Iron(II)-catalyzed sulfimidation and [2,3]-sigmatropic rearrangement of propargyl sulfides with tert-butoxycarbonyl azide. Access to N-allenylsulfenimides

Article abstract of DOI:10.1021/jo0340410

The iron(II)-catalyzed Bach reaction of tert-butoxycarbonyl azide (BocN₃) and allyl sulfides has been extended to include propargyl sulfides, which give N-allenylsulfenimide products. Using 10 mol % dppeFeCl₂ as catalyst the reaction

Full text of DOI:10.1021/jo0340410

fonyl)iminophenyliodinane (PhIdNTs)17,18 have typically
been employed with greater success. Bach and Ko¨rber
demonstrated that FeCl2 can catalyze the reaction of
N-tert-butoxycarbonyl azide (BocN3) with allylic sulfides
to give N-Boc-protected N-allylamines (Scheme 1).15
These results suggested that iron catalysis could provide
access to reactive intermediates derived directly from the
reaction of azides and sulfides. Since our group has
shown that propargyl sulfides are good partners for the
iron-catalyzed Kirmse reaction with trimethylsilyldiazo-
methane (Scheme 1),19 we investigated their use in the
iron-catalyzed Bach reaction with BocN3.
Ir on (II)-Ca ta lyzed Su lfim id a tion a n d
[2,3]-Sigm a tr op ic Rea r r a n gem en t of
P r op a r gyl Su lfid es w ith
ter t-Bu toxyca r bon yl Azid e. Access to
N-Allen ylsu lfen im id es
J ames P. Bacci, Kevin L. Greenman, and
David L. Van Vranken*
Department of Chemistry, University of California,
Irvine, California 92697
dlvanvra@uci.edu
SCHEME 1
Received J anuary 14, 2003
Abstr a ct: The iron(II)-catalyzed Bach reaction of tert-bu-
toxycarbonyl azide (BocN3) and allyl sulfides has been ex-
tended to include propargyl sulfides, which give N-allenyl-
sulfenimide products. Using 10 mol % dppeFeCl2 as catalyst
the reaction proceeds at 0 °C with a number of different
propargyl sulfides in 31-73% isolated yield. The reaction is
limited by product instability toward catalyst and termina-
tion of the catalytic cycle by excess BocN3. N-Allenylsulfen-
imide 2b smoothly undergoes catalytic hydrogenation and
a Diels-Alder reaction with cyclopentadiene.
P r ep a r a t ion of P r op a r gyl Su b st r a t es. Propargyl
sulfides 1a , 1b, and 1f were prepared by reaction of the
appropriate propargyl bromide and thiolate, whereas the
R-branched sulfide 1g was prepared from the mesylate
derived from 2-butynol (Scheme 2).20 Internal alkynes
were prepared from propargyl sulfides by deprotonation
with n-BuLi at -78 °C and reaction with either TMS-
chloride (sulfide 1c)21 or benzaldehyde (sulfide 1d) (Scheme
3).22 The alcohol 1d was acylated with acetic anhydride
to give the acetate 1e (Scheme 3). BocN3 was prepared
according to the literature procedure.23
Metal-catalyzed nitrogen atom transfer reactions have
attracted considerable attention due to their ability to
efficiently construct synthetically valuable intermediates.
Since the initial report of Kwart and Kahn,1 continued
research has resulted in the development of practical
methods for the catalytic aziridination of olefins.2-7 The
related catalytic sulfimidation reaction8-13 has also
emerged as a valuable tool, particularly in the context
of preparing allylic sulfimides, which undergo [2,3]-
sigmatropic rearrangement to give allylic sulfen-
SCHEME 2
amides.8,14-16 With the exception of TsN3
and a lone
12,16
carbonyl azide14 example, azides have been ineffective as
imido group donors for metal-catalyzed aziridinations and
sulfimidations. Nitrene precursors such as N-(p-tolylsul-
(1) Kwart, H.; Khan, A. A. J . Am. Chem. Soc. 1967, 89, 1951.
