Cu(I)-catalyzed asymmetric diamination of conjugated dienes

Article abstract of DOI:10.1021/ol801605w

(Chemical Equation Presented) A Cu(I)-catalyzed asymmetric diamination for a variety of conjugated dienes and a triene with encouraging ee's has been effectively achieved using (R)-DTBM-SEGPHOS as a chiral ligand and di-tert-butyldiaziridinone as the nitr

Full text of DOI:10.1021/ol801605w

ORGANIC
LETTERS
2008
Vol. 10, No. 19
4231-4234
Cu(I)-Catalyzed Asymmetric Diamination
of Conjugated Dienes
Haifeng Du, Baoguo Zhao, Weicheng Yuan, and Yian Shi*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
yian@lamar.colostate.edu
Received July 14, 2008
ABSTRACT
A Cu(I)-catalyzed asymmetric diamination for a variety of conjugated dienes and a triene with encouraging ee’s has been effectively achieved
using (R)-DTBM-SEGPHOS as a chiral ligand and di-tert-butyldiaziridinone as the nitrogen source.
Direct diamination of olefins provides an efficient approach
to the synthesis of vicinal diamines, which are biologically
and chemically important functional moieties.1 While various
metal-mediated and catalyzed diaminations have been
achieved,2-8 catalytic asymmetric diamination of olefins has
been less well developed and still remains a challenge in
organic synthesis. Earlier, Mun˜iz and co-workers reported
chiral auxiliary based9a and chiral Lewis acid catalyzed9b
asymmetric diamination using bisimidoosmium as reagent.
Recently, we reported Pd(0)-catalyzed asymmetric diami-
nation of conjugated dienes10a,b and asymmetric allylic and
homoallylic C-H diamination of terminal olefins.10c Previ-
ously, we have shown that Cu(I)-catalyzed diamination of
conjugated dienes and triene using di-tert-butyldiaziridinone
(2)11,12 as the nitrogen source occurs regioselectively at the
terminal double bond under mild reaction conditions (Scheme
1),8a which provides complementary regioselectivity to
(1) For leading reviews, see: (a) Lucet, D.; Gall, T. L.; Mioskowski, C.
Angew. Chem., Int. Ed. 1998, 37, 2580. (b) Mortensen, M. S.; O’Doherty,
G. A. Chemtracts: Org. Chem. 2005, 18, 555. (c) Kotti, S. R. S. S.;
Timmons, C.; Li, G. Chem. Biol. Drug Des. 2006, 67, 101.
