tert-butylsulfonamide. A new nitrogen source for catalytic aminohydroxylation and aziridination of olefins

Article abstract of DOI:10.1021/ol990761a

Formula presented The N-chloramine salt of tert-butylsulfonamide has been shown to be an efficient nitrogen source and the terminal oxidant for catalytic aminohydroxylation and aziridination of olefins, resembling closely Chloramine-T by its behavior in t

Full text of DOI:10.1021/ol990761a

ORGANIC
LETTERS
1999
Vol. 1, No. 5
783-786
tert-Butylsulfonamide. A New Nitrogen
Source for Catalytic Aminohydroxylation
and Aziridination of Olefins
Alexander V. Gontcharov, Hong Liu, and K. Barry Sharpless*
Department of Chemistry and the Skaggs Institute for Chemical Biology,
The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, California 92037
sharples@scripps.edu
Received June 23, 1999
ABSTRACT
The N-chloramine salt of tert-butylsulfonamide has been shown to be an efficient nitrogen source and the terminal oxidant for catalytic
aminohydroxylation and aziridination of olefins, resembling closely Chloramine-T by its behavior in these catalytic reactions. The sulfonyl−
nitrogen bond in the product or its derivatives is easily cleaved under mild acidic conditions, allowing for facile liberation of the amino group.
N-Chloramine salts of sulfonamides, such as Chloramine-T
(TsNClNa) and -M (MsNClNa), have been extensively used
as nitrogen sources in both asymmetric and racemic amino-
hydroxylations, aziridinations, and allylic aminations.1 How-
ever, despite their effectiveness in these reactions, they have
a substantial drawback: removal of the alkyl- or arylsulfonyl
group from the newly introduced nitrogen substituent requires
very harsh conditions.1b The o-nitrophenylsulfonyl protecting
group (Ns), introduced by Fukuyama,2 is removed under
extremely mild conditions and, virtually overnight, became
known as the most reliable protecting/activating group for
the amines. However, since the nosyl chloramine salts
(NsNClNa) have proved less reliable in both catalytic
aminohydroxylation and catalytic aziridination processes,3
we continue to be interested in finding other effective
nitrogen sources of the type EWG-N--X with an easily
cleavable EWG-N bond.
Hence, the recent report by Weinreb and co-workers that
amines protected with the tert-butylsulfonyl group (t-BuSO2
or Bus) can be deprotected under fairly mild acidic condi-
tions4 led us to try the chloramine salt of tert-butylsulfona-
mide 1 as the nitrogen source in the catalytic processes for
aminohydroxylation and aziridination of olefins. The suc-
cessful outcome is reported here.
A. Synthesis of tert-Butylsulfonamide and Its Chlor-
amine Salt. The conventional route for synthesis of alkyl-
sulfonamides (RSO2NH2) concludes with the reaction of
(1) (a) Bruncko, M.; Khuong, T.-A. V.; Sharpless, K. B. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 454. (b) Li, G.; Chang, H.-T.; Sharpless, K. B.
Angew. Chem., Int. Ed. Engl. 1996, 35, 451. (c) Rubin, A. E.; Sharpless,
K. B. Angew. Chem., Int. Ed. Engl. 1997, 36, 2637. (d) Pringle, W.;
Sharpless, K. B. Tetrahedron Lett. 1999, in press. (e) Jeong, J. U.; Tao, B.;
Sagasser, I.; Henniges, H.; Sharpless, K. B. J. Am. Chem. Soc. 1998, 120,
6844.
(3) (a) Pringle, W.; Rubin, A. E.; Sharpless, K. B. Unpublished results.
(b) However, the nosyl chloramines give excellent results in the stoichio-
metric selenium-mediated allylic amination (see ref 1a).
(2) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36,
6373.
(4) Sun, P.; Weinreb, S. M. J. Org. Chem. 1997, 62, 8604.
10.1021/ol990761a CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/30/1999

