Readily available hydrogen bond catalysts for the asymmetric transfer hydrogenation of nitroolefins

Article abstract of DOI:10.1039/c1ob05059a

This paper focuses on readily accessible thiourea hydrogen bond catalysts derived from amino acids, whose steric and electronic features are modulated by their degree of substitution at the carbinol carbon center. These catalysts were applied in the asymmetric transfer hydrogenation of nitroolefins furnishing the chiral products in up to 99% yield and 86% enantiomeric excess. The proposed catalyst's mode of action is supported by mechanistic investigations.

Full text of DOI:10.1039/c1ob05059a

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PAPER
Readily available hydrogen bond catalysts for the asymmetric transfer
hydrogenation of nitroolefins†
Jakob F. Schneider, Markus B. Lauber, Vanessa Muhr, Domenic Kratzer and Jan Paradies*
Received 11th January 2011, Accepted 14th March 2011
DOI: 10.1039/c1ob05059a
This paper focuses on readily accessible thiourea hydrogen bond catalysts derived from amino acids,
whose steric and electronic features are modulated by their degree of substitution at the carbinol carbon
center. These catalysts were applied in the asymmetric transfer hydrogenation of nitroolefins furnishing
the chiral products in up to 99% yield and 86% enantiomeric excess. The proposed catalyst’s mode of
action is supported by mechanistic investigations.
Introduction
Results and Discussion
The hydrogenation of nitroolefins and nitro acrylates yields
chiral nitro compounds, thus offering an efficient access to
chiral b-amines and b -amino acid derivatives. Chiral amines
The bifunctional13 thiourea structures14 were obtained from the
reaction of commercially available and readily accessible amino
alcohols with 3,5-(trifluormethylphenyl)thioisocyanate (Fig. 1, see
ESI† for synthetic procedures and full characterization). The
synthesized bifunctional thiourea derivatives (Fig. 1) differ in the
degree of substitution at the carbinol carbon atom (1a–1p) and can
thus be divided into three classes: structures bearing a tertiary,
secondary or primary alcohol functionality. This feature allows
studying the catalyst’s performance depending on the degree
of substitution at the carbinol functionality. The results of the
hydrogen bond mediated asymmetric transfer hydrogenation of
(E)-2-phenyl-1-nitro-propene (2a) with tert-butyl-Hantzsch’s ester
(3) are summarized in Table 1.
2
are extensively used as chiral building blocks, as resolving
agents or as chiral auxiliaries.1 Amino acid derivatives play an
important role in the generation of artificial peptide structures.
This multifaceted application of amines makes the synthesis of
enantiopure nitrogen-containing compounds an attractive field of
research. A biomimetic access to enantiopure nitro-compounds
by transfer hydrogenation of nitroolefins2 and nitroacrylates3 with
Hantzsch’s esters4,5 was first described by List et al. The applied
monofunctional cyclohexyl-diamine-derived thiourea catalysts6
furnished the hydrogenated products in excellent yields and
enantioselectivities. Apart from those Jacobsen-type catalysts,
amino alcohol related thiourea derivatives7 have been success-
fully employed in the Morita–Baylis–Hilmann reaction,8 in the
conjugate addition,9,10 in the Diels–Alder reaction11 and in the
Friedel–Crafts–alkylation of indole with nitroolefins.12 In the latter
report Ricci et al. discussed the interaction of a highly polarized
indole-NH with an alcohol group as being essential for activity
and enantioselectivity.12
Our report introduces readily available amino-alcohol-derived
thiourea structures as new catalysts for the asymmetric hydrogen
bond mediated transfer hydrogenation of nitroolefins. Our in-
vestigations show that the dihydropyridine-NH-bond (Hantzsch’s
ester) significantly contributes to the efficiency and enantioselec-
tivity of the asymmetric hydrogen transfer promoted by hydroxy
substituted thiourea derivatives.
