Iron-catalyzed aminohydroxylation of olefins

Article abstract of DOI:10.1021/ja1013536

We have discovered that N -sulfonyl oxaziridines react with a broad range of olefins in the presence of iron salts to afford 1,3-oxazolidines. This process provides access to 1,2-aminoalcohols with the opposite sense of regioselectivity produced from the copper-catalyzed oxyamination previously reported by our laboratories. Thus, either regioisomeric form of 1,2-aminoalcohols can easily be obtained from the reaction of oxaziridines with olefins, and the sense of regioselectivity can be controlled by the appropriate choice of inexpensive, nontoxic, first-row transition-metal catalyst.

Full text of DOI:10.1021/ja1013536

Published on Web 03/16/2010
Iron-Catalyzed Aminohydroxylation of Olefins
Kevin S. Williamson and Tehshik P. Yoon*
Department of Chemistry, UniVersity of Wisconsin-Madison, 1101 UniVersity AVenue, Madison, Wisconsin 53706
Received February 15, 2010; E-mail: tyoon@chem.wisc.edu
The osmium-catalyzed Sharpless aminohydroxylation1,2 is a
powerful method for the rapid transformation of alkenes into 1,2-
Table 2. Substrate Scope of the Iron-Catalyzed
Aminohydroxylationa
aminoalcohols.3 Because of the cost and toxicity of osmium salts,
however, a variety of alternate methods for olefin oxyamination
that utilize palladium4 and copper5 catalysts have been developed.
We previously reported that N-sulfonyl oxaziridines (“Davis’
oxaziridines”)6 react with olefins in the presence of copper(II)
catalysts to afford 1,3-oxazolidines.7 In this communication, we
report that iron salts8 are also effective catalysts for oxaziridine-
mediated oxyamination but provide the opposite regiomeric out-
come. Thus, the appropriate choice of inexpensive, nontoxic, first-
row transition metal in this transformation enables complementary
access to 1,2-aminoalcohols in either regioisomeric form.
This discovery resulted from screening of transition-metal salts
that we hoped might also be effective catalysts for oxaziridine
activation. We were surprised to discover that both FeBr3 and
Fe(acac)3 produced the previously unobserved regioisomer 2 from
the reaction of oxaziridine 1a and 4-methylstyrene (eq 1), albeit in
modest yields (Table 1, entries 1-3). The efficiency of the reaction
was significantly increased upon optimization of oxaziridine
structure; introduction of electron-withdrawing groups onto both
the N-sulfonyl and C-aryl substituents resulted in improved yields
(entries 4-7). Finally, we noticed that the reaction became
noticeably exothermic upon addition of the oxaziridine to the
reaction mixture, which we speculated might result in thermal
decomposition of the oxaziridine. Thus, reducing the initial reaction
temperature to 0 °C resulted in a further increase in the yield and
reproducibility of the reaction (entry 8).
The scope of the reaction under these optimized conditions is
outlined in Table 2. As in our previously reported copper-catalyzed
aminohydroxylation, styrenes proved to be exceptional substrates
for this aminohydroxylation reaction. Substituents at the ortho, meta,
and para positions of the arene (entries 2-4) are easily accom-
Table 1. Optimization of Reaction Conditions for Iron-Catalyzed
Aminohydroxylation
entry
catalyst
oxaziridine
SO2Ra
Ar
yield
cis:trans
1
2
3
4
5
6
7
8b
FeCl3
FeBr3
1a
1a
1a
1b
1c
1d
1e
1e
Bs
Bs
Bs
Ns
Ns
Ns
Ns
Ns
Ph
Ph
Ph
Ph
0%
15%
28%
38%
44%
69%
--
>10:1
>10:1
7:1
10:1
4:1
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
a Unless otherwise noted, reactions were performed using 0.5 mmol
of olefin, 2 equiv of oxaziridine, and 5 mol % Fe(acac)3 in MeCN.
b Data represent the averaged results of two reproducible experiments.
c Isolated yields. d Ratios determined by 1H NMR analysis of the
unpurified reaction mixture. e >10:1 olefin selectivity. f Reaction
conducted using 3 equiv of oxaziridine. g Two portions of Fe(acac)3
(2 × 5 mol %) and oxaziridine (2 × 2 equiv) were added to these
reactions.
4-ClC6H4
4-CF3C6H4
2,4-Cl2C6H3 88%
2,4-Cl2C6H3 92%
3:1
4:1
a Bs ) benzenesulfonyl; Ns ) 4-nitrobenzenesulfonyl. b Reaction
initiated at 0 °C and then warmed to ambient temperature over 1 h.
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4570 J. AM. CHEM. SOC. 2010, 132, 4570–4571
10.1021/ja1013536  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1a b
,
modated. The reaction is also tolerant of electronic perturbation:
aminohydroxylations of styrenes bearing electron-donating (entries
2-5) and electron-withdrawing substituents (entries 6-8) proceed
in high yields. Styrenes bearing R and ꢀ substituents also undergo
