N,O-bis(trifluoroacetyl)hydroxylamine as a useful electrophilic nitrogen source: Catalytic synthesis of N-(trifluoroacetyl)sulfilimines

Article abstract of DOI:10.1021/ol9900515

(equation presented) In the presence of catalytic quantites of Cu(OTf)₂ the novel hydroxamic acid anhydride salt functions competently in the trifluoroacetamidation of sulfides to afford N-(trifluoroacetyl)sulfilimines. The salient features of this salt include its ease of synthesis from the inexpensive, commercially available starting materials trifluoroacetic anhydride and hydroxylamine hydrochloride.

Full text of DOI:10.1021/ol9900515

ORGANIC
LETTERS
1999
Vol. 1, No. 1
149-151
N,O-Bis(trifluoroacetyl)hydroxylamine as
a Useful Electrophilic Nitrogen Source:
Catalytic Synthesis of
N-(Trifluoroacetyl)sulfilimines
C. S. Tomooka, D. D. LeCloux, H. Sasaki, and E. M. Carreira*
California Institute of Technology, Pasadena, California 91125, and Laboratorium fu¨r
Organische Chemie, ETH-Zentrum, CH-8092 Zu¨rich, Switzerland
carreira@org.chem.ethz.ch
Received April 19, 1999
ABSTRACT
In the presence of catalytic quantites of Cu(OTf)2 the novel hydroxamic acid anhydride salt functions competently in the trifluoroacetamidation
of sulfides to afford N-(trifluoroacetyl)sulfilimines. The salient features of this salt include its ease of synthesis from the inexpensive, commercially
available starting materials trifluoroacetic anhydride and hydroxylamine hydrochloride.
The development of reagents and methods that effect
oxidative functionalization of simple raw materials constitutes
an active area of research in chemistry.1 To date, among the
most versatile of such processes are oxidations that generate
epoxides, or diols.2 In this regard, the vast selection of
chalcogen (peracids, dioxirane, oxone), pnictide (oxaziri-
dines), and transition metal based oxygen-atom transfer
reagents has led to the development of a myriad of methods
that provide access to powerful building blocks for synthesis.3
In contrast, the paucity of electrophilic-nitrogen equivalents
limits the selection of methods available to effect nitrogen-
atom transfer, despite the enormous potential of such
methodology.4 Although recently there have been notable
advances in this area,4-6 there continues to be a need for
new readily available, easily prepared reagents that serve as
sources of electrophilic nitrogen. We have been interested
in the discovery and study of reaction methods and reagents
for nitrogen-atom transfer.7 Herein, we wish to report the
discovery of the hydroxamic acid anhydride salt 1 that in
the presence of catalytic Cu(II) functions competently in the
* To whom correspondence should be addressed at the ETH-Zentrum.
(1) (a) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidation of Organic
Compounds; Academic: New York, 1981. (b) Jacobsen, E. N. In Compre-
hensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A.,
Willkinson, G., Eds.; Pergamon: Oxford, U.K., 1995; Vol. 12, p 1097. (c)
Murahashi, S.-I.; Naota, T. In ref 1b, p 1177.
(2) (a) Jacobsen, E. N. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
VCH: New York, 1993; p 159. (b) Johnson, R. A.; Sharpless, K. B. In ref
2a, p 103. (c) For a review of the Sharpless dihydroxylation reaction, see:
Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. ReV. 1994,
94, 2483. (d) The continuous discovery and development of novel oxygen
atom transfer process (epoxidation) is an intensively active area of
investigation; see: Yudin, A. K.; Sharpless, K. B. J. Am. Chem. Soc. 1997,
119, 11536 and references therein.
(4) (a) Li, G.; Angert, H. H.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1996, 35, 2813. (b) Bruncko, M.; Schlingloff, G.; Sharpless, K. B.
Angew. Chem. 1993, 109, 1580. (c) For a recent demonstration of
asymmetric, catalytic amino hydroxylation to the practical synthesis of
arylglycines, see: Reddy, K. L.; Sharpless, K. B. J. Am. Chem. Soc. 1998,
120, 1207.
(5) Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless, K. B. J.
Am. Chem. Soc. 1998, 120, 6844.
(6) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc.
