129.52 (s), 127.29 (s), 125.32 (s), 122.22 (s),
78.05 (s), 68.05 (s), 45.00 (s), 32.20 (s), 28.99 (s), 25.15 (s),
22.66 (s), quaternary carbons of C6F5 ring and (C6F5)2BC6H4
were not observed; 19F NMR (C6D6, 282 MHz): d=À132.17
(d, 2F, JF,F =24.4 Hz, ortho-F), À132.26 (d, 2F, JF,F =24.4 Hz,
70 Hz); 13C NMR (CDCl3, 75 MHz) mixture of diastereo-
1
mers: d=148.03 (dm, JC,F =239 Hz), 143.84 (s), 138.42 (dm,
1
1JC,F =240 Hz), 136.88 (dm, JC,F =240 Hz), 135.29 (s), 135.15
(s), 133.96 (s), 133.37 (s), 131.67 (s), 131.37 (s), 131.19 (s),
130.99 (s), 130.35 (s), 130.29 (s), 129.93 (s), 129.60 (s), 129.50
(s), 129.26 (s), 127.90 (s), 125.27 (s), 125.01 (s), 124.52 (s),
124.48 (s), 124.43 (s), 65.99 (s), 65.72 (s), 63.56 (s), 59.43 (s),
40.15 (s), 36.64 (s), 29.88 (s), 28.46 (s), 27.88 (s), 27.63 (s),
26.08 (s), 25.86 (s), 25.78 (s), 25.38 (s), 23.05 (s), 21.31 (s),
21.28 (s), 20.43 (s), quaternary carbons of C6F5 ring and
(C6F5)2BC6H4 were not observed; 19F NMR (CDCl3,
3
ortho-F), À162.24 (t, 1F, JF,F =21.4 Hz, para-F), À162.28 (t,
1F, 3JF,F =21.4 Hz, para-F), À165.82 (m, 4F, meta-F); HR-
MS
(ESIÀ-TOF):
m/z=700.2251,
calcd.
for
[C38H30BNF10]ÀH+: 700.2239.
282 MHz): d=À131.59 (d, 2F,
JF,F =21.4 Hz, ortho-F),
4-{2-[Bis(pentafluorophenyl)boryl]benzyl}-3,3,5,5-
tetramethylmorpholine (MCAT)
À133.43 (d, 2F, JF,F =21.4 Hz, ortho-F), À161.87 (t, 1F,
3JF,F =21.4 Hz, para-F), À162.00 (t, 1F, JF,F =21.4 Hz, para-
3
F), À165.70 (m, 4F, meta-F); HR-MS (ESI+-TOF): m/z=
In a glove box, a 25-mL flame-dried Schlenk tube equipped
with a stir bar, a Teflon stopcock and a glass stopper (Glin-
demannꢅ-sealing rings were used for conical joints instead
of grease) was charged with ansa-ammonium-borate
MCATH2 (0.1 mmol, 57.9 mg) and 1.0 mL dry toluene. The
reaction mixture was degassed once with a freeze-pump-
thaw cycle, stirred at 1000 rpm and 110 8C for 30 min. All
volatiles were removed under vacuum to give 4-{2-[bis(pen-
tafluorophenyl)boryl]benzyl}-3,3,5,5-tetramethylmorpholine
as a yellow oil; yield: 57.7 mg (100%). 1H NMR (C6D6,
300 MHz): d=8.00 (d, 1H, JH,H =7.7 Hz), 7.33 (pseudo t,
1H, JH,H =7.7 Hz), 7.17 (d, 1H, JH,H =7.1 Hz), 7.04 (pseudo
t, 1H, JH,H =7.4 Hz), 3.76 (s, 2H), 3.28 (s, 4H), 0.72 (s,
1329.4427, calcd. for (C34H30BNF10)2*Na+: 1329.4515; HR-
MS
(ESIÀ-TOF):
m/z=652.2257,
calcd.
for
[C34H30BNF10]ÀH+: 652.2239.
