Modular approach for synthesis of vicinal diamines containing axial chiral 1,1′-binaphthyl from 1,2-diaminoethane by Pd-catalyzed n-arylation reactions

Article abstract of DOI:10.1021/ol103169z

A very convenient and efficient modular approach for the synthesis of vicinal diamines containing axial chiral 1,1′-binaphthyl from 1,2-diaminoethane by Pd-catalyzed N-arylation reactions has been developed. The resulting chiral diamines could be easily c

Full text of DOI:10.1021/ol103169z

ORGANIC
LETTERS
2
011
Vol. 13, No. 5
146–1149
Modular Approach for Synthesis of Vicinal
Diamines Containing Axial Chiral 1,1 -
0
1
Binaphthyl from 1,2-Diaminoethane by
Pd-Catalyzed N-Arylation Reactions
,
†,‡
†
Shifa Zhu,* Chao Wang, Lijuan Chen, Renxiao Liang, Yingfeng Yu, and
†
†
†
†
Huanfeng Jiang
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou, 510640, P. R. China, and Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai,
2
00032, P. R. China
zhusf@scut.edu.cn
Received December 29, 2010
ABSTRACT
0
A very convenient and efficient modular approach for the synthesis of vicinal diamines containing axial chiral 1,1 -binaphthyl from 1,2-
diaminoethane by Pd-catalyzed N-arylation reactions has been developed. The resulting chiral diamines could be easily converted into NHC
precursors, imidazole salts, in good yields.
Chiral vicinal diamines and their derivatives have re-
ceived much attention in the field of medicinal and asym-
Shi developed an elegant Cu- or Pd-catalyzed diamination
of alkenes using di-tert-butyldiaziridinone as the nitrogen
1
metric synthesis. The most general and effective way to
synthesize these important compounds is by metal-mediat-
3
source.
Among all the chiral vicinal diamines, 1 and 2 are most
well-known and frequently used in the asymmetric cataly-
2
ing and catalyzing the diamination of olefins. Recently,
1
a
tic process, in which, the chiral centers are on the carbon
backbone. Interestingly, the diamine type 3, where the
chiral environment is attached to the nitrogen atoms, has
†
South China University of Technology.
‡
Chinese Academy of Sciences.
1) For selected reviews: (a) Lucet, D.; Gall, T. L.; Mioskowski, C.
(
1-3
received much less attention.
Angew. Chem., Int. Ed. 1998, 37, 2580. (b) Kotti, S. R. S. S.; Timmons,
C.; Li, G. Chem. Biol. Drug Des. 2006, 67, 101.
(2) (a) Becker, P. N.; White, M. A.; Bergman, R. G. J. Am. Chem.
Soc. 1980, 102, 5676. (b) Chong, A. O.; shima, K.; Sharpless, K. B. J.
Am. Chem. Soc. 1977, 99, 3420. (c) Muniz, K.; Nieger, M. Synlett 2003,
211. (d) Muniz, K.; Nieger, M. Chem. Commun. 2005, 2729. (e) Backvall,
J.-E. Tetrahedron Lett. 1978, 163. Tl:(f) Aranda, V. G.; Barluenga, J.;
Aznar, F. Synthesis 1974, 504.
(
3) (a) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. (b)
We are interested in the N-Heterocyclic-Carbene
(NHC) catalyzed asymmetric reactions; therefore,
Du, H.; Zhao, B.; Shi, Y. Org. Synth. 2009, 86, 315. (c) Zhao, B.; Peng,
X.; Cui, S.; Shi, Y. J. Am. Chem. Soc. 2010, 132, 11009.
1
0.1021/ol103169z r 2011 American Chemical Society
Published on Web 02/02/2011

