Planar-chiral bis-silanols and diols as h-bonding asymmetric organocatalysts

Article abstract of DOI:10.1002/ejoc.201200548

The successful development of planar-chiral bis-silanols 3a-d and their application as asymmetric organocatalysts in hetero-Diels-Alder (HDA) reactions is described. All precursors were easily prepared by addition of commerically available silyl electrophiles to a dilithiated [2.2]paracyclophane derivative followed by silane oxidations. The analogous bis-carbinols 7a-c have been prepared by addition of suitable Grignard reagents to bis-methoxycarbonyl derivative 6. Both racemic as well as enantiopure planar-chiral bis-silanols and bis-carbinols were obtained in good yields. The catalytic activities of the bis-silanols were analyzed by monitoring HDA reactions between Rawal's diene and aldehydes by in situ IR spectroscopy and comparing the resulting data with those obtained in catalyses with the corresponding bis-carbinol derivatives. The results show for the first time that planar-chiral bis-silanols with hydrogen-bonding capabilities can be applied as asymmetric organocatalysts leading to enantiomerically enriched products. Enantiopure, planar-chiral [2.2]paracyclophane-based bis-silanols and their carbon diol analogs were synthesized and used as hydrogen-bond-donating organocatalysts in a hetero-Diels-Alder reaction with Rawal's diene.

Full text of DOI:10.1002/ejoc.201200548

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200548
Planar-Chiral Bis-silanols and Diols as H-Bonding Asymmetric
Organocatalysts
Christine Beemelmanns,[a][‡] Ralph Husmann,[a][‡‡] Daniel K. Whelligan,[a][‡‡‡]
Salih Özçubukçu,[a][‡‡‡‡] and Carsten Bolm*[a]
Keywords: Planar-chiral bis-silanols / Hydrogen bonds / Organocatalysis / Hetero-Diels–Alder reaction / Rawal’s diene
The successful development of planar-chiral bis-silanols 3a–
d and their application as asymmetric organocatalysts in het-
ero-Diels–Alder (HDA) reactions is described. All precursors
were easily prepared by addition of commerically available
silyl electrophiles to a dilithiated [2.2]paracyclophane deriva-
tive followed by silane oxidations. The analogous bis-carb-
inols 7a–c have been prepared by addition of suitable Grig-
nard reagents to bis-methoxycarbonyl derivative 6. Both ra-
cemic as well as enantiopure planar-chiral bis-silanols and
bis-carbinols were obtained in good yields. The catalytic ac-
tivities of the bis-silanols were analyzed by monitoring HDA
reactions between Rawal’s diene and aldehydes by in situ
IR spectroscopy and comparing the resulting data with those
obtained in catalyses with the corresponding bis-carbinol de-
rivatives. The results show for the first time that planar-chiral
bis-silanols with hydrogen-bonding capabilities can be ap-
plied as asymmetric organocatalysts leading to enantiomer-
ically enriched products.
context, we demonstrated the first application of organosil-
anols A (Figure 1) as chiral ligands in asymmetric aryl
transfer reactions.[7] Furthermore, we employed silylated
pyrrolidines as organocatalysts in the asymmetric Michael
addition of aldehydes to nitro olefins.[8] Recently, very much
work has been focused on the properties of silanediols
B.[9,10] Insightful computational and experimental studies
suggested them as potential organocatalysts, and first appli-
cations have already been demonstrated.[10] However, the
potential of chiral organosilanols as asymmetric organocat-
alysts is still largely unexplored. Here, we report on the first
syntheses of chiral bis-silanols C and their organocatalytic
applications in asymmetric HDA reactions.
Introduction
Hydrogen bonding plays a pivotal role in the field of ca-
talysis,[1] and it is the dominant activation mode in biocata-
lysis.[2] The first asymmetric organocatalytic hetero-Diels–
Alder (HDA) reaction based on activation by hydrogen
bonding was published by Rawal in 2003.[3] In the presence
of the simple chiral diol TADDOL reactions between alde-
hydes and 1-amino-3-siloxydienes occurred smoothly pro-
viding the corresponding products in moderate to very
good yields and in up to 98% ee. The field of organocata-
lysis has grown rapidly over the last decade, and the acti-
vation of substrates through covalent or Brønsted acid in-
teractions has proved to be a reliable approach to con-
structing stereogenic centers.[1]
Being both highly acidic and basic silanols undergo ex-
tensive hydrogen bonding among themselves as well as in
combination with other proton donors or acceptors.[4] Our
group has a long-standing interest in the synthesis and ap-
plication of silicon-containing compounds,[5,6] and in that
Figure 1. Silanols for catalysis.