rac-Hydrido(2-{[7-isopropyl-3,3-dimethyl-2-phenyl-
2,3-dihydro-1H-indolium-1-yl]methyl}phenyl)bis-
(pentafluorophenyl)borate(1À) (iPrICATH2)
To a solution of 1-(2-bromobenzyl)-7-isopropyl-3,3-dimeth-
yl-2-phenylindoline or (2R)-1-(2-bromobenzyl)-7-isopropyl-
3,3-dimethyl-2-phenylindoline (1.303 g, 3 mmol) in toluene
(15 mL) t-BuLi (4.1 mL, 6.1 mmol, 1.5M solution in pen-
tane) was added dropwise at À808C. The solution was al-
lowed to warm up to room temperature in about 30 min and
stirred for additional 30 min. The resultant lithium salt sus-
pension was recooled to À808C and a precooled solution
(À708C) of (C6F5)2BCl (1.141 g, 3 mmol) in toluene (5 mL)
was added in one portion. The reaction mixture was stirred
overnight at room temperature and the contents were fil-
tered. The solvent present in the filtrate was removed to
give the crude product 1-{2-[bis(pentafluorophenyl)boryl]-
benzyl}-7-isopropyl-3,3-dimethyl-2-phenylindoline as a red
oil; yield: 2.2 g.
12H); 11B NMR (C6D6, 128 MHz): d=67.36 (br. s);
1
13C NMR (C6D6, 75 MHz): d=150.94 (s), 147.19 (dm, JC,F
=
=
1
249 Hz), 140.71 (dm, 1JC,F =212 Hz), 137.82 (dm, JC,F
255 Hz), 134.75 (s), 134.00 (s), 127.68 (s), 126.32 (s), 78.88
(s), 53.87 (s), 48.29 (s), 23.69 (br. s), quaternary carbons of
C6F5 ring and (C6F5)2BC6H4 were not observed; 19F NMR
(C6D6, 282 MHz): d=À129.83 (d, 4F, JF,F =25 Hz, ortho-
C6F5), À147.00 (t, 2F, JF,F =21 Hz, para-C6F5), À161. 02 (m,
4F, meta-C6F5); HR-MS (ESI+-TOF): m/z=578.1668, calcd.
for C27H22BNOF10*H+: 578.1712.
The product was dissolved in hexane (40 mL). After 6 h
stirring at ambient temperature, the mixture was filtered.
2106
asc.wiley-vch.de
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2093 – 2110

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
27.37 (s), 27.01 (s), 25.15 (s), 22.86 (s), 22.69 (s), 22.29 (s),
1-{2-[Bis(pentafluorophenyl)boryl]benzyl}-2,2,4,7-
tetramethyl-1,2,3,4-tetrahydroquinoline (QCAT)
22.16 (s), 21.66 (s), 21.04 (s), 20.54 (s), quaternary carbons
of C6F5 ring and (C6F5)2BC6H4 were not observed; 19F NMR
In a glove box, a 25-mL flame-dried Schlenk tube equipped
with a stir bar, a Teflon stopcock and a glass stopper (Glin-
demannꢅ-sealing rings were used for conical joints instead
of grease) was charged with ansa-ammonium borate
QCATH2 (0.1 mmol, 62.5 mg) and 1.0 mL dry toluene. The
reaction mixture was degassed once with a freeze-pump-
thaw cycle, stirred at 1000 rpm and 808 for 15 h or 1108 for
5 min. All volatiles were removed under vacuum to give 1-
{2-[bis(pentafluorophenyl)boryl]benzyl}-2,2,4,7-tetramethyl-
(C6D6, 282 MHz) cis/trans isomers: d=À128.60 (d, 2F, JF,F
=
22 Hz, ortho-C6F5), À129.27 (d, 4F, JF,F =22 Hz, ortho-C6F5),
À129.96 (d, 2F, JF,F =22 Hz, ortho-C6F5), À146.68 (br. s, 2F,
para-C6F5), À147.14 (t, 1F, JF,F =21 Hz, para-C6F5), À147.46
(t, 1F, JF,F =21 Hz, para-C6F5), À161.11 (m, 4F, meta-C6F5),
À161.58 (m, 4F, meta-C6F5); HR-MS (ESI+-TOF): m/z=
652.2176, calcd. for C34H28BNF10*H+: 652.2234.
