Catalytic enantioselective tert-aminocyclization by asymmetric binary acid catalysis (ABC): Stereospecific 1,5-hydrogen transfer

Article abstract of DOI:10.1002/chem.201201532

Selective H transfer by ABC: A new asymmetric binary acid catalyst was developed to promote 1,5-H transfer specifically and stereoselectively in tert-aminocyclization reactions with excellent activity, high enantioselectivity, and broad substrate scope. The H atom (in red) was proven to transfer through a stereospecific suprafacial pathway (see scheme).

Full text of DOI:10.1002/chem.201201532

COMMUNICATION
DOI: 10.1002/chem.201201532
Catalytic Enantioselective tert-Aminocyclization by Asymmetric Binary Acid
Catalysis (ABC): Stereospecific 1,5-Hydrogen Transfer
Liujuan Chen, Long Zhang, Jian Lv, Jin-Pei Cheng, and Sanzhong Luo*[a]
Initially disclosed in the 1970s and remaining largely ig-
nored in the following decades,[1] the tert-amino effect and
its related transformations have now been recognized in the
pursuit of selective activation and functionalization of rela-
3
À
À
tively inert C H bonds, particularly sp C H bonds. In this
regard, intramolecular tert-aminocyclization, a redox-neutral
process involving a 1,n-hydride transfer, represents an intri-
3
À
Scheme 1. Activation of sp C H through 1,5-H transfer/ring closure pro-
cess.
guing cascade sp3 C H activation/C X formation process
for the synthesis of heterocyclic compounds.[2] Recently,
both Lewis and Brønsted acids have been shown to promote
this previous thermal process with greatly improved activity
and synthetic applicability.[3] In light of its atom and redox
economy as well as its significant synthetic potential, as in
the asymmetric synthesis of PNU-286607,[4] the development
of catalytic enantioselective tert-aminocyclization has been
frequently attempted, with successes reported only recently.
In 2009, Seidel and co-workers reported the first catalytic
enantioselective tert-aminocyclization reaction using a chiral
magnesium complex.[5] Chiral metal complexes such as
cobalt[6] and gold complexes[7] as well as chiral organocata-
lysts such as diphenylprolinol[8] and phosphoric acids[9] were
subsequently developed as chiral catalysts for this transfor-
mation. Despite those advances, the development of new
asymmetric catalysts is still highly desirable for further im-
provements in activity, stereoselectivity, and applicability.
The mechanistic details of tert-aminocyclization remain
À
À
garding the enantioselective catalytic process, however,
there is currently no experimental information about the
proton transfer pathway nor its stereochemical features. It
also remains unclear how a rate-limiting 1,5-H transfer dic-
À
tates the subsequent stereocenter-generating C X bond for-
mation step. Elucidation of these mechanistic details would
certainly facilitate the exploration of distinctive new designs
in asymmetric catalysts.
We have recently been developing chiral Brønsted acids,
such as chiral monophosphoric acid, as dual ligands and acid
catalysts for metal catalysis.[11] This binary catalytic system
synergistically integrates chiral Brønsted acids and metal
catalysts, leading to mutually enhanced acidity/electrophilici-
ty and multiple sites for substrate binding due to their weak
coordinating behavior. These features, together with combi-
natorial flexibility, inspired us to explore this binary acid
strategy in the hitherto less developed asymmetric tert-ami-
nocyclization reaction. Herein we present our initial efforts
in this regard, which allowed us not only to identify a re-
markably effective and selective binary acid catalyst, but to
disclose interesting mechanistic features regarding 1,5-H
transfer and the mode of stereocontrol.
We started with chiral phosphoric acid as the selected
Brønsted acid ligand in the cyclization of 1a. Previously,
Akiyama and colleagues reported that the sole use of chiral
phosphoric acid was successful in promoting the reaction of
acyclic tertiary amines with good enantioselectivity at high
temperature.[9] Unfortunately, the reaction with cyclic terti-
ary amines gave rather low enantioselectivity (e.g.,
<10% ee for 1a). In our studies, it was found that chiral
phosphoric acid alone could not catalyze the reactions of
cyclic tertiary amine 1a (Table 1, entry 1). The combination
of chiral phosphoric acid 2a with various Lewis acids was
then examined (Table 1). To our delight, the combined use
of Lewis acids and 2a resulted in smooth reactions with ac-
tivity similar to, or even better than, that with Lewis acid
alone (e.g., Table 1, entries 5 versus 22) under ambient tem-
perature. Among the many different Lewis acids screened,
obscure, particularly regarding the catalytic asymmetric pro-
cesses for this appealing redox-neutral sp C H bond activa-
tion reaction. It is known that tert-aminocyclization involves
a rate-limiting 1,5-H transfer and subsequent stereocenter-
3
À
[1,2]
À
generating C X bond formation (Scheme 1).
