Decarboxylative allylation using sulfones as surrogates of alkanes

Article abstract of DOI:10.1021/ol801951e

(Chemical Equation Presented) α-Sulfonyl functional groups are traceless activating groups that facilitate catalytic decarboxylative allylations in high yield yet can be cleaved to allow the synthesis of simple allylated alkanes. Substrate studies suggest

Full text of DOI:10.1021/ol801951e

ORGANIC
LETTERS
2008
Vol. 10, No. 20
4657-4660
Decarboxylative Allylation using
Sulfones as Surrogates of Alkanes
Jimmie D. Weaver and Jon A. Tunge*
Department of Chemistry, The UniVersity of Kansas, Lawrence, Kansas 66045
tunge@ku.edu
Received August 20, 2008
ABSTRACT
r-Sulfonyl functional groups are traceless activating groups that facilitate catalytic decarboxylative allylations in high yield yet can be cleaved
to allow the synthesis of simple allylated alkanes. Substrate studies suggest that decarboxylation to form an r-sulfonyl anion is rate-limiting.
Furthermore, the anion is formed regiospecifically under formally neutral conditions.
Recently, Craig reported an interesting decarboxylative
sigmatropic rearrangement of allyl sulfonylacetic esters
(Scheme 1).1 For all of its utility, the need for an R-
variety of nucleophilic reaction partners can be generated
via decarboxylation, the generation of sp3-hybridized car-
banion equivalents is thus far limited to the generation of
nucleophiles with pKa’s < 25. Thus, simple unstabilized
alkane nucleophiles do not undergo facile decarboxylative
coupling.
Scheme 1
We surmised that merging the reaction chemistry of Craig
with our catalytic decarboxylative coupling methodology
would allow us to greatly extend the range of alkyl groups
that undergo decarboxylative coupling. Specifically, we
expected that the sulfone could be used to facilitate synthesis
of pronucleophiles for decarboxylative coupling, accelerate
decarboxylative coupling, and be readily cleaved to form
allylated alkanes (Scheme 2).
hydrogen inherently limits the substrates for this transforma-
tion to R-unsubstituted1a or highly activated R-sulfonyl-ꢀ-
ketoesters.1b
Our group and others have been interested in developing
related catalytic decarboxylative couplings that facilitate
CsC bond formations under neutral conditions.2,3 While a
Scheme 2
(1) (a) Bourgeois, D.; Craig, D.; King, N. P.; Mountford, D. M. Angew.
Chem., Int. Ed. 2005, 44, 618. (b) Craig, D.; Grellepois, F. Org. Lett. 2005,
7, 463.
(2) For decarboxylative couplings of ꢀ-ketoesters, see: (a) Shimizu, I.;
Yamada, T.; Tsuji, J. Tetrahedron Lett. 1980, 3199. (b) Tsuda, T.; Chujo,
Y.; Nishi, S.-i.; Tawara, K.; Saegusa, T. J. Am. Chem. Soc. 1980, 102,
6381. (c) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6, 4113. (d) Mohr,
J. T.; Behenna, D. C.; Harned, A. W.; Stoltz, B. M. Angew. Chem., Int. Ed.
2005, 44, 6924. (e) Trost, B. M.; Bream, R. N.; Xu, J. Angew. Chem., Int.
Ed. 2006, 45, 3109
.
(3) (a) Waetzig, S. R.; Tunge, J. A. J. Am. Chem. Soc. 2007, 129, 14860.
(b) Burger, E., C.; Tunge, J. A. J. Am. Chem. Soc. 2006, 128, 10002. (c)
Rayabarapu, D. K.; Tunge, J. A. J. Am. Chem. Soc. 2005, 127, 13510
.
10.1021/ol801951e CCC: $40.75
Published on Web 09/12/2008
2008 American Chemical Society

