Decarboxylative Organocatalytic Allylic Amination of Morita–Baylis–Hillman Carbamates

Article abstract of DOI:10.1002/chem.201803677

The present study reports the organocatalytic enantioselective allylic amination of Morita–Baylis–Hillman carbamates efficiently catalyzed by a chiral amine in the presence of a Br?nsted acid. Chiral allylic amines were produced in high yields (up to 98 %) and enantioselectivities (up to 97 % ee). This method provides an efficient and easily performed route to prepare α-methylene-β-lactams, and other optically active β-lactams, such as the cholesterol-lowering drug Ezetimibe.

Full text of DOI:10.1002/chem.201803677

A Journal of
Accepted Article
Title: Decarboxylative Organocatalytic Allylic Amination of Morita-
Baylis-Hillman Carbamates
Authors: Vojtěch Dočekal, Michal Šimek, Martin Dračínský, and Jan
Vesely
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To be cited as: Chem. Eur. J. 10.1002/chem.201803677
Link to VoR: http://dx.doi.org/10.1002/chem.201803677
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Decarboxylative Organocatalytic Allylic Amination of Morita-
Baylis-Hillman Carbamates
Vojtěch Dočekal,[a] Michal Šimek,[a] Martin Dračínský[b] and Jan Veselý*[a]
Dedicated to Prof. Martin Kotora to his 55th anniversary.
Abstract: The present study reports the organocatalytic
enantioselective allylic amination of Morita-Baylis-Hillman
hypothesis. Conventionally used β-isocupreidine efficiently
catalyzed the model reaction, albeit with low enantiocontrol
(entry 2). Other β-isocupreidine derivatives failed to show a
higher enantiocontrol of decarboxylative AAA (see Table S1 in
SI file). Significantly reduced reactivity was observed under
catalysis with quinine and cinchonidine (entries 3, 4), with no full
conversion of 1a, even after lengthening the reaction time to
7 days. Conversely, significantly enantiomerically enriched 2a
was generated in the presence of dimeric Cinchona-based
tertiary amines, such as (DHQD)2AQN and (DHQ)2AQN, albeit in
low yields (entries 5, 6). Other screened catalysts, including
Kwon’s catalyst (entry 7), other Sharpless bases and phosphine-
(thio)urea catalysts previously developed in our group failed to
efficiently catalyze the model reaction (see Table S1 in SI file).
Based on the above, we chose (DHQD)2AQN as an
appropriate catalyst for subsequent optimization of reaction
conditions. According to our observations (Table 1), this reaction
tolerates a wide range of non-polar solvents, such as aromatic,
etheral and chlorinated solvents, in addition to a polar protic
solvent. Performing the model reaction in chlorinated solvents
and ethers led to the formation of product 2a in moderate yields
and enantioselectivities (entries 11-14), whereas higher yields
and enantioselectivities of 2a were achieved in aromatics
(entries 8-10). Based on the screening results (see also Table
S2 in SI file), bromobenzene was selected as the most suitable
solvent because 2a was obtained in high yield (75%) and
enantioselectivity (82% ee, entry 9).
carbamates efficiently catalyzed with chiral amine in the presence of
Brønsted acid. Chiral allylic amines were produced in high yields (up
to 98%) and enantioselectivities (up to 97% ee). This method
provides an efficient and easily-performed route to prepare α-
methylene-β-lactams, and other optically active β-lactams, such as
the cholesterol-lowering drug Ezetimibe.
Optically active allylic amines have been recognized as
valuable building blocks with wide applications in the synthesis
of biologically active and naturally occurring molecules.[1]
Consequently, the development of efficient enantioselective
synthetic methods for their preparation has generated
considerable research interest.[2] Among the various methods
used for this purpose,[3] direct amination via aza-Morita-Baylis-
Hillman (aza-MBH) reaction[4]
and transition metal and
organocatalyzed asymmetric allylic amination (AAA)[5] stand out
as some of the most powerful approaches.