Karlsruhe Institute of Technology, Institute of Organic Chemistry, Fritz-
Haber-Weg 6, Karlsruhe, Germany. E-mail: jan.paradies@kit.edu; Fax: +49
721 608 45637; Tel: +49 721 608 45344
† Electronic supplementary information (ESI) available: detailed experi-
mental procedures, analytical data and HPLC traces can be obtained from
the author or from the web. See DOI: 10.1039/c1ob05059a
Fig. 1 Bifunctional thiourea catalysts derived from amino alcohols (ArF =
3,5-(CF3)2–C6H3).
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Table 1 Asymmetric transfer hydrogenation of 2
carbinol functionality (entries 9–11). The ethylene spacer group
in the catalyst’s structure proved to be optimal for transfer
hydrogenation. The 2-amino-2-phenyl propanol derived catalyst
1k provided the product in 78% yield and 50% ee (entry 12). For
this reason we investigated the efficiency of the thiourea derivatives
depending on the bulkiness of the alkyl chain at the stereogenic
carbon center (entries 13–17). Surprisingly, the smallest alkyl
group, such as a methyl group (1l), already generated a highly
efficient catalyst (entry 13, 99% yield and 61% ee). Moving along in
the series of iPr (1m), Bn (1n), sBu (1o) and tBu (1p) (entry 14–17)
the enantioselectivity of the catalyzed process gradually improved
to 70% ee while the excellent activity of the catalyst was preserved
(91–99%). When the reaction was prefromed in diethylether 4a
was obtained with 77% ee but with unsatisfactory yield (55%
see ESI† for further optimization studies).17 To demonstrate that
both enantiomers of the saturated product 4a are accessible by
this methodology, we conducted the reaction with the catalyst’s
enantiomer epi-1p. The hydrogenation of 2a furnished the S-
configured product in quantitative yield with 65% enantiomeric
excess (entry 18).
We then turned our interest to the substrate scope for the
thiourea-catalyzed transfer hydrogenation of unsaturated nitro
compounds using our best performing catalyst 1p (Table 2). All
substrates were converted to the saturated nitro compounds in
good to excellent yields (84–99%). However, the enantioselectivity
of these transformations differed significantly depending on the
substitution pattern. Methyl-aryl-substituted nitroolefins were
obtained with an enantiomeric excess of 50–70% (entries 1–6).
Electron withdrawing as well as electron donatin groups on the aryl
ring are tolerated and the products were furnished with 50–67% ee.
Higher enantioselectivities up to 87% ee were observed for nitro
alkenes bearing bulkier substituents (entry 8, tBu). Additionally,
the thiourea 1p showed excellent activity in the reduction of nitro
acrylates (Table 3). The products 6a–6c were formed in excellent
yield. Surprisingly, the methyl (6a), ethyl (6b) and ipropyl (6c)
esters were obtained with almost the same enantiomeric excess
(54–60% ee) revealing an unique opportunity to synthesize a wide
variety of ester derivatives.
In order to comprehend the varied performance of the syn-
thesized catalysts a hydrogen-bonded structure can be conceived.
The formation of a ternary complex incorporating the thiourea
derivative (1p), the nitroolefin (4a) and the reducing agent 3 can
serve as a rationalization for the observed activities and enan-
tioselectivities. Literature precedent supports the assumption that
hydroxyl groups are beneficial for organocatalytic transformations
where polarized N–H bonds are involved.2c,11,12 The formation of
a N–H ◊ ◊ ◊ O hydrogen bond between a heterocycle and the catalyst
has already been proposed and investigated for the Friedel–Crafts
alkylation of indole.12 We decided to study the role of the hydroxy
group of our catalyst in the asymmetric transfer hydrogenation by
selective suppression of important substrate-catalyst interactions.
