Amination and [2,3]-sigmatropic rearrangement of propargylic sulfides using a ketomalonate-derived oxaziridine: synthesis of N-allenylsulfenimides.

Article abstract of DOI:10.1039/b307722e

Amination of propargylic sulfides with a ketomalonate-derived oxaziridine under metal free conditions gives N-Boc-N-allenylsulfenimides via [2,3]-sigmatropic rearrangement.

Full text of DOI:10.1039/b307722e

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Amination and [2,3]-sigmatropic rearrangement of propargylic
sulfides using a ketomalonate-derived oxaziridine:
synthesis of N-allenylsulfenimides
Alan Armstrong,* Richard S. Cooke and Stephen E. Shanahan
Department of Chemistry, Imperial College London, South Kensington, London,
UK SW7 2AZ. E-mail: A.Armstrong@imperial.ac.uk; Fax: ϩ44 (0) 20 75945804;
Tel: ϩ44 (0) 20 75945876
Received 9th July 2003, Accepted 8th August 2003
First published as an Advance Article on the web 14th August 2003
Table 1 Conversion of propargylic sulfides to N-allenylsulfimidesa
Amination of propargylic sulfides with a ketomalonate-
derived oxaziridine under metal free conditions gives
N-Boc-N-allenylsulfenimides
via
[2,3]-sigmatropic
rearrangement.
Introduction
The chemistry of allenes is currently attracting considerable
interest, and they are involved in several novel synthetic trans-
formations.1–3 For example, work by Hsung and co-workers on
allenamides4–7 has demonstrated the widespread synthetic
potential of aminoallene derivatives. An important feature of
Hsung’s work was the use of an electron withdrawing substi-
tuent on nitrogen to confer greater stability to the allene moiety.
However, methods of synthesis of these compounds remain
scarce. The [2,3]-sigmatropic rearrangement of propargylic
sulfimides 1 offers an attractive potential route to N-allenyl-
sulfenimides 2 (Scheme 1). Evidence for this process was first
reported by Tamura et al.8 in 1975 (Y = H), although the com-
pound isolated was a tautomer of the initial allenic product.
Tamura later reported a single example of the rearrangement
using an ethyl carbamate protecting group on nitrogen9 (Y =
CO2Et), which facilitated isolation. In this work, the sulfimide
intermediate was generated via reaction of a sulfide with an
Entry
Sulfide 4
X
R1
R2
Yield of 5 (%)
1
2
3
4
5
6
7
8
a
b
c
d
e
f
Ph
Ph
Ph
Ph
Ph
Ph
n-hexyl
n-hexyl
H
H
H
H
H
Me
CO2 Bu
Ph
I
H
H
Me
87
55
66
88
85
31
37
13
t
H
Me
Me
Me
g
h
a Typical amination procedure. To a stirred solution of oxaziridine 3
(100 mg, 0.35 mmol) in CH2Cl2 (2 ml) at Ϫ40 ЊC was added dropwise a
solution of sulfide (0.33 mmol) in CH2Cl2 (2 ml). The resulting solution
was allowed to warm to room temperature over 1 h and then the solvent
was concentrated under reduced pressure. Chromatography (10%
ether–petrol) yielded the required product.
t
aminating reagent. A tert-butoxycarbonyl (Boc; Y = CO2 Bu)
Results and discussion
protecting group would afford allenic products with even
greater synthetic potential. We recently reported the novel
oxaziridine 3 which effects efficient amination of sulfides, allow-
ing [2,3]-sigmatropic rearrangement of allylic sulfimides.10 We
wondered whether this reagent would also allow synthesis and
rearrangement of propargylic sulfides. Very recently, while our
studies were underway, Van Vranken and co-workers11 reported
the use of Bach’s sulfimidation system (FeCl2–BocN3)12 for this
purpose. This prompts us to report our results using oxaziridine
3, including the synthesis of some novel and highly functional-
ised allene systems.
The initial test substrate, sulfide 4a, was readily prepared by
reaction of propargyl bromide with thiophenol, promoted by
K2CO3 in refluxing acetone. Pleasingly, we were quickly able to
establish that by addition of a solution of 4a to 1.06 equiv. of
oxaziridine 3 in dichloromethane at Ϫ40 ЊC, followed by warm-
ing to room temperature over 1 hour, allene 5a could be isolated
in excellent yield by flash chromatography (Table 1, entry 1).
Having established the feasibility of the process, a range of
sulfides were synthesised in order to evaluate its scope. Sulfide
4b was prepared in a similar manner to 4a. Sulfides 4f–h were
prepared by analogous reactions between the appropriate thiols
and propargylic mesylates. Phenyl-substituted sulfide 4d was
obtained similarly from the tosylate of 3-phenyl-2-propyn-1-ol.
Sulfides 4c and 4e were accessed via the acetylide anion of 4a
(Scheme 2), by reaction with either CO2 or I2 as appropriate.
Carboxylic acid intermediate 6 was esterified using tert-
butyl trichloroacetimidate to give 4c. A room temperature,
Lewis acidic method of esterification13 was chosen in view of
the sensitivity of propynoates and the known base-induced
isomerisation of related compounds to allenes.14
Scheme 1
The sulfides were reacted with oxaziridine 3 under the same
conditions as those used for amination of 4a (Table 1). Yields
of allenes 5a–e (entries 1–5) from sulfide substrates unbranched
α- to sulfur (4a–e) were moderate to high. The metal-free nature
of the reaction conditions may facilitate the isolation of
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 1 4 2 – 3 1 4 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
3142

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In summary, we have discovered that oxaziridine 3 can give
good to excellent yields of aminoallene derivatives by amin-
ation of propargylic sulfides and subsequent rearrangement.
Yields are reduced by branching α- to sulfur. However, the
method still gives a useful, metal-free preparation of chiral
allenes. The metal-free reaction conditions allow synthesis of
allenes (e.g. 4c) that are likely to be difficult to obtain using
metal-mediated sulfimidation systems. Synthetic applications
of these interesting and highly functionalised allenes are under
investigation.
Acknowledgements
We thank the EPSRC (studentships to R. S. C and S. E. S) for
their support of this work, and we are also grateful to Bristol-
Myers Squibb, Pfizer, and Merck Sharpe and Dohme for
unrestricted funding.
Scheme 2
particularly sensitive allenes or those derived from sensitive sul-
fides. Of particular note are the unusual iodo-allene 5e and the
formation of 5c from propynoate ester 4c. The rearrangement
has not been previously reported for sulfides bearing a halogen
or carbonyl group at the migration terminus. Indeed, pro-
pynoate esters have proved poor substrates for the Fe-catalysed
Kirmse reaction,15 which is mechanistically related to the Bach
FeCl2–BocN3 system, due to substrate lability. Compounds like
4c are therefore likely to give poor results with those reaction
conditions.
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 1 4 2 – 3 1 4 3
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