1-{2-[Bis(pentafluorophenyl)boryl]benzyl}-7-iso-
propyl-3,3-dimethyl-2-phenylindoline (iPrICAT)
1,2,3,4-tetrahydroquinoline as a red oil; yield: 62.3 mg
1
(100%). H NMR (C6D6, 300 MHz): d=7.52 (d, 1H, JH,H
7.7 Hz), 7.16 (m, 2H), 7.05 (m, 2H), 6.59 (d, 1H, JH,H
=
=
In a glove box, a 25-mL flame-dried Schlenk tube equipped
with a stir bar, a Teflon stopcock and a glass stopper (Glin-
demannꢅ-sealing rings were used for conical joints instead
of grease) was charged with ansa-ammonium borate iPrI-
CATH2 (0.1 mmol, 70.1 mg) and 1.0 mL dry toluene. The re-
action mixture was degassed once with a freeze-pump-thaw
cycle, stirred at 1000 rpm and 1108 for 5 min. All volatiles
were removed under vacuum to give (2R)-1-{2-[bis(penta-
fluorophenyl)boryl]benzyl}-7-isopropyl-3,3-dimethyl-2-phe-
nylindoline as a red oil; yield: 69.9 mg (100%). 1H NMR
(C6D6, 300 MHz): d=7.67 (d, 1H, JH,H =7.4 Hz), 7.27–6.87
7.4 Hz), 6.32 (s, 1H), 4.69 (d, 1H, JH,H =17.6 Hz), 4.24 (d,
1H, JH,H =17.6 Hz), 2.75 (m, 1H), 2.15 (s, 3H), 1.51 (m,
2H), 1.22 (d, 3H, JH,H =6.6 Hz), 1.00 (s, 3H), 0.85 (s, 3H);
11B NMR (C6D6, 128 MHz): d=65.81 (br. s); 13C NMR
1
(C6D6, 75 MHz): d=147.67 (dm, JC,F =247 Hz), 146.64 (s),
1
144.01 (dm, 1JC,F =247 Hz), 145.44 (s), 137.78 (dm, JC,F
=
254 Hz), 136.82 (s), 134.16 (s), 133.77 (s), 128.06 (s), 126.84
(s), 126.76 (s), 126.63 (s), 118.63 (s), 114.15 (s), 54.80 (s),
51.12 (s), 47.02 (s), 29.23 (s), 27.283 (s), 23.69 (s), 21.42 (s),
20.56 (s); quaternary carbons of C6F5 ring and (C6F5)2BC6H4
were not observed; 19F NMR (C6D6, 282 MHz): d=À129.15
(d, 4F, JF,F =17 Hz, ortho-C6F5), À146.28 (t, 2F, JF,F =19 Hz,
para-C6F5), À161.01 (m, 4F, meta-C6F5); HR-MS (ESI+-
TOF): m/z=646.1748, calcd. for C32H24BNF10*Na+:
646.1740.
(m, 11H), 4.79 (d, 1H, JH,H =17.6 Hz), 4.45 (d, 1H, JH,H
=
17.6 Hz), 4.36 (s, 1H), 3.15 (m, 1H), 1.29 (s, 3H), 1.21 (d,
3H, JH,H =6.6 Hz), 1.11 (d, 3H, JH,H =6.9 Hz), 0.74 (s, 3H);
11B NMR (C6D6, 128 MHz): d=63.44 (br. s); 13C NMR
1
(C6D6, 75 MHz): d=147.23 (dm, JC,F =254 Hz), 146.64 (s),
1
146.00 (s), 143.77 (dm, JC,F =252 Hz), 139.46 (s), 139.06 (s),
1
137.61 (dm, JC,F =254 Hz), 134.91 (s), 133.64 (s), 130.37 (s),
1-{2-[Bis(pentafluorophenyl)boryl]benzyl}-8-iso-
propyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline
(iPrQCAT)
128.19 (s), 127.85 (s), 126.81 (s), 126.36 (s), 126.13 (s), 120.59
(s), 120.56 (s), 81.02 (s), 53.95 (s), 44.30 (s), 29.69 (s), 27.63
(s), 25.80 (s), 25.35 (s), 23.22 (s), quaternary carbons of C6F5
ring and (C6F5)2BC6H4 were not observed; 19F NMR (C6D6,
282 MHz): d=À129.35 (d, 4F, JF,F =24.4 Hz, ortho-C6F5),
À146.52 (t, 2F, JF,F =21.4 Hz, para-C6F5), À160.20 (m, 4F,
meta-C6F5); HR-MS (ESI+-TOF): m/z=722.2054, calcd. for
C38H28BNF10*Na+: 722.2002.