This mecha-
nistic feature poses an intriguing challenge in controlling
a likely stereoselective 1,5-H transfer as initially proved by
Reinhoudt et al.[10] in the thermal cyclization of chiral terti-
ary amines and recently verified by Akiyama et al.[9] in
chiral phosphoric acid catalyzed tert-aminocyclization. Re-
[a] L. Chen,+ Dr. L. Zhang,+ Dr. J. Lv, Prof. J.-P. Cheng, Prof. S. Luo
Beijing National Laboratory for Molecular Sciences (BNLMS)
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences
Beijing 100190 (P.R. China)
Fax : (+86)10-62554449
E-mail: luosz@iccas.ac.cn
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201532.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

Table 1. Screening and optimization.
with MgCl2. Different molar ratios of MgCl2/2j were also
examined, and a 1:4 ratio is optimal in terms of enantiose-
lectivity (Table 1, entries 20 and 21 versus 15). In our subse-
quent investigations, it was found that product enantiomeric
excess value correlates linearly with that of 2j, indicating
that a high-order MgCl2/2j complex is unlikely to be the
real catalytically active species, and that an active 1:1 com-
plex can be invoked (see the Supporting Information for the
correlation diagram). Hence, the requirement of excess
phosphoric acid beyond a 1:1 molar ratio for stereocontrol
is most likely a physicochemical consequence for full coordi-
nation with MgCl2 due to the low coordinating capability of
phosphoric acid,[11a,12] thus eliminating any possible back-
ground reaction.
Entry[a]
Lewis
Acid
Phosphoric
Acid
t [h]
Conv. [%][b]
ee [%][c]
With the optimal catalyst system in hand, the substrate
scope was next explored (Table 2). Various diester groups
(methyl, ethyl, or benzyl) are well tolerated in the reactions,
with excellent reactivity and enantioselectivity (Table 2, en-
tries 1–3). Substrates with an electron-withdrawing group
(chloro, bromo, or trifluoromethyl) meta or para to the ni-
trogen atom also gave the desired products with good isolat-
ed yields (>95%) and high enantioselectivity (92–94% ee)
(Table 2, entries 4–7). However, the substrate bearing an
electron-donating group (methoxy) meta to the nitrogen
atom showed low activity (28%) but moderate enantioselec-
tivity (66% ee; Table 2, entry 8). Prolonging the reaction
time gives no significant improvement (108 h, 34% conver-
sion, 68% ee). On the other hand, an electron-donating
group on the tetrahydroisoquinoline moieties did not influ-
ence the reaction outcome significantly (Table 2, entries 9
and 10). Notably, catalyst loading can be decreased to
2.5 mol% (MgCl2) while still maintaining good activity and
enantioselectivity (Table 2, entries 4–6). The absolute config-
uration of 1b was determined to be S ([a]20D =À81.0 (c=
1.0, CH2Cl2)) by comparing its optical rotation with pub-
lished data[7] ([a]26D =À83.1 (c=0.5, CH2Cl2)).
1[d]
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
–
2a or 2j
2a
2a
2a
2a
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2j
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
8
trace
quant.
quant.
quant.
quant.
quant.
83
quant.
90
85
–
13
rac
12
43
23
56
16
70
64
21(R)
16
19(R)
13
93
87
89
87
87
90
Mg
Ni(OTf)2
Cu(OTf)2
MgCl2
Zn(OTf)2
(OTf)2
A
G
E
MgCl2
MgCl2
MgCl2
MgCl2
MgCl2
MgCl2
MgCl2
MgCl2
MgCl2
Mg
Mg
Mg(BArF)2
Mg(SbF6)2
quant.
quant.
quant.
