Catalytic asymmetric allylic C-H activation as a surrogate of the asymmetric Claisen rearrangement

Article abstract of DOI:10.1021/ol0167255

(matrix presented) Tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-prolinato]-dirhodium [Rh₂(S-DOSP)₄] catalyzed decomposition of methyl aryldiazoacetates in the presence of alkenes results in allylic C-H activation by means of a rhodium-c

Full text of DOI:10.1021/ol0167255

ORGANIC
LETTERS
2001
Vol. 3, No. 22
3587-3590
Catalytic Asymmetric Allylic C−H
Activation as a Surrogate of the
Asymmetric Claisen Rearrangement
Huw M. L. Davies,* Pingda Ren, and Qihui Jin
Department of Chemistry, UniVersity at Buffalo, State UniVersity of New York,
Buffalo, New York 14260-3000
hdaVies@acsu.buffalo.edu
Received September 7, 2001
ABSTRACT
Tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-prolinato]-dirhodium [Rh2(S-DOSP)4] catalyzed decomposition of methyl aryldiazoacetates in the presence
of alkenes results in allylic C−H activation by means of a rhodium-carbene induced C−H insertion. The resulting γ,δ-unsaturated esters are
equivalent to products that would be traditionally obtained from an asymmetric Claisen rearrangement. Highly regio- and enantioselective
C−H insertions can be achieved, and in certain cases, good diastereocontrol is also possible.
C-H activation is conceptually a very attractive strategy for
the functionalization of simple alkanes1 and for the synthesis
of complex structures.2 The development of practical methods
for C-C bond formation by means of a catalytic asymmetric
C-H activation has long been considered to be a major
challenge.1 A major breakthrough toward this goal has been
made with the discovery of the asymmetric intramolecular
C-H insertion of metal-carbenoid intermediates.3 Traditional
metal carbenoids containing one or two electron-withdrawing
groups are effective in these intramolecular C-H insertions
but are not especially useful in asymmetric intermolecular
C-H insertions.4 We have recently reported that such C-H
insertions can be obtained if rhodium-carbenoids function-
alized with both an electron-withdrawing and an electron-
donating group are used.5 These carbenoids are much more
chemoselective than the traditional carbenoids and are far
less prone to side reactions such as carbene dimer formation.
The wide variety of asymmetric C-H activations that have
been reported using this chemistry has led us to the
realization that the C-H activation process could have
general applicability to the synthetic design of complex
molecules. We have previously reported that the C-H
activation R to an O-silyl group is equivalent to an aldol
reaction,6 while C-H activation R to a N-Boc group is
equivalent to a Mannich reaction.7 Also, the allylic C-H
(e) Demonceau, A.; Noels, A. F.; Hubert, A. J.; Teyssie, P. Bull. Soc. Chim.
Belg. 1984, 93, 945. (f) Demonceau, A.; Noels, A. F.; Hubert, A. J.; Teyssie,
P. J. Mol. Catal. 1988, 49, L13. (g) Callott, H. J.; Metz, F. Tetrahedron
Lett. 1982, 23, 4321. (h) Callott, H. J.; Metz, F. NouV. J. Chimie 1985, 9,
167.
(1) For recent reviews, see: (a) Shilov, A. E.; Shul’pin, G. B. Chem.
ReV. 1997, 97, 2879. (b) Dyker, G. Angew. Chem., Int. Ed. 1999, 28, 1698.
(c) Arndsten, B. A.; Bergman, R. G. Science 1995, 270, 1970.
(2) Johnson. J. A.; Sames, D. J. Am. Chem. Soc. 2000, 122, 6321.
(3) For reviews, see: (a) Doyle, M. P.; McKervey, M. A.; Ye, T. In
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
Wiley-Interscience: New York, 1998; pp 112-162. (b) Sulikowski, G. A.;
Cha, K. L.; Sulikowski, M. M. Tetrahedron: Asymmetry 1998, 9, 3145.
(4) For representative examples of intermolecular C-H insertions, see:
(a) Scott, L. T.; DeCicco, G. J. J. Am. Chem. Soc. 1974, 96, 322. (b)
Ambramovitch, R. A.; Roy, J. J. Chem. Soc., Chem. Commun. 1965, 542.
(c) Adams, J.; Poupart, M.-A.; Greainer, L.; Schaller, C.; Quimet, N.;
Frenette, R. Tetrahedron Lett. 1989, 30, 1749. (d) Demonceau, A.; Noels,
A. F.; Hubert, A. J.; Teyssie, P. J. Chem. Soc., Chem. Commun. 1981, 688.
(5) Aryldiazoacetates and vinyldiazoacetates have been used as carbenoid
precursors in asymmetric intermolecular C-H insertions. Other diazo
compounds that generate chemoselective donor/acceptor substituted car-
benoids are alkynyldiazoacetates and heteroaryldiazoacetates. For a general
review, see: Davies, H. M. L.: Antoulinakis, E. G. J. Organomet. Chem.
2001, 617-618, 47
(6) (a) Davies, H. M. L.; Antoulinakis, E. G.; Hansen, T. Org. Lett. 1999,
1, 383. (b) Davies, H. M. L.; Antoulinakis, E. G. Org. Lett. 2000, 2, 4153.
(7) (a) Davies, H. M. L.; Hansen, T.; Hopper, D.; Panaro, S. A. J. Am.
Chem. Soc. 1999, 121, 6509. (b) Davies, H. M. L.; Venkataramani, C. Org.
Lett. 2001, 3, 1773.
10.1021/ol0167255 CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/05/2001

