Dual-organocatalyst-promoted asymmetric cascade reaction: Highly efficient construction of enantiopure fully substituted tetrahydro-1,2-oxazines

Article abstract of DOI:10.1021/ol403463h

A four-component asymmetric α-aminoxylation/aza-Michael/Mannich cascade reaction for the construction of fully substituted chiral tetrahydro-1,2-oxazine derivatives was accomplished in high yields with excellent enantio- and diastereoselectivities under m

Full text of DOI:10.1021/ol403463h

Letter
pubs.acs.org/OrgLett
Dual-Organocatalyst-Promoted Asymmetric Cascade Reaction:
Highly Efficient Construction of Enantiopure Fully Substituted
Tetrahydro-1,2-oxazines
Hua Lin, Xing-Wen Sun,* and Guo-Qiang Lin
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433, P. R. China
S
* Supporting Information
ABSTRACT: A four-component asymmetric α-aminoxyla-
tion/aza-Michael/Mannich cascade reaction for the construc-
tion of fully substituted chiral tetrahydro-1,2-oxazine deriva-
tives was accomplished in high yields with excellent enantio-
and diastereoselectivities under mild conditions. The 1,2-
oxazine derivative could be transformed to the corresponding
multifunctional chiral amino alcohol by N−O cleavage and
fused-tricyclic 4-amino-substituted tetrahydroquinolines in
good yields with excellent stereoselectivities followed by a Friedel−Crafts reaction. Also a 4-alkoxy-substituted tetrahydro-
quinoline was achieved by C-4 inversion of a 4-amino-substituted tetrahydroquinoline.
Scheme 1. Proposed Organocatalytic Cascade Reaction for
the Synthesis of Optically Tetrahydro-1,2-oxazines
he desire for the ideal synthesis of complex natural
products has stimulated the emergence of organocatalytic
T
cascade reactions, which strive to emulate nature in the
construction of intricate molecules. In the pursuit of atom
economy, they avoid costly, time-consuming protection−
deprotection processes and the isolation of intermediates.
Particularly, they trap unstable intermediates to generate useful
enantiopure building blocks with excellent stereoselectivities,
thereby facilitating the efficient synthesis of natural products.1
Chiral secondary amine catalysts, which either activate
aldyhydes by enamine formation or iminium-ion formation,
are considered as ideal organocatalysts2 and successfully used in
cascade reactions for the construction of complicated usually
multistereocenter-containing structures from simple starting
materials.3
stereoselectivity issues, five chemoselectivity issues were
found to be challenging: (1) α-Aminoxylation intermediate I-
1 may oligomerize11 or may react with excess aldehyde 1 in the
presence of a secondary imine catalyst via an aldol reaction; (2)
imine intermediate I-2 may react with excess aldehyde 1 via a
Mannich reaction catalyzed by a secondary amine; (3) an
undesired Michael reaction between aldehyde 1 and α,β-
unsaturated aldehyde 4 may compete with the aza-Michael
addition step; (4) α,β-unsaturated aldehyde 4 and amine 3 may
be transformed to the corresponding imine in situ, bridling the
entry of α,β-unsaturated aldehyde 4 into the desired reaction
cycle; (5) a side intramolecular aldol reaction may also intefere
with the final intramolecular Mannich reaction. Herein, we
report our efforts to meet these challenges and demonstrate the
accessibility of enantioenriched fully substituted tetrahydro-1,2-
oxazines by dual-organocatalytic asymmetric cascade reactions
in moderate yields with high enantio- and diastereoselectivities.
The preliminary experiments were initiated by adding 4-
methoxyaniline to the mixture of 1a and 2a with L-proline as
the catalyst when the first α-aminoxylation reaction was
1,2-Oxazines are valuable chiral building blocks4 frequently
found in various biologically active compounds.5 They possess
remarkable synthetic utilities, often manipulated via a reductive
N−O bond cleavage that forms highly functionalized 1,4-amino
alcohols seen in a number of bioactive natural products.
Recently, there has been great progress in the synthesis of 1,2-
oxazines, particularly in the field of chiral tetrahydro-1,2-
oxazines.6 Nevertheless, to the best of our knowledge, there are
no methods presented for the synthesis of chiral fully
substituted tetrahydro-1,2-oxazines to date.