Aza-MBH reaction is a highly efficient and atom-economic
carbon-carbon forming reaction. Unfortunately, direct aza-MBH
reaction is limited when applied to electron-rich imines, such as
N-aromatic imines.[4] AAA methods predominantly use either
transition metal complexes[6],[7] or chiral amines[8] and
phosphines[9] as efficient catalysts, when racemic MBH
derivatives, such as carbonates and acetates, serve as
substrates. In comparison to direct aza-MBH reaction, AAA of
conventionally used MBH derivatives is a less atom-economic
approach because this process requires introducing a function
group and subsequent removing it during the allylation step
(Figure 1).
Despite the impressive advances made in aza-MBH and
AAA methods, the development of atom-economic catalytic
enantioselective amination reactions is still highly desirable.
Considering the above and our interest in enantioselective allylic
amination reaction,[8o,10] we report the enantioselective AAA of
MBH carbamates and its application to the synthesis of
biologically relevant motifs.
Because carbamates and carbamic acids can easily
undergo decarboxylation to generate the corresponding
amines,[11] we began testing the reactivity of racemic aniline-
derived carbamates 1 in decarboxylative allylic amination using
conventional nitrogen and phosphine nucleophiles as catalysts
(Table 1). Fortunately, the model reaction of 1a performed in
toluene at room temperature was efficiently catalyzed with
DABCO, generating allylic amine 2a in an almost quantitative
yield. Next, we enantioselectively validated our working
Figure 1. Previous approaches towards preparation of MBH-derived chiral
[a]
[b]
V. Dočekal, M. Šimek, Dr. J. Veselý
Department of Organic Chemistry
Charles University
Hlavova 8, 12843 Prague, Czech Republic
E-mail: jxvesely@natur.cuni.cz, http://orgchem.cz/vesely/
Dr. M Dračínský
amines.
Institute of Organic Chemistry and Biochemistry
Czech Academy of Sciences
Flemingovo nám. 2, 16610 Prague, Czech Republic
Supporting information for this article is given via a link at the end of
the document.
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be optimal for the model reaction (see SI file). No change in
reaction efficiency was observed when using reduced quantities
of catalysts, 10 mol % (DHQD)2AQN and 5% (1S)-CSA
(entry 10). Further reduction of catalyst loading had
a deleterious effect on the reaction yield (entry 11).
Table 1. Screening of chiral tertiary amine catalysts and optimization studies
Entry
Catalyst
Solvent
Time
[h]
Yield
[%][a]
e.e.
Table 2. Screening of additives and other optimization studies
[%][b]
1
2
DABCO
toluene
toluene
toluene
toluene
toluene
toluene
toluene
benzene
bromobenzene
mesitylene
DCM
16
90
76
20
30
62
44
n.d.
66
75
50
75
42
45
39
59
-
β-ICD
16
29
-16
19
82
-64
n.d.
80
82
84
65
63
73
75
60
3[c]
4[c]
5[c]
6[c]
7[d]
8[c]
9
quinine
168
168
168
168
168
168
112
168
112
168
168
168
60
Entry (DHQD)2AQN
[x mol %]
Additive
[y mol %]
Temp. Time
[h]
Yield
[%][a]
e.e.
[%][b]
cinchonidine
(DHQD)2AQN
(DHQ)2AQN
Kwon cat.
1[c]
2[c]
20
20
20
20
20
20
20
20
20
10
5
2,4-DNBA, [10] 25 °C 168
68
56
66
68
76
79
76
88
87
87
53
42
68
82
85
86
94
86
92
86
93
93
92
92
-66
-83
p-TsOH, [10]
BNHP, [10]
25 °C 168
25 °C 168
25 °C 168
25 °C 168
40 °C 168
3[c]
4[c]
(1S)-CSA, [10]
(1R)-CSA, [10]
(1S)-CSA, [10]
(1S)-CSA, [10]
(1S)-CSA, [10]
(1S)-CSA, [10]
(1S)-CSA, [5]
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
5[c]
6
10[c]
11
7
80 °C
40 °C
40 °C
40 °C
20
68
44
50
8[d]
12[c]
13[c]
14[c]
15
CHCl3
9[e]
Et2O
10[e]
11[c,e]
12[c,f]
13[c,f]
MTBE
(1S)-CSA, [2.5] 40 °C 168
(1S)-CSA, [10] 40 °C 168
MeOH
20
20
[a] Isolated yield after column chromatography. [b] Determined by HPLC of
purified product 2a. [c] No full conversion of 1a was observed. [d] No reaction.