In a glove box, a 25-mL flame-dried Schlenk tube equipped
with a stir bar, a Teflon stopcock and a glass stopper (Glin-
demannꢅ-sealing rings were used for conical joints instead
of grease) was charged with ansa-ammonium borate iPrQ-
CATH2 (0.1 mmol, 65.3 mg) and 1.0 mL dry toluene. The re-
action mixture was degassed once with a freeze-pump-thaw
cycle, stirred at 1000 rpm and 1108 for 2 h. All volatiles
were removed under vacuum to give 1-{2-[bis(pentafluoro-
phenyl)boryl]benzyl}-8-isopropyl-2,2,4-trimethyl-1,2,3,4-tet-
rahydroquinoline as a red oil; yield: 65.1 mg (100%). Ac-
cording to 1 H, 19F NMR the product exists as a mixture of
diastereomers at C-4 atom of quinoline ring. 1H NMR
(2R,4aR,9aS)-9-{2-[Bis(pentafluorophenyl)boryl]-
benzyl}-2-isopropyl-4a-methyl-9a-phenyl-2,3,4,4a,9,9a-
hexahydro-1H-carbazole (S-CarCAT)
To a solution of (2R,4aR,9aS)-9-(2-bromobenzyl)-2-isopro-
pyl-4a-methyl-9a-phenyl-2,3,4,4a,9,9a-hexahydro-1H-carba-
zole (0.797 g, 1.68 mmol) in toluene (10 mL) t-BuLi (2.2 mL,
3.5 mmol, 1.6M solution in pentane) was added dropwise at
À808C. The solution was allowed to warm up to room tem-
perature in about 30 min and stirred for additional 30 min.
The resultant lithium salt suspension was recooled to À808C
and a precooled solution (À708C) of (C6F5)2BCl (0.640 g,
1.68 mmol) in toluene (5 mL) was added in one portion. The
reaction mixture was stirred overnight at room temperature
and the contents were filtered. The solvent present in the fil-
trate was removed to give the crude product (2R,4aR,9aS)-
9-{2-[bis(pentafluorophenyl)boryl]benzyl}-2-isopropyl-4a-
methyl-9a-phenyl-2,3,4,4a,9,9a-hexahydro-1H-carbazole as a
red oil; yiel: 1.03 g.
(C6D6, 300 MHz) cis/trans isomers: d=8.24 (d, 1H, JH,H
=
8.0 Hz), 7.35 (pseudo t, 1H, JH,H =7.5 Hz), 7.25–6.86 (m,
11H), 6.61 (d, 1H, JH,H =11.4 Hz), 4.38 (br. s, 1H), 4.06 (br.
s, 1H), 3.91 (s, 1H), 3.62 (m, 1H), 3.36 (m, 1H), 3.26 (s,
1H), 2.79 (m, 1H), 2.62 (m, 2H), 1.46 (m, 2H), 1.25–0.93
(m, 30H). 11B NMR (C6D6, 128 MHz) cis/trans isomers: d=
70.06 (br. s), 65.33 (br. s); 13C NMR (C6D6, 75 MHz) cis/
trans isomers: d=147.80 (s), 147.47 (dm, 1JC,F =252 Hz),
144.50 (s), 143.93 (dm, 1JC,F =252 Hz), 139.40 (s), 137.63
1
(dm, JC,F =252 Hz), 135.72 (s), 135.14 (s), 133.40 (s), 133.21
(s), 132.61 (s), 131.44 (s), 129.32 (s), 128.99 (s), 128.08 (s),
126.77 (s), 126.36 (s), 126.24 (s), 125.40 (s), 124.95 (s), 124.63
(s), 124.55 (s), 124.49 (s), 123.10 (s), 123.07 (s), 117.22 (s),
49.14 (s), 44.63 (s), 44.46 (s), 38.47 (s), 31.85 (s), 31.74 (s),
30.10 (s), 29.32 (s), 28.40 (s), 28.30 (s), 27.69 (s), 27.61 (s),
The product was dissolved in hexane (10 mL). After 1 h
stirring at ambient temperature, the mixture was filtered.
Adv. Synth. Catal. 2011, 353, 2093 – 2110
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2107

Victor Sumerin et al.
FULL PAPERS
The resultant solution was cooled to À808C and allowed to
warm up to room temperature in about 30 min. The reaction
mixture was filtered and this procedure was repeated twice
to give the final product as a red oil; yield: 0.590 g (47%).