Previously, we reported the successful preparation of chiral
dihydro-1,2-oxazine using alkyl aldehyde, nitrosobenzene, and
α,β-unsaturated aldehyde.7 We envisioned that, with the
primary amine, the aldehyde intermediate I-18 would be
converted to imine in situ, which would subsequently undergo
an aza-Michael addition9/Mannich10 cascade reaction to
provide a fully substituted tetrahydro-1,2-oxazine with four
newly formed stereocenters in the presence of a chiral
secondary amine catalyst (Scheme 1). However, besides
Received: November 29, 2013
Published: January 13, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
completed,12 followed by the addition of (E)-hex-2-enal 4a and
prolinol derivative 5. Unfortunately, there was only a trace of
the desired product found in the complex reaction mixture
(Table 1, entry 1). Lowering the reaction temperature to −20
a
Scheme 2. Synthesis of Chiral Tetrahydro-1,2-oxazine
a
Table 1. Optimization of the Reaction Conditions
ee
b
c
d
entry
Ar
additive
t (°C) yield
dr
nd
(%)
1
2
3
PMP
PMP
PMP
PMP
PMP
PMP
Ph
none
none
none
none
20
0
trace
nd
nd
nd
trace
trace
42%
41%
50%
42%
44%
30%
62%
nd
nd
−20
−20
e
4
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>99
>99
>99
>99
>99
>99
>99
e
5
NaOAc (0.5 equiv) −20
AcOH (0.3 equiv)
e
a
6
−20
−20
−20
−20
The reaction was performed using nitrosobenzene 2a (0.25 mmol, 1
e
7
e
AcOH (0.3 equiv)
M), aldehyde 1 (0.75 mmol), amine 3a (1.25 mmol), α,β-unsaturated
aldehyde 4 (0.75 mmol), AcOH (30 mol %), catalyst L-proline (10
mmol %), and 5 (30 mmol %) in CHCl3. See Supporting Information
8
4-Cl-Ph AcOH (0.3 equiv)
ef
,
9
PMP
AcOH (0.2 equiv)
b
eg
,
for details. The reaction time was 2 d.
10
PMP
AcOH (0.3 equiv) −20
a
The reaction was performed using nitrosobenzene 2a (0.25 mmol, 1
M, 1 equiv), aldehyde 1a (3 equiv), amine 3 (1 equiv), α,β-unsaturated
acrylaldehyde offered lower yields, 20% and 19% respectively
(Scheme 2, 7i, 7j). It should be mentioned that, in all these
cases, over 95:5 dr and 99% ee were obtained. The absolute
configuration of the tetrahydro-1,2-oxazine products was
identified unambiguously through X-ray crystallographic
analysis of imide derivative 8a derived from the corresponding
adduct 7a (see Supporting Information for details).14
aldehyde 4a (2 equiv), 4 Å MS, catalyst L-proline, and 5 in CHCl3. See
b
Supporting Information for details. Isolated yield of product 6a.
c
d
Determined by 1H NMR of the crude product. For the
e
determination of ee, see Supporting Information. The ratio of
1a:2a:3:4a = 3:1:5:3. Catalyst 5 (20 mol %) was used, and the
reaction time was 2 d. Without 4 Å MS.
f
g
With optically pure 1,2-oxazines in hand, the synthetic utility
of the cascade products was next examined. The 1,2-oxazine
product 7a can be hydrogenolyzed to the corresponding
valuable amino alcohol derivative 9a in 95% yield by N−O
bond hydrogenolysis in the Zn/HCl system. Given the
prevalent occurrence of the chiral amino alcohol moiety in
nature, they are potential chiral building blocks used for the
preparation of conformationally restricted peptides and bio-
logically active nonproteinogenic analogues. Thus, our present
route provides an easy access to a potentially diverse set of such
compounds (Scheme 3).
°C, a suitable temperature for the intramolecular Mannich
reaction,13 gave a negative result (Table 1, entries 2, 3).
