D0a3 Synthon Equivalents for the Stereocontrolled Synthesis of Functionalized 1,4-Amino Alcohol Precursors

Article abstract of DOI:10.1021/acs.orglett.7b01268

This study demonstrates the design, synthesis, and first application of novel aminooxylating reagents that serve as a useful d⁰a³ synthon equivalents for organic synthesis. It has been demonstrated that their reaction with α,β-unsaturated aldehydes performed under aminocatalytic conditions provides a straightforward access to polysubstituted tetrahydro-1,2-oxazine derivatives, direct precursors of functionalized 1,4-amino alcohols. Target tetrahydro-1,2-oxazine derivatives have been obtained with high yields (up to 89%) and with excellent stereocontrol (up to >20:1 dr, > 99.5:0.5 er). Furthermore, the synthetic usefulness of tetrahydro-1,2-oxazines obtained has been demonstrated in various selective transformations.

Full text of DOI:10.1021/acs.orglett.7b01268

Letter
pubs.acs.org/OrgLett
d0a3 Synthon Equivalents for the Stereocontrolled Synthesis of
Functionalized 1,4-Amino Alcohol Precursors
Piotr Drelich, Marek Moczulski, and Łukasz Albrecht*
̇
́
́
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Łodz, Poland
S
* Supporting Information
ABSTRACT: This study demonstrates the design, synthesis, and
first application of novel aminooxylating reagents that serve as a
useful d0a3 synthon equivalents for organic synthesis. It has been
demonstrated that their reaction with α,β-unsaturated aldehydes
performed under aminocatalytic conditions provides a straightfor-
ward access to polysubstituted tetrahydro-1,2-oxazine derivatives, direct precursors of functionalized 1,4-amino alcohols. Target
tetrahydro-1,2-oxazine derivatives have been obtained with high yields (up to 89%) and with excellent stereocontrol (up to >20:1
dr, > 99.5:0.5 er). Furthermore, the synthetic usefulness of tetrahydro-1,2-oxazines obtained has been demonstrated in various
selective transformations.
he quest for the development of stereoselective methods
leading to biologically active molecules or privileged
Scheme 1. Importance of 1,4-Amino Alcohols and the
Synthetic Objectives of Our Study
T
structural motifs, which can serve as useful building blocks,
constitutes a highly relevant topic in contemporary organic
chemistry.1 One particularly visible trend within this research
area is related to the use of chiral catalysts to control
stereochemical reaction outcomes.2 Since the turn of the
millennium, asymmetric organocatalysis, where simple non-
racemic organic molecules are employed as catalysts, has
emerged as an effective tool widely employed in stereocontrolled
synthesis.3−5
The amino alcohol moiety represents a privileged structural
motif widely distributed in nature and present in various
molecules relevant for the life-science industry, including amino
sugars, iminosugars, sphingolipids, and sphingoids.6 Therefore,
the development of methods for their stereoselective preparation
constitutes an important, yet challenging, task in modern organic
synthesis.7 In continuation of our interest8 in the stereo-
controlled synthesis of aminohydroxylated products, we became
particularly interested in functionalized 1,4-amino alcohols as
this structural motif is present in biologically relevant molecules
(for selected examples, see Scheme 1, top).9 Interestingly, these
important building blocks are readily available from the
corresponding tetrahydro-1,2-oxazines via the N−O bond
cleavage.10 However, stereocontrolled methods for the prepara-
tion of tetrahydro-1,2-oxazines are limited and rely mostly on the
application of nitroso-Diels−Alder reaction as the key step.11
Therefore, the task of designing a readily available reagent
allowing access to functionalized, enantiomerically enriched
tetrahydro-1,2-oxazines was undertaken. We envisioned that a
possible route to these compounds might rely on the application
of γ-aminooxy-α,β-unsaturated compounds. This novel group of
aminooxylating reagents should be readily available and has
certain advantages. First, they can be considered as d0a3 synthon
equivalents. Therefore, they should be capable of reacting with
Michael acceptors in a cascade manner involving aza-Michael/
Michael reactions. Second, the nucleophilicity of the nitrogen
should be enhanced due to the presence of the oxygen atom in
the direct neighborhood (α-effect), thus making it more prone to
undergo the desired reactivity.
