Amidines for versatile ruthenium(II)-catalyzed oxidative C-H activations with internal alkynes and acrylates

Article abstract of DOI:10.1002/chem.201304944

Cationic ruthenium complexes derived from KPF₆ or AgOAc enabled efficient oxidative C-H functionalizations on aryl and heteroaryl amidines. Thus, oxidative annulations of diversely decorated internal alkynes provided expedient access to 1-aminoisoquinolines, while catalyzed C-H activations with substituted acrylates gave rise to structurally novel 1-iminoisoindolines. The powerful ruthenium(II) catalysts displayed a remarkably high site-, regio- and, chemoselectivity. Therefore, the catalytic system proved tolerant of a variety of important electrophilic functional groups. Detailed mechanistic studies provided strong support for the cationic ruthenium(II) catalysts to operate by a facile, reversible C-H activation. Ring road: Cationic ruthenium(II) complexes allowed for efficient C-H activation on (hetero)aryl amidines with alkynes and alkenes, thereby providing a step-economical access to diversely decorated isoquinolines and isoindolines, respectively (see scheme).

Full text of DOI:10.1002/chem.201304944

DOI: 10.1002/chem.201304944
Full Paper
&
CÀH Activation
Amidines for Versatile Ruthenium(II)-Catalyzed Oxidative
CÀH Activations with Internal Alkynes and Acrylates
Jie Li, Michael John, and Lutz Ackermann*[a]
Abstract: Cationic ruthenium complexes derived from KPF6
or AgOAc enabled efficient oxidative CÀH functionalizations
on aryl and heteroaryl amidines. Thus, oxidative annulations
of diversely decorated internal alkynes provided expedient
access to 1-aminoisoquinolines, while catalyzed CÀH activa-
tions with substituted acrylates gave rise to structurally
novel 1-iminoisoindolines. The powerful ruthenium(II) cata-
lysts displayed a remarkably high site-, regio- and, chemose-
lectivity. Therefore, the catalytic system proved tolerant of
a variety of important electrophilic functional groups. De-
tailed mechanistic studies provided strong support for the
cationic ruthenium(II) catalysts to operate by a facile, reversi-
ble CÀH activation.
zamidines as bidentate ligands,[10,11] rendering these NH-acidic
compounds particularly challenging substrates for catalytic CÀ
H-bond functionalization. As part of our program on catalyzed
CÀH-bond activation for sustainable synthesis,[12] we herein
report on the first ruthenium-catalyzed oxidative CÀH-bond
functionalizations with benzamidines 1. Notably, our strategy
proved to be widely applicable and enabled annulations of al-
kynes 2 and alkenes 4 to provide expedient access to diversely
substituted 1-aminoisoquinolines 3 and novel 1-iminoisoindo-
lines 5, respectively (Scheme 1).
Introduction
Aminoisoquinolines and isoindolines are important structural
motifs of various compounds with activities of relevance to
biology or medicinal chemistry,[1,2] as found in nonbenzamidine
factor VIIa inhibitors against nonthromboembolic cardiovascu-
lar disease.[3] Therefore, there is a continued strong demand
for efficient and selective syntheses of these heterocyclic scaf-
folds. In recent years, metal-catalyzed CÀH-bond activation has
been recognized as an increasingly viable tool for the prepara-
tion of substituted heterocycles.[4] These methods avoid the
synthesis and use of prefunctionalized starting materials and
thereby improve the atom- and step-economy of organic syn-
theses. While rhodium and palladium catalysts were frequently
utilized for oxidative CÀH-bond functionalizations,[4] in recent
years, less expensive[5] ruthenium complexes have attracted
considerable attention as versatile catalysts for oxidative CÀH-
bond activations.[6,7] One of the key obstacles in the develop-
ment of practically useful intermolecular CÀH-bond functionali-
zations is represented by achieving site selectivity.[4] Directing-
group assistance has proven to be one of the most powerful
strategies for ensuring site selectivity in stoichiometric and cat-
alytic CÀH-bond transformations.[8] While various Lewis-basic
directing groups were previously exploited for CÀH-bond acti-
vations,[4] ubiquitous amidines[9] have, to the best of our
knowledge, not been exploited in oxidative ruthenium(II)-cata-
lyzed CÀH-bond activation so far. This lack of available meth-
ods is likely owing to the excellent binding properties of ben-
Scheme 1. Ruthenium-catalyzed CÀH activation on amidines 1.