For this purpose we identified two significant interactions apart
from the nitro-thiourea-interaction: 1) hydrogen-bonding between
the nitro- and the hydroxy group (N O ◊ ◊ ◊ H–O); 2) hydrogen-
bonding between the Hantzsch’s ester and the hydroxy-group (N–
H ◊ ◊ ◊ O) (Scheme 1).
Entry
Catalyst
Yield (%)a
ee (%)b
1c
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
—
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
5
n.d.
81
72
26
46
39
31
70
90
88
99
78
99
91
99
94
99
99
<5 (S)d
13 (S)
<5 (R)
11 (R)
<5 (S)
16 (R)
20 (R)
40 (S)
62 (R)
61 (S)
50 (S)
61 (R)
67 (R)
60 (R)
67 (R)
70 (R)
65 (S)
1m
1n
1o
1p
epi-1p
a Yields were determined by GC with dodecane as the internal standard.
b The enantiomeric excess was determined after purification on silica gel by
HPLC with chiral stationary phase. c Reaction was performed at 40 ◦C in
toluene; n.d. not determined. d The absolute configuration was determined
by comparison with literature values (see ESI†).
Generally, the reaction is catalyzed by hydroxy-functionalized
thiourea derivatives. Catalysts bearing tertiary alcohol groups
furnished the nitro alkane 4a in good yields (entries 2 and
3), while the tryptophan-derived catalyst (1c, entry 4) was not
sufficiently active. The C2-symmetric catalysts 1d–1f (entries 5–7)
were generally less active than the corresponding unsymmetrical
thiourea derivatives. Although the catalysts 1a and 1b displayed
good activity, the enantioselectivity achieved was low (<20%
ee). Catalysts featuring a secondary alcohol function were more
active and furnished 4a in 70–90% yield (entries 8–10). Diverging
activities and enantioselectivities were observed for 1g and 1i
(entries 8 and 10, 70% yield, 20% ee and 88% yield, 62% ee)
resulting from the relative configuration of the 1,2-amino alcohol
fragment. This may be rationalized by assuming that different
conformers in 1g and 1i are present in solution. The conformations
of ephedrine- and 1,2-diphenyl-2-amino ethanol derivatives have
been studied in solid state15 and in solution by NMR.16 In most
cases the gauche conformation, featuring an internal hydrogen
bond, has been identified by coupling-constant analysis of the
vicinal protons as the most abundant conformer. However, the
catalyst systems 1g–i proved too dynamic on the NMR timescale
for coupling-constant analysis. The 2-amino-2-phenyl ethanol
substructure in catalyst 1j is isomeric to structure 1h. The catalyst
1j features a primary hydroxy functionality and furnished the
hydrogenation product 4a in high yield (entry 11, 99% yield). The
enantioselectivity is improved to 61% ee compared to catalyst 1h
(entry 9). This indicates that the transfer of stereo information
(from the catalyst to the product) is more efficient from the
chiral vicinity of the thiourea moiety than from the asymmetric
1) To suppress the simultaneous binding of the nitro-compound
to the thiourea and the hydroxy group the silylated thiourea 7 was
synthesized. In this structure, the postulated coordination of the
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Table 2 Substrate scope for the catalyzed transfer hydrogenation of nitroolefins
Entry
Nitroolefin
Product
Yield (%)a
ee (%)b
1
2
3
4
5
6
R = H
(2a)
(2b)
(2c)
(2d)
(2e)
(2f)
4a
4b
4c
4d
4e
4f
99
99
99
97
95
88
70
50
62
67
63
56
R = Me
R = OMe
R = Cl
R = F
R = CN
7
8
R = Et
R = tBu
(2g)
(2h)
4g
4h
95
76
68
87
9
84c
40
(2i)
(4i)
a After purification by column chromatography. b The enantiomeric excess was determined by HPLC with chiral stationary phase. c The yield was
determined by GC with dodecane as the internal standard.