1H NMR (CDCl3, 300 MHz): d=7.69 (d, 1H, JH,H =7.7 Hz),
3H, JH,H =6.9 Hz); 13C NMR (CDCl3, 75 MHz): d=151.86
(s), 145.45 (s), 141.54 (s), 128.55 (s), 126.75 (s), 125.84 (s),
114.73 (s), 114.51 (s), 55.67 (s), 53.45 (s), 25.05 (s).
Catalyst Recovery Procedure under an Argon
Atmosphere
7.57 (pseudo t, 1H, JH,H =7.6 Hz), 7.42 (d, 1H, JH,H
7.0 Hz), 7.32 (pseudo t, 1H, JH,H =7.7 Hz), 7.20–7.00 (m,
6H), 6.90 (pseudo t, 1H, JH,H =7.0 Hz), 6.73 (t, 1H, JH,H
7.7 Hz), 6.27 (d, 1H, JH,H =7.7 Hz), 3.90 (s, 2H), 2.40–2.20
=
The organic solution obtained after extraction of the amine
with warm 1M HCl was evaporated. The obtained solid was
dissolved in 150 mL of CH2Cl2, basified to pH 12 with aque-
ous NaOH, and heated to 408C. The resulting organic layer
was separated, dried over Na2SO4 and evaporated. The
product was dissolved in 2 mL of dry benzene and TMSBr
(191 mg, 1.25 mmol). After the solution had been refluxed
for 5 min. and then evaporated under vacuum, the crude
ansa-aminoborane QCAT was obtained; yield: 95% yield.
Without further purification the product was dissolved in
a mixture of hexane (1 mL) and toluene (1 mL). The result-
ing solution was degassed once with a freeze-pump-thaw
cycle and refilled with H2 (1.5 atm). The reaction mixture
was stirred at 1000 rpm at room temperature for 1 hour, and
a short period (5 min) of intense precipitation was observed.
The reaction mixture was filtered, washed with hexane (3ꢄ
1 mL) to give the final product QCATH2;yield: 125 mg
(80%).
=
(m, 1H), 1.90–1.28 (m, 7H), 1.27 (s, 3H), 0.88 (d, 3H, JH,H
=
7.2 Hz), 0.85 (d, 3H, J=7.2 Hz); 11B NMR (CDCl3,
128 MHz): d=63.26 (br. s); 13C NMR (CDCl3, 75 MHz): d=
1
151.07 (s), 147.15 (s), 146.30 (dm, JC,F =245 Hz), 142.56 (s),
1
140.11 (dm, 1JC,F =240 Hz), 137.34 (s), 137.27 (dm, JC,F
=
245 Hz), 135.13 (s), 128.01 (s), 127.82 (s), 127.54 (s), 127.44
(s), 127.26 (s), 126.84 (s), 126.70 (s), 120.69 (s), 118.13 (s),
117.33 (s), 105.52 (s), 77.58 (s), 50.42 (s), 48.64 (s), 46.01 (s),
39.16 (s), 32.38 (s), 29.68 (s), 25.68 (s), 19.73 (s), 19.50 (s),
quaternary carbons of C6F5 ring and (C6F5)2BC6H4 were not
observed; 19F NMR (CDCl3, 282 MHz): d=À129.70 (d, 2F,
J
F,F =24.4 Hz, ortho-F), À129.73 (d, 2F, JF,F =24.4 Hz, ortho-
3
F), À147.24 (t, 2F, JF,F =21.6 Hz, para-F), À160.64 (m, 4F,
meta-F); HR-MS (ESI+-TOF): m/z=762.2375, calcd. for
C41H32BNF10*Na+: 762.2367.
Typical Hydrogenation Procedure
In a glove box, a 25-mL flame-dried Schlenk tube equipped
with a stir bar, a Teflon stopcock and a glass stopper (Glin-
demannꢅ-sealing rings were used for conical joints instead
of grease) was charged with ansa-ammonium borate
(0.01 mmol), 5 mL dry toluene and imine (0.25–1 mmol).
The reaction mixture was degassed once with a freeze-
pump-thaw cycle and refilled with H2 (2 atm). The reaction
mixture was stirred at 1000 rpm and a suitable temperature
for a suitable time. All volatiles were removed under
vacuum to give the product (Table 1). The amines were not
purified from residual catalyst but identified by comparison
Acknowledgements
The authors are very grateful Dr. S. Heikkinen for help with
NMR, the DAAD (D/05/51658) and Academy of Finland
(123248, 139550) for the financial support.