[a] Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen, Germany
Fax: +49-241-8092391
E-mail: carsten.bolm@oc.rwth-aachen.de
[‡] New address: Harvard Medical School, BCMP,
240 Longwood Ave., Boston, MA 02115, USA
[‡‡] New address: Organisch-Chemisches Institut, Westfälische
Wilhelms-Universität, Corrensstrasse 40, 48149 Münster,
Germany
Results and Discussion
So far, planar-chiral [2.2]paracyclophanes have been pre-
dominately recognized as suitable scaffolds for phos-
phane[11] and heterocyclic carbene ligands.[12] Only lately
have their applications as organocatalysts been reported.[13]
We assumed that the rigid conformation of the [2.2]paracy-
clophane scaffold would result in a pincer-like arrangement
[‡‡‡] New address: Department of Chemistry, University of
Surrey, Guildford, GU2 7XH, UK
[‡‡‡‡] New address: Department of Chemistry, Middle East
Technical University, 06800 Ankara, Turkey
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200548.
Eur. J. Org. Chem. 2012, 3373–3376
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3373

C. Bolm et al.
SHORT COMMUNICATION
of the participating Si–OH groups allowing for an optimal Table 1. Oxidation of bis-silanes 2.
interaction with an H-bonding acceptor within a defined
distance.
Entry Substrate Oxidation method[a] T [°C] Yield [%][b]
1
2
3
4
5
6
7
8
9
2a
2a
2b
2b
2b
2c
2c
2c
2d
2d
2d
A
B
A
B
C
A
B
C
A
B
C
r.t.
50
50
r.t.
80
80
r.t.
60
60
r.t.
60
80
43
0
20
78
0
80
38
0
74
0
Several methods for the preparation of bis-silanols 3
starting from readily available racemic and enantiopure di-
bromide 1 were investigated (Scheme 1).[14] According to
known literature protocols dibromide 1 was treated with
tBuLi at –78 °C followed by addition of commerically avail-
able silyl electrophiles. First, cyclotrisiloxanes were tested
for the introduction of the desired silanol functionalities in
a one-pot procedure.[15] Unfortunately, after mild acidic
aqueous workup of the reaction mixture, no product could
be isolated. Subsequently, dichlorosilanes were investigated
as electrophiles. Following mild basic hydrolysis of the in-
termediate chlorosilane afforded the desired bis-silanol 3a
(R = Me) in only 10% yield.
10
11
[a] Method A: KMnO4; Method B: air/H2O, 5 mol-% of [Ir(1,5-
cod)Cl]2; Method C: m-CPBA. [b] After purification by column
chromatography.
With the long-term vision to broaden the structural vari-
ety of planar-chiral bis-silanols, the synthesis of an (achiral)
ferrocene-based bis-silanol was investigated (Scheme 2). In
this case, bis-silanol 5 was obtained in 23% yield through a
one-step procedure by quenching 1,1Ј-dilithiated ferrocene
with hexamethyltrisiloxane followed by treatment with di-
lute acid.
Scheme 2. Synthesis of ferrocene bis-silanol 5.
Scheme 1. Syntheses of [2.2]paracyclophane-based bis-silanols 3.