Table 3 Asymmetric reduction of nitroacrylates
2) The significance of the Lewis-basic oxygen atom in the
proposed N–H ◊ ◊ ◊ O-interaction was demonstrated by two exper-
iments: by the complete removal of the hydroxy functionality
and by masking the NH-group of the Hantzsch’s ester (3 → 9)
with a methyl group (Scheme 1b and 1c). The defunctionalized
thiourea-derivative 8 afforded the saturated nitro-compound 4a
as racemic material in DCE and Et2O (Scheme 1b). Consequently,
the complete removal of the Lewis-basic oxygen atom from
the catalysts structure generated an unselective catalyst. This
underlines the importance of the hydroxy-functionality tethered to
the catalyst for an enantioselective reaction. Use of the protected
Hantzsch’s ester 919 together with our best catalyst 1p and one
equivalent of ethanol as a proton source20 also furnished the
product 4a as racemic material (Scheme 1c, 30% yield). The
control experiment using 3 and one equiv. of ethanol as proton
source supplied 4a in 90% yield with significant enantioenrich-
ment (Scheme 1d, 50% ee). Hence, the constructive interaction
between the catalyst and the Hantzsch’s ester is essential for the
enantioselective hydrogen transfer. This conclusion is supported
by the fact, that racemic 4a was obtained when DMSO was
applied as cosolvent (DMSO/DCE, 1 : 1; see ESI†) under best
reaction conditions. Concluding this experimental data set, a
ternary complex consisting of the catalyst (1p), the nitroolefin
(2a) and the Hantzsch’s ester (3) as transient species according to
Fig. 2 seems instructive.
Entry
Nitroacrylate
Product
Yield (%)a
ee (%)b
1
2
3
R = Me (5a)
R = Et (5b)
R = iPr (5c)
6a
6b
6c
95
99
93
60
58
54
a after purification by column chromatograpy; b the enantiomeric excess
was determined by HPLC with chiral stationary phase.
nitro-compound by both the thiourea- and the hydroxy-group is
not possible, while the interaction of the Hantzsch’s ester (3) to the
Lewis-basic oxygen atom is still feasible.18 The application of 7 in
the transfer hydrogenation of 2a furnished the product 4a in lower
yield and in slightly diminished enantioselectivity (52% yield, 51%
ee; Scheme 1a). This may be explained by the lack additional
hydrogen bonds between the hydroxy- and nitro-functionality.
Additionally, the free hydroxy group in 1p might facilitate the
proton transfer to the formed nitronate species from the conjugate
hydride attack to the nitroolefin. To probe the interaction of the
nitro group with the unmasked hydroxy group in 1p we conducted
1H NMR experiments. However, the addition of 0.5, 1.0, 5.0 and
10 equiv. of nitroolefin 2a to a 0.2 M solution of catalyst 1p did not
result in significant changes in the 1H NMR-spectrum (see ESI†).
The catalyst is able to coordinate the nitroolefin in two different
ways: one in which the hydroxy group is located on the Re-face of
the nitroolefin (Fig. 2 left) and one in which the hydroxy group is
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ester (3) to avoid steric interactions of the tBu-group with the
catalyst’s side chain, resulting in the hydride delivery to the Si-face
with 76% yield and 87% enantiomeric excess.
Conclusions
We have disclosed an efficient synthesis and derivatization of chiral
bifunctional thiourea catalysts for the asymmetric transfer hydro-
genation of nitroolefins. The configurational features of 1i and 1g
led us to the development of highly active and enantioselective
catalyst structures, e.g. 1p. This catalyst displayed a rather wide
substrate scope and furnished the products in excellent yields (up
to 99%) and moderate to good enantioselectivities (up to 87%
ee). The mode of action of the catalyst was probed by selective
suppression of three distinct substrate-catalyst interactions. These
mechanistic investigations suggest a transient, ternary substrate-
catalyst-structure for the described enantioselective transfer hy-
drogenation of nitroolefins.