1994, 116, 2742. (b) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson,
B. A.; Barnes, D. M. J. Am. Chem. Soc. 1993, 115, 5328. (c) Li, Z.; Conser,
K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326. (d) For a
mechanistic discussion of the aziridination reaction, see: Li, Z.; Quan, R.
W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889.
(3) Methods of Organic Chemistry (Houben-Weyl); Helmchen, G.,
Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart,
Germany, 1996; Stereoselective Synthesis, Workbench Edition E21, Vol.
8.
(7) (a) Du Bois, J.; Hong, J.; Carreira, E. M.; Day, M. W. J. Am. Chem.
Soc. 1996, 118, 915. (b) Du Bois, J.; Tomooka, C. S.; Hong, J.; Carreira,
E. M. J. Am. Chem. Soc. 1997, 119, 3179. (c) Du Bois, J.; Tomooka, C. S.;
Hong, J.; Carreira, E. M. Acc. Chem. Res. 1997, 30, 364.
10.1021/ol9900515 CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/24/1999

trifluroacetamidation of sulfides to afford N-(trifluoroacetyl)-
sulfilimines:
N,O-Bis(trifluoroacetyl)hydroxylamine (3) is conveniently
prepared in large quantity (0.8 mol) as a crystalline solid by
treatment of neat trifluoroacetic anhydride with hydroxyl-
amine hydrochloride (Scheme 1).17 Although this hydroxamic
Scheme 1. Reagent Synthesis
The salient features of this novel salt 1 include its ease of
synthesis from the inexpensive, commercially available
starting materials trifluoroacetic anhydride and hydroxyl-
amine hydrochloride.
Only a handful of reagents are available that directly
aminate organic molecules to furnish the corresponding
nitrogenous compound. Among the more popular sources
of active electrophilic nitrogen reagents are azides,8 N-
haloamides,4,9 and the related N-arylsulfonyliminoiodoben-
zenes.6,10 Acyl and carbamoyl azides have been utilized in
alkene aziridination, although the process is of limited
preparative use. Of particular importance, Sharpless has
recently documented the use of N-haloamides and carbamates
as versatile and practical amination reagents in the catalytic
aziridination of olefins and enantioselective, catalytic amido
hydroxylation.4,5 The use of hydroxamic acid derivatives as
electrophilic nitrogen equivalents with metal catalysts,
however, lacks precedence, despite the fact that they would
enjoy some unique features as potential electrophilic ami-
nating reagents.11-15 In this regard, N-hydroxyamides and
their derivatives are trivially prepared and as a class these
enjoy greater shelf life than their N-haloamide counterparts.
Moreover, the successful development of such compounds
as electrophilic aminating reagents would afford trifluoro-
acetamides, which may be easily converted to the corre-
sponding free amine under neutral (NaBH4) or mildly
alkaline (K2CO3/H2O/MeOH, 25 °C) conditions.16
acid anhydride (3) proved sluggish in the reaction with
sulfides under a variety of conditions, we observed that the
corresponding lithium salt 1 serves as an electrophilic
nitrogen equivalent in the presence of transition-metal
catalysts. This salt was generated upon treatment of 3 with
t-BuLi in Et2O at -78 °C with warming to 23 °C. This
previously unknown salt can be isolated as an analytically
pure white solid18 following trituration with pentane. It is
worth noting that in our hands 1 can be stored for extended
periods of time at ambient temperature without decomposi-
tion. As part of a comprehensive study, we outline below
the use of this electrophilic nitrogen source for the prepara-
tion of N-(trifluoroacetyl)sulfilimines from sulfides. The
preparation of sulfilimines has been accomplished by treat-
ment of sulfides with the traditional known sources of
electrophilic nitrogen, namely, N-halosulfonamides, the
related N-arylsulfonyliminoiodobenzenes, and acyl or car-
bamoyl azides.8,19 This class of sulfur compounds enjoys rich
synthetic chemistry20 and, for example, can be utilized to
prepare aziridines21 and oxazolinones.22 Moreover, optically
active sulfilimines can be stereospecifically converted to the
corresponding optically active sulfoxides.23,24
(8) Bach, T.; Ko¨rber, C. Tetrahedron Lett. 1998, 39, 5015.
(9) Reddy, K. L.; Dress, K. R.; Sharpless, K. B. Tetrahedron Lett. 1998,
39, 3667.