(2) For examples of metal-mediated diaminations, see: Co: (a) Becker,
P. N.; White, M. A.; Bergman, R. G. J. Am. Chem. Soc. 1980, 102, 5676.
Hg: (b) Barluenga, J.; Alonso-Cires, L.; Asensio, G. Synthesis 1979, 962.
Mn: (c) Fristad, W. E.; Brandvold, T. A.; Peterson, J. R.; Thompson, S. R.
J. Org. Chem. 1985, 50, 3647. Os: (d) Chong, A. O.; Oshima, K.; Sharpless,
K. B. J. Am. Chem. Soc. 1977, 99, 3420. (e) Mun˜iz, K. Eur. J. Org. Chem.
2004, 2243. Pd: (f) Ba¨ckvall, J.-E. Tetrahedron Lett. 1978, 163. Tl: (g)
Scheme 1
Aranda, V. G.; Barluenga, J.; Aznar, F. Synthesis 1974, 504
.
(3) For recent Cu(II)-mediated intramolecular diamination, see: (a)
Zabawa, T. P.; Kasi, D.; Chemler, S. R. J. Am. Chem. Soc. 2005, 127,
11250. (b) Zabawa, T. P.; Chemler, S. R. Org. Lett. 2007, 9, 2035
.
(4) For Rh(II)- and Fe(III)-catalyzed diamination with TsNCl2, see: (a)
Li, G.; Wei, H.-X.; Kim, S. H.; Carducci, M. D. Angew. Chem., Int. Ed.
2001, 40, 4277. (b) Wei, H.-X.; Kim, S. H.; Li, G. J. Org. Chem. 2002, 67,
the Pd(0)-catalyzed diamination.7 It is highly desirable to
develop an asymmetric version of this diamination process
to enhance its synthetic utility. However, the Cu(I)-catalyzed
diamination likely proceeds via a radical mechanism (Figure
1).8,13-15 The involvement of radical intermediates presents
a challenge for asymmetric control.
4777
.
(5) For a recent Pd(II)-catalyzed intermolecular diamination of conju-
gated dienes, see: Bar, G. L. J.; Lloyd-Jones, G. C.; Booker-Milburn, K. I.
J. Am. Chem. Soc. 2005, 127, 7308
.
(6) For recent Pd(II)- and Ni-catalyzed intramolecular diamination of
olefins, see: (a) Streuff, J.; Ho¨velmann, C. H.; Nieger, M.; Mun˜iz, K. J. Am.
Chem. Soc. 2005, 127, 14586. (b) Mun˜iz, K.; Streuff, J.; Ho¨velmann, C. H.;
Nu´n˜ez, A. Angew. Chem., Int. Ed. 2007, 46, 7125. (c) Mun˜iz, K. J. Am.
Chem. Soc. 2007, 129, 14542. (d) Mun˜iz, K.; Ho¨velmann, C. H.; Streuff,
Asymmetric diamination was initially investigated using
10 mol % of CuCl with various commercially available or
J. J. Am. Chem. Soc. 2008, 130, 763
.
10.1021/ol801605w CCC: $40.75
Published on Web 09/03/2008
2008 American Chemical Society