efficient aminohydroxylation (entries 9 and 10), although the latter
are less reactive and require somewhat longer reaction times. Polar
functional groups are also tolerated, including esters (entry 5), aryl
halides (entry 6), nitro groups (entry 8), azides (entry 11), and
appropriately protected alcohols and amines (entries 12 and 13).
Dienes also proved to be outstanding substrates for this reaction.
Both symmetrical (entry 14) and unsymmetrical dienes (entries
15-17) react smoothly, and exclusive chemoselectivity for func-
tionalization of the terminal olefin was observed in aminohydroxy-
lations of monosubstituted 1,3-dienes. Finally, although enynes and
aliphatic olefins proved to be significantly less reactive substrates
for this transformation, synthetically useful yields of the amino-
hydroxylation products could be obtained under somewhat modified
reaction conditions. Thus, in the presence of 5 Å molecular sieves,
addition of 10 mol % catalyst and 4 equiv of the oxaziridine in
two portions enabled the aminohydroxylation of 1-octene and
methylenecyclohexane in 57 and 53% yield, respectively (entries
18 and 19). An enyne reacted under similar conditions to afford
the aminohydroxylation product in 52% yield (entry 20).
a Reagents and conditions: (a) 1e, 2 mol % CuCl2, 3 mol % Bu4N+Cl-,
77% yield; (b) HCl, H2O, MeOH, reflux, 88% yield; (c) PhSH, K2CO3,
97% yield; (d) 1e, 5 mol % Fe(acac)3, 90% yield; (e) HClO4, H2O, dioxane,
80 °C, 85% yield; (f) PhSH, K2CO3, 77% yield. b Ar ) 2,4-Cl2Ph.
this transformation can be controlled by the appropriate choice of
a first-row transition-metal catalyst. Current studies in our lab are
focused on elucidation of the mechanism of this new iron-catalyzed
process and the development of an enantioselective variant.
Acknowledgment. Financial support for this research was
provided by an NSF CAREER Award (CHE-0645447) and the NIH
(R01-GM084022). The NMR spectroscopy facility at UW-Madison
is funded by the NIH (S10 RR04981-01) and NSF (CHE-9629688).
At present, the mechanism of this novel reaction is unclear, as
is the origin of the complementary regioselectivity with respect to
the copper-catalyzed reaction. It is evident, however, that Fe(acac)3
is a precatalyst and not itself the catalytically active species. The
reactions between a variety of metal acetylacetonates and N-sulfonyl
oxaziridines are rapid,9 and we presume that oxidation of the acac
ligands is responsible for the initial exothermicity observed upon
addition of oxaziridine. Consistent with the necessity of a ligand
preoxidation step is the observation that no reaction occurs using
an iron complex bearing either electronically or sterically deacti-
vated acac ligands [e.g., Fe(F3acac)3 or Fe(TMHD)3].10 Catalysis
by the oxidized ligand itself is ruled out by the observation that
Na(acac) fails to promote oxyamination. Similarly, we can rule out
catalysis by trace copper impurities,11 as Cu(acac)2 produces the
regiosiomeric oxazolidine consistent with our previously reported
copper-catalyzed methodology. We are currently conducting in-
vestigations to identify the oxidation state and coordination sphere
of the catalytically active species, with the goal of identifying well-
defined iron complexes that promote the aminohydroxylation
reaction and are amenable to detailed mechanistic analysis.
The discovery of this iron-catalyzed aminohydroxylation is a
useful synthetic advance despite our lack of mechanistic certainty.
In order to highlight the complementarity of this method with the
copper-catalyzed process we reported previously, we conducted the
study summarized in Scheme 1. 4-Acetoxystyrene (3) reacts with
oxaziridine 1e in the presence of a copper catalyst (2 mol % CuCl2,
3 mol % Bu4N+Cl-) to afford 2,4-substituted oxazolidine 4, which
can be deprotected in two steps to afford aminoalcohol 5. On the
other hand, 3 reacts with 1e in the presence of 5 mol % Fe(acac)3
to afford the regioisomeric 2,5-substituted oxazolidine 6 in 90%
yield. Subjecting 6 to standard deprotection conditions affords the
natural product (()-octopamine, a biogenic trace amine suspected
to be involved in a variety of human disease states.12
Supporting Information Available: Experimental procedures and
spectral data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
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Thus, using oxaziridines as terminal oxidants, we have shown
that 1,2-aminoalcohols are available in either regioisomeric form
by vicinal oxyamination of olefins and that the regioselectivity of
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