(10) (a) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975,
361. (b) Breslow has utilized this reagent in the tosylamidation of
cyclohexane with Mn(III) or Fe(III) porphyrins; see: Breslow, R.; Gellman,
S. H. J. Chem. Soc., Chem. Commun. 1982, 1400. More recently this reagent
has been utilized in Cu-catalyzed olefin aziridination reactions.6
(11) For the asymmetric synthesis of R-amino acid derivatives via an
electrophilic amination of chiral amide cuprates, see: Zheng, N.; Armstrong,
J. D.; McWilliams, J. C.; Volante, R. P. Tetrahedron Lett. 1997, 38, 2817.
(12) Tamura has described the use of the highly reactive N-[((tri-
fluoromethyl)sulfonyl)oxy]carbamate in the thermal reaction of sulfides to
give sulfilimines. The preferred mode for reagent preparation prescribes
the use of the thallium salt of ethyl N-hydroxycarbamate; see: Tamura,
Y.; Ikeda, H.; Mukai, C.; Morita, I.; Ikeda, M. J. Org. Chem. 1981, 46,
1732.
(13) For the amination using an N-BOC-benzoylhydroxylamine, see:
Cardillo, G.; Gentilucci, L.; Bastardas, I. R.; Tolomelli, A. Tetrahedron
1998, 54, 8217.
(14) The activated ethyl [((4-nitrophenyl)sulfonyl)oxy]carbamate (NsO-
NHCO2Et) has been utilized in Michael addition reactions to activated
unsaturated acceptors to give enolates that subsequently undergo ring closure
to the corresponding aziridine; see: Fioravanti, S.; Pellacani, L.; Stabile,
S.; Tardella, P. A. Tetrahedron 1998, 54, 6169.
(16) Greene, T. W.; Wutts, P. G. M. Protecting Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991; p 353.
(17) For the preparation of the parent hydroxamic acid, see: Pomeroy,
J. H.; Craig, C. A. J. Am. Chem. Soc. 1959, 81, 6340.
(18) 19F NMR (CD2Cl2, 296 K): δ -70.3, -75.2 ppm. IR (KBr): 1786,
1655 cm-1. Anal. Calcd for C4NO3LiF6: C, 20.80; N, 6.06. Found: C,
20.67; N, 6.02.
(19) For recent developments in the synthesis of sulfilimines, see: (a)
Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S. Chem. Commun. 1996,
931. (b) Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S. J. Org. Chem.
1997, 62, 6512. (c) Bach, T.; Korber, C. Tetrahedron Lett. 1998, 39, 5015.
(20) For a recent review on sulfilimine chemistry, see: Davis, F. A.;
Zhou, P.; Chen, B.-C. Chem. Soc. ReV. 1998, 27, 13.
(21) Yoshimure, T.; Akasaka, T.; Furukawa, N.; Oae, S. Heterocycles
1977, 7, 287.
(22) Abou-Gharbia, M.; Ketcha, D. M.; Zacharias, D. E.; Swern, D. J.
Org. Chem. 1985, 50, 2224.
(23) Day, J.; Cram, D. J. J. Am. Chem. Soc. 1965, 87, 4398.
(24) For catalytic methods for the preparation of sulfoxides from sulfides,
see: (a) Brunel, J. M.; Diter, P.; Duetsch. M.; Kagan, H. B. J. Org. Chem.
1995, 60, 8086. (b) Brunel, J.-M.; Kagan, H. B. Bull. Soc. Chem. Fr. 1996,
113, 1109. (c) Brunel, J. M.; Kagan, H. B. Synlett 1996, 404. Also see:
Palucki, M.; Hanson, P.; Jacobsen, E. N. Tetrahedron Lett. 1992, 33, 7111.
For a related process, see: Cogan, D. A.; Liu, G. C.; Kim, K. J.; Backes,
B. J.; Ellman, J. A. J. Am. Chem. Soc. 1998, 120, 8011.
(15) Geneˆt has utilized tert-butyl N-(tosyloxy)carbamate as an aminating
reagent with organolithiums (n-BuLi, MeLi), organocopper (PhCu), and
ester enolates (Li+ and Zn2+); see: Geneˆt, J. P.; Mallart, S.; Greck, C.;
Piveteau, E. Tetrahedron Lett. 1991, 32, 2359. In addition, Geneˆt has utilized
lithium allyl [(arylsulfonyl)oxy]carbamates as aminating reagents; see:
Greck, C.; Bischoff, L.; Ferreira, F.; Geneˆt, J. P. J. Org. Chem. 1995, 60,
7010.