To test the hypothesis that, due to their increased acidity
and therefore H-bonding capacity, silanols have superior
organocatalytic properties to diols, catalysts 7a–c were pre-
pared. They were obtained in moderate to good yields when
diester 6 was treated with an excess of the appropriate Grig-
nard reagent (Scheme 3).[19]
After these rather disappointing initial results, a two-step
procedure to synthesize bis-silanols 3 was attempted. In the
first step, bis-silanes 2 were prepared in moderate to good
yields by treatment of dibromide 1 with tBuLi followed by
the addition of the corresponding monochlorosilanes to the
resulting dianionic intermediate. For the second step
towards bis-silanols 3 various oxidizing agents, including
KMnO4, m-CPBA and an Ir-catalyzed oxidation were
tested (Table 1).[16–18] Oxidation with KMnO4 (Method A)
was only effective with the sterically unhindered dimethyl-
substituted silyl group (Entry 1). Catalytic oxidation
(Method B) of substrate 2a using [Ir(1,5-cod)Cl]2 was less
effective, even at elevated temperature (Entry 2). Neither
Method A nor B afforded phenyl-substituted bis-silanol 3b
in reasonable yield (Entries 3 and 4). However, an improved
yield of 78% of 3b was achieved with m-CPBA as oxidant
(Method C, Entry 5). With sterically more demanding sub-
stituents on the silicon atom, oxidation with m-CPBA was
less effective when compared to the Ir-catalyzed hydrolytic
Scheme 3. Synthesis of [2.2]paracyclophane-based diols 7.
The catalytic properties of bis-silanols 3 and 5 as well as
oxidation (Entries 7, 8, 10 and 11). The enantiomerically diol 7 were explored in the HDA reaction of Rawal’s diene
pure silyl derivatives were obtained from enantiopure di- 8 with aldehyde 9a providing chiral 2,3-dihydropyran-4-one
bromide 1.[19] All obtained bis-silanols were solid, air-stable derivatives, which are important building blocks of many
compounds, which could be stored at 0 °C for weeks with- natural products with a broad range of biological ac-
out any indication of decomposition.
tivity.[20]
3374
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3373–3376

Planar-Chiral Bis-silanols and Diols
The activity and therefore hydrogen-bonding capabilities be explained by unproductive self-associative interactions in
of the new catalysts were measured by monitoring the cy- the more concentrated reaction mixture. Interestingly, diol
cloadditions by in situ IR spectroscopy.[19] Not unexpec- 7a afforded similar selectivities as bis-silanol 3a (Entries 2–
tedly, dimethyl-substituted derivatives 3a and 5 were the 4, 13 and 14). This observation indicates that for good
most active catalysts in terms of reaction rate and product asymmetric induction less acidic and less active catalysts
yield, giving the desired cycloaddition product 10a in up to are more beneficial. As expected from previous results, cata-
66% yield (Table 2, Entries 2, 3 and 6). The methyl substitu- lysts 3b and 3c were less enantioselective, possibly due to
ents seemed to be bulky enough to prevent self-condensa- the high steric hindrance of the substituents on the silicon
tion, but allowed suitable coordination of the H-bond ac- atom (Entries 11 and 12) preventing effective hydrogen
ceptor.[21] In comparison, using diol 7a as catalyst led to bonding and so providing an inadequate chiral environ-
dihydropyranone 10a in a slightly lower yield (42% yield, ment. Aromatic aldehydes reacted well affording the prod-
Entry 7) with a significantly reduced reaction rate.[19] The ucts in high yields; however, the ees were low (Entries 9 and
difference in activity between phenyl-substituted bis-silanol 10).
3b and diol derivative 7b (Entries 4 and 8) was smaller than
that between the methyl-substituted compounds (Entries 2
Table 3. Asymmetric HDA reaction using Rawal’s diene 8, alde-
hydes 9 and [2.2]paracyclophane-based organocatalysts.[a]
and 7). When the reaction with 7b was performed at ele-
vated temperatures (0 °C), the yield of 10a increased to 57%
(Entry 9). Sterically more demanding substituents on the
silicon and carbon atom hampered the coordination and
activation of the aldehyde leading to less than 25% product
formation (Entries 5 and 10). The results of these measure-
ments suggested that the strength of the hydrogen bonding
was correlated to both the acidity and the steric bulkiness
of the bis-silanols and diols.