(1R)-CSA, [10]
40 °C 168
[a] Isolated yield after column chromatography. [b] Determined by HPLC
of purified product 2a. [c] No full conversion of 1a was observed. [d]
c = 1.0 mol/l. [e] c = 2.0 mol/l. [f] Reaction with (DHQ)2AQN.
2,4-DNBA = 2,4-Dinitrobenzoic acid, BNHP = (R)-(-)-1,1'-Binaphthyl-2,2'-
diyl hydrogenphosphate, (1S)-CSA = (1S)-(+)-Camphorsulfonic acid, (1R)-
CSA = (1R)-(+)-Camphorsulfonic acid, 2.4-DNBA = 2,4-Dinitrobenzoic
acid.
Subsequently, the presence of an additional Brønsted acid
showed a strong effect on reactivity and on asymmetric
induction (Table 2). When optically active camphorsulfonic acid -
(1S)-CSA, was used together with (DHQD)2AQN, allylic amine
2a was obtained in high enantiomeric purity (94% ee, entry 4).[12]
Conversely, the co-catalytic system (DHQD)2AQN/(1R-CSA)
failed to significantly increase asymmetric induction. This
observation may be explained by the stereochemical “match-
mismatch” effect of the two sources of chirality and catalysts.
The results from the (DHQ)2AQN/(1S)CSA (and 1R-CSA)
cocatalytic system support the above effect on the
enantiocontrol of the process (entries 12-13).
After optimizing the reaction conditions, we began
exploring the scope of organocatalytic decarboxylative AAA
reaction by varying the MBH carbamate 1 (Scheme 1). The
corresponding allylic amines 2c-g, derived from MBH
carbamates containing both electron withdrawing (EWG) and
donating (EDG) groups in the para position of the aromatic ring,
were produced in high yields (74-98%) with excellent
enantioselectivities (90-97% ee). When a strong EWG such as
substrate 1h was present, the reaction rate decreased slightly;
otherwise, the reaction was completed within 2 days. Moreover,
ortho- and meta-substituted MBH carbamates 2i-k showed
similar levels of reactivity and enantiocontrol under the reported
reaction conditions. For example, the MBH carbamate 1k
reaction generated chiral allylic amine 2k (with the o-methyl
group) in a nearly quantitative yield (98%) and with 93% ee.
The reaction temperature and concentration had a marked
effect
on
reaction
efficiency
and
enantioselectivity.
Enantiocontrol slightly decreases at high temperatures (entries
6-7), and an increased concentration of 1a significantly
shortened the reaction time (entries 8, 9). Thus, a model
reaction of 1a catalyzed with (DHQD)2AQN/(1S)-CSA in
bromobenzene (c = 2 mol/l) at 40°C generated allylic amine 2a
in an 87% yield and with high enantioselectivity (93% ee) in 44 h
(entry 9).
Then, we analyzed the variation in reaction efficiency with
catalyst loading and with the (DHQD)2AQN/(1S)-CSA ratio.
Interestingly, no change in enantioselectivity was observed with
the increase in CSA, until an excess of CSA to (DHQD)2AQN
was used. The 2:1 ratio of (DHQD)2AQN/(1S)-CSA was found to
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Then, we examined MBH carbamates derived from various
anilines under optimized reaction conditions (Scheme 1). The
results showed that para-substituted aniline-derived MBH
carbamates had a significant electronic effect on reaction rate
and on selectivity. When electron rich aniline-derived
carbamates 1m or 1n were subjected to the reaction, the
corresponding products were generated in excellent yields and
with high levels of enantioselectivity. MBH carbamates with
electron-demanding substituents also produced amines 2o-q in
high yields and enantioselectivities, except strongly electron
demanding aniline-derived substrates. For example, substrate
1o led to formation of 2o in 88% yield and with 93% ee, whereas
compound 2r was produced in low yield and with moderate
enantioselectivity (65% ee) after a prolonged reaction time.
Significantly reduced enantiocontrol was also observed
when ortho-substituted aniline-derived MBH carbamate 1s was
used. This may be explained by the electron-deficient behavior
of the aniline part and by steric hindrance. Interestingly,
sterically demanding aliphatic amine-derived substrate 1t
generated the corresponding product in low yield but with
86% ee. This clearly shows that electronic effects primarily
account for reduced enantiocontrol. We also examined other
MBH carbamates, such as carbamates derived from other
aliphatic amines, aliphatic MBH alcohols, and MBH carbamates
derived from various electron deficient alkenes, but most
corresponding products, 2l and 2u-x, showed reduced
enantioselectivity (Scheme 1).