150
Org. Lett., Vol. 1, No. 1, 1999

Treatment of sulfides with 1 and 1-7 mol % Cu(OTf)2 in
dimethoxyethane (DME) at 45-85 °C cleanly furnishes
N-(trifluoroacetyl)sulfilimines in up to 95% yield (Table 1).25
at a faster rate than their electron-deficient counterparts.
Several observations that we have made in the course of our
preliminary investigations deserve noting. Following a study
of the reaction in a number of solvents (MeCN, THF, Et2O,
CH2Cl2), DME proved to be optimal. In the other solvents
either 1 was only sparingly soluble or, soon after the initiation
of the reaction, precipitates were observed with concomitant
detrimental effects on the reaction rate. Although the structure
of the active aminating reagent in solution is presently
unknown, we speculate that the adduct of Cu(II) with 1 may
correspond to the observed precipitate that subsequently
removes the catalyst from solution in solvents other than
DME.26 The amination reaction of sulfides by 3 or 1 is not
catalyzed by Brønsted acid. Thus, when sulfide, 3 or 1, and
p-toluenesulfonic acid were stirred at 60 °C for 15 h, no
sulfilimine adduct was isolated. However, although we have
observed that other metal salts such as Mg(OTf)2 and
Sn(OTf)2 function as catalysts, the best yields and rates were
obtained with either Cu(I) or Cu(II) triflates; the use
Cu(OTf)2 offers advantages, since it is readily handled on
the benchtop.
Table 1. Catalytic Amidation of Sulfides with 1a
We have demonstrated the ability of the novel salt of
hydroxamic acid anhydride 1 to serve as a source of
electrophilic nitrogen. In the presence of this reagent and
1-7 mol % Cu(OTf)2 a range of sulfides were converted to
the corresponding N-trifluoroacetylated sulfilimines in good
yields. The salient features of 1 as an aminating reagent
include its facile, convenient synthesis from inexpensive,
readily available starting materials and, importantly, the ease
with which it can be handled and stored. Ready access to
this novel reagent allows further potential applications in
inorganic coordination chemistry for the preparation of novel
transition metal nitrides and imines. Moreover, in addition
to the process reported herein, 1 may also find use in other
processes for catalytic nitrogen-transfer reactions in organic
synthesis. Such investigations are ongoing and will be
reported as results become available.
Acknowledgment. We thank the NIH, the NSF, Packard
Foundation, Sloan Foundation, Merck, Pfizer, Eli Lilly,
Zeneca, and Pharmacia-Upjohn. Additional support has been
provided by generous funds from the ETH and the Kontakt-
gruppe fu¨r Forschungsfragen (KGF). D.D.L. thanks the NIH
for a postdoctoral fellowship. We are grateful to Ube
Industries Ltd. (Tokyo) for support of H.S.
a Reaction conditions: sulfide, 5-7 mol % Cu(OTf)2, 4 (2 equiv),
dimethoxyethane (0.10 M) for 6-15 h at 45-85 °C. Upon completion, the
reaction mixture is concentrated in vacuo and purified by chromatography
on silica gel. b All of the sulfides utilized are either commercially available
or have been prepared according to known procedures.
Supporting Information Available: Full characterization
data and proton spectra for 1 and the sulfilimine products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
As shown in Table 1, the processes are applicable to a range
of sulfides including cyclic as well as acyclic dialkyl and
alkyl/aryl sulfides. Electron-rich aryl sulfides afford adducts
OL9900515
(25) The amidation reaction may be conducted with only 1% Cu(OTf)2
(Table 1, entry 1), albeit with longer reaction times. We have found that
5-7 mol % catalyst affords the products in an expeditious manner (6-10
h).
(26) It is interesting to note that of the solvents examined DME is unique
in its ability to potentially form chelates; thus, it will be interesting to
examine chiral bidentate ligands for the corresponding asymmetric amidation
of sulfides.
Org. Lett., Vol. 1, No. 1, 1999
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