Chiral N-heterocyclic carbene-Pd(0)-catalyzed asymmetric diamination of conjugated dienes and triene

Article abstract of DOI:10.1021/jo702167u

(Chemical Equation Presented) Studies show that a variety of conjugated dienes and triene can be enantioselectively diaminated using di-tert-butyldiaziridinone as nitrogen source and chiral N-heterocyclic carbene-Pd(0) complex as catalyst in good enantioselectivity (62-91% ee) with high regio- and diastereoselectivity.

Full text of DOI:10.1021/jo702167u

catalyzed allylic alkylations,5 copper- and rhodium-catalyzed
conjugated additions,6 and rhodium- and ruthenium-catalyzed
hydrosilylations.7 Chiral NHC-Pd complexes have also been
actively explored for asymmetric transformations such as
R-arylation of amides,8 oxidative kinetic resolution of secondary
alcohols,9 and allylic alkylation.10,11 Recently, we reported a
regio- and diastereoselective diamination of conjugated dienes
and trienes using di-tert-butyldiaziridinone as nitrogen source
and Pd(PPh3)4 as catalyst.12,13-18 Subsequently, we have shown
that NHC-Pd(0) complexes are also effective catalysts for this
diamination process, giving similar reactivity and selectivity with
less catalyst loading (Scheme 1).19 In our efforts to develop an
Chiral N-Heterocyclic Carbene-Pd(0)-Catalyzed
Asymmetric Diamination of Conjugated Dienes
and Triene
Liang Xu and Yian Shi*
Department of Chemistry, Colorado State UniVersity,
Fort Collins, Colorado 80523
yian@lamar.colostate.edu
ReceiVed October 5, 2007
(5) For leading references, see: (a) Tominaga, S.; Oi, Y.; Kato, T.; An,
D. K.; Okamoto, S. Tetrahedron Lett. 2004, 45, 5585. (b) Larsen, A. O.;
Leu, W.; Oberhuber, C. N.; Campbell, J. E.; Hoveyda, A. H. J. Am. Chem.
Soc. 2004, 126, 11130. (c) Okamoto, S.; Tominaga, S.; Saino, N.; Kase,
K.; Shimoda, K. J. Organomet. Chem. 2005, 690, 6001. (d) Kacprzynski,
M. A.; May, T. L.; Kazane, S. A.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2007, 46, 4554. (e) Gillingham, D. G.; Hoveyda, A. H. Angew. Chem., Int.
Ed. 2007, 46, 3860.
(6) For leading references, see: (a) Winn, C. L.; Guillen, F.; Pytkowicz,
J.; Roland, S.; Mangeney, P.; Alexakis, A. J. Organomet. Chem. 2005, 690,
5672. (b) Becht, J. M.; Bappert, E.; Helmchen, G. AdV. Synth. Catal. 2005,
347, 1495. (c) Lee, K-s.; Brown, M. K.; Hird, A. W.; Hoveyda, A. H. J.
Am. Chem. Soc. 2006, 128, 7182.
(7) For leading references, see: (a) Duan, W. L.; Shi, M.; Rong, G. B.
Chem. Commun. 2003, 2916. (b) Gade, L. H.; Ce´sar, V.; Bellemin-
Laponnaz, S. Angew. Chem., Int. Ed. 2004, 43, 1014. (c) Song, C.; Ma, C.;
Ma, Y.; Feng, W.; Ma, S.; Chai, Q.; Andrus, M. B. Tetrahedron Lett. 2005,
46, 3241. (d) Xu, Q.; Gu, X.; Liu, S.; Dou, Q.; Shi, M. J. Org. Chem.
2007, 72, 2240.
Studies show that a variety of conjugated dienes and triene
can be enantioselectively diaminated using di-tert-butyldiaz-
iridinone as nitrogen source and chiral N-heterocyclic car-
bene-Pd(0) complex as catalyst in good enantioselectivity
(62-91% ee) with high regio- and diastereoselectivity.
(8) For leading references, see: (a) Lee, S.; Hartwig, J. F. J. Org. Chem.