Results and Discussion
Oxidative alkyne annulation
Optimization studies
[a] J. Li, Dr. M. John, Prof. Dr. L. Ackermann
Institut fꢀr Organische und Biomolekulare Chemie
Georg-August-Universitꢁt
We initiated our studies by testing different reaction conditions
for the desired oxidative annulation of tolane (2a) and benza-
midine 1a. Preliminary experiments identified [RuCl2(p-
cymene)]2 as the ideal metal source and KPF6 as the cocatalytic
additive of choice. Among a set of representative solvents,
DME provided optimal results (Table 1, entries 1–5 and 8).
Tammannstrasse 2, 37077 Gçttingen (Germany)
Fax: (+49)551-39-6777
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304944.
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substituent proximal to the nitrogen atom, thus giving the
products 3ah and 3ai, respectively.
Table 1. Optimization of oxidative annulation with benzamidine 1a.[a]
Valuable electrophilic functional groups, such as fluoro,
chloro, bromo, iodo, and nitro substituents, were well tolerated
by the ruthenium catalyst when utilizing substituted benzami-
dines 1b–1h (Scheme 3). Intramolecular competition experi-
ments with substrates bearing meta-methyl or meta-trifluoro-
methyl substituents were controlled by steric interactions to
deliver the products 3ia and 3ja, respectively. In contrast,
a secondary directing-group effect led to the functionalization
at the more sterically congested CÀH bond within substrate
1k. Substrate 1l bearing a sterically hindered ortho-substituent
gave the desired product 3la in a slightly reduced yield, as
was also observed when using substrates with a less bulky N-
substitution pattern (3ma and 3na). It is worth noting that im-
portant heterocycles also proved to be viable starting materi-
als, which allowed for the efficient conversion of cyclic amidine
1o. Moreover, indole and thiophene derivatives 1p and 1q
gave the desired products of the CÀH/NÀH functionalization
process, thus delivering g-carboline 3pg and annulated aza-
benzothiophene 3qg.
Entry
Solvent
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
DMF
100
100
100
100
100
100
120
120
7
21
25
20
PhMe
m-xylene
1,4-dioxane
DME
H2O
H2O
58
46[c]
76[c]
80[c]
DME
[a] Reaction conditions: 1a (0.5 mmol), 2a (1.2 equiv), Cu(OAc)2·H2O
(1.0 mmol), [RuCl2(p-cymene)]2 (5.0 mol%), KPF6 (30 mol%), solvent
(2.0 mL). [b] Yields of isolated products. [c] 2a (2.0 equiv).
However, it is worth noting that inexpensive, nontoxic H2O[13,14]
was found to be a viable reaction medium as well (entries 6
and 7).
Interestingly, the para-methoxybenzyl (PMB)-substituted
benzamidine 1r furnished the product 3rg through a twofold
CÀH/NÀH-bond functionalization (Scheme 4), thereby high-
lighting the ability of the 1-aminoisoquinolines 3 themselves
to serve as useful substrates for directed CÀH-bond transfor-
mations.
Scope and limitations
Thereafter, the versatility of the optimized catalytic system was
probed in the oxidative annulation of differently decorated al-
kynes 2 (Scheme 2). We were pleased to find that arylalkynes
2b–d bearing different functional groups were well tolerated
by the ruthenium catalyst, as were the sulfur-containing hetero-
aromatic moieties in substrate 2e. The catalytic system was
not limited to the use of arylalkynes 2b–e, but also allowed for
the efficient conversion of the more challenging alkylalkynes
2 f and 2g. Unsymmetrically substituted alkynes 1h and 1i
were converted with high regioselectivity, placing the aromatic
Scheme 3. Scope of annulation with substituted amidines 1. [a] Isomeric
product 3 kg’ (7%) was also isolated.
Scheme 2. Ruthenium-catalyzed oxidative annulation with alkynes 2.