Entry
Catalyst
(mol-%)
Aldehyde 9
Yield of 10
ee[c]
R
[%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
(Sp)-3a (20)
(Sp)-3a (100)
(Sp)-3a (20)
(Sp)-3a (5)
(Sp)-3a (100)
(Sp)-3a (20)
(Sp)-3a (5)
(Sp)-3a (20)
(Sp)-3a (20)
(Sp)-3a (20)
(Rp)-3b (20)
(Sp)-3c (20)
(Sp)-7a (20)
(Sp)-7a (5)
Et
nPr
nPr
nPr
iPr
iPr
iPr
iBu
Ph
2-furyl
nPr
nPr
nPr
nPr
43 (10b)
90 (10a)
45 (10a)
40 (10a)
50 (10c)
42 (10c)
35 (10c)
41 (10d)
80 (10e)
70 (10f)
38 (10a)
30 (10a)
45 (10a)
40 (10a)
10 (S)
37 (S)
27 (S)
20 (S)
44 (S)
44 (S)
39 (S)
40 (S)
Ͻ 5
20 (S)
17 (R)
Ͻ 10 (S)
40 (S)
36 (S)
Table 2. HDA reaction using Rawal’s diene 8, butanal (9a) and
[2.2]paracyclophane-based organocatalysts.[a]
Entry
Catalyst
Yield of 10a [%][b]
1
2
3
4
5
6
7
–
3a
3a[c]
3b
3c
5
7a
7b
7b
7c
0
50
45
38
23
66
42
35
57
17
[a] All reactions were carried out on a 0.17 mmol scale with
2.0 equiv. of aldehyde in toluene at –40 °C under nitrogen for 16 h.
[b] After workup with AcCl; products were isolated by flash col-
umn chromatography on silica gel. [c] The enantiomeric excess was
determined by HPLC using a Chiralcel OD-H column, and the
absolute configuration assigned by comparison with ref.[3b]
8
9[d]
10
[a] All reactions were carried out on a 0.74 mmol scale with
2.0 equiv. of butanal (9a) in toluene at –40 °C under nitrogen for
16 h. [b] After workup with AcCl; products were isolated by flash
column chromatography on silica gel. [c] Use of 5 mol-% of cata-
lyst. [d] Reaction was performed at 0 °C.
Conclusions
We have synthesized racemic and enantiomerically pure
planar-chiral bis-silanols and their corresponding carbinol
derivatives. Initial studies revealed their catalytic activities
in HDA reactions of aliphatic and aromatic aldehydes with
Rawal’s diene. Although only moderate enantioselectivities
have been achieved, the study presents the first applications
of chiral bis-silanols in asymmetric organocatalysis.
Having demonstrated the catalytic activities of the di-
methyl- and diphenyl-substituted derivatives, our attention
turned to asymmetric catalyses with enantiopure planar-
chiral bis-silanols 3a–c and carbinol 7a (Table 3). The best
results were obtained with sterically more encumbered alde-
hydes such as isobutyraldehyde (Entry 6) or isovaleral-
dehyde (Entry 8) yielding up to 42% of the corresponding
products with enantiomeric excesses of up to 44% in favour
of the (S) enantiomer. Unfortunately, using stoichiometric
quantities of bis-silanol 3a (Entries 2 and 5) afforded nei-
Experimental Section
General Procedure for Catalysis: Diene 8 (0.17 mmol) and the cata-
lyst (20 mol-%) were dissolved in toluene (0.8 mL). After cooling
to –40 °C, the freshly distilled, dry aldehyde
9 (0.34 mmol,
ther full conversion nor the expected higher ee, which might 2.0 equiv.) was added, and the mixture stirred for 16 h. The solu-
Eur. J. Org. Chem. 2012, 3373–3376
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3375

C. Bolm et al.
SHORT COMMUNICATION
[8] a) R. Husmann, M. Jörres, G. Raabe, C. Bolm, Chem. Eur. J.
2010, 16, 12549–12552; b) J. O. Bauer, J. Stiller, E. Marqués-
López, K. Strohfeldt, M. Christmann, C. Strohmann, Chem.
Eur. J. 2010, 16, 12553–12558; c) K. I. Jentzsch, T. Min, J. I.
Etcheson, J. C. Fettinger, A. K. Franz, J. Org. Chem. 2011, 76,
7065–7075.
[9] For recent contributions describing the use of silanediols as
peptidomimetic enzyme inhibitors, see: a) D. Hernández, K. B.
Lindsay, L. Nielsen, T. Mittag, K. Bjerglund, S. Friis, R. Mose,
T. Skrydstrup, J. Org. Chem. 2010, 75, 3283–3293; b) J. K. Kim,
S. McN. Sieburth, J. Org. Chem. 2012, 77, 2901–2906, and ref-
erences therein.
[10] a) S. Kondo, T. Harada, R. Tanaka, M. Unno, Org. Lett. 2006,
8, 4621–4624; b) M. Liu, N. T. Tran, A. K. Franz, J. K. Lee, J.