Herein, we report that palladium can be used to catalyze
the decarboxylative coupling of sulfonylacetic esters and can
be used for the coupling of R,R-disubstituted sulfones that
are not viable reaction partners for the Carroll-like rear-
rangement developed by Craig.4 Moreover, the ability to
readily cleave the sulfone allows the formal decarboxylative
coupling of simple alkyl nucleophiles (Scheme 2). This
allows us to circumvent the limitation that the nucleophilic
components in decarboxylative allylations are currently
restricted to relatively stabilized nucleophiles.2,3
Table 2. Decarboxylative Coupling of R-Sulfonyl Esters
To begin, allyl (phenylsulfonyl)acetate (1a) was chosen
as a model substrate for reaction optimization. Substrate 1a
is prepared by the straightforward dialkylation of the parent
allyl (phenylsulfonyl)acetate. Initial attempts to effect the
decarboxylative coupling using Pd(PPh3)4 in dry toluene
resulted in successful coupling; however, the reaction mixture
contained a significant amount of 3a (Table 1). Despite
Table 1. Ligand Screening
of the R-center results in a reduced yield, R-chlorination is
readily tolerated (entries 6 and 7). Interestingly, it appears
that oxidative addition of the allylic C-O bond is more
favorable than addition of the sterically hindered quaternary
C-Cl bond. Moreover, the reactions of R-chloro substrates
are somewhat accelerated and require only 3-4 h for
completion.
The decarboxylative couplings of substrates that contain
an R-aryl group are further accelerated relative to alkyl- and
chloro-substituted sulfones. This allows the reactions of
R-aryl sulfones to take place in ca. 10 min at room
temperature rather than at 95 °C, which is required for R,R-
dialkyl sulfones. Moreover, Pd(PPh3)4 is active enough to
catalyze these reactions and the loading of catalyst can be
lowered to 1-2 mol %. The fact that R-aryl-substituted
sulfones undergo more rapid decarboxylative coupling than
alkyl analogues suggests that decarboxylation of the sulfone
is rate-limiting. In such a scenario, benzylic stabilization of
the incipient anion can account for the observed rate
acceleration.
rigorous removal of water from reagents and solvent, the
generation of protonation product 3a could not be eliminated.
Thus, a series of ligands were investigated for their ability
to minimize the amount of product 3a. It was gratifying to
find that use of rac-BINAP as a ligand with Pd2(dba)3
substantially reduced the amount byproduct with a concomi-
tant increase in the yield of desired product.
Next, we turned our attention to investigating the scope
of this transformation. As can be seen in Table 2, simple
R,R-dialkyl sulfones undergo coupling to give good yields
of product; the couplings of R,R-dialkyl sulfones generally
take 12-15 h at 95 °C for completion. While fluorination
(4) For allylation of stabilized R-sulfonyl anions, see: Giambastiani, G.;
Poli, G. J. Org. Chem. 1998, 63, 9608. (b) Trost, B. M.; Warner, R. W.
J. Am. Chem. Soc. 1982, 104, 6112. (c) Tsuji, J.; Shimizu, I.; Minami, I.;
Ohashi, Y.; Sugiura, T.; Takahashi, K. J. Org. Chem. 1985, 50, 1523. (d)
Hiroi, K.; Suzuki, Y.; Kato, F.; Kyo, Y. Tetrahedron: Asymmetry 2001,
37.
To further probe whether decarboxylation is rate-limiting,
a conformationally constrained substrate 1o was prepared
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Org. Lett., Vol. 10, No. 20, 2008