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Scheme 4. Cascade twofold CÀH/NÀH-bond functionalization.
Mechanistic studies
Given the unique activity of the alkyne-annulation catalysts,
we performed mechanistic studies to rationalize its mode of
action. To this end, intermolecular competition experiments re-
vealed electron-rich benzamidine 1c to be preferentially con-
verted (Scheme 5). This observation is in good agreement with
the in situ generated cationic ruthenium(II) complex operating
by an electrophilic activation mode.
Scheme 7. H/D exchange reactions a) in the absence and b) presence of
alkyne 2g.
Moreover, aromatic alkynes outperformed the corresponding
alkyl-substituted substrate 2g (Scheme 6).
Scheme 5. Intermolecular competition with amidines 1c and 1e.
Scheme 8. Plausible mode of action.
Oxidative alkenylation
Optimization studies
In consideration of the remarkably high catalytic efficacy of our
ruthenium(II)-catalyzed oxidative annulation of alkynes 2, we
became intrigued by developing novel oxidative twofold CÀH-
bond functionalizations with alkenes 4. Thus, we initially stud-
ied the effect exerted by representative additives and solvents
on the cross-dehydrogenative coupling of alkene 4a with ami-
dine 1b (Table 2). The reaction conditions previously optimized
for the alkyne annulation (see above) led to an unsatisfactorily
low yield of the 3-alkylydine 1-imino-isoindoline 5ba, because
significant amounts of an undesired by-product stemming
from N-deprotection were formed as well (entry 1). However,
we were delighted to observe that the chemoselectivity of the
double CÀH-bond functionalization process was significantly
improved when using AgSbF6 as the additive and DCE as the
solvent (entries 2–3). Among a variety of silver(I) salts, AgOAc
gave optimal results, which allowed for efficient catalysis to
Scheme 6. Intermolecular competition between alkynes 2.
Subsequently, we explored catalytic CÀH-bond functionaliza-
tions on benzamidine 1b in the presence of D2O as the cosol-
vent. These studies revealed a significant H/D exchange in the
ortho-positions (Scheme 7a), albeit with a considerably re-
duced deuterium incorporation when conducting the reaction
in the presence of alkyne 2g (Scheme 7b).
Given our mechanistic studies and literature precedents,[12a]
we propose a plausible catalytic cycle to involve a reversible
CÀH-bond activation, along with subsequent migratory alkyne
insertion (Scheme 8). Reductive elimination thereafter delivers
the desired product, while reoxidation generates the catalyti-
cally active ruthenium(II) complex.
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Furthermore, the para-methoxybenzyl (PMB)-substituted ben-
zamidine 1u delivered the desired products 5ua–5uc in high
yields as well.
Table 2. Optimization of oxidative annulation with alkene 4a.[a]
With the optimized reaction conditions in hand and the tert-
butyl group identified as the ideal N-substituent, we subse-
quently tested the scope of the ruthenium(II)-catalyzed cross-
dehydrogenative alkenylation with differently substituted ben-
zamidines 1 and alkenes 4 (Scheme 10). Notably, the rutheniu-
m(II) catalyst turned out to be widely applicable and tolerated
valuable electrophilic functional groups, such as fluoro, chloro,
bromo, and nitro substituents. The CÀH-bond functionaliza-
tions occurred efficiently with para- and more sterically-hin-
dered ortho-substituted amidines 1. Intramolecular competi-
tion experiments with meta-substituted arenes 1 were largely
controlled by steric interactions (5ia and 5ja), unless when
using substrates having heteroatom substituents[17] with a sec-
ondary directing-group effect (5va and 5ka).
Entry
Additive ([equiv])
Solvent
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
9
KPF6 (0.3)
AgSbF6 (0.2)
KPF6 (0.3)
DME
DME
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
120
120
120
120
120
120
120
120
100
80
18[c]
41
63
66
13
59
70
75
AgSbF6 (0.2)
AgPF6 (0.2)
AgO2CCF3 (0.2)
AgOAc (0.3)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
73[d]
69[d]
64[d]
10
11
60
[a] Reaction conditions: 1b (0.5 mmol), 4a (1.5 equiv), Cu(OAc)2·H2O
(2.0 equiv), [RuCl2(p-cymene)]2 (5.0 mol%), cat. additive, solvent (2.0 mL),
18–22 h. [b] Yields of isolated products. [c] Along with 43% of the corre-
sponding deprotected product. [d] [RuCl2(p-cymene)]2 (2.5 mol%).
occur at a reduced catalyst loading and at reaction tempera-
tures[15] as low as 608C. Terminal oxidants other than Cu-
(OAc)2·H2O, such as CuBr2, K2S2O8, or PhI(OAc)2, did not furnish
the desired products 5ba.
