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An Aldimine Cross-Coupling for the Diastereoselective Synthesis of Unsymmetrical 1 2-Diamines.

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Communications
Cross-Couplings
DOI: 10.1002/anie.200501705
An Aldimine Cross-Coupling for the
Diastereoselective Synthesis of Unsymmetrical
1,2-Diamines**
Coralie Kison, Nino Meyer, and Till Opatz*
Procedures for the reversible umpolung of the natural
reactivity of functional groups are valuable additions to
organic chemists repertoire of methods.[1–3] One of the most
prominent examples of such a reversal of polarity is the
benzoin condensation, in which an electrophilic aromatic
aldehyde is converted into a CH-acidic cyanohydrin, and
hence a pronucleophile, by addition of cyanide. Because of
the fast reversibility of cyanohydrin formation under the basic
reaction conditions, the addition of the a-deprotonated
cyanohydrin to an aldehyde cannot be used for the selective
preparation of unsymmetrical benzoins. To assign unambiguous roles to the reactants during the course of the reaction,
the temporary introduction of a hydroxy protecting group is
necessary.[4] While the OH acidity of cyanohydrins is higher or
at least equal to their CH acidity, the CH acidity of aaminonitriles should surpass their NH acidity. This holds true
in particular for Strecker products derived from aromatic
aldehydes. Therefore, it should be possible to convert Nmono- and N-unsubstituted a-aminonitriles into their conjugate anions avoiding the base-induced elimination of HCN
(retro-Strecker reaction).
Indeed, a-aryl-substituted aminonitriles yield the ketene
iminates 2 upon deprotonation with potassium hexamethyldisilazide (KHMDS; Scheme 1), while lithium bases such as
LDA lead to deprotonation at nitrogen and thus to the
irreversible retro-Strecker reaction. Only N,N-disubstituted
a-aminonitriles can be converted into stable lithium salts,
which may be used as acylanion equivalents.[5–8] In contrast to
these and other a-amino-substituted carbanion equivalents,[9]
the ketene iminates 2 have the advantage that after their
addition to an electrophile, no additional deprotection steps
are necessary to liberate the amino function. The cyano group
can be removed from the addition products under mild
conditions,[10] thus rendering these ketene iminates easily
accessible a-amino carbanion equivalents bearing a variable
N substituent.[11] Upon addition of the carbanions 2 to imines,
amide ions are formed which undergo an intramolecular
[*] C. Kison, N. Meyer, Dr. T. Opatz
Institut f&r Organische Chemie
Johannes Gutenberg-Universit.t Mainz
Duesbergweg 10–14
55128 Mainz (Germany)
Fax: (+ 49) 6131-392-4786
E-mail: opatz@uni-mainz.de
[**] This work was supported by the Fonds der Chemischen Industrie
and the University of Mainz. We thank H. Kolshorn for performing
the 2D-NMR experiments and the NOE measurements.
5662
Scheme 1. Mechanism of the diamine synthesis.
elimination of cyanide, finally yielding a-aminoimines or the
tautomeric enediamines (Scheme 1).
The course of the reaction is similar to that of the aldimine
coupling, the aza analogue of the benzoin condensation,
which requires only catalytic amounts of cyanide but does not
allow the selective cross-coupling of two different imines.[12–16]
Oxidative workup of the reaction mixture by addition of
iodine or oxygen yields diimines 3, which can serve as starting
materials for the preparation of highly substituted imidazolium salts or nucleophilic carbenes.[17, 18] On the other hand,
the one-pot reduction of the addition products with sodium
cyanoborohydride in the presence of acetic acid leads to the
formation of the diamines 4 (Table 1). In accordance with a
chelated transition state, the anti-configurated products are
predominantly formed, albeit with low diastereoselectivity:
At best, an anti/syn ratio of 4.3:1 was observed. The relative
configuration of the main products could be determined
based on the reported characteristic 1H and 13C chemical
shifts of vicinal diamines as well as the NOE data of the
diastereomeric formaldehyde aminals of the diamines 4 a and
4 m.[19–22]
In attempts to improve the diastereoselectivity of the
reduction, we found that the reaction of the pure diimines 3
with BH3·THF containing NaBH4 furnishes preferentially the
syn-configurated diamines 4 in quantitative yield (Table 2,
Method A). Compounds of this type may be applied as
combinatorially diverse pseudo-C2-symmetric N,N ligands for
asymmetric aldol reactions,[23] dihydroxylations,[24] and reductions.[25] If, on the other hand, phthalic acid is added to the
reaction mixture instead of NaBH4 (Table 2, Method B),[26]
the reduction of the diimines yields the anti-configurated
products.[27]
2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5662 –5664
Angewandte
Chemie
Table 1: 1,2-Diamines obtained by aldimine cross-coupling.[a]
No.