To evaluate this organocatalytic asymmetric system on a
large scale, 1.0 mmol of allylic carbamate 1a was used to
perform the AAA reaction, and the product 2a was obtained in
94% yield and with 92% ee (Scheme 2). Furthermore, the allylic
amine 2a was converted into α-methylidene-β-lactam 3a using
pyridinium salts 4. When tetrafluoroborate 4b was used, the
lactam 3a was obtained in excellent yield (86%) with retained
enantioselectivity (92% ee).
Scheme 2. Synthesis of enantiomerically enriched α-alkylidene-β-lactam 3a.
Enantiomerically enriched allylic amines
2
and
α-methylidene-β-lactams 3 are useful synthetic intermediates.
For example, allylic amine 2y, prepared by enantioselective
decarboxylative AAA of 1y, can be readily transformed into
Ezetimibe,[13]
a
strong cholesterol absorption inhibitor
(Scheme 3).[6d,14]
Scheme 1. Substrate scope of decarboxylative AAA using MBH-carbamates.
Scheme 3. Formal total synthesis of Ezetimibe.
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The absolute configuration of allylic amines 2 and the
corresponding α-methylidene-β-lactam 3 was assigned by single
X-ray diffraction analysis[15] of compound 2e (see SI file) and by
chemical correlation.[16] The stereogenic center (C4) has (R)-
absolute configuration. This observation is also supported by the
proposed reaction mechanism (Scheme 4).
Figure 2. Calculated (B3LYP/6-31g(d,p)) relative energy profile of the AAA
reaction. All energies are expressed as kJ/mol.
In summary, we developed and optimized a method for the
organocatalytic
decarboxylative
enantioselective
allylic
amination of readily available Morita-Baylis-Hillman carbamates.
The reaction is efficiently catalyzed by combining the co-catalytic
systems (DHQD)2AQN and (1S)-CSA, generating chiral allylic
amines in excellent yields and enantioselectivities. We showed
that this method can be used for the preparation of α-methylene-
β-lactams in a simple lactamization reaction. Moreover, the
synthetic utility of the protocol is exemplified by the formal
synthesis of a blockbuster drug, Ezetimibe. The proposed
reaction mechanism is still under investigation and ongoing
mechanistic studies in our laboratory will provide further insights
into this process.
Scheme 4. Proposed reaction mechanism of the AAA reaction.
We hypothesize that the reaction mechanism proceeds via
two key steps. First, a nucleophilic addition of the tertiary amine
of the catalyst on the terminal carbon of the electronically poor
double bond in compound 1a leads to the formation of a
positively charged intermediate while an aromatic carbamate
anion is expelled. The carbamate anion may undergo
protonation, by the camphorsulfonic acid, and decarboxylation,
thereby leading to an aniline derivative. The second step of the
reaction involves a nucleophilic addition of the aniline on the
intermediate leading to the final product 2a and to the release of
the catalyst. The camphorsulfonate anion may facilitate the loss
of the excess proton in the final product.
Experimental Section
In a vial equipped with magnetic stirring bar, were placed (DHQD)2AQN
(0.02 mmol, 0.1 eq.), (1S)-CSA (0.01 mmol, 0.05 eq.), MBH adduct
(0.2 mmol, 1.0 eq.) and bromobenzene (0.1 ml). Reaction mixture was stirred
for indicated time at 40 °C. Solvent was removed under reduced pressure. The
crude product was purified by column chromatography on silica gel with
hexane/EtOAc as an eluent.
