Dirhodium(II) tetrakis[methyl 2-oxaazetidine-4-carboxylate]: A chiral dirhodium(II) carboxamidate of exceptional reactivity and selectivity

Article abstract of DOI:10.1021/ol005730q

A new chiral azetidinone-carboxylate ligand for dirhodium(II) catalysts enhances reactivity toward diazo decomposition and selectivity toward cyclopropanation enabling diazomalonates, vinyldiazoacetates, and aryldiazoacetates to be effectively used with a dirhodium(II) carboxamidate catalyst.

Full text of DOI:10.1021/ol005730q

ORGANIC
LETTERS
2000
Vol. 2, No. 8
1145-1147
Dirhodium(II) Tetrakis[methyl
2-oxaazetidine-4-carboxylate]: A Chiral
Dirhodium(II) Carboxamidate of
Exceptional Reactivity and Selectivity
Michael P. Doyle,* Simon B. Davies, and Wenhao Hu
Department of Chemistry, UniVersity of Arizona, Tucson, Arizona
mdoyle@u.arizona.edu
Received February 25, 2000
ABSTRACT
A new chiral azetidinone−carboxylate ligand for dirhodium(II) catalysts enhances reactivity toward diazo decomposition and selectivity toward
cyclopropanation enabling diazomalonates, vinyldiazoacetates, and aryldiazoacetates to be effectively used with a dirhodium(II) carboxamidate
catalyst.
Dirhodium(II)1,2 carboxamidates are notoriously unreactive
toward diazo decomposition of substituted diazoacetates,
especially â-carbonyl derivatives such as diazomalonate.
With Rh2(5S-MEPY)4 (1), for example, diazo decomposition
does not occur over extended periods with dimethyl diazo-
malonate even in refluxing 1,2-dichloroethane (bp 83 °C).
Furthermore, Davies has reported that 1 failed to cause diazo
decomposition of vinyldiazoacetate 2 (Scheme 1), but
reactions with these diazo compounds.4-6 We now wish to
report a new chiral catalyst whose reactivity toward diazo
decomposition allows access to previously unreactive dia-
zocarbonyl compounds and whose enantioselectivity in
cyclopropanation suggests expanded uses for chiral dirhod-
ium(II) carboxamidates in catalytic metal carbene transfor-
mations.
Catalytic diazo decomposition of dimethyl diazomalonate
is not only a relatively difficult objective, often requiring
temperatures in excess of 80 °C, but reactions with alkenes
generally produce cyclopropane derivatives with low enan-
tioselectivities. Davies reported 7% ee for the product from
intermolecular cyclopropanation of styrene using dirhodium-
Scheme 1
(1) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From Cyclopropanes to
Ylides; Wiley: New York, 1998; Chapter 2.
(2) Doyle, M. P.; Forbes, D. C. Chem. ReV. 1998, 98, 911.
(3) Davies, H. M. L.; Huby, N. J. S.; Cantrell, W. R., Jr.; Olive, J. L.
Org. Chem. 1993, 58, 9468.
(4) Davies, H. M. L.; Doan, B. D. J. Org. Chem. 1999, 64, 8501. For
reviews of the effectiveness of chiral dirhodium(II) carboxylates with
styryldiazoacetates in cyclopropanation reactions see: (a) Davies, H. M.
L. Aldrichim. Acta 1997, 107. (b) Davies, H. M. L. Eur. J. Org. Chem.
1999, 2459.
(5) With chiral semicorrin-copper catalyst: Pique, C.; Fahndrich, B.;
Pfaltz, A. Synlett. 1995, 491.
allowed instead intramolecular rearrangement to a pyrazole.3
In contrast, the generally more reactive dirhodium(II) car-
boxylates and some copper(I) catalysts are amenable to
(6) With a chiral bisoxazoline-copper catalyst: Koskinen, A. M. P.;
Hassila, H. J. Org. Chem. 1993, 58, 4479.
10.1021/ol005730q CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/29/2000

