Anomalous products from intramolecular insertion reactions of rhodium carbenoids into the α-C-H bonds of ethers

Full text of DOI:10.1021/jo970842p

4
910
J . Org. Chem. 1997, 62, 4910-4911
An om a lou s P r od u cts fr om In tr a m olecu la r
In ser tion Rea ction s of Rh od iu m
Ca r ben oid s in to th e r-C-H Bon d s of Eth er s
In order to identify the factors that influence the
outcome of the intramolecular insertion reactions of
carbenoids into the C-H bonds of allylic ethers, reactions
of the R-diazo ketone 4 were investigated (eq 2). These
reactions were performed using seven structurally di-
verse rhodium complexes as catalysts.10 Analysis of the
reaction mixtures by GC revealed that the cyclopropane
J . Stephen Clark* and Alexander G. Dossetter
Department of Chemistry, University of Nottingham,
University Park, Nottingham NG7 2RD, United Kingdom
5
was the major product in all cases and that varying
amounts of the expected 3(2H)-furanone 6 were also
produced (Table 1). In addition to the expected products
C. Adam Russell and William G. Whittingham
ZENECA Agrochemicals, J ealott’s Hill Research Station,
Bracknell, Berkshire RG42 6ET, United Kingdom
(5 and 6), significant amounts of a nonpolar product were
also detected. Although this product proved to be too
unstable to isolate and fully characterize, it was identified
as the acetal 7 on the basis of NMR analysis of partially
purified material. The acetal 7 is a very unusual product,
and as far as we are aware, there is no literature
precedent for the isolation of analogous products from
the C-H insertion reactions of metal carbenoids. How-
ever, in previous studies, one of us isolated a similar
product upon cyclization of a substrate related to the
R-diazo ketone 1.11
When electron-rich rhodium complexes were used to
catalyze the reaction (entries 1-3 and 6, Table 1), the
relative amounts of the anomalous product 7 and the
3(2H)-furanone 6 produced in each reaction were similar.
However, when complexes bearing electron-withdrawing
ligands were employed as catalysts (entries 4, 5, and 7,
Table 1) there was a significant increase in the relative
amount of the acetal 7 produced.
Received May 12, 1997
Intramolecular C-H insertion reactions of metal car-
benoids are well known and have been widely used for
the stereoselective construction of cyclopentanones, γ-lac-
tones, and lactams.1 The development of asymmetric
variants of these reactions by Doyle and others has
further extended their scope.3 Recently, Adams and co-
workers demonstrated that the intramolecular insertion
reaction of a metal carbenoid into a C-H bond adjacent
to an ether oxygen can be used for the stereoselective
construction of 3(2H)-furanones.5 This reaction has been
adapted for the synthesis of tetrahydrofurans from diazo
esters by Taber.6 In addition, Lee has shown that the
insertion of a carbenoid into a C-H bond adjacent to a
silyl ether is especially favorable.7
,2
,4
In the course of our studies directed toward the
8
synthesis of neoliacinic acid, we prepared the 3(2H)-
The Rh
2 2 3 4
(O CCH ) -catalyzed reactions of two other
furanone 2 from the R-diazo ketone 1 by generation and
subsequent intramolecular insertion of a rhodium car-
benoid into the C-H bond of an allylic ether (eq 1).
allylic ethers (8a and 8b) were also investigated (eq 3).
Although the yield for this transformation was reason-
able, cyclopropanation was a significant competing pro-
cess.2 In an attempt to improve the selectivity for C-H
insertion, we explored the cyclization reactions of some
simple substrates related to 1.
These substrates were selected in order to explore the
influence that alkene substituents have on the relative
rates of cyclopropanation and C-H insertion, and on the
amount of the anomalous C-H insertion product ob-
tained. Cyclopropanation was the predominant reaction
of both substrates, and the isolated ratio of cyclopropa-
nation product to C-H insertion products was insensitive
to the substitution pattern of the alkene. Treatment of
,9
(
1) For the first examples of intramolecular C-H insertion of metal
carbenoids to give cyclopentanones, see: (a) Wenkert, E.; Davis, L. L.;
Mylari, B. L.; Solomon, M. F.; da Silva, R. R.; Shulman, S.; Warnet,
R. J .; Ceccherelli, P.; Curini, M.; Pellicciari, R. J . Org. Chem. 1982,
4
7, 3242. (b) Taber, D. F.; Petty, E. H. J . Org. Chem. 1982, 47, 4808.
the R-diazo ketone 8a with Rh
2 2 3 4
(O CCH ) afforded the
(
2) For reviews concerning the C-H insertion reactions of metal
acetal 11a as the major C-H insertion product along
with some of the aldehyde resulting from decomposition
of this acetal. In contrast, the rhodium-catalyzed reac-
tion of the substrate 8b produced the 3(2H)-furanone 10a
as the major C-H insertion product. The result obtained
carbenoids, see: (a) Taber, D. F. In Comprehensive Organic Synthesis;
Pattenden, G., Ed.; Pergamon Press: Oxford, 1991; Vol. 3, Chapter
4
.2, p 1045. (b) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091. (c)
Doyle, M. P. In Comprehensive Organometallic Chemistry II; Hegedus,
L. S., Ed.; Pergamon Press: New York, 1995; Vol. 12, Chapter 5.2, p
4
21.
