Direct addition of TMS-acetylene to aldimines catalyzed by a simple, commercially available Ir(I) complex

Article abstract of DOI:10.1021/ol017022q

(Matrix Presented) A new, convenient procedure for the addition reaction of trimethylsilylacetylene to imines is described. Simply treating a solution of aldimine and trimethylsilyl acetylene with catalytic [IrCI(COD)]₂ furnishes the adduct in preparatively useful yields. Interestingly, the reaction may be conducted in the absence of solvent.

Full text of DOI:10.1021/ol017022q

ORGANIC
LETTERS
2001
Vol. 3, No. 26
4319-4321
Direct Addition of TMS-acetylene to
Aldimines Catalyzed by a Simple,
Commercially Available Ir(I) Complex
Christian Fischer and Erick M. Carreira*
Laboratorium fu¨r Organische Chemie, ETH-Ho¨nggerberg,
CH-8093 Zu¨rich, Switzerland
carreira@org.chem.ethz.ch
Received November 9, 2001
ABSTRACT
A new, convenient procedure for the addition reaction of trimethylsilylacetylene to imines is described. Simply treating a solution of aldimine
and trimethylsilyl acetylene with catalytic [IrCl(COD)]2 furnishes the adduct in preparatively useful yields. Interestingly, the reaction may be
conducted in the absence of solvent.
Propargylic amines, like the corresponding propargylic
alcohols, can serve as important building blocks for organic
synthesis.1,2 However, while propargylic alcohols can be
prepared through a variety of transformations,3-5 in general,
reliable methods that provide access to propargylic amines
are far fewer.6-9 Carbanion addition to N-alkyl aldimines
typically prescribe the use of Lewis acidic additives (i.e.,
BF3‚OEt2) as a means of activating the aldimine substrate.
By contrast, reactions of N-acyl, N-sulfonyl, or N-aryl
aldimines proceed without necessary additional activation.
In either case, to date, imine addition reactions typically
require the use of stoichiometric quantities of alkali, alkaline
earth, or transition metal carbanions, or alternatively orga-
noboranes, -silanes, or -stannanes. Herein, we report a novel
process that is considerably simplified over previously
documented CdN addition reactions, proceeding at room
temperature and requiring only N-alkyl or N-aryl aldimines,
(1) (a) Porco, J. A., Jr.; Schoenen, F. J.; Stout, T. J.; Clardy, J.; Schreiber,
S. L. J. Am. Chem. Soc. 1990, 112, 7410.
(2) For selected examples of the use of optically active propargylic
alcohols in synthesis, see: (a) Trost, B. M.; Hipskind, P. A.; Chung, J. Y.
L.; Chan, C. Angew. Chem., Int. Ed. Engl. 1989, 28, 1502. (b) Marshall, J.
A.; Wang, X. J. J. Org. Chem. 1992, 57, 1242. (c) Roush, W. R.; Sciotti,
R. J. J. Am. Chem. Soc. 1994, 116, 6457. (d) Myers, A. G.; Zheng, B. J.
Am. Chem. Soc. 1996, 118, 4492.
(3) Stoichiometric reductions: (a) Midland, M. M.; Tramontano, A.;
Zderic, S. A. J. Am. Chem. Soc. 1977, 99, 5211. (b) Yamaguchi, S.; Mosher,
H. S.; Pohland, A. J. Am. Chem. Soc. 1972, 94, 9254. (c) Nishizawa, M.;
Yamada, M.; Noyori, R. Tetrahedron Lett. 1981, 22, 247. (d) Brown, H.
C.; Ramachandran, P. V. Acc. Chem. Res. 1992, 25, 16.
(6) For the preparation of propargylic amines, see: (a) Enders, D.;
Schankat, J. HelV. Chim. Acta 1995, 78, 970. (b) Harwood: L. M.; Vines,
K. J.; Drew, M. G. B. Synlett 1996, 1051. (c) Brasseur, D.; Marek, I.;
Normant, J.-F. Tetrahedron 1996, 52, 7235. (d) Sato, Y.; Nishimata, T.;
Mori, M. Heterocycles 1997, 44, 443. (e) Cossy, J.; Poitevin, C.; Pardo, D.