(II) (S)-N-(arylsulfonyl)prolinate 3,7 and for intramolecular
cyclopropanation of allyl â-ketoesters the highest enantio-
meric excesses yet reported were 35-40%.5,6 Thus, we were
surprised to discover that dirhodium(II) tetrakis[methyl
2-oxaazetidine-4(S)-carboxylate], Rh2(4S-MEAZ)4 (4, Scheme
2), was an effective catalyst for cyclopropanation reactions
reported in 1996 bearing the isobutyl and benzyl esters, Rh2-
(4S-IBAZ)4 and Rh2(4S-BNAZ)4.9 The X-ray structure of
Rh2(4S-BNAZ)4 describes an unusually long Rh-Rh bond
that, we suggest, is a consequence of ligand strain on the
dirhodium(II) framework that results in higher reactivity
toward diazo decomposition relative to 1. The influence of
the ligand ester on % ee is measurable, and Rh2(4S-MEAZ)4
is generally more selective than either Rh2(4S-IBAZ)4 or Rh2-
(4S-BNAZ)4 (38% ee and 25% ee, respectively, in eq 1 with
styrene). The azetidinone ligand of 4 was prepared in 93%
yield by esterification of 2-oxaazetidine-4(S)-carboxylic acid
with diazomethane,10 and Rh2(4S-MEAZ)4 was synthesized
in 53% yield (after purification) from Rh2(OAc)4 and an
8-fold molar excess of ligand in refluxing (5 h) chloroben-
zene.11
Scheme 2
Extended applications of the azetidinone-ligated dirhod-
ium(II) catalysts have shown that they are also amenable to
diazo decomposition of vinyldiazoesters. Treatment of 8 with
Rh2((R)-DOSP)4 (3, Ar ) p-CH3(CH2)11C6H4) has recently
been shown to effect intramolecular cyclopropanation in good
yield but with low enantioselectivity (eq 2).4 In contrast, the
chiral azetidinone-ligated catalysts Rh2(4S-MEAZ)4 and Rh2-
(4S-IBAZ)4 both effected significantly higher enantio-control.
Comparable studies with the corresponding phenyldiazoac-
etate (eq 3) demonstrated an even higher level of enantio-
control. In all of these studies, % ee values were determined
by gas chromatography with baseline resolution on Chiraldex
columns. Yields were determined by weight after chroma-
tography. It is notable that use of chiral copper(I) bis-
oxazoline catalyst 1212 with 10 gave a low yield of the
intramolecular cyclopropanation product (36%), with dimer
formation being a major competing process (40% yield), and
the enantiomeric excess of the cyclopropane compound was
expectedly low.13 Of the alternative chiral dirhodium(II)
carboxamidates (Scheme 3), only Rh2(5S-MEPY)4 gave a
with dimethyl diazomalonate. Reactions occurred cleanly and
in high yield in refluxing dichloromethane. Enantiocontrol
(up to 50% ee) was the highest yet reported (eq 1), and even
for cyclopropanation of the highly reactive and normally
unselective vinyl acetate the enantiometric excess of the
cyclopropanation product was 33%. Hashimoto’s dirhodium
tert-leucinate catalyst (7)8 applied to eq 1 resulted in the
formation of 6 in 88% yield, but with only 23% ee (Z )
Ph).
Scheme 3
reasonable yield of product from reaction with 10 (46%),
the product yields from use of Rh2(4S-MEOX)4 (13) or Rh2-
(7) Davies, H. M. L.; Bruzinski, P.; Fall, M. J. Tetrahedron Lett. 1996,
37, 4133.
(8) Watanabe, N.; Ogawa, T.; Ohtake, Y.; Ikegami, S.; Hashimoto, S.
Synlett 1996, 85.
(9) Doyle, M. P.; Zhou, Q.-L.; Simonsen, S. H.; Lynch, V. Synlett 1996,
697.
(10) 1H NMR (300 MHz, CDCl3) δ 6.67 (brs, 1H), 4.20 (dd, J ) 6.0,
2.4 Hz, 1H), 3.79 (s, 3H), 3.33 (ddd, J ) 15.0, 6.0, 1.5 Hz, 1H), 3.07 (ddd,
J ) 15.0, 2.4, 1.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 171.5, 166.6,
The dirhodium(II) carboxamidate Rh2(4S-MEAZ)4 belongs
to the family of chiral azetidinone-ligated catalysts first
52.5, 47.1, 43.4; [R]23 ) -51.9 (c 0.7, CH2Cl2).
D
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Org. Lett., Vol. 2, No. 8, 2000