2 2 3 4
upon cyclization of the substrate 4 using Rh (O CCH )
as the catalyst is also informative (entry 1, Table 1).
These results demonstrate that the presence of alkyl
(3) Doyle, M. P. Aldrichim. Acta 1996, 29, 3 and references therein.
4) (a) McCarthy, N.; McKervey, M. A.; Ye, T.; McCann, M.; Murphy,
(
E.; Doyle, M. P. Tetrahedron Lett. 1992, 33, 5983. (b) M u¨ ller, P.;
Polleux, P. Helv. Chim. Acta 1994, 77, 645. (c) Watanabe, N.; Ohtake,
Y.; Hashimoto, S.; Shiro, M.; Ikegami, S. Tetrahedron Lett. 1995, 36,
1
491.
5) Adams, J .; Poupart, M.-A.; Grenier, L.; Schaller, C.; Ouimet, N.;
Frenette, R. Tetrahedron Lett. 1989, 30, 1749.
(10) The complexes Rh
CCF are commercially available. For the preparation of the other
catalysts used, see: (a) Hashimoto, S.; Watanabe, N.; Ikegami, S.
Tetrahedron Lett. 1992, 33, 2709 [Rh (O CCPh ]. (b) Drago, R. S.;
Long, J . R.; Cosmano, R. Inorg. Chem. 1982, 21, 2196 [Rh (O CC ].
(c) Doyle, M. P.; Bagheri, V.; Wandless, T. J .; Harn, N. K.; Brinker, D.
A.; Eagle, C. T.; Loh, K.-L. J . Am. Chem. Soc. 1990, 112, 1906 [Rh
(NHCOCH ]. (d) Dennis, A. M.; Korp, J . D.; Bernal, I.; Howard, R.
2 2 3 4 2 2 7 15 4 2 2
(O CCH ) , Rh (O CC H ) , and Rh (O -
(
3 4
)
(
6) Taber, D. F.; Song.Y. J . Org. Chem. 1996, 61, 6706.
2
2
3 4
)
(7) Lee, E.; Choi, I.; Song, S. Y. J . Chem. Soc., Chem. Commun. 1995,
2
2
3 7 4
F )
3
21.
8) Clark, J . S.; Dossetter, A. G.; Whittingham, W. G. Tetrahedron
Lett. 1996, 37, 5605.
9) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Rosati, O.
Tetrahedron 1992, 48, 9767.
(
2
-
3 4
)
(
2 3 4
A.; Bear, J . L. Inorg. Chem. 1983, 22, 1522 [Rh (NHCOCF ) ].
(11) Russell, C. A. Unpublished results.
S0022-3263(97)00842-6 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 15, 1997 4911
Ta ble 1. Rh od iu m -Ca ta lyzed Cycliza tion Rea ction s of
Sch em e 1
th e r-Dia zo Keton e 4
product ratio (isolated yields, %)c
b
entry
catalysta
5
6
7
that obtained from the reaction of the corresponding allyl
ether 4a (entry 4, Table 1), which suggests that although
the presence of a π-system is not a prerequisite for acetal
formation, it does promote this reaction.
1
2
3
4
5
6
7
Rh
Rh
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
2
2
(O
(O
(O
(O
(O
2
2
2
2
2
CCH
CC
CCPh
CCF
CC
3
H
)
15
4
78 (51)
82
46 (23)
74 (72)
77
13 (10)
13
30 (23)
8 (8)
6
9
7
)
4
4
5
24
18
17
15
26
3
)
3 4
)
7
3
F
)
4
The presence of an additional substituent in substrate
(NHCOCH
(NHCOCF
3
)
)
4
65
55
20
19
1
2b was found to increase the amount of the acetal 14b
relative to 3(2H)-furanone 13b in both reactions, but
especially in the reaction catalyzed by Rh
(O CCF
3
4
a
Catalysts Rh2(O2CCH3)4, Rh2(O2CC7H15)4, and Rh2(O2CCF3)4
are available commercially. The other catalysts were prepared
2
2
3 4
) .
b
The results above suggest that the intramolecular
insertion of metal carbenoids into C-H bonds adjacent
to ethers may proceed by a more complex mechanism
than previously recognized.6 One possible mechanistic
rationale which accounts for our data is shown in Scheme
using literature procedures (see ref 10). Relative ratio of major
products as determined by capillary GC analysis prior to purifica-
c
tion. Yields after purification by chromatography on neutral
,12
alumina (Brockmann grade 3).
