Synthesis of allyl selenides by palladium-catalyzed decarboxylative coupling

Article abstract of DOI:10.1039/b806949b

This communication details the Pd-catalyzed decarboxylation of selenocarbonates; use of a chiral nonracemic catalyst affords enantioenriched allyl selenides which undergo stereospecific [2,3]-sigmatropic rearrangements to form enantioenriched allylic amines and chlorides. The Royal Society of Chemistry.

Full text of DOI:10.1039/b806949b

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COMMUNICATION
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Synthesis of allyl selenides by palladium-catalyzed decarboxylative
couplingw
Shelli R. Waetzig and Jon A. Tunge*
Received (in College Park, MD, USA) 25th April 2008, Accepted 2nd May 2008
First published as an Advance Article on the web 10th June 2008
DOI: 10.1039/b806949b
This communication details the Pd-catalyzed decarboxylation of
selenocarbonates; use of a chiral nonracemic catalyst affords
enantioenriched allyl selenides which undergo stereospecific
[2,3]-sigmatropic rearrangements to form enantioenriched allylic
amines and chlorides.
ð1Þ
ð2Þ
Alkyl selenides are versatile synthetic intermediates that un-
dergo well-known 1,2-elimination upon oxidation or reduction
upon treatment with radical initiators.1 Furthermore, allyl
selenides undergo [2,3]-sigmatropic rearrangements under a
method is also appealing since the only byproduct generated is
gaseous CO2. Toward this end, allyl selenocarbonate 2 was
synthesized from allylic alcohol 1 and treated with Pd(PPh3)4
in CH2Cl2 at room temperature (eqn (3)). The mixture cleanly
converted to the desired allyl selenide (3), which was isolated
in 82% yield.
variety of conditions to afford allylic amines,2 chlorides,3 and
alcohols.4 Given the stereospecific nature of the [2,3]-sigma-
tropic rearrangement, one should be able to access enantio-
enriched allylic amines, chlorides, and alcohols, provided that
the corresponding C-chiral enantiopure allyl selenides are
available.5 Although the addition of chiral selenium electro-
philes has been well established in the literature,6 a limited
number of examples describe catalytic, asymmetric C–Se bond
formation using nucleophilic selenium sources.7 This is rather
surprising given the numerous reports on asymmetric
allylation of heteroatom nucleophiles.
ð3Þ
Upon successful decarboxylation of allyl selenocarbonate 2,
various substituted allyl selenocarbonates were synthesized
and treated under the conditions of catalysis (Table 1). While
reaction of unsubstituted selenocarbonate 4a afforded the allyl
selenide 5a in only moderate yield (49%), substituted allyl
selenides were obtained in good to excellent yields. As ex-
pected for a reaction involving p-allyl palladium intermedi-
ates, the reactions of monosubstituted allyl selenocarbonates
were highly regioselective and provided linear allylation pro-
ducts (5c, 5e). Finally, the stereochemical course of the reac-
tion was probed using racemic cis-allyl selenocarbonate 4g.
Overall retention of configuration was observed, providing the
cis-substituted allyl selenide (5g) in high yield. This type of
stereospecificity has been demonstrated previously with other
soft nucleophiles, and is indicative of a double-inversion
mechanism.12
Several methods are known for the synthesis of racemic allyl
selenides,8 including the palladium-catalyzed addition of sele-
nium nucleophiles to allylic acetates.9 These methods, how-
ever, employ strong reducing agents, such as SmI2 (eqn (1)), or
require transmetalation from a stoichiometric toxic tin reagent
(PhSeSnMe3, eqn (2)). Furthermore, our attempts to repro-
duce the synthetic protocol for the synthesis of 2-cyclohexenyl
phenylselenide using SmI2 were unsuccessful.10
The success of these reactions suggested that decarboxyla-
tive selenylation was a potentially viable coupling strategy for
the asymmetric synthesis of allyl selenides. To begin, seleno-
carbonate 2 was used as a model substrate to screen chiral
ligands for their ability to induce enantioselectivity in the
reaction (Table 2). While bidentate P–N ligands failed to
promote the reaction (entries 1, 2), the Trost ligand, and
variants thereof, provided products with varying enantioselec-
tivities (entries 3–5). A survey of solvents (entries 6–8) revealed
that the (S,S)-Naphthyl-Trost ligand in toluene provided the
highest enantioselectivity (89% ee). It was noted, however,
that the reactions had problems with incomplete conversion;
Previously, we have utilized Pd-catalyzed decarboxylation as a
tool for carbon–carbon and carbon–heteroatom bond forma-
tion.11 In these reactions decarboxylation replaces transmeta-
lation, thus we expected that decarboxylative coupling would
allow us to avoid the use of SmI2 or PhSeSnMe3 reagents
that were previously required for allylic selenylation.9 Such a
Department of Chemistry, The University of Kansas, 2010 Malott
Hall 1251 Wescoe Hall Drive, Lawrence KS, USA.