designing and synthesizing new chiral NHC ligands are the
focus of our research. At present, two large families of chiral
NHC ligands dominate the literature: NHC-I (with the
chiral elements on the N-heterocycle) and NHC-II (with
Scheme 1
4
N-substituents containing chirality) (Scheme 1).
For NHC-I, the chiral center on the N-heterocycle
points away from the metal center, which actually is the
catalytic center. This, to some extent, will bring a negative
effect to the asymmetric catalytic process. NHC-I is gen-
erally synthesized from diamine 1 or 2 by palladium cata-
lyzed double N-arylation reactions (Scheme 1, eq 1). For
NHC-II, the chirality elements are attached to the nitrogen
atoms, which sit adjacent to the metal center. In this
way, the chiral substituting groups are pointing toward
the reactive center, which is important for the asym-
metric induction process. NHC-II is often prepared by
the reaction of two amines with the glyoxal or the N-aryla-
tion reaction between Ar-X or Ar-OTf with the monosub-
4c,d
stituted diamine (Scheme 1, eq 2). It is curious that using
simple 1,2-diaminoethane (DAE) as the starting material to
get the desired chiral diamine 3 by double N-arylation
reactions (Scheme 1, eq 3) has not been tried, because it is
the most straightforward way to reach the diamine 3 from
the viewpoint of retrosynthetic analysis.
Scheme 2
In this paper, we report a modular synthesis of different
kinds of chiral diamine from DAE by palladium catalyzed
N-arylation reactions. This catalytic process would be
highly desirable since the inexpensive and abundant DAE
was used as the nitrogen source. Four different diamines
derivatives: monosubstituted DAE 5, C -symmetry disub-
2
stituted DAE 6, and unsymmetry disubstituted DAE 7, 8
could be prepared in only one to two steps by using this
modular approach (Scheme 2).
Owing to the superior molecular skeleton, 1,1 -binaphthyl
5
units are frequently used as chiral elements in catalyst design.
Therefore, in this paper, we chose (R)-BINOL derived
monotriflate as the starting material to couple with DAE.
Initial efforts were made to systematically investigate
various catalytic conditions for N-arylation reactions of
monotriflate 4a with DAE as a model reaction under
different conditions. As summarized in Table 1, initially,
wewanted toselectively synthesize monosubstituted amine
best catalyst and ligand combination for this reaction; the
isolated yield could reach 49% (entry 4) when the reaction
was set in toluene at 110 °C. It is interesting to find that
almost no product was detected when THF was used as the
solvent (entry 5), as, in many N-arylation reactions, ether
solvents have been often proven superior to toluene. When
the reaction was carried out in 1,4-dioxane, however, the
yield of diamine 5a was improved to 89% (entry 6). In
order to remove the moisture adventitiously introduced by
the reagent or operator, prior dried molecular sieves (MS)
were added to the reaction system. Strangely, the yield of
desired amine 5a was decreased dramatically to 32%, and
disubsituted amine 6a was formed in 25% isolated yield
0
5
a and disubstituted diamine 6a by controlling the ratio of
triflate 4a and DAE. When excess DAE (1.5 equiv) was
employed for the N-arylation reaction, several common
combinations of palladium sources and phosphine ligands
(entry 7). It could be attributed to DAE being a very small
organic molecule, which could enter into the MS cavity.
The free DAE in the reaction solution was then decreased
were tested for the reaction. When Pd(dba) was used as
2
(less than 1.0 equiv), which resulted in the drop in yield of
the palladium source, and DPE-Phos as the ligand, only
the hydrolysis product was formed. By changing the ligand
to BINAP, monosubstituted diamine 5a could be formed
in 29% isolated yield (entries 1-2). By varing the catalysts
monosubstituted amine 5a and rise in yield of disubstituted
amine 6a. It should be noted that disubstituted amine 6a
often was detected as the coexisting byproduct in the
reaction system when the reaction was conducted at 110 °C,
although the yields are very low (entries 4, 6, 7). The
disubstituted amine 6a must proceed through monosub-
stituted amine 5a. Therefore, it is natural to think that we
can further improve the yield of monosubstituted amine 5a
by lowering the reaction temperature to diminish the amount
of disubstituted product 6a. When the reaction was set at a
temperature lower than 100 °C, disubstituted amine 6awas
and ligands, Pd(OAc) and BINAP were found to be the
2
(
4) For selected reviews: (a) Enders, D.; Niemeier, O.; Henseler, A.
Chem. Rev. 2007, 107, 5606. (b) Marion, N.; Diez-Gonzalez, S.; Nolan,
I. P. Angew. Chem., Int. Ed. 2007, 46, 2988. (c) Moore, J. L.; Rovis, T.
Top. Curr. Chem. 2010, 291, 77. For books:(d) N-Heterocyclic Carbenes
in Transition Metal Catalysis; Glorius, F., Ed.; Springer: Berlin, 2007.
(5) (a) Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103, 3155.
(b) Brunel, J. M. Chem. Rev. 2005, 105, 857.
Org. Lett., Vol. 13, No. 5, 2011
1147

