Dirhodium tetracarboxylates derived from adamantylglycine as chiral catalysts for enantioselective C-H aminations

Article abstract of DOI:10.1021/ol061742l

(Chemical Equation Presented) The dirhodium tetracarboxylate, Rh ₂(S-TCPTAD)₄, derived from adamantylglycine, is an effective chiral catalyst for both inter- and intramolecular C-H aminations.

Full text of DOI:10.1021/ol061742l

ORGANIC
LETTERS
2006
Vol. 8, No. 22
5013-5016
Dirhodium Tetracarboxylates Derived
from Adamantylglycine as Chiral
Catalysts for Enantioselective C
−H
Aminations
Ravisekhara P. Reddy and Huw M. L. Davies*
Department of Chemistry, UniVersity at Buffalo,
State UniVersity of New York, Buffalo, New York 14260-3000
hdaVies@acsu.buffalo.edu
Received July 16, 2006
ABSTRACT
The dirhodium tetracarboxylate, Rh2(S-TCPTAD)4, derived from adamantylglycine, is an effective chiral catalyst for both inter- and intramolecular
H aminations.
C
−
The development of practical catalytic methods for the
functionalization of unactivated C-H bonds is an area of
intense current interest.1 Considerable advances have been
made in recent years in many types of transformations, such
as C-H oxidation,2 C-H borylation,3 C-H alkylation,4
C-H arylation,5 and C-H amination.6 C-H amination has
been greatly enhanced due to improved methods for the
synthesis of rhodium nitrene intermediates (Scheme 1). The
Scheme 1. Generation of Rh Nitrene Intermediates
(1) (a) Sames, D.; Godula, K. Science 2006, 312, 67. (b) Davies, H. M.
L.; Beckwith, E. J. Chem. ReV. 2003, 103, 2861. (c) Doyle, M.; McKervey,
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Compounds: From Cyclopropanes to Ylides; Wiley: New York, 1998. (d)
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1999; pp 83-94.
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E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2003, 125, 9578. (c) Dick, A. R.;
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A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439. (e) Sigman, M. S.;
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Anderson, K. S.; Hillmyer, M. A. J. Am. Chem. Soc. 2005, 127, 767.
direct rhodium-catalyzed decomposition of azides is not an
effective method for generating rhodium nitrenes. The first
generally applicable method, pioneered by Breslow, was to
use preformed iodinanes.7 Che8 and Du Bois9 discovered an
improved process, in which the iodinane is generated in situ,
thereby opening up the chemistry to a range of primary amide
and sulfonamide substrates. The synthetic potential of this
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process has been beautifully illustrated by Du Bois in the
total synthesis of complex natural products such as tetro-
dotoxin10 and saxitoxin.11 Recently, Lebel reported that
tosyloxycarbamates can be used as a nitrene precursor, and
this approach also has great synthetic potential.12
During our studies on enantioselective intermolecular C-H
alkylation, we discovered that adamantane could be readily
functionalized, and we have applied this chemistry to the
synthesis of the adamantylglycine catalyst Rh2(S-PTAD)4
(Scheme 2).18 This catalyst tends to give higher enantiose-
The next natural extension for the C-H amination field
is the development of effective chiral catalysts for this type
of transformation. Chiral copper catalysts were successfully
applied to intermolecular aziridination,13 but dirhodium
tetracarboxylates are the most widely used catalysts for the
C-H amination chemistry.6,7,9 Several chiral catalysts have
been applied using preformed iodinanes as the nitrene
precursor.14 One of the most notable catalysts has been the
rhodium phthalimide catalyst developed by Hashimoto, of
which Rh2(S-TCPTTL)4 is considerably better at asymmetric
C-H amination than the unchlorinated analogue Rh2(S-
PTTL)4.15 The related catalyst Rh2(S-NTTL)4 developed by
Mu¨ller (Figure 1) also shows promise in this chemistry.16
Scheme 2. Synthesis of Rh2(S-PTAD)4 and Rh2(S-TCPTAD)4
lectivity than Rh2(S-PTTL)4 in carbenoid reactions.18 There-
fore, we became interested to see how effective Rh2(S-
PTAD)4 and its chlorinated derivative Rh2(S-TCPTAD)4
would be in C-H amination reactions.
The new catalysts were tested under the Che-Du Bois
conditions where the nitrene precursors are generated in situ.
As can be seen in the standard reaction for functionalizing
indane, Rh2(S-TCPTAD)4 was the most effective catalyst
studied (94% ee) (Table 1). Our traditional catalyst for
Table 1. Comparison of Chiral Dirhodium Catalysts
Figure 1. Chiral dirhodium catalysts.
catalyst
Rh2(OAc)4
yield, %
ee, %
45
95
86
88
81
49
25
56
12
Rh2(S-TCPTAD)4
Rh2(S-PTAD)4
Rh2(S-TCPTTL)4
Rh2(S-PTTL)4
Rh2(S-DOSP)4
Rh2(S-TBSP)4
Rh2(S-NTTL)4
Rh2(S-MEOX)4
94
59
79
Other effective catalysts have been manganese salen catalysts
developed by Katsuki14e,f and manganese porphyrin catalysts
developed by Che.8,14b-g Che has also demonstrated that a
ruthenium porphyrin catalyst is effective in C-H aminations
where the iodinane is generated in situ.17
43
(-) 11
(-) 31
34
(4) (a) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc.
Chem. Res. 2005, 38, 349. (b) Klei, S. R.; Tan, K. L.; Golden, J. T.; Yung,
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Kakiuchi, F. Acc. Chem. Res. 2002, 35, 826.
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Soc. 2006, 128, 78. (b) Li, Z.; Li, C. J. Am. Chem. Soc. 2006, 128, 56. (c)
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10
carbenoid chemistry, Rh2(S-DOSP)4, resulted in low enan-
tioselectivity (11% ee) as did Rh2(S-MEOX)4 (10% ee) and
Rh2(S-NTTL)4 (34% ee). As expected from the literature,15
Rh2(S-TCPTTL)4 gave relatively high asymmetric induction
(79% ee) but did not match the results with Rh2(S-
TCPTAD)4.
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Org. Lett., Vol. 8, No. 22, 2006