Scheme 3
Scheme 4
(Scheme 3). It is known that the most stable conformation
of the R-sulfonyl anion has the lone pair situated antiperipla-
nar to the sulfonyl phenyl group (Figure 1).5 Since the cyclic
the two-step decarboxylative coupling-reduction yields are
good (Table 3). While reduction the R,R-dialkyl substrates
Table 3. Decarboxylative Coupling-Reduction
Figure 1. Qualitative correlation of rate and stability.
nature of the anion derived from 1o cannot achieve this ideal
conformation, decarboxylation is predicted to be very slug-
gish. Indeed, 1o does not undergo reaction under our standard
conditions. However, heating the catalytic mixture in a
microwave at 200 °C for 30 min did allow the isolation of
a modest yield of coupled product 2o (Scheme 3). We believe
that this result further supports our hypothesis that decar-
boxylation is rate-limiting.6
A variety of allyl groups are also compatible with the
decarboxylative coupling (Table 2). For example, a mono-
substituted allyl substrate reacts to give product with the
standard preference for the linear product (entry 13). Reaction
of disubstituted allyl alcohol derivatives also proceed in
excellent yield, but occur with poor diastereoselectivity
(entries 9-12). Lastly, dialkyl sulfones undergo decarboxy-
lative coupling in high yield without any allylation at the
activated benzylic position (Scheme 4). The fact that
regioisomerization of the R-sulfonyl anion to the more stable
anion does not take place indicates that the coupling is
regiospecific with respect to the sulfone. Similar regiospeci-
ficity is exhibited in the decarboxylative allylations of ketone
enolates.2
expectedly gives rise to a tertiary carbon center, the R-chloro
compounds undergo double reduction to provide the second-
ary carbon.
In addition to reductive cleavage, one can take advantage
of the ability to eliminate the sulfinate,8 leading to skipped
dienes (Scheme 5).
Finally, we wanted to demonstrate the ability to remove
the sulfone after using it to facilitate coupling. Toward this
end, several substrates were subjected to decarboxylative
coupling followed by reduction using Mg in methanol.7 In
each case, clean reduction of the sulfone was achieved and
Scheme 5
(5) (a) Reetz, M. T.; Hu¨tte, S.; Goddard, R. Eur. J. Org. Chem. 1999,
2475. (b) Gais, H.-J.; Gumpel, M. v.; Raabe, G.; Mu¨ller, J.; Braun, S.;
Lindner, H. J.; Rohs, S.; Runsink, J. Eur. J. Org. Chem. 1999, 1627.
(6) (a) Corey, E. J.; Lowry, T. H. Tetrahedron Lett. 1965, 803. (b) Cram,
D. J.; Wingrove, A. S. J. Am. Chem. Soc. 1963, 85, 1100. (c) Corey, E. J.;
Lowry, T. H. Tetrahedron Lett. 1965, 795.
In conclusion, palladium-catalyzed decarboxylative cou-
pling allows the synthesis of γ,δ-unsaturated sulfones. The
(7) (a) Brown, A. C.; Carpino, L. A. J. Org. Chem. 1985, 50, 1749. (b)
Lee, G. H.; Youn, I. K.; Choi, E. B.; Lee, H. K.; Yon, G. H.; Yang, H. C.;
Pak, C. S. Curr. Org. Chem. 2004, 8, 1263.
(8) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.; Rivas,
A. R.; Palomino, P. L. Tetrahedron 2000, 56, 6099.
Org. Lett., Vol. 10, No. 20, 2008
4659

sulfone facilitates (i) alkylation reactions to construct a
nucleophile for coupling and (ii) the generation of R-sulfonyl
anions under neutral conditions using decarboxylation as a
driving force. Here there is a significant advantage to our
method as compared to more traditional allylations of
sulfones that take place under strongly basic conditions and
often require toxic additives such as HMPA to achieve
formation of quaternary C-C bonds.9,10 Finally, the sulfone
can be reductively cleaved, making it a “traceless” activating
group.11 Alternatively, the sulfone can facilitate many other
reactions; in particular, the ability to couple R-chlorosulfones
suggests our reaction as a precursor to Ramberg-Backlund
olefin synthesis.
Acknowledgment. J.D.W. thanks Shelli Waetzig for
valuable assistance. We thank the National Institute of
General Medical Sciences (1R01GM079644) for support.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(9) Our method compares favorably with the allylation of a sulfone under
strongly basic conditions. See the Supporting Information for details
.
OL801951E
(10) (a) Edwards, G. L.; Sinclair, D. J. Synthesis 2005, 3613. (b) Lenihan,
B. D.; Shechter, H. J. Org. Chem. 1998, 63, 2072. (c) Kozikowski, A. P.;
Mugrage, B. B.; Li, C. S.; Felder, L. Tetrahedron Lett. 1986, 27, 4817
.
(11) Li, W.; Lam, Y. L. J. Comb. Chem. 2005, 7, 721.
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