Experimental section
N-((S)-(2-amino-3,3-dimethylbutanol))-N¢-(3,5-bis-(trifluoro-
methyl)phenyl)thiourea (1p)
To
a solution of (S)-tert-leucinol (800 mg, 6.83 mmol,
1.0 equiv.) in dry CH2Cl2 (7.0 mL) was added 3,5-
bis(trifluoromethyl)phenylisothiocyanate (1.37 mL, 7.51 mmol,
1.10 equiv.). After stirring at 40 ◦C for 3 h, the solvent was removed
under reduced pressure. The crude product was purified by column
chromatography (SiO2, cyclohexane/ethyl acetate 80/20 v/v).
The compound was obtained as a white foamy solid (2.49 g,
6.40 mmol, 94%). m.p. 56 ◦C (capillary); Rf (cyclohexane/ethyl
acetate, 80 : 20) = 0.34; [a]2D0 -75.6 (c 0.5 in chloroform); dH
(400 MHz, acetone-d6) 9.50 (br s, 1H, OH), 8.38 (s, 2H, HAr),
7.67 (s, 1H, HAr), 7.58 (d, J = 7.4 Hz, 1H, NH), 4.64–4.55 (m, 1H,
CH), 3.94–3.83 (m, 2H, CH2, NH), 3.81–3.73 (m, 1H, CH2), 1.04
(s, 9H, CH3); dC (100 MHz, acetone-d6) 184.0 (C S), 144.1 (CAr),
132.9 (q, J = 33.0 Hz, 2C, CCF3), 125.4 (q, J = 271.9 Hz, 2C, CF3),
123.9 (2C, CHAr), 118.1 (CHAr), 64.8 (CH), 62.9 (CH2), 36.4
(C), 28.6 (3C, CH3) ppm; dF (376 MHz, CDCl3) -63.10 (m, 6F,
CF3); IR (Platinum ATR) nmax/cm-1 3265 (vw), 2965 (vw), 1532
(w), 1471 (vw), 1379 (w), 1342 (vw), 1273 (m), 1169 (w), 1124 (m),
1042 (w), 996 (vw), 972 (vw), 885 (w), 847 (vw), 700 (w), 680 (w),
571 (vw), 401 (vw); MS (FAB), m/z 389.1 ([M + H]+, 100%), 370.1
(20%), 355.1 (10%), 289.1 ([C9H7F6N2S]+, 15%); HRFABMS calcd
for C15H19F6N2OS: 389.1119, found 389.1122 [M + H]+; elemental
analysis: Found: N 6.97, C 45.97, H 4.51. C15H18F6N2OS requires
N 7.21, C 46.39, H 4.67.
Scheme 1 Mechanistic investigations for the enantioselective transfer
hydrogenation catalyzed by 1p.
Fig. 2 Postulated ternary substrate-catalyst complex leading to the
stereoselective hydride transfer.
located on the Si-face (Fig. 2 right). This results in the selective
delivery of the hydride to the enantiotopic faces, hence determining
the stereoselectivity of the reduction.21 The coordination of the
nitroolefin for the Re-face attack is less stabilized by encountering
steric clashes between the methyl group and the catalyst (Fig. 1
left). On the contrary, the coordination of the nitroolefin for the Si-
face attack is favored because now the vinylic hydrogen atom in 2a
is oriented towards the catalyst’s backbone resulting in lower steric
interactions. This model supports our experimental observations
of high selectivity with bulky substrates, together with the observed
stereochemical outcome of the product. Nitroolefin 2h (tBu-Ph)
should coordinate with its Si-face pointing towards the Hantzsch’s
Procedure for the asymmetric transfer hydrogenation of
nitroolefins and nitroacrylates
A solution of the respective nitroolefin or nitro acrylate (0.3 mmol)
in dichloroethane (0.3 mL) was cooled to 0 ◦C. Subsequently
catalyst 1p (0.06 mmol) and tBu-Hantzsch’s ester 3 (0.36 mmol)
were added successively as a solid. The reaction was stirred at
◦
0 C for 3 d. The mixture was diluted with pentane/Et2O (99 : 1
v/v, 0.7 mL) and subjected to column chromatography (SiO2,
pentane/Et2O 99 : 1–98 : 2 v/v for nitroalkanes and 95/5 v/v for
esters).