Inspection of the loading ratio of the starting materials revealed
that an excessive loading of 4-methoxyaniline was the key to
reaching higher chemoselectivity (Table 1, entry 4). Reduction
of the desired imine intermediate I-5 in situ was completed
with a 42% yield, with over 95:5 dr and 99% ee. When the
additive was examined, AcOH was found to give a better yield
(50%) (Table 1, entries 5, 6). However, aniline and 4-
choroaniline gave worse results (Table 1, entries 7, 8). Not
surprisingly, a reduced loading of catalyst 5 afforded a lower
yield (Table 1, entry 9). To our delight, the best yield was
ultimately achieved in the absence of 4 Å MS as a 62% yield,
without compromising stereoselectivities (Table 1, entry 10).
Thus, the optimal reaction conditions were finally established.
With the optimal reaction conditions identified (Table 1,
entry 10), the scope of this cascade reaction was investigated. A
variety of aldehydes for the first α-aminoxylation were
examined, with butyraldehyde and pentanal giving moderate
yields, 42% and 55% respectively (Scheme 2, 7b, 7c). A long
chain aliphatic aldehyde, such as nonanal, also proved to be a
good substrate, providing the desired 1,2-oxazine product in
good yield (Scheme 2, 7d). Terminal olifinic aldehyde, pent-4-
enal, and dec-9-enal afforded 30% and 46% yields, respectively
(Scheme 2, 7e, 7f). Linear aliphatic aldehydes bearing a
functional group, such as −OBn, could also be employed as a
substrate in the domino reaction (Scheme 2, 7g). In addition,
this method could accommodate various aliphatic α,β-
unsaturated aldehydes as well (Scheme 2, 7h). Aromatic α,β-
unsaturated aldehydes could also be applied in this reaction
system, though (E)-cinnamaldehyde and (E)-3-(furan-2-yl)-
Scheme 3. N−O Cleavage
Furthermore, the imine intermediate I-5 could be subjected
to an intramolecular Friedel−Crafts reaction in situ in the
presence of a Lewis or Brønsted acid. This one-pot multi-
component cascade reaction might furnish the corresponding
multisubstituted 4-amino-substituted tetrahydroquinoline de-
rivative 10 with five newly formed stereocenters. The
tetrahydroquinoline ring moiety is a ubiquitous structural
motif presented in numerous biologically active natural
products and pharmacologically relevant therapeutic agents.15
In particular, 4-amino-substituted tetrahydroquinoline com-
pounds, such as martinellic acid and martinelline, have become
synthetic targets of many research groups, possessing potent
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Letter
antagonist activities toward bradykinin (BK) B1 and B2
receptors.16 Screening of the acids, such as HBr, HCl, AcOH,
and BF3·OEt, proved that HBr (AcOH solution) was the
suitable Brønsted acid for this transformation. Based on the
optimal conditions, this one-pot cascade reaction provided the
corresponding 4-amino-substituted 1,2,3,4-tetrahydroquinoline
derivatives 10 in 35−54% yields, with over 95:5 dr and 99% ee
(Scheme 4).
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and characterization data; copies of
1H and 13CNMR spectra; and HPLC profiles. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
■
Scheme 4. One-Pot Synthesis of 4-Amino-Substituted
Tetrahydroquinoline Derivative
*E-mail: sunxingwen@fudan.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (21072031, 21342009) and China
Postdoctoral Science Foundation (2013M531111) is greatly
acknowledged.
REFERENCES
■
(1) For selective reviews, see: (a) Dalko, P. I.; Moisan, L. Angew.
Chem., Int. Ed. 2004, 43, 5138. (b) Berkessel, A.; Groger, H.
̈
Asymmetric Organocatalysis; Wiley-VCH: Weinheim, 2005. (c) Seayad,
J.; List, B. Org. Biomol. Chem. 2005, 3, 719. (d) Lelais, G.; MacMillan,
D. W. C. Aldrichimica Acta 2006, 39, 79. For a selected domino
reaction or cascade reaction, see: (e) Tietze, L. F.; Brasche, G.;
Gericke, K. M. Domino Reactions in Organic Synthesis; Wiley-VCH:
Weinheim, 2006. (f) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G.