References
1
[1] a) J. G. De Vries, C. J. Elsevier, in: The Handbook of
Homogeneous Hydrogenation, Wiley-VCH, Weinheim,
2008; b) J. W. Tye, Y. Darensbourg, M. B. Hall, W. B.
Tolman, in: Activation of Small Molecules, Wiley-VCH,
Weinheim, 2006, pp 121–158; c) M. Beller, C. Bolm,
in: Transition Metals for Organic Synthesis, Wiley-
VCH, Weinheim, Vol. 2, 1998, pp 1–154.
[2] a) C. E. Garrett, K. Prasad, Adv. Synth. Catal. 2004,
346, 889–900; b) D. Barbaras, J. Brozio, I. Johannsen,
T. Allmendinger, Org. Process Res. Dev. 2009, 13,
1068–1079.
[3] M. Wills, S. A. Westcott, R. T. Baker, O. Riant, H.
Adolfsson, P. G. Andersson, I. J. Munslow, in: Modern
Reduction Methods, Wiley-VCH, Weinheim, 2008,
pp 271–358.
[4] a) E. H. M. Kirton, G. Tughan, R. E. Morris, R. A.
Field, Tetrahedron Lett. 2004, 45, 853–855; b) X.
Huang, M. Ortiz-Marciales, K. Huang, V. Stepanenko,
F. G. Merced, A. M. Ayala, W. Correa, M. De Jesffls,
Org. Lett. 2007, 9, 1793–1795; c) K. Huang, M. Ortiz-
Marciales, V. Stepanenko, M. De Jesffls, W. Correa, J.
Org. Chem. 2008, 73, 6928–6931.
of their H NMR spectra with literature values.
Scaled-Up Hydrogenation of N-(4-Methoxy)phenyl-1-
phenylethylideneamine
In a glove box, a 1-L flame-dried, round-bottom Schlenk
flask equipped with a stirrer bar, a Teflon stopcock and a
glass stopper (Glindemannꢅ-sealing rings were used for
conical joints instead of grease) was charged with ansa-am-
monium borate QCATH2 (1 mol%, 156 mg, 0.25 mmol),
125 mL dry Et2O and N-(4-methoxy)phenyl-1-phenylethyli-
deneamine 1d (5.632 g, 25 mmol). The reaction mixture was
degassed once with a freeze-pump-thaw cycle and refilled
with H2 (1.6 atm). The reaction mixture was stirred at
700 rpm and at 508C for 2 h. The Et2O solution was extract-
ed with warm 1N HCl (3ꢄ150 mL). The aqueous solution
was basified to pH 12 with NaOH and extracted with
CH2Cl2 (3ꢄ50 mL). The resulting organic layer was dried
over K2CO3, passed through a short column with silica gel
and evaporated to give N-(4-methoxy)phenyl-1-phenylethyl-
amine as white crystals; yield: 5.535 g (97%); mp 65–668C.
1
The H NMR and 13C NMR data were identical to literature
1
values. H NMR (CDCl3, 300 MHz): d=7.20–7.39 (m, 5H),
[5] a) J. M. Blackwell, E. R. Sonmor, T. Scoccitti, W. E.
Piers, Org. Lett. 2000, 2, 3921–3923; b) M. Tan, Y.
Zhang, Tetrahedron Lett. 2009, 50, 4912–4915; c) D. N.
6.70 (d, 2H, JH,H =8.9 Hz), 6.48 (d, 2H, JH,H =8.9 Hz), 4.42
(q, 1H, JH,H =6.6 Hz), 3.79 (br. s, 1H), 3.70 (s, 3H), 1.51 (d,
2108
asc.wiley-vch.de
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2093 – 2110

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds
Kursanov, Z. N. Parnes, N. M. Loim, Synthesis 1974,
(MCATH2), CCDC 804255 (QCATH2), CCDC 804256
633–651.