ammonia with a sulfonyl chloride, the latter are usually easily
prepared from the corresponding sulfonic acids.
led directly to sulfonamide 1 (Scheme 2). Unfortunately, the
method calls for the use of the free base of hydroxylamine,
which is unstable, unsafe, and difficult to handle. Another
example, published by Maricich and Hoffman,8 involved
generation of the sulfinyl azide 4a by reaction of 2a (R )
Ph) with NaN3 at low temperature (Scheme 2). The inter-
mediate 4a proved explosive when warmed neat; however,
its slow decomposition in the presence of water afforded 1a
in 20% yield.
This path is efficient for making primary and secondary
alkyl sulfonamides as well as aryl and heteroaryl sulfona-
mides; however, the instability of tertiary alkyl sulfonyl
chlorides as well as their principally different mode of
reactivity toward nucleophiles5 render it impractical for most
tertiary alkyl sulfonamides. All successful syntheses to date
establish the S-N bond in a lower oxidation state sulfur
derivative, and tert-butylsulfinyl chloride (2) has been the
intermediate of choice. Sulfinyl chloride 2 is converted to 1
via a straightforward and well-documented two-step se-
quence: reaction with ammonia yields the relatively stable
tert-butylsulfinamide 3 which is then oxidized to 1 with a
variety of reagents (Scheme 1).
Scheme 2
Scheme 1
We speculated that the latter transformation might become
a practical synthetic method if the unstable, and potentially
dangerous, sulfinyl azide was not allowed to accumulate in
the reaction mixture but was instead converted to the product
immediately as formed. Indeed, performance of the reaction
in refluxing acetonitrile containing suspended sodium azide
and small amounts of water, under dropwise addition of neat
sulfinyl chloride 2, afforded reasonably pure tert-butylsul-
fonamide in 76% yield. The process is highly exothermic,
and the addition rate of 2 is adjusted to maintain gentle reflux
of the acetonitrile.9
However, there is precedent in the literature that the above
sequence can be performed in a single step. Thus Hovius
and Engberts7 found that reaction of 2 with hydroxylamine
The intermediate tert-butylsulfinyl chloride was prepared
from commercially available bis-tert-butyl disulfide in two
steps as shown in Scheme 3.10 The whole reaction sequence
was conveniently carried out on a multigram scale.
(5) Stetter, H.;Krause, M.; Last, W.-D. Chem. Ber. 1969, 102, 3357.
(6) (a) Oppolzer, W.; Wills, M.; Starkemann, C.; Bernardinelli, G.
Tetrahedron Lett. 1990, 31, 4117. (b) Martinez-Merino, V.; Gil, M. J.;
Zabalza, J. M.; Gonzalez, A. Heterocycles 1995, 41, 2737. (c) King, J. F.;
Lam, J. Y. L.; Dave, V. J. Org. Chem. 1995, 60, 2831.
(7) Hovius, K.; Engberts, B. F. N. Tettrahedron Lett. 1972, 181.
the mixture was stirred at 60 °C for 1 h (completion of the reaction was
checked by TLC and/or GC) and then chilled in an ice bath. The excess of
TBHP was destroyed by treating the mixture with a saturated aqueous
solution of sodium metabisulfite (exothermic reaction!). The organic phase
was separated and washed with saturated aqueous sodium bicarbonate and
brine and then dried with magnesium sulfate. The crude product was isolated
in 95% yield (92 g) by evaporating the solvents in a vacuum. The product
thus obtained contained traces of unreacted disulfide as the only impurity,
and it was used in the subsequent step without further purification. (b) To
a solution of tert-butyl tert-butanethiosulfinate (124 g, 0.64 mol) in 300
mL of methylene chloride, chilled in ice, was added slowly a solution of
sulfuryl chloride (86 g, 0.64 mol) in 50 mL of methylene chloride. The
resulting yellow solution was stirred for 1 h allowing it to gradually reach
room temperature. At this point NMR analysis revealed no starting material
remaining. The solvent and volatile byproducts of the reaction were removed
under aspirator vacuum at room temperature (stench!). The product was
isolated by fractional distillation of the remaining oil (boiling range 65-
69 °C at 24 mmHg). Yield: 67 g (75%) as a pale yellow oil. Occasionally,
the distilled tert-butylsulfinyl chloride was contaminated with side products
(most probably, sulfur chlorides), which gave it a deeper yellow or even
orange color. The presence of these impurities did not affect the outcome
of the next step (ref 9).
(8) Maricich, T. J.; Hoffman, V. L. J. Am. Chem. Soc. 1974, 96, 7770.
(9) Sodium azide (16.2 g, 249 mmol) was suspended in 100 mL of
acetonitrile and 10 mL of water. The mixture was heated to just below the
boiling point of acetonitrile, the source of heat was removed, and tert-
butylsulfinyl chloride (20 g, 142 mmol) was added slowly to the vigorously
stirred mixture. The reaction is highly exothermic, and the addition rate
was adjusted to maintain gentle reflux of acetonitrile. After the addition
was complete, the reaction mixture was allowed to cool to room temperature.
Ethyl acetate (50 mL) and water (40 mL) were added, and the layers were
separated. The aqueous layer was extracted once with ethyl acetate, and
the combined organic layers were washed with water and dried with MgSO4.
After the solvents were evaporated in vacuo, the residue was mixed with
100 mL of ether and the crystals were filtered and washed with ether. The
product was recrystallized from acetone to afford 14.5 g (74%) of tert-
butylsulfonamide as white crystals (mp 161-163 °C, lit.7 162-165 °C).
(10) The procedure below is a modification of the synthessis reported
in Netscher, T.; Prinzbach, H. Synthesis 1987, 683. (a) A mixture of tert-
butyl disulfide (89 g, 0.50 mol), vanadyl acetylacetonate (1.33 g, 5.0 mmol),
tert-butyl hydroperoxide (TBHP, ca. 4.1 M solution in benzene, prepared
as described elsewhere,11 10 mL), and benzene (250 mL) were stirred for
10 min at 50 °C on a water bath. Then the remainder of the TBHP solution
(146 mL, 0.60 mol total) was added slowly so that the temperature inside
the reaction flask did not rise above 80 °C. After the addition was complete,
(11) Sharpless, K. B.; Verhoeven, T. R. Aldrichimica Acta 1979, 12,
63.
784
Org. Lett., Vol. 1, No. 5, 1999