Angew. Chem., Int. Ed. 2006, 45, 7134. (g) Enders, D.; Grondal, C.;
Also, 4-amino-substituted tetrahydroquinoline derivative 10a
could be transformed to its corresponding 4-alkoxy-substituted
tetrahydroquinoline derivative 11a through an “SN2-like
substitution” process in the presence of HBr (AcOH solution)
at −20 °C with high stereoselectivity (Scheme 5).17 The
configuration of tetrahydroquinoline derivative 10 and 11a was
assigned by NOSY (see Supporting Information for details).
Huettl, M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570. (h) Grondal,
̈
C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167. (i) Pellissier, H.
Adv. Synth. Catal. 2012, 354, 237. (j) Yu, X.; Wang, W. Org. Biomol.
Chem. 2008, 6, 2037. (k) Alba, A.-N.; Companyo, X.; Viciano, M.;
Rios, R. Curr. Org. Chem. 2009, 13, 1432. (l) Grossmann, A.; Enders,
D. Angew. Chem., Int. Ed. 2012, 51, 314.
Scheme 5. C4 Functionalization of Tetrahydroquinoline
Derivative
(2) For selected reviews, see: (a) Ahrendt, K. A.; Borth, C. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243. (b) Northrup,
A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 2458. (c) List,
B. Chem. Commun. 2006, 819 and references therein. (d) Mukherjee,
S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471.
(e) Erkkila, A.; Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416.
̈
(f) Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew. Chem.,
Int. Ed. 2008, 47, 6138. (g) MacMillan, D. W. C. Nature 2008, 455,
304.
(3) For selected reviews and papers of amine-catalyzed cascade
reactions, see: (a) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A.
Chem. Commun. 2003, 551. (b) Wasilke, J.-C.; Obrey, S. J.; Baker, R.
In summary, an efficient access to enantiopure fully
substituted chiral tetrahydro-1,2-oxazine derivatives was
developed via a dual-organocatalyst promoted four-component
asymmetric α-aminoxylation/aza-Michael/Mannich cascade
reaction under mild conditions. This method allows the
synthesis of fully substituted tetrahydro-1,2-oxazine derivatives
in good yields (up to 62%), with excellent enantio- (ee >99% in
all cases) and diastereoselectivities (dr >95:5 in all cases). The
1,2-oxazine derivative can be transformed to the corresponding
multifunctional chiral amino alcohol by N−O cleavage.
Furthermore, to build on this strategy, an α-aminoxylation/
aza-Michael/Mannich/Friedel−Crafts cascade reaction was
successfully developed, affording fused tricyclic 4-amino-
substituted tetrahydroquinolines in good yields with excellent
stereoselectivities. Also a 4-alkoxy-substituted tetrahydroquino-
line was achieved by C-4 inversion of a 4-amino-substituted
tetrahydroquinoline. We are currently investigating the catalytic
mechanism of the cascade reaction and the application of this
methodology to asymmetric syntheses of some natural and
natural-like compounds and will report the results in due
course.
T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001. (c) Ramon
́
, D. J.; Yus, M.
Angew. Chem., Int. Ed. 2005, 44, 1602. (d) Guo, H.-C.; Ma, J.-A. Angew.
Chem., Int. Ed. 2006, 45, 354. (e) Enders, D.; Huttl, M. R. M.;
̈
Grondal, C.; Raabe, G. Nature 2006, 441, 861. (f) Xie, H.; Zu, L.; Li,
H.; Wang, J.; Wang, W. J. Am. Chem. Soc. 2007, 129, 10886.
(g) Carlone, A.; Cabrera, S.; Marigo, M.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2007, 46, 1101. (h) Zu, L.; Li, H.; Xie, H.; Wang, J.;
Jiang, W.; Tang, Y.; Wang, W. Angew. Chem., Int. Ed. 2007, 46, 3732.
(i) Rueping, M.; Kuenkel, A.; Tato, F.; Bats, J. Angew. Chem., Int. Ed.
2009, 48, 3699. (j) Reyes, E.; Talavera, G.; Vicario, J. L.; Badía, D.;
Carrillo, L. Angew. Chem., Int. Ed. 2009, 48, 5701. (k) Galzerano, P.;
Pesciaioli, F.; Mazzanti, A.; Bartoli, G.; Melchiorre, P. Angew. Chem.,
Int. Ed. 2009, 48, 7892. (l) Michrowska, A.; List, B. Nat. Chem. 2009,
1, 225. (m) Zhang, X.; Zhang, S.; Wang, W. Angew. Chem., Int. Ed.
