Decarboxylative Claisen rearrangement reactions of allylic tosylmalonate esters

Article abstract of DOI:10.1021/ol047577w

(Chemical Equation Presented) Two different combinations of silylating agent and base are used for one-pot [3,3]-sigmatropic rearrangement- decarboxylation reactions of tosylmalonic mono(allylic) esters under mild conditions, providing the products of formal regiospecific allylation of methyl tosylacetate at the more substituted allylic terminus.

Full text of DOI:10.1021/ol047577w

ORGANIC
LETTERS
2005
Vol. 7, No. 3
463-465
Decarboxylative Claisen Rearrangement
Reactions of Allylic Tosylmalonate
Esters
Donald Craig* and Fabienne Grellepois
Department of Chemistry, Imperial College London, South Kensington Campus,
London SW7 2AZ, UK
d.craig@imperial.ac.uk
Received November 24, 2004
ABSTRACT
Two different combinations of silylating agent and base are used for one-pot [3,3]-sigmatropic rearrangement
−decarboxylation reactions of
tosylmalonic mono(allylic) esters under mild conditions, providing the products of formal regiospecific allylation of methyl tosylacetate at the
more substituted allylic terminus.
The Claisen rearrangement continues to be the focus of
considerable synthetic chemistry research effort.1 Since its
introduction in 1972,2 the Ireland silyl ketene acetal variant
Scheme 1. Synthesis of Homoallylic Sulfones by the
Decarboxylative Claisen Rearrangement Reaction
in particular has been widely used in complex target-oriented
synthesis.3 This modified process benefits from the ease of
preparation of the ketene acetal substrates and the relatively
mild conditions for the sigmatropic rearrangement. In addi-
tion, it enables overall C-allylation of carboxylic acids using
allylic alcohols as the surrogate electrophiles, with regio-
specific allylic double-bond transposition.
We recently reported4 a novel variant of the Ireland-
Claisen rearrangement reaction in which R-tosyl silyl ketene
acetals formed in situ from allylic tosylacetates 1 in the
presence of N,O-bis(trimethylsilyl)acetamide (BSA) and
potassium acetate undergo [3,3]-sigmatropic rearrangement
followed by acetate-induced desilylation-decarboxylation in
situ to provide homoallylic sulfones 2 (Scheme 1).5,6 During
the course of this study, we became interested in examining
the effect on reactivity of introducing additional electron-
withdrawing groups on the R-position of substrates 1.7
Specifically, we wished to look at the decarboxylative
Claisen rearrangement (dCr) reactions8 of methyl allyl esters
(1) For recent reviews on Claisen and related rearrangements, see: Martin
Castro, A. M. Chem. ReV. 2004, 104, 2939-3002.
(2) (a) Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94, 589-
5898.
(3) For review on the Ireland-Claisen rearrangement: (a) Pereira, S.;
Srebnik, M. Aldrichimica Acta 1993, 26 (1), 17-29. (b) Chai, Y.; Hong,
S.; Lindsay, H. A.; McFarland, C.; McIntosh, M. Tetrahadron 2002, 58,
2905-2928.
(4) Bourgeois, D.; Craig, D.; King, N. P.; Mountford, D. M. Angew.
Chem., Int. Ed. 2005, 44, 618-621.
(5) For the first report of a stepwise Ireland-Claisen rearrangement
followed by decarboxylation in a separate step, see: Davidson, A. H.;
Eggleton, N.; Wallace, I. H. J. Chem. Soc., Chem. Commun. 1991, 378-
380.
(6) For a related Carroll-type reaction, see: Hatcher, M. A.; Posner, G.
H. Tetrahedron Lett. 2002, 43, 5009-5012.
10.1021/ol047577w CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/11/2005

