Iridium(I)-catalyzed stereospecific decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates

Article abstract of DOI:10.1021/ol702115h

(Chemical Equation Presented) Ir(I)-catalyzed decarboxylase allylic amidation of chiral branched benzyl allyl imidodicarboxylates has been shown to proceed with complete retention of enantiomeric purity and configuration. The transformation is stereospecific and appears to be quite general, accommodating a wide range of R groups.

Full text of DOI:10.1021/ol702115h

ORGANIC
LETTERS
2007
Vol. 9, No. 23
4801-4804
Iridium(I)-Catalyzed Stereospecific
Decarboxylative Allylic Amidation of
Chiral Branched Benzyl Allyl
Imidodicarboxylates
Om V. Singh and Hyunsoo Han*
Department of Chemistry, The UniVersity of Texas at San Antonio, One UTSA Circle,
San Antonio, Texas 78249
hyunsoo.han@utsa.edu
Received August 28, 2007
ABSTRACT
Ir(I)-catalyzed decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates has been shown to proceed with complete
retention of enantiomeric purity and configuration. The transformation is stereospecific and appears to be quite general, accommodating a
wide range of R groups.
We recently reported the Ir(I)-catalyzed regio- and enantio-
selective decarboxylative allylic amidation of benzyl allyl
imidodicarboxylates 1, which could directly give rise to the
formation of N-Cbz-protected chiral allylic amines 2 (Figure
1).1,2 The reaction was effected by [Ir(COD)Cl]2, a chiral
reaction conditions. For example, upon the decarboxylative
allylic amidation, benzyl 4-phenylbut-2-enyl imidodicar-
boxylate (3) could not furnish the chiral branched allylic
amidation product 4 (due to a competing elimination reaction
to form 1-phenyl-1,3-butadiene) (eq 1), and the conversion
of the allylic substrates 5 to 6 suffered from modest regio-
and enantioselectivities (eq 2).
Figure 1. Ir(I)-catalyzed decarboxylative allylic amidation.
phosphoramidite ligand L*, DBU, and proton sponge (PS)
in THF and appeared to show some generality, accommodat-
ing a variety of R groups.
However, during the course of further investigation of the
scope and limitations of the reaction, it was found that some
allylic substrates did not work well under the determined
Herein, we disclose the Ir(I)-catalyzed stereospecific
decarboxylative allylic amidation of 7 to 8 (Figure 2), which
10.1021/ol702115h CCC: $37.00
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Scheme 1. Preparation of Optically Enriched Branched Allyl
Benzyl Imidodicarboxylates
Figure 2. Ir(I)-catalyzed stereospecific decarboxylative allylic
amidation reaction of optically enriched branched benzyl allyl
imidodicarboxylates.
conversion of the resulting optically enriched allylic alcohols
13 and their acetates 14 to the corresponding benzyl
imidodicarboxylates 7 and ent-7, respectively (see the
Supporting Information [SI] for details).
can provide not only 4 and 6 but also the decarboxylative
allylic amidation products that could not be easily accessed
by the Ir(I)-catalyzed regio- and enantioselective decarboxyl-
ative allylic amidation of 1.
The Ir(I)-catalyzed decarboxylative allylic amidation reac-
tions of 7 and ent-7 were conducted under the determined
conditions involving [Ir(COD)Cl]2, a chiral phosphoramidite
ligand L*, and DBU in THF,6 and the results are depicted
in Table 1. The stereospecific decarboxylative allylic ami-
dation appears to be quite general, accommodating a wide
range of R groups such as aryl (entries 1 and 2), benzyl (entry
3), oxygen atom functionalized at the R-carbon (entries 4-6),
oxygen atom functionalized at the â-carbon (entry 7),
cyclohexyl (entry 8), and cyclohexenyl (entries 9 and 10).
At the outset, racemic benzyl 1-(tert-butyldiphenylsilyl-
oxy)-but-3-ene-2-yl imidodicarboxylate (rac-9) was prepared
(see below), and subjected to the reaction conditions involv-