2010, 49, 1481. (n) Jones, S. B.; Simmons, B.; Mastracchio, A.;
MacMillan, D. W. C. Nature 2011, 475, 183. (o) Ling, J.-B.; Su, Y.;
Zhu, H.-L.; Wang, G.-Y.; Xu, P.-F. Org. Lett. 2012, 14, 1090.
(4) For selected examples, see: (a) Tsoungas, P. G. Heterocycles 2002,
57, 915. (b) Pulz, R.; Al-Harrasi, A.; Reißig, H.-U. Org. Lett. 2002, 4,
754
dx.doi.org/10.1021/ol403463h | Org. Lett. 2014, 16, 752−755

Organic Letters
Letter
2353. (c) Tishkov, A. A.; Reißig, H.-U.; Loffe, S. L. Synlett 2002, 863.
(d) Buchholz, M.; Reißig, H.-U. Eur. J. Org. Chem. 2003, 3524. (e) Al-
Harrasi, A.; Reißig, H.-U. Angew. Chem., Int. Ed. 2005, 44, 6227. For
the total synthesis of (+)-phyllantidine from a cyclopropane, see:
(f) Carson, C. A.; Kerr, M. A. Angew. Chem., Int. Ed. 2006, 45, 6560.
(5) For selected examples, see: (a) Yu, Q.-S.; Zhu, X.; Holloway, H.
W.; Whittaker, N . F.; Brossi, A.; Greig, N. H. J. Med. Chem. 2002, 45,
3684. (b) Judd, T. C.; Williams, R. M. Angew. Chem., Int. Ed. 2002, 41,
4683. (c) Suzuki, M.; Kambe, J.; Tokuyama, H.; Fukuyama, T. Angew.
Chem., Int. Ed. 2002, 41, 4686. (d) Katoh, T.; Itoh, E.; Yoshino, T.;
Terashima, S. Tetrahedron 1997, 53, 10229. (e) Uchida, I.; Takase, S.;
Kayakiri, H.; Kiyoto, S.; Hashimoto, M.; Tada, T.; Koda, S.;
Morimoto, Y. J. Am. Chem. Soc. 1987, 109, 4108. (f) Bass, P. D.;
Gubler, D. A.; Judd, T. C.; Williams, R. M. Chem. Rev. 2013, 113,
6816. For a selected review, see: (g) Sukhorukov, A. Y.; Ioffe, S. L.
Chem. Rev. 2011, 111, 5004.
(f) Michael, J. P. Nat. Prod. Rep. 2005, 22, 627. (g) Sridharan, V.;
Suryavanshi, P. A.; Menendez, J. C. Chem. Rev. 2011, 111, 7157.
́
(16) (a) Witherup, K. M.; Ransom, R. W.; Graham, A. C.; Bernard,
A. M.; Salvatore, M. J.; Lumma, W. C.; Anderson, P. S.; Pitzenberger,
S. M.; Varga, S. L. J. Am. Chem. Soc. 1995, 117, 6682. For reviews of
synthetic studies towards Martinella alkaloids, see: (b) Nyerges, M.
Heterocycles 2004, 63, 1685. (c) Lovely, C. J.; Badarinarayana, V. Curr.
Org. Chem. 2008, 12, 1431.
(17) Luo, C. S.; Huang, Y. J. Am. Chem. Soc. 2013, 135, 8193.
(6) For selected examples of the synthesis of 1,2-oxazines, see:
(a) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96, 137. For
selected examples of the synthesis of tetrahydro-1,2-oxazines, see:
(b) Vogt, P. F.; Miller, M. J. Tetrahedron 1998, 54, 1317. (c) Koide, K.;
Finkelstein, J. M.; Ball, Z.; Verdine, G. L. J. Am. Chem. Soc. 2001, 123,
398. (d) Young, I. S.; Williams, J. L.; Kerr, M. A. Org. Lett. 2005, 7,
953. (e) Young, I. S.; Kerr, M. A. Angew. Chem., Int. Ed. 2003, 42,
3023. (f) Kumarn, S.; Shaw, D. M.; Longbottom, D. A.; Ley, S. V. Org.