(iPrQCATH2) and CCDC 804257 (iPrICATH2). These
data can be obtained free of charge from The
ˇ
ˇ
´
[6] a) A. V. Malkov, K. Vrankovµ, S. Stoncius, P. Kocovsky,
J. Org. Chem. 2009, 74, 5839–5849; b) F.-M. Gautier, S.
Jones, S. J. Martin, Org. Biomol. Chem. 2009, 7, 229–
231; c) P. Kocovsky, S. Stoncius, T. C. Nugent, in: Chiral
Amine Synthesis: Methods, Developments and Applica-
tions, Wiley-VCH, Weinheim, 2010, pp 131–154.
[7] a) S. G. Ouellet, A. M. Walji, D. W. C. Macmillan, Acc.
Chem. Res. 2007, 40, 1327–1339; b) M. Rueping, E. Su-
giono, F. R. Schoepke, Synlett 2010, 852–865.
[8] a) C. Zhu, T. Akiyama, Org. Lett. 2009, 11, 4180–4183;
b) C. Zhu, T. Akiyama, Adv. Synth. Catal. 2010, 352,
1846–1850.
[9] D. Chen, J. Klankermayer, Chem. Commun. 2008,
2130–2131.
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif or on application
to The Director, CCDC, 12 Union Road, Cambridge
DB2 1EZ, UK (Fax: int.code: +(1223)-336-033; e-
mail: deposit@ccdc.cam.ac.uk).
ˇ
´
ˇ
À
À
[19] It is noted that the real N H···H B dihydrogen bond
distance in ansa-ammonium borates should be 10–15%
shorter than those observed by X-ray diffraction. Due
to the tendency of the X-ray technique to give too
À
short X H bonds, compared to neutron scattering; see:
T. Steiner, Angew. Chem. 2002, 114, 50–80; Angew.
Chem. Int. Ed. 2002, 41, 48–76.
[20] Ansa-ammonium borates are only slightly soluble in
[10] D. Chen, Y. Wang, J. Klankermayer, Angew. Chem.
2010, 122, 9665–9668; Angew. Chem. Int. Ed. 2010, 49,
9475–9478.
toluene at room temperature.
[21] a) T. A. Rokob, A. Hamza, I. Pµpai, J. Am. Chem. Soc.
2009, 131, 10701–10710; b) M. Ullrich, A. J.Lough,
D. W. Stephan, J. Am. Chem. Soc. 2009, 131, 52–53;
c) H. Wang, R. Frçhlich, G. Kehr, G. Erker, Chem.
Commun. 2008, 5966–5968.
[11] a) P. A. Chase, G. C. Welch, T. Jurca, D. W. Stephan,
Angew. Chem. 2007, 119, 8196–8199; Angew. Chem.
Int. Ed. 2007, 46, 8050–8053; b) P. A. Chase, T. Jurca,
D. W. Stephan, Chem. Commun. 2008, 1701–1703;
c) C. Jiang, O. Blacque, H. Berke, Chem. Commun.
2009, 5518–5520; d) P. Spies, S. Schwendemann, S.
Lange, G. Kehr, R. Frçhlich, G. Erker, Angew. Chem.
2008, 120, 7654–7657; Angew. Chem. Int. Ed. 2008, 47,
7543–7546; e) S. J. Geier, P. A. Chase, D. W. Stephan,
[22] R. Roesler, W. E. Piers, M. Parvez, J. Organomet.
Chem. 2003, 680, 218–222.
[23] Two sets of different perfluorophenyl signals were ob-
served in solution by 19F NMR in the case of QCATH2,
iPrQCATH2 and iPrICATH2. These findings highlight
a significant barrier of rotation of BACTHUNRGTNEUNG(C6F5)2 moiety
˝
Chem. Commun. 2010, 4884–4886; f) G. Eros, H.
À
around the B C bond, which caused a fixed conforma-
tion of ansa-ammonium borates. Moreover, the X-ray
structures of all ansa-ammonium borates exhibited the
presence of additional hydrogen bonds between methyl
Mehdi, I. Pµpai, T. A. Rokob, P. Kirµly, G. Tµrkµnyi, T.
Soós, Angew. Chem. 2010, 122, 6709–6713; Angew.
Chem. Int. Ed. 2010, 49, 6559–6563.
[12] Probably to prevent retro-hydroboration, see: D. J.
Parks, W. E. Piers, G. P. A. Yap, Organometallics 1998,
17, 5492–5503.
[13] a) V. Sumerin, F. Schulz, M. Atsumi, C. Wang, M.
Nieger, M. Leskelꢀ, T. Repo, P. Pyykkç, B. Rieger, J.