ing [Ir(COD)Cl]2, a chiral phosphoramidite ligand L*, DBU,
and proton sponge (PS) in THF. Racemic 2-N-benzyloxy-
carbonylamino-1-(tert-butyldiphenylsilyloxy)-but-3-ene (rac-
10) was obtained in excellent reaction yield and regioselec-
tivity (eq 3). Further experiments revealed that PS was not
required for the reaction. These results indicate that the
optically enriched chiral benzyl allyl imidodicarboxylates 7
should lead to the corresponding optically enriched allylic
amidation products 8 with complete retention of configura-
tion under the above conditions, because (1) Ir(I)-catalyzed
allylic alkylation followed a double inversion mechanism
through the Ir-π-allyl intermediates, and the interconversion
between the Ir-π-allyl intermediates was slow relative to the
other catalytic steps (see Figure 2)3,4 and (2) the branched
allylic acetates and carbonates were better (with respect to
regioselectivity) and faster substrates than their linear
counterparts in the Ir(I)-catalyzed allylic substitution reac-
tions.3,5
Except for entries 1 and 2, all other allylic amidation
products in entries 3-10 either were not possible to obtain
or were obtained with modest regio- and enantioselectivities
from the corresponding decarboxylative allylic amidation
reactions of 1. The data from Table 1 also show that the
optical purities of the allylic substrates were completely
translated into those of the allylic amidation products with
retention of configuration, as expected from the double
inversion mechanism and the slow interconversion between
the Ir-π-allyl intermediates. The presence of an additional
adjacent chiral center did not interfere with chirality transfer
(entries 9 and 10). Such complete chirality transfer in the
Ir(I)-catalyzed decarboxylative allylic amidation of 7 and
ent-7 is in sharp contrast to the corresponding Ir(I)-catalyzed
stereospecific allylic alkylation, where considerable erosion
in chirality transfer took place.3b
With such a premise, a variety of optically enriched benzyl
allyl imidodicarboxylates 7 and their enantiomers ent-7 were
prepared from the corresponding aldehydes 11 in three or
four steps according to the general procedure shown in
Scheme 1.1,3a 7 and ent-7 were obtained by the enzymatic
resolution of the racemic allylic alcohols 12 followed by the
To ascertain the absolute stereochemistry at the allylic
carbon of the amidation products and to determine the ee of
the amidation product in entry 3, the amidationproduct 15
was transformed to N-Cbz protected L-phenylalanine by the
oxidative cleavage of the terminal double bond.7 The optical
rotation of the resulting product matched that in the literature
(Scheme 2).8
(1) Singh, O. V.; Han, H. J. Am. Chem. Soc. 2007, 129, 774-775.
(2) For general reviews for the decarboxylative allylations: (a) Tunge,
J. A.; Burger, E. C. Eur. J. Org. Chem. 2005, 1715-1726. (b) Tsuji, J.
Proc. Jpn. Acad., Ser. B 2004, 80, 349-358. For more recent references
on the decarboxylative allylic C-N bond-forming reactions: (c) Wang,
C.; Tunge, J. A. Org. Lett. 2006, 8, 3211-3214. (d) Mellegaard-Waetzig,
S. R.; Rayabarapu, D. K.; Tunge, J. A. Synlett 2005, 2759-2762.
(3) (a) Bartels, B.; Garcia-Yebra, C.; Rominger, F.; Helmchen, G. Eur.
J. Inorg. Chem. 2002, 2569-2586. (b) Bartels, B.; Helmchen, G. Chem.
Commun. 1999, 741-742.
Scheme 2. Synthesis of N-Cbz-Protected L-Phenylalanine
(4) For recent reviews on the Ir(I)-catalyzed allylations: (a) Helmchen,
G.; Dahuz, A.; Dubon, P.; Schelwies, M.; Weihofen, R. Chem. Commun.
2007, 675-691. (b) Takeuchi, R.; Kezuka, S. Synthesis 2006, 3349-3366.
(c) Miyabe, H.; Takemoto, Y. Synlett 2005, 1641-1655.
(5) Polet, D.; Alexakis, A.; Tissot-Croset, K.; Corminboeuf, C.; Ditrich,
K. Chem. Eur. J. 2006, 12, 3596-3609.
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Org. Lett., Vol. 9, No. 23, 2007