91
quant.(95)[e]
98
E
E
2j
2j
2j
quant.
quant.
quant.
quant.
quant.
quant.
99
G
6
3
15
15
15
18
G
MgCl2
MgCl2
MgCl2
2j (1:3)[f]
2j (1:1)[f]
83
–
rac
–
–
Mg
(2j)2
[a] Reaction conditions: 1a (0.05 mmol), Lewis acid (0.0025 mmol,
5 mol%), phosphoric acid (0.01 mmol, 20 mol%), MS (4 ꢁ, 15 mg),
CH2Cl2 (0.5 mL) at ambient temperature under Ar. [b] Conversions were
1
Other tertiary amines were also examined (Table 3). The
determined by H NMR spectroscopy. [c] Enantiomeric excess was deter-
use of MgACTHNUGRTNEUNG(BF4)2 was found to provide optimal activity and
mined by HPLC. [d] Without Lewis acid. [e] Isolated yield.
enantioselectivity. In all these cases, the reactions occurred
smoothly under rather mild reaction conditions at ambient
temperature to afford the desired products in quantitative
yields with moderate to good enantioselectivity. Both cyclic
and acyclic tertiary amines can be incorporated into the cur-
rent protocol with good enantioselectivity. For example, the
reactions of cyclic tertiary amines with five-, six-, or seven-
membered rings gave 48–89% ee (Table 3, entries 1–4).
Challenging substrates such as dibutylamino 3o and dial-
MgCl2 was found to deliver an encouraging 43% ee
(Table 1, entry 5). A survey of various phosphoric acids was
next conducted in the presence of 5 mol% MgCl2 (Table 1,
entries 8–15). Biphenyl phosphoric acid 2j, bearing 2,4-bis-
fluorophenyl groups, turned out to be the best co-catalyst
for this transformation, and the tetrahydroquinoline product
3a was obtained in 95% isolated yield and 93% ee at ambi-
ent temperature in 15 h. To the best of our knowledge, this
represents the best result for this type of substrate.
Magnesium salts with different anions were also examined
(Table 1, entries 16–19), most of which gave similar chemical
outcomes and enantioselectivity. Interestingly, although the
reaction catalyzed by the magnesium salt of 2j proceeded
quite smoothly, it surprisingly afforded only racemic product
(Table 1, entry 23). This observation highlights the critical
role of free phosphoric acid and its synergistic combination
AHCTUNGTREGUNlNN ylamino 3p also worked very well to furnish 70 and
69% ee, respectively (Table 3, entries 5 and 6).
Mechanistic studies were then undertaken to elucidate
the 1,5-H transfer pathway as well as the accompanying
mode of stereocontrol. Firstly, deuterium-labeled substrates
1s and 1t were synthesized to probe the hydrogen transfer
pathway. In the reaction of rac-1s, the ratio between H-
transferred product 3s-H and D-transferred product 3s-D
was found to be 3.6:1, catalyzed by the rac-2j/MgCl2 combi-
nation after quantitative conversion, indicating a large pri-
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Enantioselective tert-Aminocyclization
COMMUNICATION
Table 3. Substrate scope of tert-aminocyclization.
Table 2. Survey of substrate scope.
Entry[a]
1[d]
2[d]
Product
t [h
[
Yield [%][b]
ee [%][c]
Entry[a]
Product
t [h] Yield [%][b] ee [%][c]
16
21
99
98
89
88
1
2
3
15
6
95
98
98
93
92
92
18
3[e]
30
16
99
95
81
48
4[d]
11
>99
93
4[e]
5[d]
6[d]
7
66
66
15
24
95
95
97
28
94
93
92
66
5[f]
10
99
70
6[f]
18
21
95
95
69
74
7[e]
8
8[f]
20
99
86
9
15
64
>99
92
85
[a] Reaction conditions: 1a (0.05 mmol), Lewis acid (0.0025 mmol,
5 mol%), phosphoric acid (0.01 mmol, 20 mol%), MS (4 ꢁ, 15 mg),
CH2Cl2 (0.5 mL) under Ar. [b] Isolated yield. [c] Determined by HPLC.