Am. Chem. Soc. 2008, 130, 14117–14119; b) V. Sumer-
in, F. Schulz, M. Nieger, M. Atsumi, C. Wang, M. Le-
skelꢀ, P. Pyykkç, T. Repo, B. Rieger, J. Organomet.
Chem. 2009, 694, 2654–2660.
À
À
or phenyl C H and perfluorophenyl F C atoms. Addi-
tionally, in the X-ray structure of iPrICATH2 a strong
intramolecular phenyl-perfluorophenyl p-p stacking of
3.7 Š was found.
[24] a) M. Tomasulo, S. Sortino, A. J. P. White, F. M.
Raymo, J. Org. Chem. 2005, 70, 8180–8189; b) S. E.
Denmark, S. Venkatraman, J. Org. Chem. 2006, 71,
1668–1676.
[25] M. Rueping, C. Brinkmann, A. P. Antonchick, I. Ato-
diresei, Org. Lett. 2010, 12, 4604–4607.
[14] The pKa values of the corresponding N-benzylamines
were predicted by ACD/Labs version 5.11 software, see
Supporting Information.
[26] (R)-3,3’-Bis(2,4,6-triisopropylphenyl)-1,1’-binaphthyl-
2,2’-diyl hydrogen phosphate.
[27] M. Rueping, M. Stçckel, T. Theissmann, announced
manuscript.
[15] J. T. Lai, Synthesis 1984, 122–123.
[16] According to 1H NMR and X-Ray diffraction studies
iPrQCATH2 exists as a mixture of diastereomers at the
C-4 atom of the tetrahydroquinoline ring (2.1:1, cis/
trans).
[28] a) A. Błaszczyk, J. Skolimowski, Chem.-Biol. Interact.
2006, 162, 70–80; b) G. Dorey, B. Lockhart, P. Lestage,
P. Casara, Bioorg. Med. Chem. Lett. 2000, 10, 935–939;
c) S. L. Roach, R. I. Higuchi, M. E. Adams, Y. Liu,
D. S. Karanewsky, K. B. Marschke, D. E. Mais, J. N.
Miner, L. Zhi, Bioorg. Med. Chem. Lett. 2008, 18,
3504–3508; d) K. Tsushina, K. Osuma, N. Matsuo, N.
Itaya, Agric. Biol. Chem. 1989, 53, 2529–2530; e) P. H.
Briner, Can. Pat. Appl. CA 2,133,942, 1995.
[29] V. Sumerin, F. Schulz, M. Nieger, M. Leskelꢀ, T. Repo,
B. Rieger, Angew. Chem. 2008, 120, 6090–6092;
Angew. Chem. Int. Ed. 2008, 47, 6001–6003.
[30] a) H. Fritz, H.-G. Gerber, Justus Liebigs Ann. Chem.
1975, 1422–1434; b) A. Fꢁrstner, P. Hannen, Chem.
Eur. J. 2006, 12, 3006–3019.
[17] According to 19F NMR of QCATH2, iPrQCATH2 and
iPrICATH2, their perfluorophenyl rings are not equal,
presumably due to a significant barrier of rotation.
[18] The X-ray crystal structure studies of MCATH2 and
À
À
QCATH2 showed that the N H···H B dihydrogen
bonds (DHB) presented in the structures were ex-
tremely short, in the order of 1.65 Š. While DHBs in
iPrQCATH2, iPrICATH2 are much longer: 1.93 Š and
1.96 Š, respectively. See Supporting Information. Crys-
tallographic data (excluding structure factors) for the
structure reported in this work have been deposited
with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 804254
Adv. Synth. Catal. 2011, 353, 2093 – 2110
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2109

Victor Sumerin et al.
FULL PAPERS
[31] J. G. Rodriguez, A. Urrutia, Tetrahedron 1998, 54,
HPLC retention times with the sample produced by re-
duction with S-TRIP Brønsted acid/Hantzsch ester re-
ported previously: R. I. Storer, D. E. Carrera, Y. Ni,
D. W. C. MacMillan, J. Am. Chem. Soc. 2006, 128, 84–
86.
15613–15618.
[32] (R)-4-Methoxy-N-(1-phenylethyl)benzenamine
is
formed as the major enantiomer. The absolute configu-
ration was assigned based on the comparision of chiral
2110
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2093 – 2110