R1
R2
R3
R4
Prod.
Yield [%][b]
d.r. (anti:syn)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Ph2CH
Ph2CH
Ph2CH
Ph2CH
Ph2CH
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Me
Me
Me
Me
iPr
iPr
iPr
iPr
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2-Naph
2-Naph
2-Naph
2-Naph
Ph
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
Ph
4-Py
Ph
4-ClC6H4
4-ClC6H4
Ph
1-Naph
4-ClC6H4
4-ClC6H4
Ph
1-Naph
4-ClC6H4
4-ClC6H4
Ph
1-Naph
Ph
4-Tol
4-Tol
Ph
4-ClC6H4
Ph
4-Tol
4-ClC6H4
4-ClC6H4
Ph
4-Tol
4-ClC6H4
4-ClC6H4
Ph
4-Tol
4-ClC6H4
4-ClC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
63
64
34
41
68
60
55
59
42
60
55
58
55
35
37
33
32
1.2:1
1.3:1
1.2:1
1.2:1
1.7:1
1.7:1
1.6:1
1.7:1
2.3:1
2.4:1
1.6:1
1.5:1
3.2:1
2:1
1.4:1
1.6:1
4.3:1
synthesis of a class of highly substituted unsymmetrical 1,2-diamines, of which only a few members are known.
Experimental Section
Diamines 4 (general procedure): To a
stirred solution of the aminonitrile 1
(1.7 mmol) in anhydrous THF (1.5 mL)
was added a solution of KHMDS
(373 mg, 1.87 mmol) in anhydrous
THF (2 mL) at 50 8C under an argon
atmosphere. After 3 min, a solution of
the imine (1.7 mmol) in anhydrous
THF (1 mL) was added, and the reaction mixture was allowed to warm up to
20 8C within 100 min. Solid NaCNBH3
(427 mg, 6.8 mmol) was added to the
[a] Naph = naphthyl, Py = pyridyl, Tol = tolyl. [b] Yield after purification by preparative thin-layer
solution followed by a mixture of acetic
chromatography.
acid (0.6 mL, 10.5 mmol) and ethanol
(6.4 mL, 109 mmol). The reaction mixture was stirred overnight at room
Table 2: 1,2-Diamines obtained by diastereoselective reduction of ditemperature. After addition of ethyl acetate (40 mL) and phase
imines.
separation, the organic layer was washed several times with 1n NaOH
and finally with brine and dried over Na2SO4, and the solvent was
removed in vacuo. The product was purified by preparative thin-layer
chromatography.
For the preparation of the diimines 3, the argon atmosphere was
replaced by air when the reaction mixture reached 20 8C. The
solution was allowed to warm up to room temperature, and after
extraction with ethyl acetate and washing with brine, the product was
isolated in analogy to the procedure described for the diamines 4.
Analytical data of 4 b (mixture of diastereomers, anti/syn 1.3:1):
weakly reddish solid, Rf (silica gel 60; cyclohexane/EtOAc 10:1 +
1 % EtNMe2): 0.70. 1H NMR (300 MHz, CDCl3), COSY, HMQC,
HMBC: d = 7.34–6.56 (m, 44 H, anti + syn), 6.40 (pseudo-d, 2 H,
aniline-2,6-H syn, Japp = 8.5 Hz), 6.31 (pseudo-d, 2 H, aniline-2,6-H
anti, Japp = 8.5 Hz), 4.58 (s, 1 H, Ph2CH anti), 4.56 (s, 1 H, Ph2CH syn),
No.
Prod.