[d] In the presence of MgCl2 (2.5 mol%) and phosphoric acid
(0.005 mmol, 10 mol%). [e] At 608C with ClCH2CH2Cl as solvent. [f] At
308C.
10
99
[a] Reaction conditions: 1a (0.05 mmol), Lewis acid (0.0025 mmol,
5 mol%), phosphoric acid (0.01 mmol, 20 mol%), MS (4 ꢁ, 15 mg),
CH2Cl2 (0.5 mL) at ambient temperature under Ar. [b] Isolated yield.
[c] Enantiomeric excess was determined by HPLC. [d] In the presence of
MgCl2 (2.5 mol%) and phosphoric acid (0.005 mmol, 10 mol%).
mary kinetic isotope effect (kH/kD =3.6) in both cases
(Scheme 2, [Eq. (1)]). That the rate-limiting step comprises
1,5-H transfer can thus be verified in the context of asym-
metric catalysis.
1,5-Suprafacial hydrogen transfer is known to be a favora-
ble process,[13] and in the tert-aminocyclization reaction this
was experimentally proven by Reinhoudt and co-workers in
the thermal cyclization of optically pure 2-vinyl-N,N-di-
Scheme 2. The tert-aminocyclization of deuterated substrates 1s and 1t.
ACHTUNGTRENNUNG
alkylanilines (the tertiary amines).[10b,d] To track the pathway
of hydrogen transfer in the catalytic asymmetric process,
deuterated substrate 1t was subjected to catalysis by (S)-2j/
MgCl2. The reaction afforded exclusively a single isomer,
cis-3t, with 96% ee in quantitative yield (Scheme 2,
[Eq. (2)]). Both the transferred deuterium and the bridge-
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

S. Luo et al.
head deuterium atoms were found to be at the same face of
3t,[14] and this 1,3-cis configuration is maintained in the reac-
tion catalyzed by rac-2j/MgCl2 (Scheme 2, [Eq. (2)]). In con-
sistency with Reinhoudtꢂs previous studies, the 1,3-cis con-
figurations between the transferred hydrogen and bridge-
head group supports a suprafacial 1,5-H transfer, and this
transfer is highly stereospecific in the current process, as un-
equivocally proven by the observed high enantio- and dia-
stereoselectivity (Scheme 2, [Eq. (2)]).
The labeling experiments also showed quite unexpected
yet interesting results, revealing some hidden mechanistic
features (Scheme 2, [Eq. (1)]). In subjecting rac-1s to cataly-
sis by (S)-2j/MgCl2, H-transferred product 3s-H and D-
transferred product 3s-D were obtained in equal amounts
(molar ratio 1:1), overriding the kinetically preferable hy-
drogen transfer, as is the case with the racemic 2j/MgCl2
combination.
DFT calculations were conducted to explore the mecha-
nistic details. Indeed, suprafacial 1,5-H transfer is generally
favored by 2.8 kcalmolÀ1 over antarafacial transfer for both
thermal and MgCl2-catalyzed processes (see the Supporting
Information for details). Further DFT calculations on the
MgCl2-catalyzed process with a model compound revealed
a major activation barrier for 1,5-H transfer (TS1, Figure 1)
followed by a small conformational change in the resulting
helical zwitterionic intermediate (TS2, Figure 1), leading to
À
C C formation without any detectable energy barrier. Con-
À
sequently, C C formation would occur without significant
charge redistribution and structural equilibration, and thus
the stereochemistry of the helical zwitterionic intermediate
can be largely retained and transferred.
Scheme 3. Proposed transition states.
transfer with rac-1s, as shown in Scheme 2, [Eq. (1)]. The
selective activation in complex I initiates 1,5-Hb transfer (I,
Scheme 3), leading to the chiral helical zwitterionic inter-
À
mediate III. After a small conformational change, the C C
bond would be form spontaneously with preserved stereo-
chemistry.
In conclusion, we have developed a highly effective asym-
metric binary acid catalyst MgX2/2j for tert-aminocyclization
reactions. The identified optimal catalytic system exhibits
extremely high activity and good enantioselectivity for
a broad range of substrates. Preliminary mechanistic studies
indicated that the catalytic 1,5-H transfer proceeds stereo-
specifically in a suprafacial manner. The chiral binary acid
complex selectively recognizes and activates one helical con-
formation, required for 1,5-suparafacial hydrogen transfer,
explaining the observed stereoselectivity. Further investiga-
tions and detailed mechanistic studies to explore asymmetric
Figure 1. The transition states TS1 and TS2, corresponding to 1,5-H
transfer and conformational change, respectively, for MgCl2-catalyzed
tert-aminocyclization.
