A chiral rhodium carboxamidate catalyst for enantioselective C-H amination

Article abstract of DOI:10.1021/ja8031955

Rh₂(S-nap)₄, a chiral dirhodium tetracarboxamidate complex, has been developed and shown to be an effective catalyst for the asymmetric, intramolecular C-H amination of sulfamate esters. Enantiomeric excesses range from 60-99% for a collection of disparately substituted 3-arylpropylsulfamates. In addition, Rh₂(S-nap)₄ is found to promote chemoselective allylic C-H oxidation of unsaturated sulfamates, a property not observed with other dirhodium complexes tested to date. Copyright

Full text of DOI:10.1021/ja8031955

Published on Web 06/27/2008
A Chiral Rhodium Carboxamidate Catalyst for Enantioselective C-H
Amination
David N. Zalatan and J. Du Bois*
Department of Chemistry, Stanford UniVersity, Stanford, California 94305-5080
Received April 30, 2008; E-mail: jdubois@stanford.edu
Catalytic intramolecular C-H amination has advanced as a
general technology for chemical synthesis.1 The utility of the
heterocyclic products fashioned from such processes validates
efforts to identify chiral transition-metal complexes capable of
effecting asymmetric insertion (Figure 1). On a more fundamental
Figure 1. Optically active amine derivatives through C-H amination.
level, the challenges associated with the design of a catalytic system
able to support a reactive oxidant that can discriminate between
two hydrogen atoms on a prochiral methylene center are significant.
Nonetheless, success of this type has been realized in enantiose-
lective C-H insertion reactions of diazoalkane derivatives and in
selectinstancesinvolvingintra-andintermolecularC-Hamination.2–5
This report describes the development and performance of Rh2(S-
nap)4, a valerolactam-derived dirhodium complex that affords some
of the highest levels of asymmetric control to date in cyclization
reactions of sulfamate esters. The strong preference of this catalyst
for promoting allylic C-H bond insertion is also highlighted.
Our earliest efforts to identify chiral catalysts for asymmetric
Figure 2. Evaluating catalyst performance for C-H amination.
C-H amination focused primarily on dirhodium tetracarboxylate
complexes derived from R-amino acids. In all cases examined,
Test reactions with 3-phenylpropylsulfamate, PhIdO, 3 Å
molecular sieves, and 2 mol% of the rhodium dimer revealed the
importance of the sulfonamide N-H group on catalyst performance
(Figure 2). Rh2(S-nap)4 is notably more effective than either
Rh2(PTPI)4 2 or the N-methylated complex 3. Although these data
appear to show some link between catalyst turnover number and
redox potential, other factors are clearly influencing the efficiency
of this process. This fact is exemplified with Rh2(4S-MEOX)4 5, a
complex that has a relatively high oxidation potential of 742 mV
but affords <10% of the cyclized product under standard reaction
conditions.7 In comparison to Rh2(S-nap)4, the architecture of the
4S-MEOX ligand severely crowds the axial sites on the rhodium
centers. It is our feeling that steric effects between the ligands and
substrate are exacerbated in the 4S-MEOX system, thus adversely
affecting the rate of the C-H insertion event and, in turn, the overall
performance of the reaction.
Rh2(S-nap)4, is an effective catalyst for oxidation reactions with
3-aryl-substituted propylsulfamate esters (Table 1). Enantiomeric
excesses are generally >80%, and the conditions tolerant of most
common functional groups. In one case, the isolated heterocycle
(entry 1) has been converted to the corresponding (S)-N-CBz-ꢀ-
amino acid following a two-step protocol (see Figure 1).11 This
correlation establishes the absolute stereochemistry of the product
in entry 1 as S.12,13
cyclized sulfamate products were formed with conspicuously poor
enantiomeric induction (0-20% ee). Studies to evaluate % ee as a
function of product conversion clearly established that the enan-
tiomeric ratio was decreasing over the reaction time course. Such
results are indicative of a change in catalyst structure owing to the
lability of the bridging carboxylate groups. Our interest thus turned
toward alternative classes of ligands including carboxamide-based
designs. In principle, the strongly donating carboxamidate groups
increase the capacity of the dirhodium centers for backbonding to
the π-acidic nitrene ligand, thus affording a more stable and
potentially more discriminating oxidant.6,7 Unfortunately, simple
dirhodium tetracarboxamidate complexes such as Rh2(cap)4 1 are