Org. Chem. 2011, 76, 7186–7194; c) N. T. Tran, T. Min, A. K.
Franz, Chem. Eur. J. 2011, 17, 9897–9900; d) A. G. Schafer,
J. M. Wieting, A. E. Mattson, Org. Lett. 2011, 13, 5228–5231;
e) N. T. Tran, S. O. Wilson, A. K. Franz, Org. Lett. 2012, 14,
186–189.
[11] a) D. K. Whelligan, C. Bolm, J. Org. Chem. 2006, 71, 4609–
4618; b) C. Bolm, D. K. Whelligan, Adv. Synth. Catal. 2006,
348, 2093–2100; for reviews, see: c) S. E. Gibson, J. D. Knight,
Org. Biomol. Chem. 2003, 1, 1256–1269; d) G. J. Rowlands,
Org. Biomol. Chem. 2008, 6, 1527–1534.
[12] a) C. Bolm, T. Focken, G. Raabe, Tetrahedron: Asymmetry
2003, 14, 1733–1746; b) T. Focken, J. Rudolph, C. Bolm, Syn-
thesis 2005, 429–436; c) A. Fürstner, M. Alcarazo, H. Krause,
C. W. Lehmann, J. Am. Chem. Soc. 2007, 129, 12676–12677; d)
for a new approach, see: P. Lennartz, G. Raabe, C. Bolm, Isr.
J. Chem. 2012, 52, 171–179.
[13] a) D. C. Braddock, I. D. MacGilp, B. G. Perry, Adv. Synth. Ca-
tal. 2004, 346, 1117–1130; b) J. F. Schneider, F. C. Falk, R.
Fröhlich, J. Paradies, Eur. J. Org. Chem. 2010, 2265–2269; c)
J. R. Fulton, J. E. Glover, L. Kamara, G. J. Rowlands, Chem.
Commun. 2011, 47, 433–435; d) see also: J. Paradies, Synthesis
2011, 3749–3766; e) for a special issue on the chemistry of
[2.2]paracyclophanes, see: Isr. J. Chem. 2012, 52, 18–192.
[14] a) H. J. Reich, D. J. Cram, J. Am. Chem. Soc. 1969, 91, 3527–
3533; b) P. J. Pye, K. Rossen, R. A. Reamer, N. N. Tsou, R. P.
Volante, P. J. Reider, J. Am. Chem. Soc. 1997, 119, 6207–6208;
c) D. C. Braddock, I. D. MacGilp, B. G. Perry, J. Org. Chem.
2002, 67, 8679–8681.
tion was then cooled to –78 °C, diluted with dichloromethane
(5 mL) and treated with acetyl chloride (0.34 mmol, 2.0 equiv.). Af-
ter stirring at –78 °C for 20 min, the reaction mixture was warmed
to room temp., and satd. aq. NaHCO3 (15 mL) was added. The
aqueous layer was separated and extracted with diethyl ether (3
times). The combined organic phases were dried with MgSO4, fil-
tered and concentrated. The resulting liquid was subjected to col-
umn chromatography [pentane, pentane/diethyl ether (4:1), (3:1)] to
afford dihydropyranones 10 as pale yellow oils.
Supporting Information (see footnote on the first page of this arti-
cle): Analytical data for all compounds, summary of ReactIR mea-
surements, general procedure for the catalysis, NMR spectra.
Acknowledgments
We are grateful to the Fonds der Chemischen Industrie (FCI) and
the Deutsche Forschungsgemeinschaft (DFG) within the SPP 1179
(“Organocatalysis”) for financial support. C. Beemelmanns thanks
the Studienstiftung des deutschen Volkes and the FCI for fellow-
ships during her undergraduate and graduate studies, and D. K. W.
acknowledges the Alexander-von-Humboldt-Stiftung for a post-
doctoral fellowship.
[1] a) M. Meot-Ner (Mautner), Chem. Rev. 2005, 105, 213–284;
b) I. Rozas, Phys. Chem. Chem. Phys. 2007, 9, 2782–2790; c)
Hydrogen Bonding in Organic Synthesis (Ed.: P. Pihko), Wiley-
VCH, Weinheim, 2009; for reviews on hydrogen-bond-medi-
ated catalysis, see: d) P. R. Schreiner, Chem. Soc. Rev. 2003, 32,
289–296; e) C. Bolm, T. Rantanen, I. Schiffers, L. Zani, Angew.