Herein, we present our studies on the application of novel
aminooxylating reagents in the stereocontrolled synthesis of
polysubstituted tetrahydro-1,2-oxazine derivatives 1. Amino-
Received: April 26, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01268
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
catalytic cascade activation mode of α,β-unsaturated aldehydes 2
via sequential iminium ion/enamine formation was selected as a
model organocatalytic activation as it usually provides high levels
of stereoinduction.5 The developed strategy benefits from high
efficiency, broad substrate scope, and offers a straightforward
access to direct precursors of 1,4-amino alcohols.
Optimization studies were initiated using cinnamaldehyde 2a
and γ-aminooxy-α,β-unsaturated ester 3a as model reactants
(Table 1). Initially, the reaction was performed at room
reaction was accomplished within 24 h, affording 1a with
excellent yield as a single stereoisomer.
With the optimization studies accomplished, the scope and
limitations of the developed synthetic strategy was studied.
Initially, different cinnamaldehyde derivatives 2 were evaluated
in the reaction cascade. To our delight, the reaction proved to be
unbiased toward both the electronic properties and the position
of the substituents on the aromatic ring in 2 (Table 1, entries 1−
12). The yields were high, and both the enantio- and
diastereoselectivity of the cascade were excellent, providing the
tetrahydro-1,2-oxazines 1a−l as single stereoisomers in all of the
cases. Furthermore, the reaction proceeded efficiently for
aliphatic α,β-unsaturated aldehydes 2m−o (Table 2, entries
Table 1. Enantio- and Diastereoselective Synthesis of
a
Tetrahydro-1,2-oxazines 1: Optimization Studies
Table 2. Enantio- and Diastereoselective Synthesis of
a
Tetrahydro-1,2-oxazines 1: Reaction Scope
b
c
d
solvent
cat. (additive)
conv
dr
er
b
c
R1
Pg
yield (%)
dr
er
1
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
toluene
CH3CN
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
4a (−)
4b (−)
4c (−)
4d (−)
4a (−)
4a (−)
4a (−)
51
22
<5
<5
48
27
46
21
72
59
44
>20:1
nd
>99.5:0.5
nd
2
1
Ph
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Cbz
Boc
Cbz
88 (1a)
55 (1b)
58 (1c)
73 (1d)
87 (1e)
88 (1f)
86 (1g)
84 (1h)
80 (1i)
82 (1j)
77 (1k)
64 (1l)
63 (1m)
68 (1n)
58 (1o)
67 (1p)
89 (1q)
82 (1a)
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
14:1
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
99:1
3
nd.
nd
2
4-NO2C6H4
4-CNC6H4
4-CF3C6H4
4-BrC6H4
4-ClC6H4
3-ClC6H4
4-CH3C6H4
4-CH3OC6H4
2-CH3OC6H4
3,4-(CH3O)2C6H3
1-Naphthyl
Me
4
nd
nd
3
5
>20:1
>20:1
>20:1
nd
>99.5:0.5
>99.5:0.5
>99.5:0.5
nd
4
6
5
7
6
e
8
4a (PNBA)
7
e
9
4a (BA)
>20:1
>20:1
>20:1
>20:1
>99.5:0.5
>99.5:0.5
>99.5:0.5
>99.5:0.5
8
10
11
12
4a (NaOAc)
4a (DABCO)
4a (PDMABA)
9
10
11
12
13
14
15
16
17
18
e
>90 (88)
>20:1
8:1
a
Reactions performed on a 0.1 mmol scale using 2a (2.0 equiv) and 3a
b
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>99.5:0.5
>99.5:0.5
>99.5:0.5
97:3
(1.0 equiv) in 0.2 mL of the solvent for 24 h. Conversion as
determined by 1H NMR of a crude reaction mixture. The isolated yield
Hex
c
1
is given in parentheses. Determined by H NMR of a crude reaction
PhCH2CH2
Z-3-Hexenyl
Ph
d
e
mixture. Determined by a chiral stationary phase HPLC. PNBA = 4-
NO2C6H4CO2H. BA = C6H4CO2H. PDMABA = 4-(Me2N)-
C6H4CO2H.