Table 1. Optimization of Reaction Conditions for the N-Arylation
of DAE and 4a
Scheme 3. Pd(OAc) -Catalyzed N-Arylation of DAE with
2
Triflate 4
a
a
e
yield (%)
entry
cat.
ligand
4a:DAE temp
5a
nd
6a
nd
b
1
Pd(dba)
Pd(dba)
2
DPE-Phos
BINAP
DPE-Phos
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
2.4:1
3.0:1
3.0:1
110
110
110
110
110
110
110
80
b
2
2
29
3
nd
b
3
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
2
2
2
nd
b
4
49
trace
c
5
trace nd
6
89
32
71
84
97
trace
d
7
25
nd
nd
nd
8
9
90
1
0
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
100
110
110
110
11
2
trace 61
1
2
2
nd
nd
69
b
1
3
2
38
a
Unless otherwise noted, the reaction was performed in 1,4-dioxane
for 12 h using 10 mol % catalyst and 20 mol % ligand under N . [4a] =
.25 M. In toluene. In THF. In the presence of molecular sieve (100
2
b
c
d
0
e
mg MS/0.25 mmol of 4a). Isolated yield.
a
Unless otherwise noted, the reaction was performed in 1,4-dioxane
for 12 h (for 5) or 17 h (for 6) using 10 mol % Pd(OAc) and 20 mol %
BINAP under N . [4a] = 0.25 M. The substrate ratio for preparation of
2
not observed (entries 8, 9, 10). To our delight, the reaction
yield rose surprisingly to almost quantitative yield (97%)
when the reaction was executed at 100 °C (entry 10).
After success in the selective N-arylation ofDAE with4a
to give the monosubstituted amine 5a, we then tried to
selectively prepare disubstituted amine 6a by controlling the
starting material ratio. Using similar reaction conditions,
changing the ratio of 4a:DAE from 1:1.5 to 2.4:1, diamine
2
the monosubstituted diamine 5 is 4:DAE = 1:1.5; for preparation of the
disubstituted diamine 6 it is 4:DAE = 3:1. The reaction temperature is
b
100 and 110 °C, respectively, for 5 and 6. Treated with HCl(concd) in
MeOH at room temperature for 8 h.
0
the corresponding C
again, Me
-symmetry product 6b in 98% yield. Once
2
N-substituted 6d was formed only in a trace amount.
2
6
a was selectively formed in 61% yield (Table 1, entry 11). By
We developed a very efficient method for N-arylation of
simple DAE with (R)-BINOL-derived triflates to prepare
mono- and disubstituted diamines. This system works
particularly well for mono-N-arylation reactions, in which
the yield is up to 97% for product 5a. Therefore, we next
wanted to explore the further transformation of amine 5.
As shown in Scheme 4, amine 5 could be easily converted
into the unsymmetric diamine 7 (by second N-arylation)
and 8 (by reductive amination). Interestingly, as summar-
ized in the top part of Scheme 4, the more bulky substrates
such as naphthyl-OTf, 2,4,6-mesityl-OTf, and 2,6-diiso-
propylphenyl-OTf gave more satisfactory yields of pro-
ducts of 7 (58-75%). The less bulky phenyl-OTf, however,
gave only a 30% yield of the desired amine product 7a; a
possible reason could be formation of trisubstituted amine
products due to the relatively small steric hindrance of the
phenyl group. For the reductive amination (the bottom
part of Scheme 4), the results are more general for different
kinds of aldehyde substrates with the yields ranging from
59% to 71%. It is worth mentioning that the reaction
conditions for the reductive amination reaction in Scheme 4
are not optimized.
increasing the ratio of 4a:DAE to 3:1, the product yield was
further enhanced to 69% (entry 12). Using toluene as the
solvent gave a lower yield (entry 13), which is consistent with
the trends found in the mono-N-arylation reactions in Table 1.
With the success in selecively obtaining mono- and disub-
stituted amine 5a and 6a from 4a and DAE catalyzed by
Pd(OAc) and BINAP, the scope of the starting material was
2
then investigated (Scheme 3). As summarized in the top part
of Scheme 3, the substituted triflate 4b (R = OMOM) and 4c
(R = H) could afford the products 5b and 5c as well in the
same good yields. Among them, MOMO-protected amine 5b
could be easily deprotected in HCl alcohol solution affording
0
5b in almost quantitative yield. With triflate 4d (R = NMe ),
2
however, only a trace product was given; presumably the
relative strong cordination capability of the lone pair on the
nitrogen atom prohibited the reductive elimination step.
Similarly, two molecular triflates 4b (R = OMOM) and 4c
(R = H) could also be coupled with one DAE giving the
corresponding disubstituted amine 6b and 6c, although in
relatively lower yields (44% and 63%). When amine 6b was
treated with HCl, two hydroxyl groups were released leading to
1
148
Org. Lett., Vol. 13, No. 5, 2011