On the basis of DFT studies, plausible transition states
were proposed to explain the experimental observations
(Scheme 3). A 1:1 ratio of Mg2+/2j is invoked to be the cat-
alytically active species based on the linear correlation re-
sults (see the Supporting Information for details). Accord-
ingly, upon complexation with Mg/2j, both Ha and Hb on
the isoquinoline methylene carbon atom may participate in
1,5-H transfer, requiring two different helical conformations
I and II, respectively, due to the suprafacial constraint. Of
the two complexes, I is favored over II owing to its space
tolerance (Scheme 3). This preferential activation can even
override the H/D isotope effect, resulting in equal H and D
redox-neutral sp3 C H bond functionalization with asym-
À
metric binary acid catalysis are currently underway.
Experimental Section
General procedure for binary acid catalyzed tert-aminocyclization:
MgCl2 (0.24 mg, 5 mol%), catalyst 2j (5.72 mg, 20 mol%), and molecular
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Enantioselective tert-Aminocyclization
COMMUNICATION
sieves (4 ꢁ, 15 mg) were added to a Schlenk-type flask under Ar. CH2Cl2
(0.25 mL) was then added, and the resulting mixture was stirred for
30 min. A solution of compound 1a (0.05 mmol 1a in 0.25 mL CH2Cl2)
was added, and the resulting reaction mixture was stirred for 15 h at
room temperature under Ar. The product was purified by silica gel
column chromatography (EtOAc/PE 1:20 with 2% Et3N) to give product
3a as a colorless liquid.
[7] G. Zhou, F. Liu, J. Zhang, Chem. Eur. J. 2011, 17, 3101–3104.
[8] K. Kang, S. M. Kim, D. Y. Kim, J. Am. Chem. Soc. 2010, 132,
11847–11849.
[9] K. Mori, K. Ehara, K. Kurihara, T. Akiyama, J. Am. Chem. Soc.
2011, 133, 6166–6169.
[10] a) W. Verboom, D. N. Reinhoudt, R. Visser, S. Harkema, J. Org.
Chem. 1984, 49, 269–276; b) W. H. N. Nijhuis, W. Verboom, D. N.
Reinhoudt, J. Am. Chem. Soc. 1987, 109, 3136–3138; c) L. C. Groe-
nen, W. Verboom, W. H. N. Nijhuis, D. N. Reinhoudt, G. J. V.
Hummel, D. Feil, Tetrahedron 1988, 44, 4637–4644; d) W. H. N. Nij-
huis, W. Verboom, A. A. El-Fadl, S. Harkema, D. N. Reinhoudt, J.
Org. Chem. 1989, 54, 199–209; e) W. H. N. Nijhuis, W. Verboom,
A. A. El-Fadl, G. J. V. Hummel, D. N. Reinhoudt, J. Org. Chem.
1989, 54, 209–216.
[11] a) J. Lv, X. Li, L. Zhang, S. Luo, J.-P. Cheng, Org. Lett. 2010, 12,
1096–1099; b) J. Lv, L. Zhang, Y. Zhou, Z. Nie, S. Luo, J.-P. Cheng,
Angew. Chem. 2011, 123, 6740–6744; Angew. Chem. Int. Ed. 2011,
50, 6610–6614; c) J. Lv, L. Zhang, S. Hu, J.-P. Cheng, S. Luo, Chem.
Eur. J. 2012, 18, 799–803.
Acknowledgements
This project was supported by the Natural Science Foundation of China
(NSFC 20972163 and 21025208) and the Ministry of Science and Technol-
ogy (2012CB821600).