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(R)-2-(4-Methylphenyl)-1-nitropropane (4a)
H (250 MHz, CDCl3) 7.45–7.23 (m, 5H, HAr), 4.63–4.46 (m, 2H,
CH2NO2), 3.75–3.59 (m, 1H, CH), 1.42 (d, J = 7.0 Hz, 3H, CH3);
dC (125 MHz, CDCl3) 140.8 (C), 129.0 (2C, CHAr), 127.6 (CHAr),
126.9 (2C, CHAr), 81.9 (CH2), 38.6 (CH), 18.7 (CH3).
Soc., 2006, 128, 7170–7171; (l) D. A. Yalalov, S. B. Tsogoeva and S.
Schmatz, Adv. Synth. Catal., 2006, 348, 826–832; (m) M. P. Lalonde,
Y. G. Chen and E. N. Jacobsen, Angew. Chem., 2006, 118, 6514–6518;
Angew. Chem., Int. Ed., 2006, 45, 6366–6370; (n) T. Takemoto, Org.
Biomol. Chem., 2005, 3, 4299–4306; (o) P. R. Schreiner, Chem. Soc.
Rev., 2003, 32, 289–296.
d
8 A. Lattanzi, Synlett, 2007, 2106–2110.
9 M. P. Sibi and K. Itoh, J. Am. Chem. Soc., 2007, 129, 8064–8065.
10 R. P. Herrera, D. Monge, E. Martin-Zamora, R. Fernandez and J. M.
Lassaletta, Org. Lett., 2007, 9, 3303–3306.
11 (a) C. Gioia, L. Bernardi and A. Ricci, Synthesis, 2010, 161–170; (b) C.
Gioia, A. Hauville, L. Bernardi, F. Fini and A. Ricci, Angew. Chem.,
Int. Ed., 2008, 47, 9236–9239, Angew. Chem. Int. Ed., 2008, 120, 9376–
9379.
12 P. R. Herrera, V. Sgarzani, L. Bernardi and A. Ricci, Angew. Chem.,
2005, 117, 6734–6737; Angew. Chem., Int. Ed., 2005, 44, 6576–6579.
13 J. A. Ma and D. Cahard, Angew. Chem., Int. Ed., 2004, 43, 4566–4583;
Angew. Chem., 2004, 116, 4666–4683.
Acknowledgements
We acknowledge the Fond der Chemischen Industrie for a Kekule´-
Grant to J. F. Schneider and a Liebig-Grant to J. Paradies. This
work was also supported by a Grant to M. B. Lauber from the
Landesgraduiertenfo¨rderung of the State of Baden-Wu¨rttemberg.
We like to thank Prof. Stefan Bra¨se for his kind support.
14 the synthesis of the thiourea derivatives 1j, 1k and 1p have been
reported, but were not applied in hydrogen bond catalysis; 1j and 1k
were reported as racemic mixtures see: (a) S. F. Nielsen, A. Kharazmi
and M. Larsen, Chem. Abstr., 2008, 148, 471720WO 2008043840;
(b) F. Z. Dorwald, J. B. Hansen, J. P. Mogensen, T. M. Tagmose, B.
Pirotte, P. Lebrun, P. De Tullio and S. Boverie, Chem. Abstr., 1999, 130,
196306WO9907672 for 1p see: I. J. Munslow, A. R. Wade, R. J. Deeth
and P. Scott, Chem. Commun., 2004, 2596–2597.