activation of silyl enol ethers can be considered as a surrogate
of a Michael reaction.8 In this paper we describe our
preliminary studies on allylic C-H activation of alkenes.
As illustrated in Scheme 1, the successful implementation
Scheme 2
Scheme 1
of this process would lead to γ,δ-unsaturated esters contain-
ing two stereocenters. The standard synthetic strategy to
prepare such compounds would be by the Claisen rearrange-
ment.9
The successful development of the intermolecular C-H
activation of rhodium carbenoids requires the availability of
appropriate chiral catalysts. A number of chiral catalysts have
now been examined,10 but still the most broadly applicable
catalyst is tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-proli-
nato]-dirhodium [Rh2(S-DOSP)4],11 the original catalyst that
was used in the first effective rhodium carbenoid induced
asymmetric intermolecular C-H activation.12
used by Muller for the allylic C-H activation of cyclohexene
were not optimum. Rh2(S-DOSP)4 results in much higher
enantioselectivity when hydrocarbon solvents are used.14
Thus, by running the reaction using 2,2-dimethylbutane as
solvent, the enantioselectivity in the formation of 4 was
improved to 93% ee.15 The diastereoselectivity, however,
remained poor, and cyclopropanation was still a competing
reaction. In order for this reaction to be realistically described
as a surrogate for the Claisen rearrangement, the cyclopro-
panation side reaction needs to be eliminated and the
diastereoselectivity needs to be improved.
One of the intriguing features of cyclopropanations with
aryldiazoacetates is that cyclopropanation rarely occurs with
trans disubstituted or more highly substituted alkenes.12 We
have also found that in order to control the diastereoselec-
tivity of C-H insertions at methylene positions, considerable
size differentiation between the two methylene substituents
is required.5 On the basis of these observations, the silyl
derivatives 6 were considered to be attractive substrates for
C-H activation. Rh2(S-DOSP)4 catalyzed decomposition of
5 in the presence of the TMS derivative 6a in 2,2-
dimethylbutane resulted in C-H insertion to form 7a without
any cyclopropanation. Furthermore, the diastereoselectivity
for 6a had improved to 70:30.16 An even greater improve-
ment was obtained with the tert-butyldiphenylsilyl derivative
6b, as the diastereomer ratio of 7b was 94:6 and the major
diastereomer was obtained in 95% ee.
We have previously described that the allylic C-H
activation of cyclohexadienes and cycloheptatriene by methyl
phenyldiazoacetate occurs in >90% ee.13 Muller10a has
reported the only example of asymmetric allylic C-H
activation of a simple alkene (Scheme 2). The reaction of
methyl phenyldiazoacetate (1) with cyclohexene using
CH2Cl2 as solvent resulted in a 52:48 diastereomeric mixture
of the C-H insertion products 2 as well as the cyclopropane
3. Hydrogenation of the mixture 2 resulted in the formation
of the cyclohexyl derivative 4 in 75% ee.
On the basis of our considerable experience with Rh2(S-
DOSP)4 catalysis, we realized that the reaction conditions
One of the most unexpected aspects of the C-H insertions
of aryldiazoacetates is the remarkable level of chemoselec-
tivity that is observed.5 To determine if similar chemo-
selectivity is possible for the allylic C-H insertions, the
reaction of 1-alkylcyclohexenes and other funtionalized
(8) Davies, H. M. L.; Ren, P. J. Am. Chem. Soc. 2001, 123, 2070.
(9) For a review, see: (a) Wipf, P. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 5, pp 827-874.
(10) (a) Muller, P.; Tohill, S. Tetrahedron 2000, 56, 1725. (b) Axten, J.
M.; Ivy, R.; Krim, L.; Winkler, J. D. J. Am. Chem. Soc. 1999, 121, 6511.
(11) (a) Davies, H. M. L. Eur. J. Org. Chem. 1999, 2459. (b) Davies,
H. M. L. Aldrichimica Acta 1997, 30, 105.
(14) Davies, H. M. L.; Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall, M.
J. J. Am. Chem. Soc. 1996, 118, 6897.
(12) (a) Davies, H. M. L.; Hansen, T. J. Am. Chem. Soc. 1997, 119,
9075. (b) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem.
Soc. 2000, 122, 3063.
(13) (a) Davies, H. M. L.; Stafford, D. G.; Hansen, T. Org. Lett. 1999,
1, 233. (b) Davies, H. M. L.; Stafford, D. G.; Hansen, T.; Churchill, M. R.;
Keil, K. M. Tetrahedron Lett. 2000, 41, 2035.
(15) The absolute configuration of 4 was determined to be (R) by
comparison to a known sample (see ref 12b). The absolute configuration
of the other C-H insertion products is assigned by analogy.
(16) Relative stereochemistry is readily achived on the basis of distinctive
chemical shifts in the proton NMR. For details, see: Davies, H. M. L.;
Ren, P. Tetrahedron Lett. 2001, 42, 3149.
3588
Org. Lett., Vol. 3, No. 22, 2001