(2) Mahy, J . P.; Bedi, G.; Battioni, P.; Mansuy, D. J . Chem. Soc.,
Perkin Trans. 2 1988, 1517.
(3) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Org. Chem. 1991,
56, 6744.
(4) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328.
(5) Li, Z.; Conser, K. R.; J acobsen, E. N. J . Am. Chem. Soc. 1993,
115, 5326.
(6) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Am. Chem. Soc.
1994, 116, 2742.
Rea ction Con d ition s. Bach has prepared N-allyl-
sulfenimides by dissolving the allyl sulfide and BocN3 in
CH2Cl2 and adding solid FeCl2 to initiate the reaction.
When these conditions were applied to propargyl sulfide
1a , the desired N-allenylsulfenimide 2a was obtained in
49% yield (Scheme 4). The reaction was relatively slow,
with product formation occurring over 15 h. As previously
observed by Bach, no reaction occurs without catalyst.
(7) Li, Z.; Quan, R. W.; J acobsen, E. N. J . Am. Chem. Soc. 1995,
117, 5889.
(8) Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S.; Baird, C. P.;
Sparey, T. J .; Taylor, P. C. J . Org. Chem. 1997, 62, 6512.
(9) Bach, T.; Ko¨rber, C. Tetrahedron Lett. 1998, 39, 5015.
(10) Bach, T.; Ko¨rber, C. Eur. J . Org. Chem. 1999, 1033.
(11) Nishikori, H.; Ohta, C.; Oberlin, E.; Irie, R.; Katsuki, T.
Tetrahedron 1999, 55, 13937.
(12) Murakami, M.; Uchida, T.; Katsuki, T. Tetrahedron Lett. 2001,
42, 7071.
(13) Ohta, C.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3885.
(14) Migita, T.; Hongoh, K.; Naka, H.; Nakaido, S.; Kosugi, M. Bull.
Chem. Soc. J pn. 1988, 61, 931.
(17) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975, 361.
(18) So¨dergren, M. J .; Alonso, D. A.; Bedekar, A. V.; Andersson, P.
G. Tetrahedron Lett. 1997, 38, 6897.
(19) Prabharasuth, R.; Van Vranken, D. L. J . Org. Chem. 2001, 66,
5256.
(20) Denmark, S. E.; Harmata, M. A.; White, K. S. J . Org. Chem.
1987, 52, 4031.
(21) Davidsohn, W. E.; Henry, M. C. Chem. Rev. 1967, 67, 73.
(22) Dai, W.-M.; Wu, J .; Fong, K. C.; Lee, M. Y. H.; Lau, C. W. J .
Org. Chem. 1999, 64, 5062.
(23) Carpino, L. A.; Carpino, B. A.; Crowley, P. J .; Giza, C. A.; Terry,
P. H. Organic Syntheses; Wiley: New York, 1973; Collect. Vol. V, p
157. CAUTION: BocN3 is potentially explosive.
(15) Bach, T.; Ko¨rber, C. J . Org. Chem. 2000, 65, 2358.
(16) Murakami, M.; Katsuki, T. Tetrahedron Lett. 2002, 43, 3947.
10.1021/jo0340410 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/10/2003
J . Org. Chem. 2003, 68, 4955-4958
4955

SCHEME 3
SCHEME 5
SCHEME 4
The reaction was also attempted with PdCl2(PhCN)214 as
catalyst, but was unsuccessful.
found to be product instability toward the iron catalyst
and termination of the catalytic cycle by excess BocN3.
When N-allenylsulfenimide 2a and 10 mol % of dppe-
FeCl2 were stirred at room temperature for 15 min, half
of the material was converted to products that did not
move on silica gel and only 49% of the N-allenylsulfen-
imide was recovered. Iron-catalyzed decomposition of
product seems to be the primary cause of incomplete
mass balance. A low concentration of BocN3 leads to
higher catalyst turnover; when the typical reaction was
repeated with slow addition of BocN3, only trace amounts
of starting sulfide were recovered and the N-allenyl-
sulfenimide 2a was isolated in 69% yield. Thus, when
concentrations of BocN3 are kept low, the catalyst
remains active long enough to completely consume the
starting material. When 2 equiv of BocN3 was used in
the reaction, the yield of N-allenylsulfenimide 2a de-
creased to 49% and 41% unreacted sulfide was recovered,
supporting the idea that the reaction of BocN3 (which
leads to catalyst destruction) competes with the reaction
of sulfide.