E-mail: tunge@ku.edu
w Electronic supplementary information (ESI) available: Spectra and
characterization of all new compounds. See DOI: 10.1039/b806949b
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Table 1 Palladium-catalyzed decarboxylative selenylation
containing ligands have been shown to coordinate transition
metals as ligands and we thought it might be possible that the
product could inhibit the reaction by binding to the catalyst.13
This could explain slower rates at higher conversions, and
could affect enantioselectivity by creating some achiral cata-
lyst. However, product inhibition was not a problem when the
reactions were run with racemic catalyst.
Allyl
Yield (%)
49a
Allyl
Yield (%)
83
Alternately, the partial conversion could be attributed to a
kinetic resolution of the racemic substrate. To test for this
latter mechanism, selenocarbonate 2 was treated under our
standardized reaction conditions (entry 7). The reaction com-
pletely stopped at 53% conversion, at which time the starting
material and the product were both isolated (eqn (4)). The
product allyl selenide was afforded in 46% yield and 89% ee.
The unreacted selenocarbonate (S)-2 was isolated with high
enantiopurity (92% ee), showing that, indeed, an efficient
kinetic resolution was taking place. With the ee of the reactant
and the conversion of the reaction, the selectivity factor (S)
calculated for the decarboxylative selenylation is 31.9, which is
characteristic of a quite efficient kinetic resolution. In fact,
similar kinetic resolutions have been demonstrated for allyla-
tions of allylic carbonates and acetates with other soft nucleo-
philes, where allylic carbonates in the presence of sulfur
nucleophiles have shown very similar conversions and selec-
tivity factors.12,14 However, this is the first example that
utilizes selenium nucleophiles for the palladium-catalyzed
kinetic resolution of allyl-LG species.
66
72c
99
95b
90
a
b
2.5 mol% catalyst used. Isolated linear product with E : Z ratio =
c
3.9 : 1. E/Z = 10 : 1.
the reactions often reached B50% conversion within the first
2 h followed by a drastic decrease in rate, such that the
reaction would only reach B55–80% completion after 24 h.
Furthermore, forcing the reaction to proceed past 50% con-
version by heating the reaction or extending the reaction time
had a deleterious effect on the enantioselectivity (entries 9, 10).
The low conversions and high enantioselectivities were
initially attributed to two possible scenarios. First, selenium-
ð4Þ
Table 2 Optimization of enantioselective allylic selenylation
Treatment of selenocarbonate (ꢁ)-4g under the same condi-
tions resulted in the identical conversion as (ꢁ)-2 (eqn (5)).
The enantioselectivities obtained for the starting material and
products were higher than those observed for unsubstituted
cyclohexenyl selenocarbonate 2. The selectivity factor calcu-
lated for this reaction was remarkably high at 80, showing that
just the addition of the ester functional group had a dramatic
impact on the reaction.