Method
Yield [%][a]
d.r. (anti:syn)
4.45 (d, 1 H, 1-H anti, J = 5.3 Hz), 4.30 (d, 1 H, 1-H syn, J = 7.5 Hz),
1
4a
A
65
1:5.5
3.88 (d, 1 H, 2-H anti, J = 5.3 Hz), 3.63 (d, 1 H, 2-H syn, J = 7.5 Hz),
2
4b
A
69
1:20
2.17 (s, 3 H, Ph-CH3 syn), 2.15 ppm (s, 3 H, Ph-CH3 anti). 13C NMR,
3
4e
A
67
1:6
DEPT (75.5 MHz, CDCl3), HMQC, HMBC: d = 145.2 (aniline-C1
4
4l
A
55
1:11
syn), 144.5 (aniline-C1 anti), 144.1 (2 C), 142.9, 142.4, 140.0, 139.9,
5
4m
A
73
3:10
139.2, 138.6, 132.8, 132.6, 129.5–126.6 (partly overlapping signals),
6
4a
B
65
27:1
114.0 (2 C, aniline-C2,6 syn), 113.6 (2 C, aniline-C2,6 anti), 65.6 (C2
7
4b
B
69
9:1
syn), 64.4 (C2 anti), 63.9 (C1 syn), 63.5 (Ph2CH anti), 63.4 (Ph2CH
8
4e
B
67
3.5:1
syn), 62.5 (C1 anti), 20.3 ppm (2 C, Ph-CH3). IR (NaCl, film): ñ = 3405
(m, NH), 3347 (m, NH), 3060 (m), 3026 (m), 2917 (m), 2863 (m), 1616
[a] Method A: BH3·THF, NaBH4 ; Method B: BH3·THF, phthalic acid.
(m), 1519 (s), 1490 (s), 1453 (m), 1090 (m), 700 (s) cm 1. FD-MS: m/z
[b] Overall yield after chromatographic purification of the diimine. The
(%) = 230.4 (16) [Cl-PhCH=NHPh-CH3]+, 231.4 (2), 232.4 (7), 272.5
reduction is quantitative.
(42) [Ph2CH-NH=CHPh]+, 273.5 (9), 503.0 (100) [M+H]+, 504.0 (44),
505.0 (37), 506.0 (10). ESI-HRMS: calcd for [C34H31ClN2+H]+:
503.2254, found: 503.2246.
Compared to other methods[28] that employ the attachReduction of the diimines 3 (Method A): To a stirred solution of
ment of amino groups to preexisting carbon frameworks such
the diimine 3 (0.5 mmol) in anhydrous THF (4 mL) was added solid
as alkenes,[29, 30] aziridines,[31] epoxides,[32] and diols,[33] the
NaBH4 (9.5 mg, 0.25 mmol) under argon atmosphere, and the mixture
selective aldimine cross-coupling has the advantage that a
was cooled to 0 8C. A fresh solution of BH3·THF (0.75 mL, 1m in
THF) was added, and stirring was continued for 30 min at 0 8C and for
single regioisomer is formed independent of the substitution
a further 15 h at room temperature. After addition of ethanolamine
pattern of the reactants. The reaction sequence does not
(0.5 mL), the mixture was stirred for 3–18 h and partitioned between
require protecting-group operations and can be performed in
ethyl acetate and water. The organic layer was washed with water and
one pot. In addition, either the syn- or anti-configurated
dried over Na2SO4, and the solvent was removed in vacuo.
vicinal diamine can be obtained, depending on the choice of
Reduction of the diimines 3 (Method B): A stirred solution of the
the workup and reduction conditions. Therefore, the aldimine
diimine 3 (0.5 mmol) and phthalic acid (166 mg, 1 mmol) in anhycross-coupling represents a simple and flexible method for the
drous THF (4 mL) was cooled to 20 8C under argon atmosphere.
Angew. Chem. Int. Ed. 2005, 44, 5662 –5664
2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5663
Communications
After addition of a BH3·THF solution (1 mL, 1m in THF), the mixture
was gradually warmed to room temperature, and stirring was
maintained for a further 15 h. The workup procedure and the
isolation of the product were performed as described for Method A.
[31] M. Egli, L. Hoesch, A. S. Dreiding, Helv. Chim. Acta 1985, 68,
220 – 230.
[32] P. OBrien, P. Poumellec, Tetrahedron Lett. 1996, 37, 5619 – 5622.
[33] D. Pini, A. Iuliano, C. Rosini, P. Salvadori, Synthesis 1990, 1023 –
1024.
Received: February 15, 2005
Revised: May 17, 2005
Published online: July 29, 2005
.
Keywords: C C coupling · carbanions · diamines · reduction ·
umpolung
[1] D. Seebach, Angew. Chem. 1979, 91, 259 – 278; Angew. Chem.