À
Keywords: asymmetric catalysis
hydrogen transfer · Lewis acid · phosphoric acid
·
C H activation
·
[12] The chiral phosphoric acid was washed extensively with concentrat-
ed HCl to remove any metal salt impurities. See previous discussions
on this issue: M. Hatano, K. Moriyama, T. Maki, K. Ishihara,
Angew. Chem. 2010, 122, 3911–3914; Angew. Chem. Int. Ed. 2010,
49, 3823–3826. The fact that different magnesium salts (some of
which are soluble in organic solvents) perform similarly suggests
that solubility is not a concern under the present conditions.
[13] a) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part A:
Structure and Mechanism, Springer, 2007, pp. 621; b) B. Andes
Hess, Jr., L. J. Schaad, J. Pancir, J. Am. Chem. Soc. 1985, 107, 149–
154.
[1] a) O. Meth-Cohn, H. Suschitzky, Adv. Heterocycl. Chem. 1972, 14,
211–278; b) O. Meth-Cohn, Adv. Heterocycl. Chem. 1996, 65, 1–37.
[2] a) P. Mꢃtyus, O. ꢄliꢃs, P. Tapolcsꢃnyi, ꢅ. Polonka-Bꢃlint, B. Halꢃsz-
3
À
Dajka, Synthesis 2006, 2625–2639; For reviews on sp C H bond ac-
tivation, see: b) K. R. Campos, Chem. Soc. Rev. 2007, 36, 1069; c) R.
Jazzar, J. Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin,
Chem. Eur. J. 2010, 16, 2654.
[3] For Lewis acid catalysis, see: a) S. J. Pastine, K. M. McQuaid, D.
Sames, J. Am. Chem. Soc. 2005, 127, 12180–12181; b) K. M.
McQuaid, D. Sames, J. Am. Chem. Soc. 2009, 131, 402–403; c) P. A.
Vadola, D. Sames, J. Am. Chem. Soc. 2009, 131, 16525–16528; d) K.
Mori, S. Sueoka, T. Akiyama, J. Am. Chem. Soc. 2011, 133, 2424–
2426; e) G. Zhou, J. Zhang, Chem. Commun. 2010, 46, 6593–6595;
f) S. J. Pastine, D. Sames, Org. Lett. 2005, 7, 5429–5431; g) K. M.
McQuaid, J. Z. Long, D. Sames, Org. Lett. 2009, 11, 2972–2975;
h) S. Murarka, C. Zhang, M. D. Konieczynska, D. Seidel, Org. Lett.
2009, 11, 129–132; For Brønsted acid catalysis, see: i) C. Zhang,
C. K. De, R. Mal, D. Seidel, J. Am. Chem. Soc. 2008, 130, 416–417;
j) C. Zhang, S. Murarka, D. Seidel, J. Org. Chem. 2009, 74, 419–422.
[4] J. C. Ruble, A. R. Hurd, T. A. Johnson, D. A. Sherry, M. R. Barba-
chyn, P. L. Toogood, G. L. Bundy, D. R. Graber, G. M. Kamilar, J.
Am. Chem. Soc. 2009, 131, 3991–3997.
[14] The chemical shifts and configurations of Ha, Hb, and Hc in 3a were
1
assigned and determined based H NMR and NOE analysis (see the
Supporting Information for details). Accordingly, the configurations
of deuterated products (e.g., cis-3t) can be assigned by comparison
of the respective proton signal as well as in analogy to the deter-
mined absolute configurations of 3a.
[5] S. Murarka, I. Deb, C. Zhang, D. Seidel, J. Am. Chem. Soc. 2009,
131, 13226–13227.
Received: May 2, 2012
[6] W. Cao, X. Liu, W. Wang, L. Lin, X. Feng, Org. Lett. 2011, 13, 600–
603.
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

S. Luo et al.
Asymmetric Catalysis
L. Chen, L. Zhang, J. Lv, J.-P. Cheng,
S. Luo* ......................... &&&& — &&&&
Catalytic Enantioselective tert-Amino-
cyclization by Asymmetric Binary
Acid Catalysis (ABC): Stereospecific
1,5-Hydrogen Transfer
Selective H transfer by ABC: A new
asymmetric binary acid catalyst was
developed to promote 1,5-H transfer
specifically and stereoselectively in
tert-aminocyclization reactions with
excellent activity, high enantioselectiv-
ity, and broad substrate scope. The H
atom (in red) was proven to transfer
through a stereospecific suprafacial
pathway (see scheme).
&
6
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!