15 (a) E. A. Collier, R. J. Davey, S. N. Black and R. J. Roberts, Acta
Crystallogr., Sect. B: Struct. Sci., 2006, 62, 498–505; (b) R. A. Hearn,
G. R. Freeman and C. E. Bugg, J. Am. Chem. Soc., 1973, 95, 7150–
7154; (c) A. Gorman, R. O. Gould, A. M. Gray, P. Taylor and M. D.
Walkinshaw, J. Chem. Soc., Perkin Trans. 2, 1986, 739–746.
16 (a) H. Tsai and J. D. Roberts, Magn. Reson. Chem., 1992, 30, 828–830;
(b) J. W. Huffman and R. P. Elliott, J. Org. Chem., 1965, 30, 365–367;
(c) W. J. Close, J. Org. Chem., 1950, 15, 1131–1134; (d) J. B. Hyne,
Can. J. Chem., 1961, 39, 2536–2542.
Notes and references
1 (a) H. Murakami, in Novel Optical Resolution Technologies (Ed.:
K. Sakai), Springer, Berlin, 2007, p. 288; (b) D. Enders, Tetrahedron:
Asymmetry, 1997, 8, 1895–1946; (c) R. M. Barmore, S. R. Logan and
B. C. VanWagenen, Tetrahedron Lett., 1998, 39, 3451–3454.
2 (a) J. F. Schneider, F. C. Falk, R. Fro¨hlich and J. Paradies, Eur. J. Org.
Chem., 2010, 12, 2265–2269; (b) A. Fryszkowska, K. Fisher, J. M.
Gardiner and G. M. Stephens, J. Org. Chem., 2008, 73, 4295–4298;
(c) N. J. A. Martin, L. Ozores and B. List, J. Am. Chem. Soc., 2007,
129, 8976–8977; (d) M. A. Swiderska and J. D. Stewart, Org. Lett.,
2006, 8, 6131–6133.
3 N. J. A. Martin, X. Cheng and B. List, J. Am. Chem. Soc., 2008, 130,
13862–13863.
4 For reviews on organocatalytic transfer hydrogenation see: (a) S. L.
You, Chem.–Asian J., 2007, 2, 820–827; (b) S. G. Ouellet, A. M. Walji
and D. W. C. MacMillan, Acc. Chem. Res., 2007, 40, 1327–1339; (c) S. J.
Connon, Org. Biomol. Chem., 2007, 5, 3407–3417.
17 The conditions for the transfer hydrogenation with 1p were further
explored, but did not lead to any significant enhancement in activity or
selectivity (see ESI†).
5 For thiourea-catalyzed transfer hydrogenation see: (a) Z. G. Zhang and
P. R. Schreiner, Synlett, 2007, 1455–1457; (b) D. Menche, S. Bohm, J.
Li, S. Rudolph and W. Zander, Tetrahedron Lett., 2007, 48, 365–369;
(c) D. Menche, J. Hassfeld, J. Li, G. Menche, A. Ritter and S. Rudolph,
Org. Lett., 2006, 8, 741–744; (d) D. Menche and F. Arikan, Synlett,
2006, 841–844.
6 (a) Enantioselective Organocatalysis (ed.: P. I. Dalko) Wiley-VCH
Verlag, Weinheim, New York, 2007; (b) Asymmetric Organocatalysis
(ed.: A. Berkessel, H. Gro¨ger) Wiley-VCH Verlag, Weinheim, New
York 2005; (c) P. I. Dalko and L. Moisan, Angew. Chem., 2004, 116,
5248–5286; Angew. Chem., Int. Ed., 2004, 43, 5138–5175.
7 (a) Hydrogen Bonding in Organic Synthesis (Ed.: P. M. Pihko) Wiley-
VCH, Weinheim 2009; (b) Z. G. Zhang and P. R. Schreiner, Chem.
Soc. Rev., 2009, 38, 1187–1198; (c) D. A. Yalalov, S. B. Tsogoeva, T. E.