95:5
d
Ph
>99.5:0.5
a
Reactions performed on a 0.2 mmol scale using 2a (2.0 equiv) and 3a
b
(1.0 equiv) in 0.4 mL of CHCl3 for 48 h. Determined by 1H NMR of
a crude reaction mixture. Determined by a chiral stationary-phase
temperature in CHCl3 in the presence of diphenylprolinol
trimethylsilyl ether 4a12 as the catalyst (Table 1, entry 1). To our
delight, it was found that the designed compound 3a could serve
as an efficient aminooxylating reagent in the stereocontrolled
domino reaction leading to the formation of tetrahydro-1,2-
oxazine 1a. Notably, the cascade proceeded with excellent
stereoselectivity. However, the reaction yield had to be
improved. Disappointingly, neither the catalyst screening
(Table 1, entries 1−4) nor the solvent optimization (performed
with the catalyst 4a, Table 1, compare entries 1, 5−7) led to the
improvement of the chemical efficiency of the reaction.
Interesting results were obtained when the additive screening
was performed (Table 1, entries 8−12). It was found that both
acidic (benzoic acid, BA, Table 1, entry 10) and basic additives
(NaOAc, Table 1, entry 11) increased the conversion. Therefore,
the use of an additive containing both acidic and basic moieties
(4-(dimethylamino)benzoic acid, PDMBA, Table 1, entry 12)
was attempted. To our delight, in the presence PDMABA the
c
HPLC directly on the aldehyde or after the transformation of the
aldehyde into the corresponding alcohol or 1,3-dioxolane (for details,
d
see the Supporting Information). Reaction performed on a 5 mmol
scale using 10 mol % of the catalyst 4a.
13−16). Notably, the presence of different functional groups was
tolerated in their side chain (phenyl group or double bond,
compounds 1o,p), further expanding the scope of the developed
methodology (Table 2, entries 15 and 16). The possibility of
replacing a protecting group at the nitrogen atom proved
possible as demonstrated in the synthesis of Boc-protected
tetrahydro-1,2-oxazine 1q (Table 2, entry 17). Finally, the
reaction cascade was fully scalable as it could be performed at 5
mmol scale, obtaining comparable results (Table 2, compare
entries 1 and 18).
B
DOI: 10.1021/acs.orglett.7b01268
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Organic Letters
Letter
Functionalized 1,2-tetrahydroxazines 1 obtained could serve
as versatile building blocks as demonstrated in selected selective
transformations (Scheme 2). In the beginning, cleavage of the
Scheme 3. Enantio- and Diastereoselective Synthesis of
Tetrahydro-1,2-oxazines 1: Reaction Scope
Scheme 2. Synthetic Applications of Tetrahydro-1,2-oxazine
1a
N−O bond was attempted (Scheme 2, top). However, initial
experiments showed that the aldehyde moiety had to be
protected prior to the cleavage. The acetal formation was
realized under standard reaction conditions, yielding 6a that was
subjected to hydrogenolysis. Under these conditions, both the
deprotection of the nitrogen atom and the N−O bond cleavage
occurred. Initially formed 1,4-amino alcohol spontaneously
cyclized to give δ-lactam 7a in a fully chemoselective manner.
Notably, a transformation of 1a to 7a could be performed
without purification of any intermediate increasing the
attractiveness of the methodology. The usefulness of the 1,2-
tetrahydroxazines 1 obtained was further confirmed in a
chemoselective transformation of 1a into bicyclic δ-lactone 8a
and δ-lactam 9a (Scheme 2, bottom). Chemoselective reduction
of the aldehyde moiety followed by acid-promoted intra-
molecular transestrification led to a δ-lactone 8a. The formation
of δ-lactam 9a was initiated through the reductive amination of
1a followed by spontaneous lactamization.