Scope and limitations
To test the scope of our ruthenium-catalyzed oxidative alkeny-
lation, we first evaluated the influence exerted by the N-sub-
stituent of benzamidines 1 (Scheme 9). The less sterically hin-
dered iso- or n-butyl-substituted substrates 1s and 1t gave in-
ferior results as compared to the tert-butyl analogue 1b. Inter-
estingly, detailed spectroscopic studies[16] on the product’s con-
nectivity revealed that the reduced steric bulk of the N-
substituent strongly influenced the chemo- and diastereoselec-
tivity of the isoindoline formation in that the substituted nitro-
gen atom of the amidine underwent the CÀN bond formation.
Scheme 10. Scope of oxidative 1-iminoisoindoline synthesis.
Mechanistic studies
To unravel the working mode of our novel 1-imino-isoindoline
synthesis, we performed intermolecular competition experi-
ments between differently substituted benzamidines 1. These
experiments revealed that the electron-rich substrate 1b is in-
herently more reactive (Scheme 11), which is reminiscent of
the observation made within the ruthenium-catalyzed oxida-
tive alkyne annulation (see above).
Furthermore, we performed reactions with the isotopically
labeled cosolvent [D4]-MeOH. These studies highlighted the
Scheme 9. Variation of N-substituents in substrates 1.
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Scheme 13. Copper(II)-mediated oxidative alkene formation.
Scheme 11. Intermolecular competition experiment.
high catalytic activity of the optimized cationic ruthenium(II)
catalyst by giving a remarkable conversion of the substrate 1c
within only 15 min. Evidence for a H/D exchange reaction was
gathered by examination of the reisolated benzamidine 1c
and product 5ca (Scheme 12). Interestingly, we were also able
to isolate the intermediate 6ca, being indicative of a reaction
sequence comprising of an initial oxidative alkenylation and
a subsequent intramolecular aza-Michael reaction. Both prod-
ucts 5ca and 6ca showed deuterium incorporation in the a-
position to the carbonyl group, which is likely owing to the
rapid H/D exchange on the NH-acidic amidine group prior to
the intramolecular conjugate addition.
Scheme 14. Proposed catalytic cycle.
9, while reductive elimination and reoxidation by Cu(OAc)2·H2O
regenerate the catalytically active ruthenium(II) complex. The
desired product 5 is obtained through an intramolecular aza-
Michael addition of compound 9, followed by dehydrogena-
tion of the thus obtained intermediate 6.
Conclusion
Scheme 12. CÀH activation in the presence of [D4]-MeOH.
In summary, we have reported on the unprecedented ruthe-
nium(II)-catalyzed oxidative CÀH-bond functionalization on
easily accessible aryl amidines with alkynes and alkenes. Thus,
in situ formed cationic ruthenium(II) complexes allowed for
alkyne annulations by CÀH/NÀH-bond functionalizations to
Moreover, we verified that the dehydrogenative formation
of product 5ca was indeed viable in the absence of the ruthe-
nium catalyst, thus solely being mediated by the copper(II) oxi-
dant (Scheme 13).
Based on our mechanistic studies, we propose the initial CÀ give diversely substituted 1-aminoisoquinolines, which served
H-bond activation to occur by a reversible metalation event
(Scheme 14), which thereby rationalizes the high activity of the
cationic ruthenium(II) complexes. The thus formed cyclo-
ruthenated complex 7 then undergoes an insertion with
alkene 4 to give the intermediate 8. Subsequently, b-hydride
elimination gives rise to the product of oxidative alkenylation
as viable substrates for catalyzed CÀH-bond activations reac-
tions themselves. Furthermore, novel oxidative alkenylations of
benzamidines proved to be viable with versatile cationic ruthe-
nium(II) complexes and, thereby, provided access to structural-
ly diverse iminoisoindolines. Detailed mechanistic studies were
indicative of a reversible CÀH-bond activation step.