As in the Chloramine-T-based aminohydroxylations, high
yields of aminoalcohols resulted and competitive formation
of diols was not detected. The regioselectivity of the
aminohydroxylation is substrate-dependent but becomes
irrelevant if the mixture of these racemic regioisomers is
intended for closure to the corresponding aziridine (as
described in our previous report,1c the isomers A and B
converge to give the same racemic aziridine). In the present
case, the option for easier liberation of the free amino group
should significantly increase the synthetic value of these
transformations.
Scheme 3
C. Aziridination of Olefins. The aziridination of olefins
with Chloramine-T-catalyzed by phenyltrimethylammonium
tribromide (PTAB)1e provides another case where use of Bus-
NClNa (5) has no deleterious effect on the catalytic process.
The aziridinations using 5 (Table 2) were carried out in
acetonitrile at room temperature with 10 mol % of PTAB as
the catalyst.
Treatment of 1 with 1 equiv of tert-butyl hypochlorite and
1 equiv of sodium hydroxide gave the corresponding
chloramine salt 512 which was used as the nitrogen source
in all the catalytic oxidative aminations described here.
B. Aminohydroxylation of r,â-Unsaturated Amides.
Rubin and Sharpless1c recently described the very efficient
osmium-catalyzed aminohydroxylation of R,â-unsaturated
amides with Chloramine-T as the nitrogen source. The
turnover rates, chemoselectivities, and yields for this class
of substrate proved to be substantially higher than those for
any of the other olefin classes already known to undergo
aminohydroxylation. In Table 1, we present the results of
aminohydroxylation of R,â-unsaturated amides using the new
chloramine salt 5 under essentially the same reaction
conditions as reported previously using Chloramine-T.1c,16
As for aminohydroxylation, the results are similar to those
obtained in the earlier study with Chloramine-T.1e High yields
of aziridines are generally observed with simple unfunction-
alized olefins. Most often, aziridines are the only reaction
Table 2. Aziridination of Alkenes with Bus-NClNa Salt in the
Presence of PTAB as a Catalyst (Alkene/Bus-NClNa ) 1:1.2
mol, PTAB 10 mol %, MeCN, rt, 10 h)
Table 1. Aminohydroxylation of R,â-Unsaturated Amides
(Reaction Conditions: Olefin, BusNClNa (1.2 equiv),
K2OsO2(OH)4 (0.5 mol %), t-BuOH-H2O 1:1, rt, 12 h)
Org. Lett., Vol. 1, No. 5, 1999
785