2001, 66, 3402. (b) Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C.
Chem. Commun. 2002, 2704.
(9) For leading references, see: (a) Jensen, D. R.; Sigman, M. S. Org.
Lett. 2003, 5, 63. (b) Chen, T.; Jiang, J-J.; Xu, Q.; Shi, M. Org. Lett. 2007,
9, 865.
N-Heterocyclic carbenes (NHCs) have emerged as highly
effective ligands for a variety of metal-catalyzed transforma-
tions.1 Compared to phosphines, carbene ligands usually form
more stable complexes with metals and often do not require
excess ligands. Their electron richness and steric bulkiness are
also generally favorable to the oxidative addition and reductive
elimination processes involved in many reactions.1 In recent
years, high levels of enantioselectivities have also been achieved
for a wide variety of metal-catalyzed transformations with chiral
NHCs as ligands,2 such as iridium-catalyzed hydrogenation of
alkenes,3 ruthenium-catalyzed metathesis reactions,4 copper-
(10) Bonnet, L. G.; Douthwaite, R. E. Organometallics 2003, 22, 4187.
(11) For additional leading references on chiral NHC-Pd complexes,
see: (a) Clyne, D. S.; Jin, J.; Genest, E.; Gallucci, J. C.; RajanBaBu, T. V.
Org. Lett. 2000, 2, 1125. (b) Perry, M. C.; Cui, X.; Burgess, K.
Tetrahedron: Asymmetry 2002, 13, 1969. (c) Fu¨rstner, A.; Seidel, G.;
Kremzow, D.; Lehmann, C. W. Organometallics 2003, 22, 907.
(12) (a) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. (b)
Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 7496.
(13) For leading reviews on diamination, 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.
(14) For examples of metal-mediated diaminations of olefins, see the
following. 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) Aranda, V. G.; Barluenga, J.;
Aznar, F. Synthesis 1974, 504.
(1) For leading reviews, see: (a) Herrmann, W. A. Angew. Chem., Int.
Ed. 2002, 41, 1290. (b) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H.
M.; Yang, C.; Nolan, S. P. J. Organomet. Chem. 2002, 653, 69. (c) Bedford,
R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. ReV. 2004, 248, 2283. (d)
Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366. (e) Crabtree,
R. H. J. Organomet. Chem. 2005, 690, 5451. (f) Kantchev, E. A. B.; O’
Brien, C. J.; Organ, M. G. Aldrichimica Acta 2006, 39, 97. (g) Hahn, F. E.
Angew. Chem., Int. Ed. 2006, 45, 1348. (h) Nolan, S. P. N-Heterocyclic
Carbenes in Synthesis; Wiley-VCH: Weinheim, Germany, 2006. (i) Glorius,
F. N-Heterocyclic Carbenes in Transition Metal Catalysis; Springer: Berlin,
2007.
(2) For leading reviews, see: (a) Ce´sar, V.; Bellemin-Laponnaz, S.; Gade,
L. H. Chem. Soc. ReV. 2004, 33, 619. (b) Douthwaite, R. E. Coord. Chem.
ReV. 2007, 251, 702. (c) Gade, L. H.; Bellemin-Laponnaz, S. Coord. Chem.
ReV. 2007, 251, 718.
(3) For leading references, see: (a) Powell, M. T.; Hou, D-R.; Perry,
M. C.; Cui, X.; Burgess, K. J. Am. Chem. Soc. 2001, 123, 8878. (b) Perry,
M. C.; Cui, X.; Powell, M. T.; Hou, D-R.; Reibenspies, J. H.; Burgess, K.
J. Am. Chem. Soc. 2003, 125, 113.
(4) For leading references, see: (a) Seiders, T. J.; Ward, D. W.; Grubbs,
R. H. Org. Lett. 2001, 3, 3225. (b) Van Veldhuizen, J. J.; Garber, S. B.;
Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954. (c)
Funk, T. W.; Berlin, J. M.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128,
1840. (d) Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2007, 129,
3824.
(15) For recent Cu(II)-mediated intramolecular diamination of olefins,
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.