To investigate the effect of the phosphine ligand,
catalyst solutions were prepared by stirring dppp and
dppf with FeCl2 in refluxing dichloroethane until the
FeCl2 went into solution. When a solution of propargyl
sulfide 1b and BocN3 was added to the chilled catalyst
solution, N-allenylsulfenimide 2b was formed in yields
of 57% and 56%, respectively. These yields are slightly
lower than those obtained with the preformed dppeFeCl2
catalyst. Other iron(II) catalysts were examined in the
sulfimidation/[2,3] rearrangement (FeF2, FeBr2, FeI2,
Fe(acac)2, Fe(OAc)2, and FeBF4‚6H2O). None were com-
pletely soluble in refluxing 1,2-dichloroethane with the
exception of Fe(acac)2, which failed to catalyze the reac-
tion. Despite incomplete solubility FeBr2 and FeI2 did pro-
duce N-allenylsulfenimide, but with low conversion. In
addition to simple ferrous salts, a number of other insol-
uble catalysts were examined with dichloroethane as the
reaction solvent (AuBr3, AuCl3, AuCl‚DMS, CuBr, CuOTf‚
1/2PhH, Cu(OTf)2, HfCl4, Mn(OAc)2, NiCl2, (COD)RuCl2,
and RuCl3) but, as expected, no reaction was observed.
Several soluble metal catalysts were examined: AuCl‚
PPh3, CuCN, CuI, [(COD)IrCl]2, Ir(acac)3, dpppNiCl2,
Cl2Ni(PPh3)2, Pd(acac)2, Rh2(OAc)4, and Sn(OTf)2. Pd(acac)2
Since FeCl2 has poor solubility under the reaction
conditions, we hypothesized that better results might be
achieved using a completely soluble catalyst. In sol-
vents that solubilize FeCl2 such as MeCN and DMF, no
reaction was observed, but when dppeFeCl2 was dis-
solved in refluxing 1,2-dichloroethane and then cooled to
room temperature, the reaction proceeded in 15 min to
give product 2a in 54% yield. Immediately following the
addition of propargyl sulfide 1a and BocN3 to the cat-
alyst solution, violent nitrogen evolution was observed
and the reaction mixture became hot. Although obvious
nitrogen evolution ceased after 3 min, product con-
tinued to form over 15 min. At 0 °C, nitrogen evolution
was less vigorous and ceased after approximately 5 min.
N-Allenylsulfenimide 2a was isolated in 70% yield after
6 h (comparable yields are obtained when the reaction
is run for 2 h).
Catalyst deactivation was hypothesized to be the cause
of incomplete conversion of sulfide, as BocN3 was present
at the end of the reaction (by GC-MS). The reaction with
sulfide 1a was run at 0 °C and an additional 5 mol % of
catalyst was added after 2 h as a solution in 1,2-
dichloroethane. The majority of the starting material was
consumed (3% recovered vs 14% with no added catalyst),
confirming that catalyst had been deactivated during the
course of the reaction.
Since initial evolution of nitrogen gas was not accomp-
anied by consumption of starting material, we believe a
stable Fe‚NBoc complex is formed (Scheme 5).15 The
stable complex may be an iron-nitrene precursor24 or an
iron-nitrene25 that reacts with sulfide to produce a
sulfimide that rearranges to the N-allenylsulfenimide
product and liberates the iron catalyst to continue the
catalytic cycle.
A series of experiments were performed to better
understand the pathway(s) that lead to catalyst deactiva-
tion and/or limit the yield of N-allenylsulfenimide prod-
ucts. The two major factors that limit the reaction were
(24) Wigley, D. E. Prog. Inorg. Chem. 1994, 42, 239.
