A Heck-type reaction involving carbon - Heteroatom double bonds. Rhodium(I)-catalyzed coupling of aryl halides with N-pyrazyl aldimines [25]

Full text of DOI:10.1021/ja003306e

J. Am. Chem. Soc. 2000, 122, 12043-12044
12043
benzylidene-p-toluenesulfonamide (TosNdCHPh), did not pro-
duce any of the desired ketone or ketimine product when using
selected phosphines in combination with these catalyst precursors.
We presumed that the insertion of aldehyde or imine into a
transition metal-aryl linkage, which would be formed from
oxidative addition of the aryl halide, was slow.
A Heck-Type Reaction Involving
Carbon-Heteroatom Double Bonds.
Rhodium(I)-Catalyzed Coupling of Aryl Halides with
N-Pyrazyl Aldimines
Tatsuo Ishiyama*,‡ and John Hartwig*
To overcome this problem, we used aldimines bearing an
ancillary donor atom that would coordinate to the metal, deliver
the imine to the metal center, and facilitate insertion. This strategy
followed the lead of Jun and Hong, who showed that N-
pyridylimines undergo C-H additions to olefins more rapidly
than do aldehydes or simple imines.22 After evaluating several
N-heterocyclic imines as substrates, we found that N-pyrazyl
imines23 reacted with phenyl iodide in the presence of rhodium(I)
catalysts to form the corresponding ketimine.
Department of Chemistry, Yale UniVersity
P.O. Box 208107, New HaVen, Connecticut 06520-8107
ReceiVed September 7, 2000
The transition metal-catalyzed reaction of organic halides or
triflates with alkenes to generate substituted olefins, generally
referred to as the Heck reaction, is one of the most important
catalytic carbon-carbon bond-forming processes.1-6 Recent
advances with this reaction have included the olefination of
chloroarenes using highly active catalysts,7,8 the formation of
polycyclic systems by cascade events,9,10 and enantioselective
variants using optically active ligands.11-14 In contrast to this now
common reaction, the analogous process using aldehydes or
aldimines, instead of alkenes, has not been developed. We disclose
a set of rhodium-catalyzed intermolecular Heck-type reactions
between aryl iodides and N-heterocyclic aldimines to form the
corresponding ketimines, which form ketones upon hydrolysis
(eq 1).
We found that a 1,4-relationship between the nitrogen donor
atom and the imine carbon atom was most favorable. The N-2-
pyridyl derivatives (2-Pyr)NdCHPh participated in the coupling
process, indicating that the nitrogen at the 4-position of the pyrazyl
ring provides an electronic effect and does not trigger a binuclear
mechanism. However, N-heterocyclic aldimines derived from
benzaldehyde bearing longer tethers, such as the N-(2-pyridyl-
methyl) or N-[2-(2-pyridyl)ethyl] derivatives [2-Pyr(CH2)n]Nd
CHPh (n ) 1, 2) were not suitable substrates. Benzaldehyde-
N,N-pentamethylene hydrazone ((CH2)5N-NdCHPh), which
contains a 1,3-relationship between the nitrogen donor and the
imine carbon, also did not produce any ketimine product.
Rhodium(I) complexes generated in situ from [RhCl(COD)]2
and 1 equiv per rhodium of the sterically unhindered trialkyl-
phosphines P(n-Pr)3 provided the most active catalysts. Complexes
generated from PPh3 produced coupled products in yields that
were generally 20% lower than those with the unhindered tri-
alkylphosphine, but catalysts containing P(o-Tol)3, dppf, and P(t-
Bu)3 were ineffective. Complexes formed from Pd(dba)2 or Ni-
(COD)2 and these phosphine ligands were ineffective, despite their
catalytic activity in the common Heck processes involving olefins.
We also evaluated several bases and solvents for this process.
Among the combinations tested, NaOBut and m-xylene (method
A) and K2CO3 and diglyme (method B) were most effective. The
combination of strong base and polar solvent led to decomposition
of the aldimine before any coupling occurred.
Representative Heck-type couplings between aryl halides and
N-pyrazyl aldimines in the presence of the most active catalyst,
comprised of 2.5 mol % of [RhCl(COD)]2 and 5 mol % of P(n-
Pr)3, are summarized in Table 1. To allow for convenient analysis
of isolated products, the initially formed ketimine was converted
to the corresponding ketone by acid hydrolysis. The reaction
occurred smoothly when using aryl iodides as substrate. Aryl
bromides reacted much more slowly (entry 2), and no coupling
was observed with aryl chlorides. However, electron-rich, electron-
poor, and ortho-substituted aryl iodides all reacted with the
aldimines to give good yields when using one of the base and
solvent combinations. To achieve acceptable yields from the
coupling of electron-poor aryl iodides with electron-poor aldi-
mines (entry 10) and from the coupling of aryl iodides bearing
an ortho substituent (entries 12 and 13), 10-20 mol % of catalyst
was required.