(16) For Rh(II)- and Fe(III)-catalyzed diamination of olefins 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, 4777.
(17) 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.
(18) For a recent Pd(II)-catalyzed intramolecular diamination of terminal
olefins, see: Streuff, J.; Ho¨velmann, C. H.; Nieger, M.; Mun˜iz, K. J. Am.
Chem. Soc. 2005, 127, 14586.
(19) Xu, L.; Du, H.; Shi, Y. J. Org. Chem. 2007, 72, 7038.
10.1021/jo702167u CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/21/2007
J. Org. Chem. 2008, 73, 749-751
749

TABLE 1. Asymmetric Diamination with NHC-Pd Complexesa
R ) Et
conv (%)c
R ) p-MeOPh
conv (%)c ee (%)e
entry
catalyst
ee (%)d
1
2
3
8a
8b
8c
8d
8d
8e
8e
8f
28
49
30
81
100
85
100
78
100
48
64
82
91
71
69
70
71
73
71
90
<10
15
<10
nd
nd
nd
4
FIGURE 1. Chiral NHC-Pd complexes.
5b
6
56
74
SCHEME 1
7b
8
100
73
9b
10
8f
8g
58
<10
76
nd
a All reactions were carried out with diene (0.20 mmol), di-tert-
butyldiaziridinone (2) (0.30 mmol), NaOtAm (0.06 mmol), and NHC-
Pd(allyl)Cl (0.02 mmol) in THF (0.1 mL) at 65 °C for 12 h in an NMR
tube unless otherwise noted. b The reactions were carried out with NaOtAm
(0.03 mmol) and NHC-Pd(allyl)Cl (0.01 mmol) in a vial with stirring. (It
was found that the conversion for diamination can be improved with 8d-f
when the reaction was carried out in a vial with stirring as compared to in
an NMR tube. However, in the case of 8a-c and 8g, the conversion for
diamination was not significantly improved with stirring.) c Conversion
1
was determined by H NMR analysis of the crude reaction mixture. d The
ee was determined by chiral GC (Chiraldex B-DM column). e The ee was
determined by chiral HPLC (Chiralpak AD-H column).
SCHEME 2
1) and NaOtAm24 using 1,3-hexadiene and 1-(p-methoxyphe-
nyl)butadiene as substrates. The results are summarized in Table
1. Among the catalysts tested, complexes 8a-c, bearing ortho-
monosubstituted phenyl groups, gave 64-91% ee for 1,3-
hexadiene (Table 1, entries 1-3). It appears that enantioselec-
tivity increases with the size of the ortho substituent on the
N-phenyl group. Unfortunately, these catalysts gave low conver-
sions for both 1,3-hexadiene and 1-(p-methoxyphenyl)butadiene
(Table 1, entries 1-3). A similar trend was also observed for a
closely related unsymmetric NHC-Pd complex 8g (Table 1,
entry 10). Complexes 8d-f, bearing ortho,ortho-disubstituted
phenyl groups, gave higher conversions with less amount of
catalyst (5 mol %) but lower ee’s (Table 1, entries 4-9). The
higher conversion obtained with these catalysts could be due
to the steric hindrance of the carbene ligand, which may facilitate
the reductive elimination step in the catalytic cycle.19 As shown
by the X-ray structure of 8e (Supporting Information), ligands
with ortho,ortho-disubstituted phenyl groups can provide a chiral
environment around the Pd, thus giving reasonable enantiose-
lectivity for the diamination. Lower ee’s obtained with these
ligands as compared to ligands with ortho monosubstituted
phenyl groups in complexes such as 8b and 8c suggest that
ligands with ortho,ortho-disubstituted phenyl groups are less
efficient for stereodifferentiation than those with ortho-mono-
substituted phenyl groups.
asymmetric version of this diamination, chiral NHC ligands have
been examined along with chiral phosphine based ligands.20
Herein we wish to report our preliminary studies on chiral
NHC-Pd(0)-catalyzed diamination of dienes and triene.