Lett. 2005, 7, 4189. (g) Kumarn, S.; Shaw, D. M.; Ley, S. V. Chem.
Commun. 2006, 3211. (h) Yoon, S. C.; Kim, K.; Park, Y. J. J. Org.
Chem. 2001, 66, 7334. (i) Yamamoto, Y.; Momiyama, N.; Yamamoto,
H. J. Am. Chem. Soc. 2004, 126, 5962. (j) Sibi, M. P.; Ma, Z. H.;
Jasperse, C. P. J. Am. Chem. Soc. 2005, 127, 5764. (k) Momiyama, N.;
Yamamoto, Y.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 1190.
(l) Lu, M.; Zhu, D.; Lu, Y.; Hou, Y.; Tan, B.; Zhong, G. Angew. Chem.,
Int. Ed. 2008, 47, 10187. (m) Zhu, D.; Lu, M.; Chua, P. J.; Tan, B.;
Wang, F.; Yang, X.; Zhong, G. Org. Lett. 2008, 10, 4585.
(7) Lin, H.; Tan, Y.; Sun, X.-W.; Lin, G.-Q. Org. Lett. 2012, 14, 3818.
(8) For aminoxylation of aldehydes and ketones, see: (a) Zhong, G.
Angew. Chem., Int. Ed. 2003, 42, 4247. (b) Brown, S. P.; Brochu, M. P.;
Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808.
(c) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M. Tetrahedron Lett.
2003, 44, 8293. For ketones, see: (d) Bøgevig, A.; Sunden
́
, H.;
Cordova, A. Angew. Chem., Int. Ed. 2004, 43, 1109. (e) Hayashi, Y.;
́
Yamaguchi, J.; Sumiya, T.; Shoji, M. Angew. Chem., Int. Ed. 2004, 43,
1112. For a review, see: (f) Yamamoto, H.; Momiyama, N. Chem.
Commun. 2005, 3514.
(9) For selected reviews on organocatalytic asymmetric aza-Michael
reactions, see: (a) Kwong, F. Y.; Wang, J.; Li, P.; Choy, P. Y.; Chan, A.
S. C. ChemCatChem 2012, 4, 917. (b) Enders, D.; Wang, C.; Liebich, J.
X. Chem.Eur. J. 2009, 15, 11058. (c) Krishna, P. R.; Sreeshailam, A.;
Srinivas, R. Tetrahedron 2009, 65, 9657.
(10) For selected reviews on organocatalytic asymmetric Mannich
́
reactions, see: (a) Cordova, A. Acc. Chem. Res. 2004, 37, 102. (b) Ting,
A.; Schaus, S. E. Eur. J. Org. Chem. 2007, 5797. (c) Mukherjee, S.;
Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471.
(d) Pihko, P. M.; Majander, I.; Erkkila, A. In Topics in Current
Chemistry, Vol. 291: Enamine Catalysis; List, B., Ed.; Springer: Berlin,
2009; p 29. (e) Benohoud, M.; Hayashi, Y. In Science of Synthesis:
Asymmetric Organocatalysis 1; Enamine Catalysis of Mannich Reactions;
List, B., Ed.; Thieme: Stuttgart, 2012; p 73.
(11) Hayashi, Y.; Yamaguchi, J.; Sumiya, T.; Hibino, K.; Shoji, M. J.
Org. Chem. 2004, 69, 5966.
(12) Stirring for 30 min is needed for the imine intermediate I-2
formation to obtain higher diastereoselectivities.
(13) Hayashi, Y.; Tsuboi, W.; Ashimine, I.; Urushima, T.; Shoji, M.;
Sakai, K. Angew. Chem., Int. Ed. 2003, 42, 3677.
(14) CCDC 950659.
(15) (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron 1996,
52, 15031. (b) Kouznetsov, V.; Palma, A.; Ewert, C.; Varlamov, A. J.
Heterocycl. Chem. 1998, 35, 761. (c) Mitchinson, A.; Nadin, A. J. Chem.
Soc., Perkin Trans. 1 2000, 17, 2862. (d) Michael, J. P. Nat. Prod. Rep.
2008, 25, 166. (e) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223.
755
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