We initially evaluated complexes generated from Pd(dba)2, Ni-
(COD)2, and [RhCl(COD)]2 to uncover a Heck-type coupling of
iodobenzene with aldehydes and aldimines under various reaction
conditions. Several research groups have recently shown that
complexes of these metals catalyze the formation of alcohols and
amines by the addition of organic halides15-17 or main group
organometallic reagents to aldehydes and imines.18-21 In contrast
reactions of aryl halides with typical aldehydes and imines, such
as benzaldehyde, N-benzylideneaniline (PhNdCHPh) and N-
‡ Permanent Address: Division of Molecular Chemistry, Graduate School
of Engineering, Hokkaido University, Sapporo 060-8628, Japan.
(1) Herrmann, W. A. I. Applied Homogeneous Catalysis with Organome-
tallic Compounds; Wiley-VCH: Weinheim, 2000; pp 712-732.
(2) Brase, S.; de Mejeire, A. Metal-catalyzed Cross-coupling Reactions;
Wiley-VCH: Weinheim, 1998; pp 99-167.
(3) Tsuji, J. Palladium Reagents and Catalysis; Wiley: Chichester, 1995.
(4) For Co-, Rh-, and Ir-catalyzed Heck reactions see: Iyer, S. J.
Organomet. Chem. 1995, 490, C27.
(5) For Ni-catalyzed Heck reactions see: Iyer, S.; Ramesh, C.; Ramani,
A. Tetrahedron Lett. 1997, 38, 8533.
(6) For platinum-catalyzed Heck reactions see: Kelkar, A. A. Tetrahedron
Lett. 1996, 37, 8917.
(7) Shaughnessy, K. H.; Kim, P.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 2123.
(8) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
(9) Overman, L. E. Pure Appl. Chem. 1994, 66, 1423.
(10) Demeijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33,
2379.
(11) Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738.
(12) Carpenter, N. E.; Kucera, D. J.; Overman, L. E. J. Org. Chem. 1989,
54, 5846.
(13) Shibasaki, M.; Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 7371.
(14) Hayashi, T.; Kubo, A.; Ozawa, F. Pure Appl. Chem. 1992, 64, 421.
(15) Majumdar, K. K.; Cheng, C.-H. Org. Lett. 2000, 2, 2295.
(16) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc. 1999,
121, 3545.
(17) Quan, L. G.; Lamrani, M.; Yamamoto, Y. J. Am. Chem. Soc. 2000,
122, 4827.
(18) Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65, 4450.
(19) Ueda, M.; Miyaura, N. J. Organomet. Chem. 2000, 595, 31.
(20) Oi, S.; Moro, M.; Inoue, Y. Chem. Commun. 1997, 1621.
(21) Ichiyanagi, T.; Kuniyama, S.; Shimizu, M.; Fujisawa, T. Chem. Lett.
1998, 1033.
Arylrhodium halide and iminoacylrhodium hydride complexes
were prepared to determine their kinetic and chemical competence
to be reaction intermediates. These two types of complexes would
be formed by oxidative addition of aryl iodide or aldimine to a
phosphine-ligated Rh(I) halide complex. Although it is well
accepted that Heck reactions are initiated by aryl halide oxidative
(22) Jun, C.-H.; Hong, J.-B. Org. Lett. 1999, 1, 887.
(23) El-Ansary, A. L.; Darwish, N. A.; Issa, Y. M.; Hassib, H. B. Egypt.
J. Chem. 1991, 33, 129-145.
10.1021/ja003306e CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/17/2000

12044 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Communications to the Editor
Table 1. Rh-Catalyzed Coupling of Aryl Halides with Aldimines 1
Scheme 2
(eq 1)a
yield/%b (time/h)
entry
aryl halide
PhI
PhBr
PhI
PhI
4-MeOC6H4I
4-MeOC6H4I
4-MeOC6H4I
4-CF3C6H4I
4-CF3C6H4I
4-CF3C6H4I
PhI
1, Ar2 )
Ph
method A
method B
1
2
3
4
5
6
7
8
9
10
11
12
13
83 (26)
32 (168)
71 (50)
64 (26)
77 (26)
79 (26)
82 (26)
50 (98)
55 (50)
68c (5)
19 (50)
45d (5)
26d (5)
86 (26)
47 (168)
82 (74)
77 (146)
99 (50)
84 (50)
83 (98)
73 (50)
80 (50)
66c (50)
95 (26)
67d (50)
74d (74)
Ph
4-MeOC6H4
4-CF3C6H4
4-MeOC6H4
Ph
4-CF3C6H4
4-MeOC6H4
Ph
4-CF3C6H4
2-MeC6H4
Ph
arylrhodium 2 and free aldimine 1 in nearly quantitative yields.
Presumably, these products are formed by the reductive elimina-
tion of aldimine followed by oxidative addition of iodotoluene.
Moreover, the generation of 2 and free imine from 3 in the
absence of base occurred more rapidly than did the generation of
coupled product from heating 3, tolyl iodide, and base. Thus, the
products resulting from heating of 3 with iodotoluene and base
probably form from reaction of free aldimine with 2.