1
Acknowledgements
To support the proposed mechanism, we performed a
computational search for possible transition-state (TS) structures
at the DFT level. Because the (DHQD)2AQN catalyst is a rather
large molecule, we performed the TS search with a smaller
model consisting of 5-methylquinuclidin-2-yl-ethan-1-ol, as
shown in Figure 2. We found transition states structures with
modest energy barriers of 147 and 93 kJ/mol, respectively, for
both proposed key steps of the AAA reaction. The structure of
the intermediate with the covalently linked catalyst is crucial for
the stereochemical outcome of the reaction. Therefore, we also
performed a DFT search for the conformation with the lowest
energy intermediate without any truncation of the catalyst
structure, and we found that the Si face of the double bond is
blocked by the quinuclidine and by the quinolone part of the
catalyst in this conformation, thus leaving the Re face exposed
to the addition of the aniline. This preferred conformation
supports the formation of the final product with R configuration,
in agreement with the experimental findings.
JV thanks the Czech Science Foundation (No 16-23597S)
for funding this study. VD thanks the Charles University Grant
Agency (No 1504217) for the financial support and MD thanks
the Czech Science Foundation (No 18-11851S). The authors
also thank Dr. Hybelbauerová and Dr. Tošner for the NMR
service, Dr. Štícha for the MS analysis, Dr. Císařová for the
X-ray analysis, Dr. Kaminský for computational studies and Dr.
Carlos V. Melo for proofreading.
Keywords: Enantioselective allylic aminination • Cinchona
alkaloids • MBH derivatives • Brønsted acid • Chiral allylic
amines
[1]
a) E. G. Brown, Ring Nitrogen and Key Biomolecules; Springer, Boston,
1998; b) T. Henkel, R. M. Brunne, H. Muller, F. Reichel Angew. Chem.
Int. Ed. 1999, 38, 643-647; c) R. Hili, A. K. Yudin, Nat. Chem. Biol.
2006, 2, 284-287; d) V. Farina, J. T Reeves, C. H. Senanayake, J. J.
Song, Chem. Rev. 2006, 106, 2734-2793.
[2]
For books and reviews, see: a) J. A. Ellman, T. D. Owens, T. P. Tang,
Acc. Chem. Res. 2002, 35, 984-995; b) B. M. Trost, M. L. Crawley,
Chem. Rev. 2003, 103, 2921-2944; c) T. C. Nugent (Ed.), Chiral Amine
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Synthesis, Wiley-VCH, New York, 2008; d) E. M. Skoda, G. C. Davis, P.
Wipf, Org. Process Res. Dev. 2012, 16, 26-34.
Peng, J. Lei, K. Jiang, Y.-C. Chen, Angew. Chem. Int. Ed. 2009, 48,
5737-5740; e) J.-R. Huang, H.-L. Cui, J. Lei, X.-H. Sun, Y.-C. Chen,
Chem. Commun. 2011, 47, 4784-4786; f) A.-J. Lin, H.-B. Mao, X. Zhu,
H.-M. Ge, R.-X. Tan, C. J. Zhu, Y.-X. Cheng, Chem. Eur. J. 2011, 17,
13676-13679; g) C.-K. Pei, X.-C. Zhang, M. Shi, Eur. J. Org. Chem.
2011, 4479-4484; h) W.-S. Sun, X.-Z. Ma, L. Hong, R. Wang, J. Org.
Chem. 2011, 76, 7826-7833; i) L. Huang, Y. Wei, M. Shi, Org. Biomol.
Chem. 2012, 10, 1396-1405; j) M.-X. Zhao, M.-X. Chen, W.-H. Tang,
D.-K. Wei, T.-L. Dai, M. Shi, Eur. J. Org. Chem. 2012, 3598-3606; k) H.
Zhang, S.-J. Zhang, Q.-Q. Zhou, L. Dong, Y.-C. Chen, Beilstein J. Org.
Chem. 2012, 8, 1241-1245; l) G. Ma, M. P. Sibi, Org. Chem. Front.
2014, 1, 1152-1156; m) L. Yao, C.-J. Wang, Adv. Synth. Catal. 2015,
357, 384-388; n) N. Baioui, H. Elleuch, F. Rezgui, Synth. Commun.
2016, 46, 1796-1802; o) M. Kamlar, I. Císařová, S. Hybelbauerová, J.
Veselý, Eur. J. Org. Chem. 2017, 1926-1930.
[3]
For recent representative examples, see: a) S. Kobbelgaard, K.
Brandes, K. A. Jørgensen, Chem. Eur. J. 2008, 14, 1464-1471; b) G.