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2009, 48, 9792–9826; i) P. Thansandote, M. Lautens, Chem. Eur. J. 2009,
15, 5874–5883, and references therein.
Experimental Section
[5] The prices of platinum, rhodium, gold, iridium, palladium, and rutheni-
um were 1482, 1015, 1363, 800, 701, and 80 US$ per troy oz, respective-
ly, as of September 2013; see: http://taxfreegold.co.uk/preciousmetal-
pricesusdollars.html.
[6] For recent reviews on ruthenium-catalyzed CÀH-bond functionaliza-
tions, see: a) V. S. Thirunavukkarasu, S. I. Kozhushkov, L. Ackermann,
Chem. Commun. 2014, 50, 29–39; b) S. I. Kozhushkov, L. Ackermann,
Chem. Sci. 2013, 4, 886–896; c) P. B. Arockiam, C. Bruneau, P. H. Dixneuf,
Chem. Rev. 2012, 112, 5879–5918; d) L. Ackermann, R. Vicente, Top.
Curr. Chem. 2009, 292, 211–229; e) L. Ackermann, Chem. Commun.
2010, 46, 4866–4877.
Representative procedure A: ruthenium(II)-catalyzed oxida-
tive alkyne annulation
A suspension of 1a (88.0 mg, 0.50 mmol), 2a (178 mg, 1.00 mmol),
[RuCl2(p-cymene)]2 (15.3 mg, 5.0 mol%), KPF6 (27.6 mg, 30 mol%),
and Cu(OAc)2·H2O (199 mg, 2.00 mmol) in DME (2.0 mL) was stirred
at 1208C for 22 h under an atmosphere of N2. At ambient tempera-
ture, H2O (20 mL) was added and the reaction mixture was extract-
ed with EtOAc (3ꢁ20 mL). The combined organic layers were
washed with brine (20 mL) and dried over Na2SO4. The solvent was
evaporated in vacuo and the remaining residue was purified by
column chromatography on silica gel (n-hexane/EtOAc 100:1) to
yield product 3aa (141 mg, 80%) as a yellow solid.
[7] For selected recent examples of ruthenium(II)-catalyzed oxidative
alkyne or alkene annulation by CÀH-bond activation, see: a) J. Nan, Z.
Zuo, L. Luo, L. Bai, H. Zheng, Y. Yuan, J. Liu, X. Luan, Y. Wang, J. Am.
Chem. Soc. 2013, 135, 17306–17309; b) J. Li, L. Ackermann, Tetrahedron
2014, 70, DOI: 10.1016/j.tet.2013.10.003; c) M. C. Reddy, R. Manikandan,
M. Jeganmohan, Chem. Commun. 2013, 49, 6060–6062; d) J. D. Dooley,
S. Reddy Chidipudi, H. W. Lam, H. Wai, J. Am. Chem. Soc. 2013, 135,
10829–10836; e) L. Wang, L. Ackermann, Org. Lett. 2013, 15, 176–179;
f) J. Zhang, A. Ugrinov, P. Zhao, Angew. Chem. Int. Ed. 2013, 52, 6681–
6684; g) M. Deponti, S. I. Kozhushkov, D. S. Yufit, L. Ackermann, Org.
Biomol. Chem. 2013, 11, 142–148; h) W. Ma, K. Graczyk, L. Ackermann,
Org. Lett. 2012, 14, 6318–6321; i) K. Parthasarathy, N. Senthilkumar, J.
Jayakumar, C.-H. Cheng, C. Hong, Org. Lett. 2012, 14, 3478–3481; j) C.