Chem. 2005, 117, 1788–1793; Angew. Chem. Int. Ed. 2005, 44,
1758–1763; f) M. S. Taylor, E. N. Jacobsen, Angew. Chem.
2006, 118, 1550–1573; Angew. Chem. Int. Ed. 2006, 45, 1520–
1543; g) A. G. Doyle, E. N. Jacobsen, Chem. Rev. 2007, 107,
5713–5743; h) X. Yu, W. Wang, Chem. Asian J. 2008, 3, 516–
532; i) P. Merino, I. Delso, T. Tejero, D. Roca-Lopez, A. Isasi,
R. Matute, Curr. Org. Chem. 2011, 15, 2184–2209.
[2] Modern Biocatalysis: Stereoselective and Environmentally
Friendly Reactions (Eds.: W.-D. Fessner, T. Anthonsen), Wiley-
VCH, Weinheim, 2009.
[3] a) Y. Huang, A. K. Unni, A. N. Thadani, V. H. Rawal, Nature
2003, 424, 146; b) A. K. Unni, N. Takenaka, H. Yamamoto,
[15] S. McN. Sieburth, W. Mu, J. Org. Chem. 1993, 58, 7584–7586.
[16] P. D. Lickiss, R. Lucas, J. Organomet. Chem, 1996, 521, 229–
234.
V. H. Rawal, J. Am. Chem. Soc. 2005, 127, 1336–1337; c) for [17] Y. Lee, D. Seomoon, S. Kim, H. Han, S. Chang, P. H. Lee, J.
mechanistic work see: X. Zhang, H. Du, Z. Wang, Y.-D. Wu,
K. Ding, J. Org. Chem. 2006, 71, 2862–2869.
[4] V. Chandrasekhar, R. Boomishankar, S. Nagendran, Chem.
Rev. 2004, 104, 5847–5910.
Org. Chem. 2004, 69, 1741–1743.
[18] a) Y. Nagai, K. Honda, T. Migita, J. Organomet. Chem. 1967,
8, 372–373; b) L. H. Sommer, L. A. Ulland, G. A. Parker, J.
Am. Chem. Soc. 1972, 94, 3469–3471.
[5] a) C. Bolm, A. Kasyan, K. Drauz, K. Günther, G. Raabe, An-
gew. Chem. 2000, 112, 2374–2376; Angew. Chem. Int. Ed. 2000,
39, 2288–2290; b) M. Mortensen, R. Husmann, E. Veri, C.
Bolm, Chem. Soc. Rev. 2009, 38, 1002–1010.
[6] a) C. Bolm, A. Kasyan, P. Heider, S. Saladin, K. Drauz, K.
Günther, C. Wagner, Org. Lett. 2002, 4, 2265–2267; b) C. Bolm,
S. Saladin, A. Kasyan, Org. Lett. 2002, 4, 4631–4633; c) C.
Bolm, S. Saladin, A. Claßen, A. Kasyan, E. Veri, G. Raabe,
Synlett 2005, 461–464; d) C. Bolm, A. Kasyan, S. Saladin, Tet-
rahedron Lett. 2005, 46, 4049–4051.
[19] For more details, see Supporting Information.
[20] For examples, see: a) K. A. Jørgensen, Angew. Chem. 2000,
112, 3702–3733; Angew. Chem. Int. Ed. 2000, 39, 3558–3588;
b) T. Tozawa, H. Nagao, Y. Yamane, T. Mukaiyama, Chem.
Asian J. 2007, 2, 123–134 and references cited therein.
[21] For a review on the activation of carbonyl groups by Brønsted-
acid-assisted Brønsted acid interactions including intra- and
intermolecular H-bonding (single-point activation), see: H. Ya-
mamoto, K. Futatsugi, Angew. Chem. 2005, 117, 1958–1977;
Angew. Chem. Int. Ed. 2005, 44, 1924–1942.
[7] S. Özçubukçu, F. Schmidt, C. Bolm, Org. Lett. 2005, 7, 1407–
1409.
Received: April 25, 2012
Published Online: May 16, 2012
3376
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3373–3376