(4S-MPPIM)4 (14) being less than 20%, but with each of
these catalysts enantiomeric excesses for the cyclopropane
product were less than 5%.
Two additional cyclopropanation reactions exemplify the
relative advantages of the uses of these catalysts. A striking
comparison is seen in the results from diazo decomposition
of phenyldiazoacetate 15, which results in the formation of
a cyclopropane product having two adjacent quaternary
centers (eq 4). Here, carboxamidate Rh2(4S-MEAZ)4 (4) is
superior to carboxylate 3 by a wide margin, and the product
formed using this azetidinone catalyst was, after one recrys-
tallization, enantiomerically pure (>99.9% ee). A second
example is diazo decomposition of 17 (eq 5) in which
enantiocontrol from 3 is the same as that from Rh2(4S-
MEAZ)4. Here the overall low % ee values may reflect steric
influences from the terminal dimethyl and phenyl substituents
since with the styryldiazoacetate analogues corresponding
to 8, much higher % ee values for 3 were realized.4
Note that, as Davies originally observed,14 enantioselec-
tivities from the use of 3 in pentane are higher than those
for reactions performed in dichloromethane. However, as
seen from the data for eqs 3-5, the differences are highly
variable. In contrast, and reflecting the rigidity of their
structures,1 the chiral dirhodium(II) carboxamidates show no
variability in % ee values as a function of solvent.15
With regard to catalyst reactivity toward diazo decomposi-
tion, Rh2(4S-MEAZ)4 does not react with diazo esters at -78
°C. Those dirhodium(II) carboxylate catalysts employed by
Davies are active at these low temperatures.4
In summary, the chiral 2-oxaazetidine-4-carboxylate-
ligated dirhodium(II) catalysts, but especially Rh2(4S-
MEAZ)4, offers high potential to significantly broaden the
applicability of diazocarbonyl compounds for asymmetric
synthesis.
Acknowledgment. We are grateful to the National
Science Foundation and to the National Institutes of Health
(GM 46503) for their support of this research.
By analogy with results obtained by Davies,4 the absolute
configuration of 9 formed through catalysis by Rh2(4S-
MEAZ)4 or Rh2(4S-IBAZ)4 was opposite to that obtained
with Rh2(R-DOSP)4. In other words, the principal enantiomer
formed with dirhodium(II) carboxamidate catalysts having
the oxaazetidine-4(S)-carboxylate ligands had the (1R,5S)-
absolute configuration that is depicted in eq 2. Chromato-
graphic analyses on chiral GC columns show that 3 provides
products 9, 11, 16, and 18 with the same absolute configura-
tions as does 4.
Supporting Information Available: Experimental and
spectral data that include the synthesis of Rh2(4S-MEAZ)4
and diazo compounds, their characterization, and those of
the reaction products. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL005730Q
(13) Doyle, M. P.; Peterson, C. S.; Zhou, Q.-L.; Nishiyama, H. J. Chem.
Soc., Chem. Commun. 1997, 211.
(14) Davies, H. M. L.; Hutcheson, D. K. Tetrahedron Lett. 1993, 34,
7243.
(11) 13C NMR of bis-acetonitrile complex (125 MHz, CDCl3) δ 188.8,
188.2, 173.4, 173.3, 115.3, 52.9, 52.1, 51.9, 43.5, 42.6, 2.4; [R]24D ) -214
(c 0.7, CH3CN).
(12) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726.
(15) Doyle, M. P.; Zhou, Q.-L.; Charnsangavej, C.; Longoxsria, M. A.;
McKervey, M. A.; Garcia, C. F. Tetrahedron Lett. 1996, 37, 4129.
Org. Lett., Vol. 2, No. 8, 2000
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