Int. Ed. Engl. 1979, 18, 239 – 258.
[2] D. Seebach, Angew. Chem. 1969, 81, 690 – 700; Angew. Chem.
Int. Ed. Engl. 1969, 8, 639 – 649.
[3] H. Stetter, Angew. Chem. 1976, 88, 695 – 704; Angew. Chem. Int.
Ed. Engl. 1976, 15, 639 – 647.
[4] K. Deuchert, U. Hertenstein, S. HInig, Synthesis 1973, 777 – 779.
[5] C. R. Hauser, H. M. Taylor, T. G. Ledford, J. Am. Chem. Soc.
1960, 82, 1786 – 1789.
[6] J. D. Albright, Tetrahedron 1983, 39, 3207 – 3233.
[7] D. Enders, J. P. Shilvock, Chem. Soc. Rev. 2000, 29, 359 – 373.
[8] J. Kant, J. Heterocycl. Chem. 1990, 27, 2129 – 2132.
[9] P. Beak, W. J. Zajdel, D. B. Reitz, Chem. Rev. 1984, 84, 471 – 523.
[10] C. H. Mitch, Tetrahedron Lett. 1988, 29, 6831 – 6834.
[11] N. Meyer, F. Werner, T. Opatz, Synthesis 2005, 945 – 956.
[12] H. H. Strain, J. Am. Chem. Soc. 1928, 50, 2218 – 2223.
[13] M. Cariou, R. Carlier, J. Simonet, Bull. Soc. Chim. Fr. 1986, 781 –
792.
[14] J. Correia, J. Org. Chem. 1983, 48, 3343 – 3344.
[15] H.-D. Becker, J. Org. Chem. 1970, 35, 2099 – 2102.
[16] J. S. Walia, L. Guillot, J. Singh, M. S. Chatta, M. Satyanarayana,
J. Org. Chem. 1972, 37, 135 – 137.
[17] A. J. Arduengo III, R. Krafczyk, R. Schmutzler, H. A. Craig,
J. R. Goerlich, W. J. Marshall, M. Unverzagt, Tetrahedron 1999,
55, 14 523 – 14 534.
[18] F. Glorius, WO 2004007465, 2004.
[19] P. Mangeney, T. Tejero, A. Alexakis, F. Grosjean, J. Normant,
Synthesis 1988, 255 – 257.
[20] M. Largeron, M.-B. Fleury, J. Org. Chem. 2000, 65, 8874 – 8881.
[21] M. Periasamy, G. Srinivas, G. V. Karunakar, P. Bharathi,
Tetrahedron Lett. 1999, 40, 7577 – 7580.
[22] B. Hatano, A. Ogawa, T. Hirao, J. Org. Chem. 1998, 63, 9421 –
9424.
[23] S. Kobayashi, H. Uchiro, Y. Fujishita, I. Shiina, T. Mukaiyama, J.
Am. Chem. Soc. 1991, 113, 4247 – 4252.
[24] E. J. Corey, P. DaSilva Jardine, S. Virgil, P.-W. Yuen, R. D.
Connell, J. Am. Chem. Soc. 1989, 111, 9243 – 9244.
[25] N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1996, 118, 4916 – 4917.
[26] Z.-H. Lu, N. Bhongle, X. Su, S. Ribe, C. H. Senanayake,
Tetrahedron Lett. 2002, 43, 8617 – 8620.
[27] Notably, the diastereoselectivity of the reduction with commercially available NaBH4-stabilized BH3·THF depends on the age
of the reagent: While a fresh solution predominantly yields the
syn product, aged batches of the reagent lead to the formation of
the anti product. See: J. Kollonitsch, J. Am. Chem. Soc. 1961, 83,
1515.
[28] D. Lucet, T. Le Gall, C. Mioskowski, Angew. Chem. 1998, 110,
2724 – 2772; Angew. Chem. Int. Ed. Engl. 1998, 37, 2580 – 2627.
[29] A. Chong, K. Oshima, K. B. Sharpless, J. Am. Chem. Soc. 1977,
99, 3420 – 3426.
[30] J. Barluenga, F. Aznar, M. C. S. De Mattos, W. B. Kover, S.
Garcia-Granda, E. Perez-Carreno, J. Org. Chem. 1991, 56, 2930 –
2932.
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