Figure 2. Asymmetric diamination of diene 7a with selected
monophosphorus and nitrogen-containing ligands.18
Figure 1. Proposed catalytic cycle for Cu(I)-catalyzed diamination.
commercially available chiral bisphosphine ligands17 were
subsequently studied for the diamination of trans-1-phe-
nylbutadiene (7a) with a 2/1 ratio of CuCl and ligand. It
was found that steric bulkiness on the phosphine atoms had
a large impact on the enantioselectivities (Figure 3). En-
easily prepared chiral monophosphorus and nitrogen-contain-
ing ligands16 and trans-1-phenylbutadiene (7a) as a test
Scheme 2
substrate at room temperature for 6 h (Scheme 2). As shown
in Figure 2, all the reactions went smoothly to give
diamination product 3a with high conversions, but with 0 to
12% ee. To search for more promising ligands, a series of
(7) For Pd(0)-catalyzed intermolecular diamination, see: (a) Du, H.;
Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. (b) Xu, L.; Du, H.;
Shi, Y. J. Org. Chem. 2007, 72, 7038. (c) Du, H.; Yuan, W.; Zhao, B.; Shi,
Y. J. Am. Chem. Soc. 2007, 129, 7496.
(8) For Cu(I)-catalyzed intermolecular diamination, see: (a) Yuan, W.;
Du, H.; Zhao, B.; Shi, Y. Org. Lett. 2007, 9, 2589. (b) Zhao, B.; Yuan, W.;
Du, H.; Shi, Y. Org. Lett. 2007, 9, 4943. (c) Zhao, B.; Du, H.; Shi, Y. Org.
Lett. 2008, 10, 1087.
Figure 3. Asymmetric diamination of diene 7a with selected
bisphosphine ligands.19
(9) For leading references on asymmetric diamination using bisimi-
doosmium as reagent, see: (a) Mun˜iz, K.; Nieger, M. Synlett 2003, 211.
(b) Mun˜iz, K.; Nieger, M. Chem. Commun. 2005, 2729.
(10) (a) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007,
129, 11688. (b) Xu, L.; Shi, Y. J. Org. Chem. 2008, 73, 749. (c) Du, H.;
Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2008, 130, 8590.
couragingly, the diamination of 7a with (R)-DTBM-SEG-
PHOS (L12)17f gave 90% conversion and 56% ee (Figure
3).
To improve the enantioselectivity, the reaction conditions,
including solvent, temperature, and the ratio of ligand and
(11) Greene, F. D.; Stowell, J. C.; Bergmark, W. R. J. Org. Chem. 1969,
34, 2254.
(12) For a leading review on diaziridinone, see: Heine, H. W. In The
Chemistry of Heterocyclic Compounds; Hassner, A., Ed.; John Wiley &
Sons, Inc.: Hoboken, NJ, 1983; p 547.
(13) For a leading review on metal-promoted radical reactions, see: Iqbal,
J.; Bhatia, B.; Nayyar, N. K. Chem. ReV. 1994, 94, 519.
(17) For leading references on L7-L12, see: (a) Kagan, H. B.; Dang,
T.-P. J. Am. Chem. Soc. 1972, 94, 6429. (b) Miyashita, A.; Yasuda, A.;
Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc.
1980, 102, 7932. (c) Mashima, K.; Matsumura, Y.-i.; Kusano, K.-h.;
Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya,
H. J. Chem. Soc., Chem. Commun. 1991, 609. (d) Lipshutz, B. H.; Noson,
K.; Chrisman, W. J. Am. Chem. Soc. 2001, 123, 12917. (e) Hatano, M.;
Terada, M.; Mikami, K. Angew. Chem., Int. Ed. 2001, 40, 249. (f) Lipshutz,
B. H.; Lower, A.; Noson, K. Org. Lett. 2002, 4, 4045.
(14) For leading reviews on CuX-catalyzed atom transfer reactions see:
(a) Patten, T. E.; Matyjaszewski, K. Acc. Chem. Res. 1999, 32, 895. (b)
Clark, A. J. Chem. Soc. ReV. 2002, 31, 1.
(15) For a leading review on nitrogen-centered radicals, see: Stella, L.
In Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-
VCH: Weinheim, Germany, 2001; Vol. 2, p 407.
(16) For leading references on L1-L6, see: (a) Hattori, T.; Shijo, M.;
Kumagai, S.; Miyano, S. Chem. Express 1991, 6, 335. (b) Ref 10a. (c)
Sewald, N.; Wendisch, V. Tetrahedron: Asymmetry 1998, 9, 1341. (d)
Hayashi, T.; Yamamoto, K.; Kumada, M. Tetrahedron Lett. 1974, 15, 4405.
(e) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566. (f)
Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem.
Soc. 1991, 113, 726. (g) Lowenthal, R. E.; Masamune, S. Tetrahedron Lett.
1991, 32, 7373.
(18) The reactions were carried out with trans-1-phenylbutadiene (0.20
mmol), di-tert-butyldiaziridinone (2) (0.30 mmol), CuCl (0.02 mmol), and
ligand L1-L5 (0.02 mmol), except for L6 (0.01 mmol) in benzene-d6 (0.60
mL) at room temperature for 6 h. The conversions were determined by
1
crude H NMR, and the ee’s were determined by chiral HPLC.
(19) The same conditions as ref 18 except for L7-L12 (0.01 mmol).
4232
Org. Lett., Vol. 10, No. 19, 2008

