cis-Enhanced cyclopropanation catalysts: Reaction chemistry of three isomers of Rh2[N(C6H5)COCH3]4

Article abstract of DOI:10.1016/S0040-4039(03)00222-3

The catalytic activities of three structural isomers of Rh₂[N(C₆H₅)COCH₃]₄ in cyclopropanation reactions were surveyed. These studies showed cis cyclopropanation selectivity with bulky alkenes for 2,2

Full text of DOI:10.1016/S0040-4039(03)00222-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2593–2595
cis-Enhanced cyclopropanation catalysts: reaction chemistry of
three isomers of Rh2[N(C6H5)COCH3]4
Cassandra T. Eagle,* David Farrar, Grant N. Holder, Michelle L. Hatley, Shirley L. Humphrey,
Elizabeth V. Olson, Maria Quintos, Joseph Sadighi and Tom Wideman
A. R. Smith Department of Chemistry, Appalachian State University, Boone, NC 28608, USA
Received 27 November 2002; revised 22 January 2003; accepted 22 January 2003
Abstract—The catalytic activities of three structural isomers of Rh2[N(C6H5)COCH3]4 in cyclopropanation reactions were
surveyed. These studies showed cis cyclopropanation selectivity with bulky alkenes for 2,2-cis- and 2,2-trans-
Rh2[N(C6H5)COCH3]4. © 2003 Elsevier Science Ltd. All rights reserved.
Rhodium carboxylates have been used as catalysts for
carbenoid transformations, allowing the synthesis of
the cyclopropyl unit of pyrethroid insecticides as well as
a variety of other compounds, incorporating a C1-unit
into the CꢀC bond in an alkene.1 However, in cases
where diastereomeric products are formed, these cata-
lysts typically give rise to unacceptably low diastereose-
lectivities. Electron deficient catalysts such as the
rhodium perfluorocarboxylates show essentially no
diastereoselectivity, yielding cis–trans ratios of unity.
Increasing the electron density about the rhodium cen-
ters through the use of rhodium carboxamidates yields
more selective catalysts. These catalysts, however, allow
the steric interactions of the alkene and carbene to
influence the direction of the reaction, giving rise to
excess of trans cyclopropanes.2
such as ortho substituted rhodium benzoates, have the
potential of catalyzing cyclopropane production with
excesses of cis isomers.3 Even with the bulkiest carboxy-
lates, however, the cis–trans ratios did not exceed 1.22.
The bulky equatorial ligands of the catalyst force the
substituents of the incipient cyclopropane into a cis
orientation. Imogai et al., synthesized cis-cyclo-
propanes by cyclopropenation of alkynes, followed by
catalytic hydrogenation.4 However, the lesser availabil-
ity of alkynes relative to alkenes and the additional
synthetic step render this method less than optimal.
In an effort to combine the greater selectivities of the
carboxamidate derived catalysts with the cis directing
effects of a sterically encumbered axial site, we have
turned our attention to N-substituted dirhodium tetra-
kiscarboxamidates. Varying the substituents on the
amide nitrogen provides a facile method for extensive
modification of these catalysts.
Demonceau and co-workers, in screening a variety of
rhodium carboxylates and benzoates, have shown that
catalysts with substituents in proximity of the axial site,
We report herein the application of three isomeric
N-substituted
rhodium
phenylacetamidates
(Rh2[N(C6H5)C(O)CH3]4) to diastereoselective control
of cyclopropanation. Four isomers of
Rh2[N(C6H5)C(O)CH3]4 are possible, the 2,2-trans (2,2-
t), 2,2-cis (2,2-c), 3,1 (3,1) and 4,0 (4,0), where the
numbers indicate the number of nitrogen atoms bonded
to each rhodium atom and the cis–trans designates the
orientation of the nitrogen atoms around the rhodium
(Fig. 1). We previously reported the synthesis and
characterization of 2,2-t;5 Bear and Kadish6 reported
that of 2,2-c and 3,1; while no report of 4,0 has yet
been made.7 To date, no study has been made of the
efficacy of these catalysts to control the diastereoselec-
tivity of carbenoid reactions.
Figure 1. Four Isomers of rhodium tetrakisacetamidates.
Keywords: cyclopropanation; rhodium catalysts; catalysis; rhodium
carboxamides; carbene.
* Corresponding author. E-mail: eaglect@appstate.edu
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00222-3