Entry
Ligand
Solvent
Conv. (%)
ee 3 (%)
1
2
3
4
5
6
7
8
9
10
tBu-Phox
Quinap
Trost
Np-Trost
Bicyclic-Trosta
Np-Trost
Np-Trost
Np-Trost
Np-Trost
Np-Trost
C6D6
C6D6
C6D6
C6D6
C6D6
THF
Tol-d8
CD2Cl2
C6D6
Tol-d8
12
0
78
60
88
50
54
ND
N/A
28
73
14
69
89
60
34
ð5Þ
With the ability to synthesize enantioenriched allyl selenides, it
seemed that the transformation of the allyl selenides to the
corresponding allylic chlorides and amines via a [2,3]-sigma-
tropic rearrangement to give enantioenriched allylic amines
and chlorides would be also be synthetically useful. Sharpless
published a report in 1979 on the oxidation of achiral allyl
selenides with N-chlorosuccinimide (NCS) or Chloramine-T.3
Although the reported yields for the allylic aminations are
92b
100c
63d
69
a
b
c
d
See ESIw for ligand structure. Run at 50 1C. Run for 48 h. Run
at 0 1C.
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relatively low, these reactions are known to proceed through a
cyclic transition state, which should facilitate the transfer of
chirality to the products.15 While this principle has been
demonstrated with related aminations of chiral allyl selenides,
the authors distinctly point out that the stereochemical integ-
rity of the allylic rearrangement ‘‘must await methods for the
preparation of stereohomogenous allylic selenides.’’2
strating that chiral, nonracemic allylic amines and chlorides
can be readily obtained by a [2,3]-sigmatropic rearrangement
from a common allyl selenide precursor.
We thank the Petroleum Research Fund of the American
Chemical Society (44453-AC1) and the National Science
Foundation (CHE-0548081) for funding.
To this end, we treated the isolated enantioenriched allyl
selenide (R,R)-5g under the conditions reported for allylic
amination (eqn (6)).2 We were pleased to find the reaction
provided the desired allylic amine in good yield and very high
enantioselectivity. The conservation of enantiomeric excess
(cee) of this reaction was 96% and absence of the correspond-
ing diastereomer supports the hypothesis of a highly ordered
cyclic transition state for this stereospecific reaction.
Notes and references
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Oxford, New York, 1999Organoselenium Chemistry: Modern
Developments in Organic Synthesis, ed. T Wirth, Springer, Berlin,
2000.
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7154; H. J. Reich, J. Org. Chem., 1975, 40, 2570.
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2000, 208, 201.
6. D. M. Browne and T. Wirth, Curr. Org. Chem., 2006, 10, 1893;
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Tetrahedron, 1999, 55, 1, and references therein.
ð6Þ
Enantioselective formation of carbon–halogen bonds is an
important synthetic challenge. While the enantioselective
halogenation of ketones via chiral enolates or chiral halogen-
ating reagents is well known,16 the enantioselective halogena-
tion of less activated allylic systems still represents an obstacle
in synthesis. In light of the high retention of stereochemistry
for the [2,3]-sigmatropic rearrangement to form allylic amine
(S,S)-6g, we were curious if similar chirality transfer would be
possible from a chloroselenide derived from NCS. Therefore,
allyl selenide (R,R)-5g was treated with 1 equivalent of NCS in
CD2Cl2. We were pleased to find that mixture provided clean
conversion of allyl selenide (R,R)-5g to the allylic chloride in
1 h at room temperature (eqn (7)). Due to the volatility of the
allylic chloride, the yield was determined by 1H NMR spectro-
scopy based on an internal standard. Following reaction
completion, the reaction mixture was subjected to chiral-phase
gas chromatography, where the product was found to have
84% ee and a diastereomeric ratio of 16 : 1 in favor of the
desired product.
7. M. Iwaoka and S. Tomoda, Top. Curr. Chem., 2000, 208, 55.
Optically active alcohols can be converted to optically active alkyl
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10. See ESIw for experimental details.
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ð7Þ
In conclusion, we have developed a palladium-catalyzed
decarboxylative selenylation reaction that affords allyl
selenides in good yields. Employing a chiral palladium catalyst
results in the kinetic resolution of selenocarbonates to provide
both the allyl selenide and selenocarbonate in high enantio-
selectivities. The synthesis of enantioenriched allyl selenides
allows for further manipulations of these products, demon-
ꢀc
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Chem. Commun., 2008, 3311–3313 | 3313