Ta ble 2. Rh od iu m -Ca ta lyzed Cycliza tion Rea ction s of
1
. In this mechanism, the acetal product arises by
th e r-Dia zo Keton es 12a a n d 12b
oxygen-assisted hydride transfer to the electrophilic
carbon of the carbenoid i.13 This affords a reactive
intermediate (ii), which contains both an enolate and
oxonium ion. Intramolecular attack of the oxonium ion
by the oxygen atom of the enolate (ii or iii) then affords
the acetal v. In principle, the 3(2H)-furanone iv could
also be produced from the enolate. However, further
experiments are required to ascertain whether or not the
isolated yieldb (%)
3
(2H)-furanone iv is produced in this manner. The
entry substrate
catalysta
13
14
ratioc
intermediacy of an oxonium ion is supported by the
trends observed upon treatment of the substrates 4, 8a ,
and 8b with Rh
(O CCH ) . The highest proportion of
2 2 3 4
1
2
3
4
12a
12a
12b
12b
Rh
Rh
Rh
Rh
2
2
2
2
(O
(O
(O
(O
2
2
2
2
CCH
CCF
CCH
3
)
4
4
55
35
62
18
8
40
14
40
(96:4)
(36:64)
3
)
4
3
)
CCF
3
)
4
the anomalous product relative to the expected insertion
product is obtained upon cyclization of the R-diazo ketone
8a . This is consistent with our postulated reaction
mechanism because alkyl substituents on the alkene
would stabilize development of incipient positive charge
in the allyl system during formation of the oxonium ion.
In addition, electron-deficient catalysts favor formation
of the anomalous product. This can be accounted for by
an increase in the rate of hydride transfer to the more
electrophilic carbenoid generated and stabilization of the
rhodium enolate (ii or iii) by electron withdrawal from
the metal center.
a
Catalysts Rh2(O2CCH3)4 and Rh2(O2CCF3)4 are commercially
available. Yields after purification by chromatography on neutral
alumina (Brockmann grade 3). Relative ratio of major products
as determined by capillary GC analysis prior to purification.
b
c
substituents at the terminus of the alkene promotes
formation of the acetal product (11a /b or 7) at the
expense of the 3(2H)-furanone (10a /b or 6).
At this juncture, it was important to establish if the
formation of anomalous products is a general phenom-
enon during the intramolecular C-H insertion reactions
of ethers or is restricted to allylic ethers. It was also
desirable to explore the two C-H insertion reaction
manifolds without the complication of competitive cyclo-
propanation. Hence, the cyclization reactions of the
substrates 12a and 12b were investigated (eq 4, Table
We are currently performing further experiments in
order to fully elucidate the mechanism by which car-
benoids undergo insertion into ether C-H bonds, and the
results of these studies will be reported in due course.
Ack n ow led gm en t. We thank the EPSRC for the
award of a CASE Studentship (to A.G.D.).
2
). The cyclization of the R-diazo ketone 12a catalyzed
by either Rh
2
(O CCH or Rh (O CCF provided the
2
3
)
4
2
2
3 4
)
expected C-H insertion product 13a along with the
acetal 14a . However, the outcome of this reaction was
strongly influenced by the complex used for carbenoid
Su p p or tin g In for m a tion Ava ila ble: Details of the ex-
perimental procedures for the preparation and cyclization of
diazo ketones 4, 8a ,b, and 12a ,b and spectroscopic data for
compounds 4-14 (10 pages).
generation. When Rh
lyst, the 3(2H)-furanone 13a was isolated in 55% yield
along with 8% of the acetal 14a . However, when Rh (O
CCF was employed as the catalyst, analysis of the
crude reaction mixture by GC indicated an approximately
:2 ratio of products (13a :14a ), although roughly equiva-
2 2 3 4
(O CCH ) was used as the cata-
J O970842P
2
2
-
3 4
)
(12) (a) Taber, D. F.; Ruckle, R. E., J r. J . Am. Chem. Soc. 1986,
108, 7686. (b) Doyle, M. P.; Westrum, L. J .; Wolthuis, W. N. E.; See,
M. M.; Boone, W. P.; Bagheri, V.; Pearson, M. M. J . Am. Chem. Soc.
1
1
993, 115, 958. (c) Pirrung, M. C.; Morehead, A. T., J r. J . Am. Chem.
lent amounts of the two products were isolated. The
acetal 14a proved to be relatively stable in comparison
to the acetals obtained by cyclization of the allylic ethers
and could be isolated in good yield. The relative ratio of
the acetal 14a to the 3(2H)-furanone 13a was lower than
Soc. 1994, 116, 8991. (d) Taber, D. F.; You, K. K.; Rheingold A. L. J .
Am. Chem. Soc. 1996, 118, 547.
(13) Hydride transfer has been proposed to account for the formation
of other anomalous products during C-H insertion reactions of
rhodium carbenoids: Doyle, M. P.; Dyatkin, A. B.; Autry, C. L. J . Chem.
Soc., Perkin Trans. 1 1995, 619.