G.; Peglion, J.-L.; Dessinges, A. Synlett 1998, 3, 251. (f) Courtois, G.; Desre,
V.; Miginiac, L. J. Organomet. Chem. 1998, 570, 279. (g) Florio, S.; Troisi,
L.; Capriati, V.; Suppa, G. Eur. J. Org. Chem. 2000, 65, 3793.
(7) For Cu-mediated addition of terminal acetylenes to N-alkyl imines
at elavated temperatures, see: Rohm and Haas Co. U.S. Patent 2,665,311,
1950.
(8) For recent pioneering reports of dialkylzinc additions to imines, see:
Porter, J. R.; Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. J. Am. Chem.
Soc. 2001, 123, 984.
(9) For representative additions of carbanions to imines, see: (a) Cogan,
D. A.; Ellman, J. A. J. Am. Chem. Soc. 1999, 121, 268. (b) Hamada, T.;
Mizojiri, R.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2000, 122, 7138. (c)
Knudsen, K.; Risgaard, T.; Nishiwaki, N.; Gothelf, K. V.; Jørgensen, K.
A. J. Am. Chem. Soc. 2001, 123, 5843. (d) Ferraris, D.; Young, B.; Dudding,
T.; Lectka, T. J. Am. Chem. Soc. 1998, 120, 4548. (e) Wipf, P.; Kendall,
C.; Stephenson, C. R. J. J. Am. Chem. Soc. 2001, 123, 5122
(4) Catalytic methods: (a) Helal, C. J.; Magriotis, P. A.; Corey, E. J. J.
Am. Chem. Soc. 1996, 118, 10938. (b) Matsumura, K.; Hashiguchi, S.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1997, 119, 8738.
(5) For the addition of lithium and magnesium acetylides to trifluoro-
methyl aryl ketones, see: (a) Tan, L.; Chen, C.-Y.; Tillyer, R. D.;
Grabowski, E. J. J.; Reider, P. Angew. Chem., Int. Ed. 1999, 38, 711. (b)
For a recent report on the addition of aromatic aldehydes with alkynylzinc
reagents generated in situ from terminal acetylenes and dimethylzinc, see:
Li, Z.; Upadhyay, V.; DeCamp, A. E.; DiMichele, L.; Reider, P. J. Synthesis
1999, 1453. (c) For a recent study of chelation-controlled stannylacetylene
additions to aldehydes, see: Evans, D. A.; Halstead, D. P.; Allison, B. D.
Tetrahedron Lett. 1999, 40, 4461.
10.1021/ol017022q CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/22/2001

trimethylsilylacetylene, and catalytic amounts (4-5 mol %)
of [IrCl(COD)]2 (Scheme 1). Importantly, it is worth noting
An initial screening of transition-metal complexes known
to form metal acetylides led us to identify [IrCl(COD)]2 as
unique in its extraordinary ability to catalyze the addition
of trimethylsilylacetylene to aldimines at room temperature.
As shown in Scheme 1 and Table 1 (entries 1-5), N-benzyl
Scheme 1
Table 1. Addition Reaction of Me3SiCtC-H to Aldiminesa
that the Ir(I) catalyst is a commercially available, air-stable,
and easily handled complex; moreover, the additions can be
carried out in the absence of solvent, providing for a highly
atom-economical process.