(25) Verma, A. K.; Nazif, T. N.; Achim, C.; Lee, S. C. J . Am. Chem.
Soc. 2000, 122, 11013.
4956 J . Org. Chem., Vol. 68, No. 12, 2003

TABLE 1. Ir on (II)-Ca ta lyzed Su lfim id a tion /
Rea r r a n gem en t of P r op a r gyl Su lfid es
SCHEME 6
fide, shows the lowest conversion of all sulfides studied;
alkyl sulfide 2f was isolated in 31% yield. The effect of
branching R to sulfur was tested with propargyl sul-
fide 1g; chiral allene 2g was isolated in 52% yield. Bach
has suggested that R-branching decreases the nucleo-
philicity of sulfur,15 a possible explanation for the poor
yield of 2g.
Rea ctivity of N-Allen ylsu lfen im id es. Simple di-
alkyl allenamines are prone to hydrolysis and polymer-
ization, making them difficult to prepare and handle.26
Hsung and co-workers have prepared allenamides that
are considerably more stable and easier to handle and
have used them for [4+2] cycloadditions and a tandem
m-CPBA oxidation/[4+3] cycloaddition.27-29 The N-alle-
nylsulfenimides produced in this study were purified by
silica gel chromatography. However, neat N-allenyl-
sulfenimides are not completely stable to storage even
at -20 °C. In contrast, solutions of N-allenylsulfenimides
in aprotic solvents such as benzene, hexane, or ether may
be stored for over a month at -20 °C without significant
decomposition.
The N-allenylsulfenimide products (2a , 2b, and 2c)
were unreactive with a variety of electrophiles at am-
bient temperature (e.g., PhCHO/SnCl2, triphosgene, and
PhNCO). Reaction with stronger electrophiles such as Br2
or BF3‚Et2O/PhCHO resulted in numerous unidentifiable
products. Removal of the benzenesulfanyl group with
NaBH4 gave intermediates that were too reactive to
isolate. Likewise, the attempted removal of the Boc group
with TFA gave numerous unisolable products. Both the
benzenesulfanyl and Boc groups appear to have a deac-
tivating effect on reactivity; as soon as either was
removed, the intermediates became too reactive for
isolation or functionalization in situ.
The N-allenylsulfenimide 2b was reacted with cyclo-
pentadiene to give the Diels-Alder adduct 3 (Scheme 6).
To the best of our knowledge, the work of Hsung27,28 and
the work of Tamaru30,31 represent the only other ex-
amples of [4+2] cycloadditions with allenamides. These
allenamides underwent inverse electron demand [4+2]
was the only catalyst that reacted with BocN3 and a
propargyl sulfide, but gave numerous products, none of
which appeared to correspond to a nitrene transfer
product. To our knowledge, the Bach15 reaction with
iron(II) halides and the Migita14 reaction of Pd(II) (which
was ineffective with propargyl sulfides and BocN3) are
the only reactions in which metals efficiently catalyze
nitrene transfer reactions from azidoformates.
Su bstitu en t Effects. Propargyl sulfides 1a -f were
prepared to test the sensitivity of the sulfimidation/
rearrangement reaction toward different functionality.
Terminal alkyne 1b was expected to form an N-allenyl-
sulfenimide product that would be more reactive toward
the iron catalyst, but allene 2b was isolated in 73% yield
(Table 1). The trimethylsilyl-substituted alkyne 1c was
prepared to test the effect of steric hindrance distal to
sulfur and also provides a unique functional handle for
further elaboration; the TMS-allene 2c was isolated in
52% yield. Tolerance of polar functionality was tested
with alcohol 1d and acetate 1e, which were converted to
the homoallenyl alcohol 2d and homoallenyl acetate 2e
in 53% and 69% isolated yields, respectively. Phenethyl
sulfide 1f, which is more nucleophilic than an aryl sul-
(26) Saalfrank, R. W.; Lurz, C.-J . In Methoden Der Organischen
Chemie (Houben-Weyl); Kropf, H., Schaumann, E., Eds.; Georg Thi-
eme: Stuttgart, Germany, 1993; p 3093.