Kornhaaß, J. Li, L. Ackermann, J. Org. Chem. 2012, 77, 9190–9198;
k) R. K. Chinnagolla, M. Jeganmohan, Chem. Commun. 2012, 48, 2030–
2032; l) L. Ackermann, L. Wang, A. V. Lygin, Chem. Sci. 2012, 3, 177–
180; m) L. Ackermann, A. V. Lygin, Org. Lett. 2012, 14, 764–767; n) B. Li,
H. Feng, S. Xu, B. Wang, Chem. Eur. J. 2011, 17, 12573–12577; o) L. Ac-
kermann, S. Fenner, Org. Lett. 2011, 13, 6548–6551; p) L. Ackermann,
A. V. Lygin, N. Hofmann, Angew. Chem. 2011, 123, 6503–6506; Angew.
Chem. Int. Ed. 2011, 50, 6379–6382, and references cited therein.
[8] For selected reviews, see: a) D. A. Colby, R. G. Bergman, J. A. Ellman,
Chem. Rev. 2010, 110, 624–655; b) T. Satoh, M. Miura, Top. Organomet.
Chem. 2007, 24, 61–84; c) D. Alberico, M. E. Scott, M. Lautens, Chem.
Rev. 2007, 107, 174–238; d) L. Ackermann, Top. Organomet. Chem.
2007, 24, 35–60; e) I. Omae, Coord. Chem. Rev. 2004, 248, 995–1023.
[9] For examples of metal-catalyzed oxidative couplings with or for the for-
mation of benzamidines through CÀH-bond functionalizations, see: a) Y.
Wang, Q. Zhu, Adv. Synth. Catal. 2012, 354, 1902–1908; b) X. Wei, M.
Zhao, Z. Du, X. Li, Org. Lett. 2011, 13, 4636–4639; c) Y. Wang, H. Wang,
J. Peng, Q. Zhu, Org. Lett. 2011, 13, 4604–4607; d) G. Brasche, S. L.
Buchwald, Angew. Chem. 2008, 120, 1958–1960; Angew. Chem. Int. Ed.
2008, 47, 1932–1934; for a selected recent stoichiometric CÀH activa-
tion, see: e) V. Rad’kov, V. Dorcet, J.-F. Carpentier, A. Trifonov, E. Kirillov,
Organometallics 2013, 32, 1517–1527; for the recent use of arylguani-
dines, see: f) J. Shao, W. Chen, M. Giulianotti, R. A. Houghten, Y. Yu, Org.
Lett. 2012, 14, 5452–5455, and references cited therein.
Representative procedure B: ruthenium(II)-catalyzed oxida-
tive coupling with alkenes
A suspension of 1b (95.0 mg, 0.50 mmol), 4a (75.0 mg, 0.75 mmol),
[RuCl2(p-cymene)]2 (7.7 mg, 2.5 mol%), AgOAc (41.5 mg, 50 mol%),
and Cu(OAc)2·H2O (199 mg, 2.00 mmol) in DCE (2.0 mL) was stirred
at 1008C for 22 h under an atmosphere of N2. At ambient tempera-
ture, the reaction mixture was extracted with EtOAc (3ꢁ20 mL)
and the combined organic layers were washed with brine (20 mL)
and dried over Na2SO4. The solvent was evaporated in vacuo and
the remaining residue was purified by column chromatography on
silica gel (n-hexane/EtOAc 12:1) to yield product 5ba (105 mg,
73%) as a white solid.
Acknowledgements
Support by the European Research Council under the Europe-
an Community’s Seventh Framework Program (FP7 2007–
2013)/ERC Grant agreement no. 307535 and the Chinese Schol-
arship Council (fellowship to J.L.) is gratefully acknowledged.
Keywords: alkenylation
activation · reaction mechanisms · ruthenium
·
alkynes
·
annulation
·
CÀH
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Received: December 18, 2013
Published online on && &&, 0000
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Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
FULL PAPER
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CÀH Activation
J. Li, M. John, L. Ackermann*
&& – &&
Amidines for Versatile Ruthenium(II)-
Catalyzed Oxidative CÀH Activations
with Internal Alkynes and Acrylates
Ring road: Cationic ruthenium(II) com-
plexes allowed for efficient CÀH activa-
tion on (hetero)aryl amidines with al-
kynes and alkenes, thereby providing
a step-economical access to diversely
decorated isoquinolines and isoindo-
lines, respectively (see scheme).
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
7
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers! ÞÞ