A possible mechanism for the coupling process involving an
arylrhodium halide complex that reacts with imine is shown in
Scheme 2. This mechanism includes (a) oxidative addition of aryl
halide to rhodium(I) to form an arylrhodium(III) complex, (b)
insertion of aldimine 1 into the rhodium-carbon bond to give a
rhodium(III) amide complex 6, perhaps after the prior coordination
of the aldimine nitrogen, (c) â-hydride elimination from 6 to give
ketimine 4 and hydridorhodium(III) complex 7,28,29 and (d)
reductive elimination of HX from 7 to regenerate the starting
rhodium(I) complex.
2-MeC6H4I
2-MeC6H4I
2-MeC6H4
a All reactions were conducted using aryl halide (1.0 equiv), 1 (1.0
equiv), 1 (1.5 equiv), RhCl(COD)/P(n-Pr)3 (5 mol %), and base (1.5
equiv). Method A: NaOBut/m-xylene/135 °C. Method B: K2CO3/
diglyme/160 °C. b GLC yields of biaryl ketones after hydrolysis of
ketimines with 6 N HCl at room temperature for 16 h. c 10 mol % of
catalyst was used. d 20 mol % of catalyst was employed.
Scheme 1a
Additional studies will be required to define the exact structures
of the intermediates because several observations are not explained
by this mechanism. For example, no reaction occurred between
arylrhodium 2 and aldimine 1 in the absence of base, suggesting
that the base modifies the arylrhodium complex prior to insertion.
In addition, the ratio of ketimine and amine products formed from
reaction of 2 with aldimine was different from the ratio observed
in the catalytic process. Thus, reaction of imine with an aryl-
rhodium(III) complex is a reasonable step in the catalytic process,
but the precise ligand set on the arylrhodium complex that reacts
with aldimine is probably different from that in 2.27
Insertions of olefins into late metal-carbon bonds are common,
but such insertions of imines and aldehydes are rare, perhaps
because they form a reactive late metal-amide or -alkoxide from
a more stable metal-alkyl or -aryl. Imine and aldehyde insertion
has been postulated as a step in the metal-catalyzed additions of
organic halides15-17 and main group organometallic reagents18-21
to aldehydes, ketones, and imines. However, direct evidence for
this step from studies of discrete intermediates has not been
obtained. Our studies on the reaction of aldimine 1 with
arylrhodium complex 2 provide evidence that this elementary step
is part of a stoichiometric reaction involving a well-known aryl
halide complex.
An understanding of imine and aldehyde insertions should point
toward a set of new catalytic processes based on analogies to
those that involve olefin insertion. Further mechanistic work and
further development of such catalytic processes will be the subject
of future studies.
addition,1-3 oxidative addition of an aldimine C-H bond is a
reasonable initial step for the process reported here. Indeed, both
iodotoluene and N-benzylideneaminopyrazine (1) reacted with
24
Rh(I)(PPh3)3 to form the oxidative addition products (4-
MeC6H4)Rh(I)2(PPh3)2 (2) and [{(C4H3N2)Nd}(Ph)C]Rh(H)(I)-
(PPh3)2 (3) shown in Scheme 1.25,26
Reactions of these two complexes with their complementary
reagents are summarized in Scheme 1.27 Arylrhodium complex 2
reacted with excess of aldimine 1 at 135 °C, the temperature of
the catalytic process, in the presence of NaOBut and PPh3 in
m-xylene to form two coupling products: ketimine 4 and amine
5 (40:60) in a combined yield of 60% (Scheme 1). This combined
yield is comparable to that obtained from the catalytic reactions
employing PPh3 as ligand. No reaction between arylrhodium 2
and aldimine 1 occurred in the absence of base. Iminoacyl
complex 3 reacted with an excess of 4-iodotoluene in the presence
of NaOBut to form ketimine and amine (4:5 ) 85:15), but the
combined yield was only 40%. Importantly, reaction of iminoacyl
complex 3 with tolyl iodide in the absence of base produced
Acknowledgment. We thank the Department of Energy for support
of this work.
Supporting Information Available: Experimental procedures for
Table 1 and Scheme 1, including preparation of 2 and 3, and spectral
analyses of all reaction products (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
(24) Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G. J. Chem.
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(25) Mori, K.; Mizoroki, T.; Ozaki, A. Bull. Chem. Soc. Jpn. 1976, 49,
758.
(26) Suggs, J. W. J. Am. Chem. Soc. 1979, 101, 489.
(27) The source of the hydrogens required for the formation of amine
product has not yet been identified.
JA003306E
(28) For similar â-hydrogen elimination from transition metal amido
complexes see this and the following reference. Hartwig, J. F. J. Am. Chem.
Soc. 1996, 118, 7010.
(29) Fryzuk, M. D.; Piers, W. E. Organometallics 1990, 9, 986.