products, so that product isolation is simple and does not
require chromatography. The aziridination is stereospecific:
for example, cis- and trans-â-methylstyrene give exclusively
the cis- and trans-aziridines, respectively. The exocyclic
olefin, methylenecyclohexane, also gave substantial amounts
of the rearranged allylic sulfonamide. The low yield of the
aziridine from 1,4-cyclohexadiene is likely due to competitive
oxidation to the arene, well-precedented in oxidations of this
particular diene.
Scheme 4
D. Amine Deprotection. Two tert-butylsulfonamides
obtained via a nucleophilic openings of representative
aziridine 6 (Scheme 4) were deprotected using the conditions
developed by Weinreb.4 The Bus-protected primary amides
gave high yields of the free amines upon treatment with a
solution of triflic acid in methylene chloride in the presence
of anisole. The product is conveniently separated from the
side products by acid-base extractions.
In conclusion, an improved synthesis of tert-butyl sul-
fonamide 1 has been developed and its derived chloramine
salt 5 was shown to be an efficient nitrogen source in
aminohydroxylation and aziridination of olefins, mirroring
closely the behavior of Chloramine-T in these catalytic
reactions. As disclosed by Weinreb et al.4 in the publication
that inspired the present study, the t-BuSO2 group is easily
cleaved under reasonably mild acidic conditions.
(12) N-Chloro-tert-butylsulfonamide, sodium salt (5) was prepared
according to the procedure analogous to one published previously for
MeSO2NCl Na.13 tert-Butyl hypochlorite14 (5.54 g, 51.1 mmol) was added
slowly to a stirred solution of 1 (7.0 g, 51.1 mmol) in a standardized aqueous
solution of sodium hydroxide (0.993 M, 51.1 mmol, 51.5 mL, Aldrich) at
room temperature. The resulting mixture was stirred for 1 h and then
concentrated to dryness in a vacuum. The solid was triturated with diethyl
ether, filtered, and dried in a vacuum oven at 80 °C for 10 h to afford 9.7
g (98%) of the anhydrous 5 as a white powder. Analysis of the product by
iodometric titration15 revealed an available chlorine content of 35.1% (theor.
36.6%).
(13) Rudolph, J.; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B. Angew.
Chem., Int. Ed. Engl. 1996, 35, 2810.
Acknowledgment. We thank the National Institute of
General Medical Sciences, National Institutes of Health (GM-
28384), the National Science Foundation (CHE-9531152),
and the W. M. Keck Foundation for financial support and
are grateful to A. E. Rubin for helpful discussions.
(14) Mintz, M. J.; Walling, C. Organic Syntheses; Wiley: New York,
1973; Collect. Vol. V, p 184.
(15) Titration was performed by following the protocol established for
Chloramine T: Reagent Chemicals: American Chemical Society Specifica-
tions, 8th ed.; American Chemical Society: Washington, DC, 1993; pp 242-
244.
(16) All the new compounds were characterized using proton and carbon
NMR spectra whose key features closely matched those for the previously
reported N-tosyl analogues.
OL990761A
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Org. Lett., Vol. 1, No. 5, 1999