of tosylmalonic acid,9 which would in principle provide a
concerted, regiospecific alternative to the stepwise, regio-
selective metal-catalyzed allylic alkylation reactions of
methyl tosylacetate under basic conditions.10 Herein we
compare the effectiveness of several alternatives to the
BSA-KOAc reagent system for the decarboxylative Claisen
rearrangement reaction of methyl allyl tosylmalonates and
show that [3,3]-sigmatropic rearrangement is a viable strategy
for the formal regiospecific allylation of methyl 2-tosyl-
acetate.
Table 1. Preparation of Tosyl-Substituted Allylic Malonate
Esters 4a-j
The tosyl-substituted allylic malonate esters 4a-j required
for this study were prepared by alkylation of tosyl fluoride11
with an excess of the potassium salt of the corresponding
allylic malonate esters 3a-j12 in DMSO (Table 1).13,14
Expecting that the presence of the additional methyl ester
group would lower the temperature required for the dCr
reactions to proceed, the tosyl-substituted cinnamyl malonate
ester 4a was submitted initially to the conditions previously
described4 (1 equiv of BSA and 0.1 equiv of KOAc), at room
temperature (Table 2, entry 1). The carboxymethyl-substi-
tuted homoallylic sulfone 5a was formed in high yield (81%).
No reaction was observed when 0.1 equiv of BSA was
employed. Substitution of KOAc with Et3N (0.1 equiv) also
gave 5a (entry 2). This behavior was in marked contrast to
that of monoesters 1, which had undergone rearrangement
but not decarboxylation on exposure to BSA-Et3N.4 This
prompted a study of the reaction of 4a with several silylating
agent-base combinations. With chlorosilanes in place of
BSA, zero or low levels of conversion into 5a were observed
(entries 3 and 4). However, treatment of 4a with silyl
triflates15 (2.1 equiv) and Et3N or DBU (2.1 equiv) gave good
(7) For Ireland-Claisen rearrangements of silyl ketene acetals derived
from simple methyl allyl malonates involving desilylation and decarboxy-
lation in a separate step, see: Fehr, C.; Galindo, J. Angew. Chem., Int. Ed
2000, 39, 569-573.
(8) For recent examples of regio- and enantioselective metal-catalyzed
decarboxylative allylation reactions, see: Burger, E. C.; Tunge, J. A. Org.
Lett. 2004, 6, 2603-2605, 4113-4115.
yields of 5a, much more rapidly than the BSA-KOAc
system (entries 6-8).
(9) For high-temperature thermal decarboxylative Claisen rearrangement
of â-ketoester-derived silyl enol ethers involving silatropic rearrangement,
see: Coates, R. M.; Sandefur, L. O.; Smillie, R. D. J. Am. Chem. Soc.
1975, 97, 1619-1621. We thank a referee for bringing this article to our
attention.
Table 2. Decarboxylative Claisen Rearrangement of 4a at
Room Temperature
(10) For metal-catalyzed allylic alkylation reactions of methyl 2-tosyl-
acetate, see: (a) Godleski, S. A.; Villhauer, E. B. J. Org. Chem. 1984, 49,
2246-2252. (b) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J. Am. Chem.
Soc. 1985, 107, 2033-2046. (c) Masumaya, Y.; Hirai, H.; Kurusu, Y.;
Segawa, K. Bull. Chem. Soc. Jpn. 1987, 60, 1525-1526. (d) Masumaya,
Y.; Mitsunaga, Y.; Kurusu, Y.; Segawa, K. Bull. Chem. Soc. Jpn. 1987,
60, 3431-3432.
(11) (a) Hirsh, E.; Hu¨nig, S.; Reissig, H.-U. Chem. Ber. 1982, 115, 399-
401. (b) Kende, A. S.; Mendoza, J. S. J. Org. Chem. 1990, 55, 1125-
1126. (c) Sandanayaka, V. P.; Zask, A.; Venkatesan, A. M.; Baker, J.
Tetrahedron Lett. 2001, 42, 4605-4607.
(12) Allylic malonate esters 3a-j were prepared by a two-step se-
quence: malonic acid monomethyl ester was prepared by treatment of
Meldrum’s acid with methanol (Brooks, D. W.; Castro de Lee, N.; Peevey,
R. Tetrahedron Lett. 1984, 25, 4623-4626); subsequent condensation with
the allylic alcohol in the presence of DCC and DMAP provided 3a-j (see
Supporting Information).
(13) A dramatic drop in yield was observed using less than 4 equiv of
the potassium salt of allylic malonate esters 3a-j or using less concentrated
reaction mixtures. The excess allylic malonate ester 1a-j may easily be
recovered after purification by chromatography (see Supporting Informa-
tion).
entry silylating agent (equiv) base (equiv)
time
yielda
1
2
3
4
5
6
7
8
BSA (1)
BSA (1)
TMSCl (2.1)
TBDMSCl (2.1)
TBDMSOTf (1.2)
TBDMSOTf (2.1)
TBDMSOTf (2.1)
TMSOTf (2.1)
KOAc (0.1) 4 h
81%
59%
9%
Et3N (0.1)
DBU (2.1)
DBU (2.1)
DBU (1.2)
DBU (2.1)
Et3N (2.1)
DBU (2.1)
15 h
22 h
24 h
18 h
15 min
30 min
0%
43%
83%
73%
1 h 30 min 80%
a Isolated yield.
(14) No reaction was observed using LDA in THF at -78 °C.
Comparable yields were obtained using NaH at 50 °C instead of t-BuOK
at room temperature.
Next, a more thorough comparison of the two dCr reagent
systems was carried out. Substrates 4a-j were subjected to
464
Org. Lett., Vol. 7, No. 3, 2005