Initial studies on asymmetric diamination were based on chiral
N-aryl-substituted N-heterocyclic carbenes derived from (R,R)-
diphenylethylenediamine, which were reported by Grubbs in
the ruthenium-catalyzed ring-closing metathesis.4a,c On the basis
of the reported procedures, imidazolium salts 7 were prepared
from the chiral diamine in two steps (Scheme 2),4a,c and
corresponding NHC-Pd(allyl)Cl complexes 8 were generated
by treatment of the imidazolium salts and [Pd(allyl)Cl]2 with
KOtBu in THF9a,21 (Scheme 2) (Figure 1).22,23 The X-ray
structure of NHC-Pd complex 8e is shown in Supporting
Information.
Asymmetric diamination was examined with catalysts gener-
ated in situ from NHC-Pd(allyl)Cl complexes 8a-g (Figure
Although similar conversions were obtained for 1,3-hexadiene
with 8d-f (Table 1, entries 5, 7, and 9), catalyst 8e showed
higher reactivity than 8d and 8f for 1-(p-methoxyphenyl)-
butadiene (Table 1, entries 5, 7, and 9). To further investigate
the catalyst’s reactivity and selectivity, diamination with 8e was
extended to other substrates. As shown in Table 2, various dienes
(20) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129,
11688.
(21) (a) Viciu, M. S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4,
4053. (b) Viciu, M. S.; Germaneau, R. F.; Navarro-Fernandez, O.; Stevens,
E. D.; Nolan, S. P. Organometallics 2002, 21, 5470.
(22) For a related chiral NHC-Pd complex, see ref 9a.
(23) For a recent reference on Ni-catalyzed aldehyde-alkyne reductive
couplings with related chiral N-heterocyclic carbenes, see: Chaulagain, M.
R.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2007, 129, 9568.
(24) For leading references, see: (a) Reference 21b. (b) Marion, N.;
Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am.
Chem. Soc. 2006, 128, 4101.
750 J. Org. Chem., Vol. 73, No. 2, 2008

TABLE 2. Catalytic Asymmetric Diamination of Dienes and
Trienea
the conversion is low. The information obtained in this study
will be useful for the development of new NHC-Pd catalysts
with both high reactivity and enantioselectivity via electronic
and steric tuning of ligands. As compared to the chiral
phosphine-based catalysts,20 the NHC-Pd catalysts can poten-
tially be more stable and active, thus requiring less catalyst
loading. Further studies are currently underway.
Experimental Section
All diamination products in Table 2 are known and give
satisfactory spectroscopic characterization.20
Representative Asymmetric Diamination Procedure (Table
2, Entry 6). A 2.0-mL vial was charged with complex 8e (0.0201
g, 0.030 mmol), sodium tert-pentoxide (0.0099 g, 0.090 mmol),
and a stirrer bar. The vial was sealed with a septum, evacuated,
and then filled with argon three times. THF (0.1 mL) (freshly
distilled from sodium) was then added via a syringe. After stirring
at room temperature for 10 min, 1-phenylbutadiene (0.078 g, 0.60
mmol) was added (for a solid substrate, it was added earlier along
with the Pd catalyst), followed by addition of di-tert-butyldiaziri-
dinone (0.153 g, 0.90 mmol). Upon stirring at 65 °C for 12 h, the
reaction mixture was purified by flash chromatography (silica gel,
hexane/ether ) 5/1) to give the diamination compound as a colorless
oil (0.136 g, 76% yield, 74% ee). Colorless oil; [R]22 ) +23.9°
D
1
(c 1.04, CHCl3); H NMR (300 MHz, CDCl3) δ 7.32-7.26 (m,
5H), 6.01 (ddd, J ) 16.2, 9.6, 8.4 Hz, 1H), 5.18 (d, J ) 16.2 Hz,
1H), 5.13 (d, J ) 9.6 Hz, 1H), 4.14 (s, 1H), 3.63 (d, J ) 8.4 Hz,
1H), 1.32 (s, 9H), 1.26 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
159.1, 144.0, 140.9, 128.9, 127.8, 125.8, 115.8, 64.9, 63.3, 53.6,
53.4, 29.0, 28.8.