The Rh2(S-TCPTAD)4-catalyzed reactions were then ex-
amined with a range of substrates, and the results are
summarized in Table 2. The most efficient conditions for
the reaction temperature. The absolute configurations of 5a,
7a, and 7c were shown to be (R) by comparison of optical
rotation with literature values.15 The absolute configurations
of the other products are tentatively assigned to be (R) by
analogy.
Selective C-H amination could be very useful for the
rapid synthesis of pharmaceutical agents. An illustration of
this potential is the enantioselective synthesis of the (R)
enantiomer of the anti-Parkinson agent Rasagiline (9) shown
in Scheme 3.19 Alkylation of the sulfonamide 5a with
Table 2. Rh2(S-TCPTAD)4-Catalyzed Intermolecular C-H
Aminationa
Scheme 3. Synthesis of Rasagiline
propargyl bromide to form 8, followed by removal of the
nosyl group in 8 using Fukuyama’s protocol,20 readily
generates 9. Both enantiomers of Rh2(TCPTAD)4 can be
accessed,18 and so, in principle, either enantiomer of 9 could
be selectively formed.
The Rh2(S-TCPTAD)4-catalyzed enantioselective C-H
amination can be extended to intramolecular reactions as
illustrated in Table 3. Lebel’s method12 was used for
generating the nitrene precursors in these examples. Reaction
Table 3. Rh2(S-TCPTAD)4-Catalyzed Intramolecular C-H
Aminationa
a General procedure: A solution of PhI(OAc)2 (1.5 equiv) in trifluoro-
toluene (10 mL) was added over 30 min to a solution of substrate (5 equiv),
NsNH2 (1 equiv), MgO (2.3 equiv), and the catalyst (2 mol %) in
trifluorotoluene (15 mL) at 23 °C. The reaction mixture was sirred for 3 h
and then filtered to remove the precipitated solids. The filtrate was
concentrated, and the residue was purified by column chromatography.
carrying out these reactions were addition of a solution of
PhI(OAc)2 in trifluorotoluene to a solution of the substrate
(5 equiv), NsNH2, MgO, and the catalyst in trifluorotoluene
at room temperature. This resulted in the formation of the
products in good yields (65-92%) and reasonable enanti-
oselectivities (62-78%). An excess of the substrate is
optimal for these reactions as the efficiency of the reaction
decreases considerably if less trapping agent is available.
Because of solubility issues associated with the reagents used
in this study, the reaction could not be improved by lowering
a General procedure: K2CO3 (1.5 mmol, 3 equiv) and the catalyst (2
mol %) were added to a solution of N-tosyloxycarbamate (0.5 mmol) in
dichloromethane (10.0 mL) at 23 °C. The resulting suspension was stirred
for 4 h. The mixture was filtered to remove the precipitate, and the solvent
was removed under vacuum. The product was then purified by column
chromatography.
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Org. Lett., Vol. 8, No. 22, 2006
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of the N-tosyloxycarbamates 10 generated the oxazolidinones
11 in good yields. With acyclic substrates 10a-c, the
enantioselectivity was quite reasonable (79-82% ee) but the
C-H amination of the cyclic substrate 10d was less
enantioselective (43% ee).
In summary, these studies demonstrate that Rh2(S-
TCPTAD)4 is an effective catalyst for enantioselective C-H
amination. Further studies are in progress to refine the
structure of this adamantyl-derived catalyst to achieve even
higher enantioselectivity in both inter- and intramolecular
C-H aminations.
Acknowledgment. Financial support of this work by the
National Science Foundation (CHE-0350536) is gratefully
acknowledged.
Supporting Information Available: Experimental data
for the reported reactions. This material is available free of
charge via the Internet at http://pubs.acs.org.
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