We have been interested in the development of practical
C-C bond-forming reactions involving Zn-acetylides wherein
the combination of amine and Zn(II) synergistically effect
the in situ generation of reactive alkynilides.10 In principle,
the use of the amine is superfluous, as the transformation
involves net atom-transfer of the acetylene proton to the
product heteroatom. Consequently, we sought to identify a
metal complex that would insert into the terminal acetylene
C-H to serve formally as the repository of the proton and
alkynilide fragments and, importantly, subsequently possesses
suitable reactivity to undergo addition to imines.11
Late transition-metal σ-bound alkynilides enjoy a rich,
diverse coordination and reaction chemistry.12,13 Typically,
these species serve as precursors to metal vinylidenes or
allenylidenes that participate in oligomerization14,15 or ring-
closing metathesis.16 However, such alkynilides have not
been used in nucleophilic addition reactions with CdX
electrophiles of use for fine chemicals synthesis.12
a In a typical reaction, 1.5 equiv of Me3SiCtCH and aldimine are
sequentially added to 5 mol % of [IrCl(COD)]2 in THF at 23 °C and stirred
for 24 h. b Reaction time is 36 h, and 2.0 equiv of acetylene was used.
aldimines derived from aromatic as well as aliphatic alde-
hydes participate in the Ir-catalyzed addition reaction. With
the latter class of substrates, it should be noted that
unbranched (entry 3), along with branched (entries 2 and
4), aldimines work well. As shown in entry 6, an aldimine
prepared from p-methoxyaniline is also a substrate. The use
of such imines has recently received attention, because N-aryl
protecting groups are readily oxidatively cleaved.17 We have,
nonetheless, focused on the use of N-benzyl-derived aldi-
mines, as the resultant protected amines are more convenient
intermediates for synthesis.
The efficiency and practicality of the process is demon-
strated by a series of addition reactions, which we have
carried out under solvent-free conditions (Scheme 2). Thus,
when a suspension of the Ir(I) complex in neat N-benzyl
aldimine is treated with trimethylsilylacetylene, adducts are
formed cleanly in preparatively useful yields (69-85%).
We have made a few observations in the course of the
preliminary study that are worth noting as they suggest
further avenues to pursue. First, at elevated temperatures (60
°C) the yield drops significantly (48% for the benzaldehyde
derived N-benzylimine). When the reaction components are
heated to 120 °C, no adduct was observed and the imine
(10) (a) Frantz, D. E.; Fa¨ssler, R.; Carreira, E. M. J. Am. Chem. Soc.
1999, 121, 11245. (b) Frantz, D. E.; Fa¨ssler, R.; Carreira, E. M. J. Am.
Chem. Soc. 2000, 122, 1806. (c) Frantz, D. E.; Fa¨ssler, R.; Tomooka, C.
S.; Carreira, E. M. Acc. Chem. Res. 2000, 33, 373. (d) Boyall, D.; Lo´pez,
F.; Sasaki, H.; Frantz, D.; Carreira, E. M. Org. Lett. 2000, 2, 4233. (e)
Sasaki, H.; Boyall, D.; Carreira, E. M. HelV. Chim. Acta 2001, 84, 964. (f)
Bode, J. W.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 3611. (g) Anand,
N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687.
(11) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.;
VCH: Weinheim, 1995.
(12) (a) Normant, J. F.; Alexakis, A. Synthesis 1981, 841. (b) Santos,
A.; Lopez, J.; Galan, A.; Gonzalez, J.; Tinoco, P.; Echavarren, A. M.
Organometallics 1997, 16, 3482. (c) Yi, C. S.; Liu, N.; Rheingold, A. L.;
Liable-Sands, L. M.; Guzei, I. A. Organometallics 1997, 16, 3729. (d)
Carmona, D.; Vega, C.; Fernando, J. L.; Atencio, R.; Oro, L. A.; Lamata,
M. P.; Viguri, F.; San Jose, E. Organometallics 2000, 19, 2273. (e)
Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M. J. Am. Chem.
Soc. 2001, 123, 3393.
(13) Sakaguchi, S.; Kubo, T.; Ishii, Y. Angew. Chem., Int. Ed. 2001,
2534. In this work, Ishii has reported the Ir-catalyzed synthesis of imines
by the coupling of aldehydes, amines, and alkynes. It should be noted that
at the end of this manuscript the authors describe a “failed” reaction in
which a byproduct is isolated in an unspecified yield that corresponds to
the adduct of acetylene plus aldimine. Although it is not the focus of the
study, this process may be related to the one that we independently describe
herein.