ineffective catalysts for C-H amination because of their propensity
to undergo facile one-electron oxidation when combined with
PhI(OAc)2 or related hypervalent iodine reagents (Figure 2).8 The
resulting mixed-valent Rh2+/Rh3+ dimer appears to be catalytically
inactive for C-H amination. Accordingly, in order for a dirhodium
carboxamide to promote nitrene-mediated insertion, we concluded
that its oxidation potential would have to be increased significantly
relative to that of Rh2(cap)4.
The basis for the design of Rh2(S-nap)4 4 was Rh2(PTPI)4 2, a
complex originally developed by Hashimoto for asymmetric alkene
cyclopropanation (Figure 2).9 The measured Rh2+/Rh2+fRh2+
/
Rh3+ redox potential for Rh2(PTPI)4 is 120 mV vs SCE, marking
the rather significant influence of the proximal phthalimide group
on the donating strength of the carboxamidate ligand.10 We reasoned
that replacement of the phthalimide moiety with a 2° sulfonamide
would allow for intramolecular hydrogen bonding between the N-H
and the carbonyl oxygen of the amide, further shifting the rhodium
oxidation to higher potential. The recorded CV data for both Rh2(S-
nap)4 4 and its N-methylated analogue 3 confirm this hypothesis
(330 and 242 mV, respectively).
Cognizant of the fact that aziridination of homoallyl sulfamates
is highly favored with Rh-tetracarboxylate catalysts, we were
surprised to observe the five-membered sulfamidate as the major
product in the reaction promoted by Rh2(S-nap)4 (entry 1, Table
2).1b This particular result is striking given the strong preference
for sulfamate esters to yield six-membered ring heterocycles and
the fact that the closely related Rh2(PTPI)4 catalyst affords primarily
the aziridine. The bias for Rh2(S-nap)4 toward allylic insertion
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10.1021/ja8031955 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Enantioselective Cyclization of Sulfamate Estersa
Figure 3. Results suggestive of a concerted insertion mechanism.
ring opening are obtained from this reaction, a result consistent
with a concerted, nitrene-type oxidation.16
Rh2(S-nap)4 displays unprecedented performance for the enan-
tioselective intramolecular amination of benzylic and allylic C-H
bonds. Despite our still nascent understanding of the factors that
influence catalyst turnover numbers and asymmetric control, the
design and development of this unique dirhodium complex should
further advance methods for C-H functionalization. Continued
efforts in this laboratory will attempt to elucidate the nuanced
relationship between oxidation potential, ligand structure, and
substrate design on catalytic function.
Acknowledgment. D.N.Z. is supported by an Achievement
Rewards for College Scientists (ARCS) Foundation Stanford
Graduate Fellowship. This work has been made possible in part
by a grant from the NIH and with gifts from Pfizer, Amgen, and
GlaxoSmithKline.
a Reactions conducted for 2 h with 2 mol % Rh2(S-nap)4, 1.2 equiv
PhIdO, and 3 Å powdered MS in CH2Cl2. Enantiomeric excess (% ee)
determined by chiral HPLC analysis. In two cases (entries 4 and 8) 4
mol % catalyst was used.
Supporting Information Available: General experimental protocols
and characterization data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
Table 2. Chemoselective Allylic C-H Bond Insertion
References
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a Product ratio determined by 1H NMR of the unpurified reaction
mixture. b Enantiomeric excess (% ee) determined by chiral HPLC
analysis. c Yield in parentheses obtained with 4 mol % catalyst.
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(10) By contrast, Rh2(OAc)4 has an oxidation potential of 1150 mV vs. SCE.
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appears to be general, occurring with both styrenyl and non-styrenyl
olefins. Cis olefins perform optimally in these reactions to give
vinyl-substituted oxathiazinanes with enantiomeric excesses >80%.
Although levels of asymmetric induction are modest for trans and
terminal olefins, allylic C-H insertion is still favored.
The remarkable influence of Rh2(S-nap)4 on chemoselectivity
intimates a possible change in mechanism from the concerted-
asynchronous nitrene pathway generally accepted for dirhodium
tetracarboxylate-promoted reactions (e.g., Rh2(OAc)4).14,15 To test
for the possibility that a stepwise, radical C-H abstraction/rebound
may be operative, a cyclopropane clock substrate was submitted
to the amination protocol (Figure 3). No products of cyclopropane
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