Scheme 4. Enantio- and diastereoselective synthesis of
tetrahydro-1,2-oxazines 1 − mechanistic considerations
Further scope studies were focused on the utilization of
various γ-aminooxy-α,β-unsaturated compounds 3 (Scheme 3).
Reactions proceeded efficiently for aminooxylating reagents
3c−e bearing different electron-withdrawing substituents on the
double bond including methyl or phenyl ketone and sulfone
moieties. Importantly, the introduction of various electron-
withdrawing groups created new functionalization possibilities.
For instance, methyl ketone 1r could participate in the acid-
promoted intramolecular aldol reaction, providing cyclohex-2-
en-1-one derivative 10 in 67% yield. Notably, only (3S,4S,5S)-1r
underwent cyclization leaving the other diastereomer of 1r intact.
In order to assign the absolute configuration of the products 1,
X-ray analysis of 1f was performed (Scheme 4, top).13 On the
basis of the obtained results, a plausible reaction mechanism was
proposed (Scheme 4, bottom). The catalytic cycle was initiated
by the condensation of the aminocatalyst 4a with the
corresponding α,β-unsaturated aldehyde 2 to give the reactive
iminium ion 11 that underwent the aza-Michael reaction with the
aminooxylating reagent 3. The reaction occurred in a
diastereoselective manner from the side opposite to the bulky
substituent originating from the aminocatalyst 4a. It was
postulated that the subsequent, enamine-mediated intramolec-
ular Michael addition proceeded through the chairlike transition
state 12 to afford a six-membered heterocyclic ring in 13 with all
substituents occupying equatorial positions. Hydrolytic cleavage
of the catalyst 4a liberated the product 1 and furnished the
catalytic cycle. Notably, in this reaction PDMABA acts as an
amphiprotic cocatalyst facilitating proton transfers.
In conclusion, we have designed a new group of amino-
oxylating reagents that serve as general d0a3 synthon equivalents.
C
DOI: 10.1021/acs.orglett.7b01268
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
107, 5416. (d) Mukherjee, S.; Yang, J.-W.; Hoffmann, S.; List, B. Chem.
Rev. 2007, 107, 5471. (e) Melchiorre, P.; Marigo, M.; Carlone, A.;
Bartoli, G. Angew. Chem., Int. Ed. 2008, 47, 6138. (f) Melchiorre, P.
Angew. Chem., Int. Ed. 2012, 51, 9748. (g) Albrecht, Ł.; Jiang, H.;
Jørgensen, K. A. Chem. - Eur. J. 2014, 20, 358.
(6) (a) Compain, P., Martin, O. R., Eds. Iminosugars: From Synthesis to
Therapeutic Applications; Wiley-VCH: Weinheim, 2007. (b) Danishef-
sky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35, 1380.
(c) Koskinen, P. M.; Koskinen, A. M. P. Synthesis 1998, 1998, 1075.
(d) Kolter, T.; Sandhoff, K. Angew. Chem., Int. Ed. 1999, 38, 1532.
(e) Howell, A. R.; So, R. C.; Richardson, S. K. Tetrahedron 2004, 60,
11327. (f) Liao, J. Y.; Tao, J. H.; Lin, G. Q.; Liu, D. G. Tetrahedron 2005,
61, 4715. (g) Hemeon, I.; Bennet, A. J. Synthesis 2007, 2007, 1899.
(h) Pfrengle, F.; Reissig, H.-U. Chem. Soc. Rev. 2010, 39, 549.
Their usefulness in the stereocontrolled synthesis of tetrahydro-
1,2-oxazines 1 via an aminocatalytic reaction cascade has been
demonstrated for the first time. The developed method benefits
from the broad scope and excellent stereocontrol. Furthermore,
due to the presence of various functional groups in the
heterocyclic ring, the obtained products are capable of
participating in various chemoselective transformations with
the N−O bond cleavage leading to 1,4-amino alcohol derivatives
being the most relevant.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications Web site. Screening details, experimental
procedures, characterization of the products, NMR data, and CIF
information (PDF). The Supporting Information is available free
of charge on the ACS Publications website at DOI: 10.1021/
acs.orglett.7b01268.