the two contrasting sets of conditions. Also, several of the
substrates (4g,h,j) underwent rearrangement-decarboxyla-
tion with a high degree of stereoselectivity.16 Table 3
summarizes the results.
Table 3. Decarboxylative Claisen Rearrangement Reaction of
Tosyl-Substituted Allylic Malonate Ester 4a-j
As only rearranged and decarboxylated products 5 were
isolated from these transformations (even when using BSA
in conjunction with nonnucleophilic Et3N), it seems likely
that the silyl esters formed initially in the [3,3]-sigmatropic
rearrangement process lose CO2 by a mechanism other than
desilylation-decarboxylation.4 We speculate that silatropic
rearrangement17 of the silyl esters gives a new silyl ketene
acetal, which undergoes hydrolysis during isolation/purifica-
tion (Scheme 2). This explanation is consistent with the need
for 1 equiv of silylating agent, since it is effectively
consumed by formation of the silyl ketene acetal derivatives
of the isolated products 5.
Scheme 2. Proposed Mechanism for the Decarboxylative
Claisen Rearrangement Reaction Mediated by the Trialkylsilyl
Triflate/Amine Combination
In summary, these studies show that the dCr reaction
provides an effective, regiospecific alternative for metal-
catalyzed allylation of methyl tosylacetate. Present studies
are directed toward probing the relative rates of monorear-
rangement of unsymmetrical bis(allylic) tosylmalonates. The
results of these investigations will be reported in due course.
Acknowledgment. This research was supported by the
European Community Human Potential program (Marie
Curie Individual Fellowship) under Contract HPMT-CT-
2002-02015.
a Method A: BSA (1.0 equiv), KOAc (0.1 equiv), CH2Cl2, rt, 4-15 h.
Method B: TBDMSOTf (2.1 equiv), DBU (2.1 equiv), CH2Cl2, rt, 15-30
min. b Isolated yield. c No reaction was observed at room temperature, but
5c was isolated in 4% yield after reaction in CH2Cl2 under reflux for 18 h.
d “Anti” product. e Extensive decomposition was observed.
Supporting Information Available: Experimental pro-
cedures, full characterization of compounds 4a-j and 5a-
c,e-j, and copies of 1H NMR and 13C NMR spectra of 3a-
j, 4a-j, 5a-c,e-j. This material is available free of charge
via the Internet at http://pubs.acs.org.
the BSA-KOAc (respectively 1 and 0.1 equiv; method A)
and TBDMSOTf-DBU (each 2.1 equiv; method B) condi-
tions. In most cases, 5 was formed in similar yields under
OL047577W
(16) Structures of 5g,h,j were assigned by comparison of their NMR
spectra with those of related compounds. For 5g,h see: ref 3. For 5j, see:
Ireland, R. E.; Maienfisch, P. J. Org. Chem. 1988, 53, 640-651.
(17) Slutsky, J.; Kwart, H. J. Am. Chem. Soc. 1973, 95, 8678-8685.
(15) Kobayashi, M.; Masumoto, K.; Nakai, A.; Nakai, T. Tetrahedron
Lett. 1996, 37, 3005-3008.
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