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C. T. Eagle et al. / Tetrahedron Letters 44 (2003) 2593–2595
The catalysts were synthesized by refluxing rhodium
acetate and an excess of N-phenyl acetamide in
chlorobenzene. The three isomers were separated by
flash column chromatography on silica gel using ethyl
acetate/hexanes.5 Cyclopropanations were conducted
by slow addition (via syringe pump) of ethyl diazoac-
etate solution to a solution containing one mole percent
catalyst and a ten fold excess of alkene. The products
were examined by gas chromatography with a mass
selective detector (see Table 1).
All three rhodium acetamidate isomers exhibit an
increase in the cis–trans ratio as the bulk of the alkene
R group (CH2=CHR) increases. This trend is in con-
trast to the decrease in cis–trans ratio expected (vide
infra) with increasing steric bulk. While the cis–trans
ratios of the cyclopropanes produced with 3,1 never
exceed unity, those produced by 2,2-c and 2,2-t did
exceed unity, with 2,2-c resulting in a cis/trans ratio of
1.78 with the bulkiest alkene.
The alkene can approach the rhodium bound carbene
with one of two possible orientations. This is shown in
Scheme 1, following a mechanistic path similar to one
put forth by Davies and co-workers.8 Our mechanism is
a modification of that of Davies and co-workers in that
the carbenoid eclipses a pair of the carboxamidate
ligands on the rhodium center. This eclipsing conforma-
tion is consistent with recent DFT calculations9 and
X-ray crystallographic structures of10 and Fenske–Hall
calculations11 on rhodium carbenoid analogs. The
alkene could approach with the R group oriented
toward the Z group of the carbene, as depicted by IA.
This approach, however, results in steric repulsion
between the R and Z groups. Alternatively, the alkene
could approach with the R group oriented away from
the carbene Z group (toward the pendent arm Y) as
depicted by IB. For unsubstituted amides (Y=H), ori-
entation IB effectively eliminates the steric repulsion.
The former approach leads to cis-cyclopropanes, while
the latter leads to trans-cyclopropanes. Consequently,
the ‘B’ route is favored over the ‘A’ route for catalysts
in which the pendent arm is the diminutive hydrogen
atom. Thus as the size of R or Z increases, the domina-
tion of route ‘B’ would also increase, resulting in ever
greater percentages of trans cyclopropanes. Indeed,
Scheme 1. Proposed mechanism for the reaction between the
rhodium stabilized carbene and an alkene.
Doyle has demonstrated this quite clearly employing
bulky diazoesters (thus, bulky Z groups rather than our
bulky R groups) to produce cyclopropanes with trans
selectivities well in excess of 90%.12
Rhodium catalysts based on N-substituted carboxami-
dates introduce another factor to the diastereoselectiv-
ity of the cyclopropanation reactions. As shown with
IB, the steric repulsion between R and Y (the amide
substituent) now competes with that between R and Z
in directing the course of the reaction. In cyclopropana-
tions catalyzed by 2,2-cis-[Rh2(N{C6H5}COCH3)4], the
RꢁY repulsion becomes the dominant factor as the size
of the R group increases. Cyclohexene is essentially a
1,2-cis-disubstituted alkene, having two ethyl groups,
with the caveat that these ethyl groups are ‘pinned’
together, thus minimizing the steric repulsion between
R and Y. Consequently, the cis/trans ratio of these
cyclopropanes is quite small (0.3, see Table 1). Indeed,
3,1 and 2,2-t show similarly small ratios. As the size of
the monosubstituted alkenes increases from cyclohex-
ene to 2,4,6-trimethyl styrene, the cis/trans ratio
increases steadily to approximately 1.8. Indeed, the
same trend is seen with the 3,1 and 2,2-t isomers,
though to a lesser degree.
Table 1. Catalyst diastereoselectivitiesa
Alkene
3,1
2,2-t
2,2-c
Cyclopropanations catalyzed with 3,1 almost certainly
occur at the least congested site, that with only one
pendant phenyl group. Even this one pendant Y group
appears to be sufficient to induce some cis-cyclopropa-
nation. As the size of the R group increases from
ethoxy to trimethylphenyl, the cis–trans ratio increases
from 0.7 to 1.0, the opposite of the decrease one expects
with increasing alkene bulk (vide supra). Clearly, even
Cyclohexene
Ethyl vinyl ether
Styrene
0.2
0.7
0.8
1.0
0.3
0.6
1.2
1.2
0.3
1.0
1.1
1.8
Trimethyl styrene
a Diastereoselectivities are reported as cis/trans ratios as determined
by GC.

C. T. Eagle et al. / Tetrahedron Letters 44 (2003) 2593–2595
2595
this single pendant Y group of the acetamidate ligand is
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This research was supported by an award from
Research Corporation and a Supplemental Award of
the Camille and Henry Dreyfus Foundation Grant
Program in Chemistry for Liberal Arts Colleges. The
authors thank Appalachian State University Research
Council. We also thank Johnson Matthey Inc. for the
loan of rhodium salts.