Jiang, R. Halder, Y. Fang, B. List, Angew. Chem. Int. Ed. 2011, 50,
9752-9755; c) Z. Cui, Y.-J. Chen W.-Y. Gao, C.-G. Feng, G.-Q. Lin, Org.
Lett. 2014, 16, 1016-1019; d) J. M. Bauer, W. Frey, R. Peters, Angew.
Chem. Int. Ed. 2014, 53, 7634-7638; e) R.-R, Liu, D.-J. Wang, L. Wu, B.
Xiang, G.-Q. Zhang, J.-R. Gao, Y.-X. Jia, ACS Catal. 2015, 5, 6524-
6528; f) J. Kong, M. McLaughlin, K. Belyk, R. Mondschein, Org. Lett.
2015, 17, 5520-5523; g) Y. Huang, R.-Z. Huang, Y. J. Zhao, J. Am.
Chem. Soc. 2016, 138, 6571-6576; h) J. M. Bauer, W. Frey, R. Peters,
Chem. Eur. J. 2016, 22, 5767-5777; i) X.-W. Qian, Z.-J. Xue, Q. Zhao,
Z. Cui, Y.-J. Chen, C.-G. Feng, G.-Q. Lin, Org. Lett. 2017, 19, 5601-
5604; j) L.-J. Xiao, Ch.-Y. Zhao, L. Cheng, B.-Y. Feng, W.-M. Feng, J.-
H. Xie, X.-F. Xu, Q.-L. Zhou, Angew. Chem. Int. Ed. 2018, 57, 3396-
3400.
[9]
For enantioselective allylic amination catalyzed by chiral phosphines,
see: a) C.-W. Cho, J.-R. Kong, M. J. Krische, Org. Lett. 2004, 6, 1337-
1339; b) T.-Z. Zhang, L.-X. Dai, X.-L. Hou, Tetrahedron: Asymmetry
2007, 18, 1990-1994; c) G.-N. Ma, S.-H. Cao, M. Shi, Tetrahedron:
Asymmetry 2009, 20, 1086-1092; d) H.-P. Deng, Y. Wei, M. Shi, Eur. J.
Org. Chem. 2011, 1956-1960; e) X. Zhao, T. Kang, J. Shen, F. Sha, X.
Wu, Chin. J. Chem. 2015, 33, 1333-1337; f) L.-L. Zhu, H.-W. Hu, L. Qi,
Y. Zheng, W.-H. Zhong, Eur. J. Org. Chem. 2016, 2139-2144.
[4]
For reviews and books about MBH/aza-MBH reaction, see: a)
D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003, 103,
811-892; b) G. Masson, C. Housseman, J. Zhu, Angew. Chem. Int. Ed.
2007, 46, 4614-4628; c) V. Declerck, J. Martinez, F. Lamaty, Chem.
Rev. 2009, 109, 1-48; d) M. Shi, F.-J. Wang, M.-X. Zhao,
The Chemistry of the MBH Reaction, RSC Publishing, London, 2011;
e) D. Basavaiah, G. Veeraraghavaiah, Chem. Soc. Rev. 2012, 41, 68-
78; f) Y. Wei, M. Shi, Chem. Rev. 2013, 113, 6659-6690; g) H.
Pellissier, Tetrahedron 2017, 73, 2831-2861.
[10] B. Formánek, M. Šimek, M. Kamlar, I. Císařová, J. Veselý J. Org. Chem.
2018, submitted.
[11] For selected examples, see: a) S. L. Johnson, D. L. Morrison, J. Am.
Chem. Soc. 1972, 94, 1323-1334; b) M. Ciclosi, C. Fava, R. Galeazzi,
M. Orena, J. Sepulveda-Arques, Tetrahedron Lett. 2002, 43, 2199-
2202; c) S. R. Mellegaard-Waetzig, D. K. Rayabarapu, J. A. Tunge,
Synlett 2005, 18, 2759-2761; d) B. Wan, Ma S., Angew. Chem. Int. Ed.
2013, 52, 441-445; e) Y. Zou, F.-L. Zhu, Z.-C. Duan, Y.-H. Wang, D.-Y.
Zhang, Z. Cao, Z. Zheng, X.-P. Hu, Tetrahedron Lett. 2014, 55, 2033-
2036; f) A. Kondoh, Y. Kamata, M. Terada, Org. Lett. 2017, 19, 1682-
1685; and references therein.