Table 1. Ir(I)-Catalyzed Decarboxylative Allylic Amidation of Chiral Branched Benzyl Allyl Imidodicarboxylatesa
1
a All reactions were performed at 0.2 mmol scale. b Isolated yields. c Ratios of branched and linear regioisomers were determined by H NMR of crude
reaction mixtures. d Enantiomeric excesses (ee’s) were determined by using chiral HPLC. e ee was determined by conversion to N-Cbz-protected L-phenylalanine.
fContains two diasteromers due to the additional stereocenter (the carbon with *).
In summary, the highly stereospecific decarboxylative
allylic amidation reaction of chiral branched benzyl allyl
imidodicarboxylates has been developed, and the reaction
is effected by [Ir(COD)Cl]2, a chiral phosphoramidite ligand
L*, and DBU in THF at room temperature. Since the reaction
is believed to proceed by the double inversion mechanism
involving the Ir-π-allyl intermediate, complete chirality
transfer has been observed. The developed stereospecific
decarboxylative allylic amidation of 7 and ent-7 is nicely
complementary to the corresponding decarboxylative allylic
amidation of 1. Since these two decarboxylative allylic
amidations can provide N-Cbz (one of the most popular
nitrogen protection groups)-protected chiral allylic amines,
they are in turn complementary to the stereoselective allylic
aminations9-12 and amidations (for the formation of N-Boc-/
Ts-/Ns-protected chiral allylic amines)13,14 developed by other
(9) Takeuchi, R.; Ue, N.; Tanabe, K.; Yamashita, K.; Shiga, N. J. Am.
Chem. Soc. 2001, 123, 9525-9534.
(10) (a) Yamashita, Y.; Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem.
Soc. 2007, 129, 7508-7509. (b) Leitner, A.; Shekhar. S.; Pouy, M. J.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 15506-15514. (c) Leitner,
A.; Shu, C.; Hartwig, J. F. Org. Lett. 2005, 7, 1093-1096. (d) Kiener, C.
A.; Shu, C.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
14272-14273. (e) Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 15614-15615. (f) Shu, C.; Leitner, A.; Hartwig, J. F. Angew. Chem.,
Int. Ed. 2004, 43, 4797-4800.
(6) An achiral catalytic system involving [Ir(COD)Cl]2 and P(OPh)3,
which was used for the allylic amination (ref 9), was not effective for the
reaction, and the addition of a base such as DBU and Et3N was fruitless.
(7) Carlsen. P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org.
Chem. 1981, 46, 3936-3938.
(8) Kokinak, S.; Leondiads, L.; Ferderigos, N. Org. Lett. 2005, 7, 1723-
1724.
Org. Lett., Vol. 9, No. 23, 2007
4803

research groups and us, and should be of particular value in
the asymmetric synthesis of chiral allylic amines and more
complex nitrogen-containing compounds.15
to Dr. K. Ditrich, BASF, Germany for a generous gift of a
chiral amine for the synthesis of ligand L*.
Supporting Information Available: Complete experi-
1
mental procedures for all new compounds and H and 13C
Acknowledgment. Financial support from the National
Institutes of Health (GM 08194) and The Welch Foundation
(AX-1534) is gratefully acknowledged. We are also grateful
spectra of the compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(11) (a) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621-1624. (b) Tissot-
Croset, K.; Polet, D.; Alexakis, A. Angew. Chem., Int. Ed. 2004, 43, 2426-
2428.
(12) (a) Weihofen, R.; Dahnz, A.; Brunner, B.; Streiff, S.; Duebon, P.;
Helmchen, G. Org. Lett. 2005, 7, 1239-1242. (b) Welter, C.; Koch, O.;
Lipowsky, G.; Helmchen, G. Chem. Commun. 2004, 896-897. (c) Lip-
owsky, G.; Helmchen, G. Chem. Commun. 2004, 116-117.
(13) Singh, O. V.; Han, H. Tetrahedron Lett. 2007, 48, 7094-7098.
OL702115H
(14) (a) Weihofen, R.; Tverskoy, O.; Helmchen, G. Angew. Chem., Int.
Ed. 2006, 45, 5546-5549. (b) Weihofen, R.; Dahnz, A.; Tverskoy, O.;
Helmchen, G. Chem. Commun. 2005, 3541-3543.
(15) For a review: Johannsen, M.; Jorgensen, K. A. Allylic amination.
Chem. ReV. 1998, 98, 1689-1708.
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