(7) (a) O’Brien, P. Angew. Chem., Int. Ed. 1999, 38, 326. (b) Nilov, D.;
Reiser, O. Adv. Synth. Catal. 2002, 344, 1169. (c) Bodkin, J. A.; McLeod,
M. D. J. Chem. Soc., Perkin Trans. 1 2002, 2733. (d) Bruncko, M.;
Schlingloff, G.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1997, 36,
1483. (e) Reddy, K. L.; Sharpless, K. B. J. Am. Chem. Soc. 1998, 120,
1207. (f) Ibrahem, I.; Cor
(g) Liao, W.-W.; Ibrahem, I.; Cor
(h) Dziedzic, P.; Vesely, J.; Cordova, A. Tetrahedron Lett. 2008, 49, 6631.
(i) Dziedzic, P.; Schyman, P.; Kullberg, M.; Cordova, A. Chem. - Eur. J.
́
dova, A. Tetrahedron Lett. 2005, 46, 2839.
́
dova, A. Chem. Commun. 2006, 674.
Screening details, experimental procedures, character-
ization of the products, NMR data, and X-ray data (PDF)
X-ray data for compound 1f (CIF)
́
́
2009, 15, 4044. (j) Albrecht, Ł.; Jiang, H.; Dickmeiss, G.; Gschwend, B.;
Hansen, S. G.; Jørgensen, K. A. J. Am. Chem. Soc. 2010, 132, 9188.
(8) Drelich, P.; Skrzyn
4302.
(9) (a) Thompson, D.; Oster, G. JAMA, J. Am. Med. Assoc. 1996, 275,
1339. (b) Kowey, P. R.; Stoenescu, M. L. Prog. Cardiovasc. Dis. 2005, 48,
139.
(10) (a) Wovkulich, P. M.; Uskokovic, M. R. J. Am. Chem. Soc. 1981,
103, 3956. (b) Galvani, G.; Lett, R.; Kouklovsky, C. Synlett 2015, 26,
1340. (c) Galvani, G.; Calvet, G.; Blanchard, N.; Kouklovsky, C. Org.
́
ska, A.; Albrecht, Ł. Eur. J. Org. Chem. 2016,
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: lukasz.albrecht@p.lodz.pl.
ORCID
Łukasz Albrecht: 0000-0002-4669-7670
Notes
Biomol. Chem. 2008, 6, 1063. (d) Zhang, D.; Suling, C.; Miller, M. J. J.
̈
Org. Chem. 1998, 63, 885. (e) Keck, G. E.; Fleming, S.; Nickell, D.;
Weider, D. Synth. Commun. 1979, 9, 281. (f) Cicchi, S.; Goti, A.; Brandi,
A.; Guarna, A.; De Sarlo, F. Tetrahedron Lett. 1990, 31, 3351. (g) Keck,
G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron Lett. 1995, 36, 7419.
(11) For examples of the enantioselective nitroso-Diels−Alder
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project was financially supported by the Ministry of Science
and Higher Education, Poland, within the “Iuventus Plus”
programme realized in the period 2015-2017, project no. 0008/
IP3/2015/73. Thanks are expressed to Dr. Jakub Wojciechowski
(Faculty of Chemistry, Lodz University of Technology) for
performing X-ray analysis.
reaction, see: (a) Sunden
́
, H.; Dahlin, N.; Ibrahem, I.; Adolfsson, H.;
Cordova, A. Tetrahedron Lett. 2005, 46, 3385. (b) Maji, B.; Yamamoto,
́
H. J. Am. Chem. Soc. 2015, 137, 15957. (c) Yamamoto, Y.; Yamamoto, H.
Angew. Chem., Int. Ed. 2005, 44, 7082. (d) Lu, M.; Zhu, D.; Lu, Y.; Hou,
Y.; Tan, B.; Zhong, G. Angew. Chem., Int. Ed. 2008, 47, 10187.