(27) Wei, L.-L.; Xiong, H.; Douglas, C. J .; Hsung, R. P. Tetrahedron
Lett. 1999, 40, 6903.
(28) Wei, L.-L.; Hsung, R. P.; Xiong, H.; Mulder, J . A.; Nkansah, N.
T. Org. Lett. 1999, 1, 2145.
(29) Wei, L.-L.; Mulder, J . A.; Xiong, H.; Zificsak, C. A.; Douglas, C.
J .; Hsung, R. P. Tetrahedron 2001, 57, 459.
(30) Kimura, M.; Wakamiya, Y.; Horino, Y.; Tamaru, Y. Tetrahedron
Lett. 1997, 38, 3963.
(31) Horino, Y.; Kimura, M.; Wakamiya, Y.; Okajima, T.; Tamaru,
Y. Angew. Chem., Int. Ed. 1999, 38, 121.
J . Org. Chem, Vol. 68, No. 12, 2003 4957

azide (143 mg, 1.0 mmol) in 0.1 mL of 1,2-dichloroethane was
added via syringe to the cooled catalyst solution. The reaction
mixture was stirred under N2 at 0 °C for 6 h (comparable yields
are obtained with a reaction time of 2 h). The crude oil was
purified by silica gel chromatography with gradient elution (1f
3% EtOAc/hexanes) to yield 2a as a clear oil (193 mg, 70%): 1H
NMR (500 MHz, CDCl3, 298 K) δ 7.27-7.35 (m, 4H), 7.17-7.20
(m, 1H), 4.90 (q, J ) 3.2 Hz, 2H), 1.95 (t, J ) 3.2 Hz, 3H), 1.47
(s, 9H); 13C NMR (125 MHZ, CDCl3, 298 K) δ 207.5, 155.2, 138.8,
128.9, 126.8, 125.7, 110.4, 82.4, 80.4, 28.2, 18.6; IR (thin film)
3061, 2979, 2931, 1717, 1585, 1292 cm-1; TLC Rf 0.40 (10%
EtOAc/hexanes); GC-MS (CI/NH3) m/z (rel intensity) 278 (10),
239 (38), 178 (100); HRMS (CI/NH3) m/z calcd for C15H20NO2S
[M + H]+ 278.1214, found 278.1206.
cycloaddition at the internal allenyl double bond. In
contrast, we observed normal electron demand [4+2]
cycloaddition at the terminal allenyl double bond. Het-
erogeneous catalytic hydrogenation of 2b successfully
gave the Z-enamide 4 in 70% isolated yield, despite the
presence of sulfur. The syn addition of hydrogen was
confirmed by the diagnostic 7.9 Hz coupling constant
between vinylic protons of enamine 4.
In conclusion, we have shown that Bach reaction of
BocN3 with allyl sulfides works efficiently with propargyl
sulfides when dppeFeCl2 is used as the catalyst precur-
sor. The resulting N-allenylsulfenimides are sufficiently
stable that they can be used in Diels-Alder reactions or
hydrogenated to Z-enamides.
Ack n ow led gm en t. We thank NSF CHE 9623903
and the Alfred P. Sloan Foundation for financial sup-
port. K.L.G. is a recipient of a graduate fellowship
sponsored by Pharmacia Corp.
Exp er im en ta l Section
Rep r esen ta tive P r oced u r e: N-Allen ylsu lfen im id e, 2a .
To a flame-dried round-bottom flask equipped with a magnetic
stir bar was added dppeFeCl2 (53 mg, 0.10 mmol) and 1,2-
dichloroethane (0.9 mL). The resulting mixture was heated to
reflux and stirred under N2 until a clear brown solution was
obtained. The solution was allowed to cool to room temperature
and was then cooled to 0 °C in an ice bath. A solution of
propargyl sulfide 1a (162 mg, 1.0 mmol) and tert-butoxycarbonyl
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O0340410
4958 J . Org. Chem., Vol. 68, No. 12, 2003