onstrate the subtle balance of factors that influence the C-H
insertion. Reaction at a methyl position is not favored,
presumably because the methyl C-H bonds are simply
stronger than methylene or methine C-H bonds. The methine
C-H bond is expected to be the weakest bond, but tertiary
sites are not very accessible for the bulky rhodium carbenoid
complex.5 Even though all of the substrates have at least
two allylic methylene groups, the neighboring alkyl sub-
stituent sterically hinders attack to the nearest methylene
center, leading to the formation of a diasteromeric mixture
of a single regioisomer (9 + 10). In each case, excellent
enantioselectivity is obtained but the diastereoselectivity is
moderate.
Scheme 3
The study was further extended to acyclic alkenes as
summarized in Scheme 5. Rh2(S-DOSP)4 catalyzed decom-
cyclohexenes (8) were examined (Table 1). Even though two
or three allylic sites are present in each substrate 8, only a
single C-H insertion regioisomer (9 + 10) is produced in
virtually every case. The only exception is the reaction with
Scheme 5
Table 1. C-H Insertion of Substituted Cyclohexenes
position of 5 in the presence of 2-methyl-2-pentene (12a)
resulted in the formation of diastereomeric C-H insertion
products, 13a and 14a in a ratio of 75:25. A trace (4%) of
the primary allylic C-H insertion product was also observed.
Similar reactivity was seen when trans-3-hexene and 1,1-
diphenyl-1-butene were used as substrates. In all instances,
the major diastereomer 13 was formed with high asymmetric
induction, ranging from 86% to 96% ee.
The next substrate that was studied was R-pinene (15),
which would probe whether kinetic resolution and double
stereodifferentiation would be important factors in this
chemistry. Very impressive levels of kinetic resolution had
been previously observed in C-H insertions on substituted
pyrrolidines.7b The reaction of (+)-15 with Rh2(S-DOSP)4
at 23 °C resulted in the highly efficient formation of the
C-H insertion products 16 and 17 in 93% combined yield
and a diastereomer ratio of 98:2.17 In contrast, the reaction
of (+)-15 with Rh2(R-DOSP)4 appears to be a miss-matched
reaction; only a 62% yield of C-H insertion products 16
and 17 was obtained, and the diastereomer ratio was reversed
to 24:76. Repeating the Rh2(S-DOSP)4 catalyzed reaction of
5 at 0 °C but using (()-15 as substrate resulted in the
ethylcyclohexene 8b, where a 23:1 mixture of regioisomeric
C-H insertion products, 9b, 10b, and 11, is formed (Scheme
4). The reactions with the 1-alkylcyclohexenes 8a-d dem-
Scheme 4
(17) The determination of the relative and absolute stereochemistry for
16 and 17 is described in detail in Supporting Information.
Org. Lett., Vol. 3, No. 22, 2001
3589

formation of 16 and ent-17 in a 88:12 ratio. The major
diastereomer 16 was produced in 99% ee. On the basis of
these results, one can conclude that the kinetic selectivity
factor is around six while the high enantioselectivity for the
formation of 16 is due to a combination of the kinetic
resolution and the chiral differentiation of the catalyst.
In the Rh2(S-DOSP)4 catalyzed reaction with (()-15, reaction
of 5 with (+)-15 preferentially produces the syn product 16,
while the reaction of 5 with (-)-15, produces ent-16a as
the minor product.
The preliminary studies described herein demonstrate that
the intermolecular C-H activation by rhodium-carbenoid
induced C-H insertion is a promising new method for the
stereoselective construction of γ,δ-unsaturated esters, prod-
ucts that would be typically prepared by a Claisen rear-
rangement. In addition to the excellent regiocontrol that is
possible with this chemistry, the reaction can be extended
to systems that allow double stereodifferentiation and kinetic
resolution to occur. Future studies will be directed toward
determination of the full synthetic potential of this novel
transformation.
Scheme 6
Acknowledgment. Financial support of this work by the
National Science Foundation (CHE 0092490) is gratefully
acknowledged. We thank Tore Hansen for some preliminary
studies in this area.
Supporting Information Available: Full experimental
data of all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL0167255
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Org. Lett., Vol. 3, No. 22, 2001