(e) Harrison, A.; Melchionna, M.; Franco, P.; Hlavac, J.; Dahse, H. M.;
Miller, M. J.; Murakamo, T. New J. Chem. 2014, 38, 5491. For other
stereocontrolled approaches, see: (f) Zhu, D.; Lu, M.; Chua, P. J.; Tan,
B.; Wang, F.; Yang, X.; Zhong, G. Org. Lett. 2008, 10, 4585. (g) Kang, Y.-
B.; Sun, X.-L.; Tang, Y. Angew. Chem., Int. Ed. 2007, 46, 3918. (h) Lin,
H.; Sun, X.-W.; Lin, G.-Q. Org. Lett. 2014, 16, 752. (i) Kumarn, S.;
Oelke, A. J.; Shaw, D. M.; Longbottom, D. A.; Ley, S. V. Org. Biomol.
Chem. 2007, 5, 2678. (j) Hardman, A. M.; So, S. S.; Mattson, A. E.; Novi,
M.; Petrillo, G.; Sancassan, F.; Tavani, C. Org. Biomol. Chem. 2013, 11,
5793. (k) Cheng, S.; Yu, S. Org. Biomol. Chem. 2014, 12, 8607.
(12) For seminal reports, see: (a) Marigo, M.; Wabnitz, T. C.;
Fielenbach, D.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 794.
(b) Marigo, M.; Fielenbach, D.; Braunton, A.; Kjærsgaard, A.; Jørgensen,
K. A. Angew. Chem., Int. Ed. 2005, 44, 3703. (c) Hayashi, Y.; Gotoh, H.;
Hayashi, T.; Shoji, M. Angew. Chem., Int. Ed. 2005, 44, 4212. For
reviews, see: (d) Jensen, K. L.; Dickmeiss, G.; Jiang, H.; Albrecht, Ł.;
Jørgensen, K. A. Acc. Chem. Res. 2012, 45, 248. (e) Donslund, B. S.;
Johansen, T. K.; Poulsen, P. H.; Halskov, K. S.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2015, 54, 13860.
REFERENCES
■
(1) (a) Schreiber, S. L. Science 2000, 287, 1964. (b) Busacca, C. A.;
Fandrick, D. R.; Song, J. J.; Senanayake, C. H. Adv. Synth. Catal. 2011,
353, 1825.
(2) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive
Asymmetric Catalysis; Springer: Berlin, 1999. (b) Mikami, K.; Lautens,
M. New Frontiers in Asymmetric Catalysis; Wiley-Interscience, 2007.
(3) For selected reviews on organocatalysis, see: (a) Gaunt, M. J.;
Johansson, C. C. C.; McNally, A.; Vo, N. C. Drug Discovery Today 2007,
12, 8. (b) Bella, M.; Gasperi, T. Synthesis 2009, 2009, 1583. (c) Palomo,
́
C.; Oiarbide, M.; Lopez, R. Chem. Soc. Rev. 2009, 38, 632.
(d) Goudedranche, S.; Raimondi, W.; Bugaut, X.; Constantieux, T.;
Bonne, D.; Rodriguez, J. Synthesis 2013, 45, 1909. (e) Krawczyk, H.;
Dzięgielewski, M.; Deredas, D.; Albrecht, A.; Albrecht, Ł. Chem. - Eur. J.
2015, 21, 10268.
(4) For selected reviews on organocatalytic multicatalytic and domino
synthetic strategies, see: (a) Wende, R. C.; Schreiner, P. R. Green Chem.
2012, 14, 1821. (b) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem.
2010, 2, 167. (c) Yu, X.; Wang, W. Org. Biomol. Chem. 2008, 6, 2037.
(13) CCDC 1530190 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
(d) Enders, D.; Grondal, C.; Huttl, M. R. M. Angew. Chem., Int. Ed. 2007,
̈
46, 1570.
(5) For selected reviews on asymmetric aminocatalysis, see: (a) Seayad,
J.; List, B. Org. Biomol. Chem. 2005, 3, 719. (b) List, B. Chem. Commun.
2006, 819. (c) Erkkila, A.; Majander, I.; Pihko, P. M. Chem. Rev. 2007,
̈
D
DOI: 10.1021/acs.orglett.7b01268
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