a All reactions were carried out with diene or triene (0.6 mmol), di-tert-
butyldiaziridinone (2) (0.9 mmol), NaOtAm (0.09 mmol), and 8e (0.03
mmol) in THF (0.1 mL) at 65 °C for 12 h. The absolute configurations are
not determined, and the stereochemistry indicated represents the relative
stereochemistry. b A mixture of E and Z isomers was used. For entry 2,
diene (1.33 mmol, E/Z ) 1/1.2; E isomer, 0.60 mmol); for entry 4, diene
(1.09 mmol, E/Z ) 1.2/1; E isomer, 0.60 mmol); for entry 5, diene (0.96
mmol, E/Z ) 1.67/1; E isomer, 0.60 mmol). c Isolated yield based on diene
or triene. d The ee was determined by chiral GC (Chiraldex B-DM column)
after removal of tert-butyl groups. e The ee was determined by chiral GC
(Chiraldex B-DM column). f The ee was determined by chiral HPLC
(Chiralpak AD-H column) after removal of tert-butyl groups. g The ee was
determined by chiral HPLC (Chiralpak AD-H column).
Table 2, Entry 1. Colorless oil; [R]22D ) +24.9° (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3) δ 5.87 (ddd, J ) 17.1, 10.2, 8.4 Hz,
1H), 5.14 (d, J ) 17.1 Hz, 1H), 5.04 (d, J ) 10.2 Hz, 1H), 3.45
(d, J ) 8.4 Hz, 1H), 3.24 (q, J ) 6.3 Hz, 1H), 1.30 (s, 9H), 1.27
(s, 9H), 1.16 (d, J ) 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
157.9, 140.0, 115.5, 63.6, 55.3, 53.0, 52.5, 29.1, 28.9, 21.2.
Table 2, Entry 2. Colorless oil; [R]22D ) +7.7° (c 1.15, CHCl3);
1H NMR (300 MHz, CDCl3) δ 5.87 (ddd, J ) 17.4, 10.2, 8.4 Hz,
1H), 5.14 (d, J ) 17.4 Hz, 1H), 5.04 (d, J ) 10.2 Hz, 1H), 3.62
(d, J ) 8.4 Hz, 1H), 3.01 (t, J ) 5.7 Hz, 1H), 1.57-1.48 (m, 2H),
1.32 (s, 9H), 1.31 (s, 9H), 0.87 (t, J ) 7.5 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 158.4, 140.8, 115.2, 60.9, 60.2, 53.1, 52.6, 29.1,
29.0, 27.3, 9.1.
and a triene can be effectively diaminated in 57-97% yield
and 62-78% ee. The diamination with 8e proceeded highly
regioselectively at the internal double bond with high diaste-
reoselectivity, which is similar to the diamination using (IPr)-
Pd(allyl)Cl (4) (Scheme 1).
Acknowledgment. We are grateful for generous financial
support from the Camille and Henry Dreyfus Foundation. We
thank Ms. O. Andrea Wong and Dr. Haifeng Du for experi-
mental assistance.
In conclusion, it has been found that chiral NHC-Pd catalysts
are promising for asymmetric diamination of conjugated dienes
and triene using di-tert-butyldiaziridinone as nitrogen source,
giving diamination products in good yields and ee’s with high
regio- and diastereoselectivities. The carbene structure has a
large impact on both the reactivity and enantioselectivity.
Catalysts such as 8d-f are very active, giving high conversions
for diamination with 5 mol % catalyst. High enantioselectivity
(90-91% ee) can be obtained with catalysts 8c and 8g while
Supporting Information Available: Preparation procedures and
characterization of chiral NHC-Pd(allyl)Cl complexes, character-
ization of diamination products, X-ray data of complex 8e, 1H and
13C NMR spectra of chiral NHC-Pd(allyl)Cl complexes and
diamination products, and data for determination of enantiomeric
excess of diamination products. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO702167U
J. Org. Chem, Vol. 73, No. 2, 2008 751