[5]
[6]
For selected reviews, see: a) M. Johannsen, K. A. Jørgensen, Chem.
Rev. 1998, 98, 1689-1708; b) R. L. Grange, E. A. Clizbe, P. A. Evans,
Synthesis 2016, 48, 2911-2968.
For palladium-catalyzed AAA of MBH derivatives, see: a) S. Rajesh, B.
Banerji, J. Iqbal, J. Org. Chem. 2002, 67, 7852-7857; b) T. Nemoto, T.
Fukuyama, E. Yamamoto, S. Tamura, T. Fukuda, T. Matsumoto, Y.
Akimoto, Y. Hamada, Org. Lett. 2007, 9, 927-930; c) Y. Wang, L. Liu,
D. Wang, Y.-J. Chen, Org. Biomol. Chem. 2012, 10, 6908-6913; d) X.
Wang, F. Meng, Y. Wang, Z. Han, Y.-J. Chen, L. Liu, Z. Wang, K. Ding,
Angew. Chem. Int. Ed. 2012, 51, 9276-9282; e) X. Wang, P. Guo, Z.
Han, X. Wang, Z. Wang, K. Ding, J. Am. Chem. Soc., 2014, 136, 405-
411; f) X. Wang, X. Wang, Z. Han, Z. Wang, K. Ding, Org. Chem. Front.
2017, 4, 271-276.
[12] For ion pair catalytic system based on Cinchona alkaloid derived
primary amine and CSA, see: Ch. Liu, Q. Zhu, K.-W. Huang, Y. Lu, Org.
Lett. 2011, 13, 2638-2641.
[13] a) S. B. Rosenblum, T. Huynh, A. Afonso, H. R. Davis Jr., N. Yumibe, J.
W. Clader, D. A. Burnett, J. Med. Chem. 1998, 41, 973-980; b) J. W.
Clader, J. Med. Chem. 2004, 47, 1-9.
[7]
[8]
For iridium-catalyzed AAA of other substrates, see: a) J. F. Hartwig, L.
M. Stanley, Acc. Chem. Res. 2010, 43, 1461-1475; b) Z. Lu, S. Ma,
Angew. Chem. Int. Ed. 2008, 47, 258-297; c) B. M. Trost, D. L. Van
Vranken, Chem. Rev. 1996, 96, 395-422.
[14] a) M. Humpl, J. Tauchman, N. Topolovčan, J. Kretschmer, F. Hessler, I.
Císařová, M. Kotora, J. Veselý, J. Org. Chem. 2016, 81, 7692-7699.
[15] X-ray crystallographic data for 2e have been deposited with the
Cambridge Crystallographic Data Centre (CCDC) under deposition
numbers CCDC 1839452.
For enantioselective allylic aminations catalyzed by chiral amines, see:
a) J. N. Kim, H. J. Lee, J. H. Gong, Tetrahedron Lett. 2002, 43, 9141-
9146; b) Y.-H. Du, X.-L. Han, X.-Y. Lu, Tetrahedron Lett. 2004, 45,
4967-4971; c) S.-J. Zhang, H. L. Cui, K. Jiang, R. Li, Z.-Y. Ding, Y.-C.
Chen, Eur. J. Org. Chem. 2009, 5804-5809; d) H.-L.Cui, X. Feng, J.
[16] J. Liu, Z. Han, X. Wang, Z. Wang, K. Ding, J. Am. Chem. Soc. 2015,
137, 15346 (CCDC number 1414059 in SI file).
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10.1002/chem.201803677
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Vojtěch Dočekal, Michal Šimek, Martin
Dračínský, Jakub Kaminský, Jan
Veselý*
Page No. – Page No.
Decarboxylative Organocatalytic
Allylic Amination of Morita-Baylis-
Hillman Carbamates
Decarboxylative amination: Organocatalytic enantioselective allylic amination of Morita-Baylis-Hillman carbamates efficiently catalyzed with
chiral amine in the presence of Brønsted acid produces chiral allylic amines in high yields (up to 98%) and enantioselectivities (up to 97% ee).
This method provides an efficient, atom-economic and easily-performed route to prepare α-methylene-β-lactams and other optically active
β-lactams.
This article is protected by copyright. All rights reserved.