(14) (a) Kishimoto, Y.; Eckerle, P.; Miyatake, T.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1994, 116, 12131. (b) Ilg, K.; Werner, H. Angew.
Chem. 2000, 112, 1691.
(15) Ohmura, T.; Yorozuya, S.; Yamamoto, Y.; Miyaura, N. Organo-
metallics 2000, 19, 365.
(16) (a) Fu¨rstner, A.; Picquet, M.; Bruneau, C.; Dixneuf, P. H. Chem.
Commun. 1998, 1315. (b) Picquet, M.; Touchard, D.; Bruneau, C.; Dixneuf,
P. H. New. J. Chem. 1999, 23, 141. (c) Saoud, M.; Romerosa, A.; Peruzzini,
M. Organometallics 2000, 19, 4005.
(17) (a) Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 2000,
122, 8180. (b) Ishitani, H.; Kobayashi, S. Chirality 2000, 12, 540.
4320
Org. Lett., Vol. 3, No. 26, 2001

aldimines. Finally, the addition reactions can be conducted
in the presence of added phosphines with a range of effects.
Thus, for example, while in the presence of triphenylphos-
phine no product formation is observed after 2 days under
otherwise identical conditions to that reported above, the
presence of tri-tert-butylphosphine leads to rate acceleration.
Such ligand-dependent phenomena will certainly be useful
in the subsequent identification and study of asymmetric
processes.
Scheme 2
We have documented a novel process involving the direct
addition of TMS-acetylene to aldimines which is convenient
and remarkably simple. The propargylic amines are formed
at room temperature, with the addition reaction requiring
catalytic [IrCl(COD)]2, itself a commercially available, stable,
and easily handled complex. Additionally it can be carried
out in the absence of solvent, providing for a highly atom-
economical process. In the broadest context, the observations
we have described provide new opportunities for the
development of synthetically useful transition-metal mediated
C-C bond-forming reactions involving activation of simple
hydrocarbons at room temperature to provide access to
versatile building blocks for chemical synthesis.
can be recovered unchanged. These observations are con-
sistent with the known oligomerization chemistry of acety-
lenes in the presence of Ir(I) at elevated temperatures.18,19
Second, the use of N-p-methoxyphenyl-derived aldimine
leads to enhanced rates. Third, to date only silylacetylenes,
as exemplified by trimethylsilylacetylene, participate in the
addition reaction. Although this may at first consideration
seem limiting, the use of silylacetylenes in the reaction
provides wide leeway in the subsequent functionalization of
the adducts. In this respect, numerous mild methods may be
employed for the desilylation of silylacetylenes to furnish
terminal acetylenes that are themselves substrates for sub-
sequent elaboration, such as alkylation, carboxylation, Zn-
catalyzed aldehyde additions, and Cu- and Pd-mediated
processes.20 Thus, the use of silylacetylene, itself an item of
commerce, furnishes useful propargylamine adducts that are
the synthetic equivalent of C2H2 addition reactions to
Acknowledgment. We thank the ETH for an internal
research grant. We thank Mr. Tobias Ritter for helpful
discussions.
Supporting Information Available: Experimental details
and characterization for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL017022Q
(20) (a) Castro, C. E.; Stephens, R. D. J. Org. Chem. 1963, 28, 2163.
(b) Simandi, L. I. In The Chemistry of Functional Groups, Supplement C,
pt 1; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1983; pp 529-534.
(c) Chodkiewicz, W. Ann. Chim. (Paris) 1957, 2, 819. (d) Sevin, A.;
Chodkiewicz, W.; Cadiot, P. Bull. Soc. Chim. Fr. 1974, 913. (e) Sonogashira,
K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467.
(18) At 0 °C the reaction does not proceed; however upon warming the
same reaction mixture to room temperature, product formation can be
observed.
(19) See for example: Takeuchi, R.; Tanaka, S.; Nakaya, Y. Tetrahedron
Lett. 2001, 42, 2991.
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