Scheme 4. Preparation of Diamine 7 and 8 by Second N-Arylation
or Reductive Amination Reactions
Scheme 5. Preparation of Imidazole Salt 9 from Diamine 6 or 7
found a variety of applications in asymmetric olefin metath-
6,7
esis, allylic alkylations, etc. By using our methods, imida-
zole salts 9a and 9b could be prepared in only three steps in
good yields. More importantly, three different C -symmetry
2
imidazole salts, 9d, 9e, and 9f, could be synthesized in only
two steps with satisfactory yields (61%-70%). They are
potentially very hopeful chiral NHC precursors due to
the important C -symmetry element.
2
In conclusion, we have developed a very convenient
and efficient modular approach for the synthesis of
0
vicinal diamines containing axial chiral 1,1 -binaphthyl
from DAE by Pd-catalyzed N-arylation reactions. The
resulting chiral diamine 6 or 7 reacted with triethyl
orthoformate affording imidazole salt 9 in good yields,
which are the most commonly used NHC precursors.
We believe these structures to be interesting chiral
vicinal diamines and imidazole salts, particularly the
As mentioned in the introduction of this paper, our
ultimate goal is synthesizing structurally interesting chiral
NHCs and studying their catalytic applications in asym-
metric reactions. With synthesizing these versatile vicinal
C -symmetric ones, and will find broad applications in
2
asymmetric catalytic processes. Further applications of
these vicinal diamines and imidazole salts in catalysis
are underway in our laboratory.
0
diamines containing axial chiral 1,1 -binaphtyl from DAE,
we then worked on their potential applications for the
synthesis of imidazole salts, the most common precursors
of NHC. By simply following the literature procedure with a
Acknowledgment. The authors thank the National Nat-
uralScience Foundation of China (No. 20902028), Guang-
dong Natural Science Foundation (Nos. 9451064101002851
and 10351064101000000), and The National Basic Research
Program of China (973) (No. 2011CB808600) for financial
support. This work was also supported by “the Fundamen-
tal Research Funds for the Central Universities, SCUT
6
bit of modification, six different imidazole salts 9a-9f were
synthesized in good yields (61%-79%) (Scheme 5). Among
them, imidazole salts 9a and 9b are known compounds which
6
a
were first reported by Hoveyda in 2002 and have already
(
6) (a) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda,
(
No. 2009ZM0302)”.
A. H. J. Am. Chem. Soc. 2002, 124, 4954. (b) Salinger, D.; Bruckner, R.
Synlett 2009, 109.
Supporting Information Available. Typical experimen-
(
7) Selected publications: (a) Van Veldhuizen, J. J.; Gillingham,
D. G.; Garber, S. B.; Kataoka, O.; A Hoveyda, H. J. Am. Chem. Soc.
003, 125, 12502. (b) Larsen, A. O.; Leu, W.; Oberhuber, C. N.;Campbell,
tal procedure and characterization for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
2
J. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130. (c) Lee, Y.; Li,
B.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 11625.
Org. Lett., Vol. 13, No. 5, 2011
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