Shubina, I. M. Martynova and T. Clark, Angew. Chem., 2008, 120,
6726–6730; Angew. Chem., Int. Ed., 2008, 47, 6624–6628; (d) A. G.
Doyle and E. N. Jacobsen, Chem. Rev., 2007, 107, 5713–5743; (e) S. W.
Wei, D. A. Yalalov, S. B. Tsogoeva and S. Schmatz, Catal. Today, 2007,
121, 151–157; (f) K. Liu, H. F. Cui, J. Nie, K. Y. Dong, X. J. Li and
J. A. Ma, Org. Lett., 2007, 9, 923–925; (g) M. S. Taylor and E. N.
Jacobsen, Angew. Chem., 2006, 118, 1550–1573; Angew. Chem., Int.
Ed., 2006, 45, 1520–1543; (h) S. J. Connon, Chem.–Eur. J., 2006, 12,
5418–5427; (i) T. Akiyama, J. Itoh and K. Fuchibe, Adv. Synth. Catal.,
2006, 348, 999–1010; (j) S. B. Tsogoeva and S. W. Wei, Chem. Commun.,
2006, 1451–1453; (k) H. B. Huang and E. N. Jacobsen, J. Am. Chem.
18 (a) S. Grabowsky, M. F. Hesse, C. Paulmann, P. Luger and J. Beckmann,
Inorg. Chem., 2009, 48, 4384–4393; (b) L. C. Dias, M. A. B. Ferreira
and C. F. Tormena, J. Phys. Chem. A, 2008, 112, 232–237; (c) J. F.
Blake and W. L. Jorgensen, J. Org. Chem., 1991, 56, 6052–6059; (d) S.
Shambayati, S. L. Schreiber, J. F. Blake, S. G. Wierschke and W. L.
Jorgensen, J. Am. Chem. Soc., 1990, 112, 697–703; (e) Yu.-L. Frolov,
M. G. Voronkov, N. V. Strashnikova and N. I. Shergina, J. Mol. Struct.,
1992, 270, 205–215.
19 J. D. Webb, V. S. Laberge, S. J. Geier, D. W. Stephan and C. M. Crudden,
Chem. Eur. J., 2010, 16, 4895–4902.
20 B. E. Norcross, P. E. Klinedinst and F. H. Westheimer, J. Am. Chem.
Soc., 1962, 84, 797–802.
21 (a) X.-Q. Zhu, Y. Tan and C.-T. Cao, J. Phys. Chem. B, 2010, 114,
2058–2075; (b) D. Richter and H. Mayr, Angew. Chem., 2009, 121,
1992–1995, Angew. Chem., Int. Ed., 2009, 48, 1958–1961; (c) L. Simon
and J. M. Goodman, J. Am. Chem. Soc., 2008, 130, 8741–8747; (d) X.-
Q. Zhu, H.-Y. Wang, J.-S. Wang and Y.-C. Liu, J. Org. Chem., 2001,
66, 344–347; (e) X.-Q. Zhu, H.-L. Zou, P.-W. Yuan, Y. Liu, L. Cao and
J.-P. Cheng, J. Chem. Soc., Perkin Trans. 2, 2000, 1857–1861; (f) X. Q.
Zhu, Y. C. Liu and J. P. Cheng, J. Org. Chem., 1999, 64, 8980–8981;
(g) J.-P. Cheng, Y. Lu, X.-Q. Zhu and L. J. Mu, J. Org. Chem., 1998,
63, 6108–6114; (h) H. P. Merjer and U. K. Pandit, Tetrahedron, 1985,
41, 467–472; (i) H. P. Merjer, J. C. G. Van Niel and U. K. Pandit,
Tetrahedron, 1984, 40, 5185–5195; (j) U. K. Pandit, J. B. Steevens and
F. R. Mascabre, Bioorg. Chem., 1973, 2, 293–300.
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