CuCl, were further investigated. It was found that solvent
has a significant effect on both reactivity and enantioselec-
tivity (Table 1, entries 1-7), and benzene-d6 proved to be
Table 2. Catalytic Asymmetric Diamination of Dienes and
Trienea
Table 1. Studies on Reaction Conditions for Asymmetric
Diamination of 7aa
CuCl
L12
conv.
(%)b ee (%)c
entry (mol %) (mol %)
solvent
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
10
10
10
12
15
10
5
5
5
5
5
5
5
10
5
5.5
DME
Et2O
CDCl3
CD2Cl2
THF
toluene-d8
C6D6
C6D6
C6D6/PhCH3 (11/1, v/v)
C6D6/PhCH3(11/1, v/v) 72
C6D6/PhCH3 (11/1, v/v)
C6D6/PhCH3 (11/1, v/v)
PhCH3
63
43
78
100
21
77
90
24
73
44
42
19
35
33
53
56
58
63
65
61
56
65
9
10
11
12
13
5
5
5.5
74
89
30
a All the reactions were carried out with trans-1-phenylbutadiene (7a)
(0.20 mmol), di-tert-butyldiaziridinone (2) (0.30 mmol), and solvent (0.60
mL). For entries 1-8, the reactions were carried out at rt for 6 h. For entries
9-13, the reactions were carried out at 0 °C for 20 h. b The conversion
was determined by crude 1H NMR. c The ee was determined by chiral HPLC
(Chiralpak AD-H column).
the best solvent. The ratio of ligand and CuCl was also very
important, and only 24% conversion was obtained with
slightly higher ee when 1:1 CuCl and L12 were used (Table
1, entry 8). Lowering the temperature improved the enan-
tioselectivity (Table 1, entries 9-13), increasing to 65% ee
at 0 °C (a small amount of toluene was added to avoid
solidification of benzene-d6). Overall, the best reaction
conditions involve 10 mol % of CuCl and 5.5 mol % of L12
in benzene-d6 with a small amount of toluene at 0 °C (Table
1, entry 10).
Under the optimized conditions, a variety of conjugated
dienes can be regio- and enantioseletively diaminated at the
terminal double bond in 59-93% yield with 62-74% ee’s
(Table 2, entries 1-10). The ee could be further improved
after recrystallization (Table 2, entry 2). For cis-1-phenylb-
utadiene, isomerization of the cis double bond occurred
during the reaction and mainly gave E-isomer product in 70%
ee which was a little higher than direct diamination of trans-
1-phenylbutadiene (Table 2, entry 1 vs 5). When a mixture
of trans- and cis-dienes was subjected to the reaction
conditions, the diamination product of the E isomer was
formed predominately with only a trace amount of Z isomer
(Table 2, entries 6 and 7). Asymmetric diamination of 1,1-
disubstituted butadienes gave slightly higher ee’s (Table 2,
entries 8-10). When a triene was diaminated at room
temperature in benzene-d6, the diamination product was
obtained in 58% ee (Table 2, entry 11). Asymmetric
diamination of trans-1-phenyl-3-methylbutadiene led to 90%
yield with only 23% ee (Table 2, entry 12), suggesting that
the steric effect and radical stability are important factors
for the enantioselectivity.
a All the reactions were carried out with olefin (0.20 mmol), di-tert-
butyldiaziridinone (2) (0.30 mmol), CuCl (0.02 mmol), L12 (0.011 mmol),
benzene-d6 (0.55 mL), and toluene (0.050 mL) at 0 °C under argon for
20 h unless otherwise stated. b Isolated yield based on diene or triene. c The
ratio was determined by 1H NMR. d Only a trace amount of isomer was
observed by H NMR. e The reaction was carried out in benzene-d6 at rt
1
for 20 h. f The ee was determined by chiral HPLC (Chiralpak AD-H
column). g The ee after recrystallization from hexanes. h Not determined.
In summary, catalytic asymmetric diamination for a variety
of conjugated dienes and a triene with encouraging ee’s has
been achieved using CuCl/L12 as the catalyst and di-tert-
butyldiaziridinone as the nitrogen source. These results show
that Cu(I)-catalyzed asymmetric diamination is feasible
despite the fact that the diamination likely involves radical
intermediates. Ligand (R)-DTBM-SEGPHOS (L12) provides
a very promising lead for further improvement. Searches for
Org. Lett., Vol. 10, No. 19, 2008
4233

more effective chiral ligands, studies of different nitrogen
sources, and expansion of the substrate scope will be carried
out.
Supporting Information Available: The asymmetric
diamination procedure, the characterization of the diamina-
tion products, and data for the determination of enantiomeric
excess of diamination products along with the NMR spectra
of diamination products. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. We are grateful to the generous
financial support from the General Medical Sciences of the
National Institutes of Health (GM083944-01).
OL801605W
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Org. Lett., Vol. 10, No. 19, 2008