Rh-catalyzed alkene oxidation: a highly efficient and selective process for preparing N-alkoxysulfonyl aziridines

Article abstract of DOI:10.1016/j.tet.2006.07.099

Unique alkoxysulfonyl aziridine heterocycles were prepared through selective intra- and intermolecular alkene oxidation reactions. These methods are general and perform efficiently at low Rh-catalyst loadings (1-2 mol %) with only a slight excess of an in

Full text of DOI:10.1016/j.tet.2006.07.099

Tetrahedron 62 (2006) 11331–11342
Rh-catalyzed alkene oxidation: a highly efficient and selective
process for preparing N-alkoxysulfonyl aziridines
y
*
Kiran Guthikonda, Paul M. Wehn, Brian J. Caliando and J. Du Bois
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA
Received 29 May 2006; revised 9 July 2006; accepted 14 July 2006
Available online 15 September 2006
Abstract—Unique alkoxysulfonyl aziridine heterocycles were prepared through selective intra- and intermolecular alkene oxidation reac-
tions. These methods are general and perform efficiently at low Rh-catalyst loadings (1–2 mol %) with only a slight excess of an inexpensive
commercial oxidant, PhI(OAc)2. For intermolecular processes, trichloroethylsulfamate was identified as a novel and markedly effective
N-atom source, allowing reactions to be conducted with limiting amounts of the olefin substrate. The aziridine products submit to facile,
nucleophilic ring opening; these processes are regioselective and can be used to prepare polyfunctionalized amines, including a-aminoketones
via the direct addition of Me2SO.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
in both intra- and intermolecular processes.5b,6,7 Our
methodsthusmakeavailablealargeanddiversesetofalkoxy-
sulfonyl-substituted aziridine products. In this report, we
describe in detail the preparation and electrophilic reactivity
of these novel compounds.
The versatility of aziridines as precursors to amine deriva-
tives drives the development of preparative methods for
this unique class of heterocycles.1,2 Catalytic nitrogen atom
transfer to alkenes is a particularly appealing strategy for
the generation of aziridines because of the ready availability
of olefinic starting materials and the direct nature of such
a process. For this reason, intensive efforts by numerous
labs have taken aim at the problem of alkene aziridination.3
These studies have identified Cu-based catalysts as the most
universal for promoting oxidation with hypervalent iodo-
imine-derived reagents of the general form PhI]NSO2Ar.
Nevertheless, the vast majority of reported protocols for ef-
fecting nitrene transfer employ multiple equivalents of the
starting alkene, and thus the application of these processes
has been largely relegated to simple, inexpensive substrates.4
In our lab, alkoxysulfonamides (sulfamate esters) were found
to be exceptional substrates for Rh-catalyzed C–H amination
reactions (Fig. 1).5 Related studies have further revealed the
effectiveness of sulfamate esters for synthesizing aziridines
2. Results and discussion
2.1. Intra- and intermolecular aziridination
Interest in developing selective methods for alkene aziridi-
nation followed from our discovery that sulfamate esters
were excellent substrates for Rh-catalyzed intramolecular
C–H amination.5a Given the greater reactivity of p-bonds
compared with s-C–H centers toward chemical oxidants,
we assumed that the Rh-mediated conditions would likely
promote cyclization of homoallyl-derived sulfamates. Such
expectations were indeed realized when homoallyl ester 1
was mixed with 2 mol % Rh2(oct)4, PhI(OAc)2, and MgO
to give the corresponding bicyclic aziridine 2 in 83% yield
(Fig. 2). This unusual heterocycle is remarkably stable to
chromatographic purification, and yet sufficiently reactive
for ring opening under ambient conditions with common
nucleophiles (vide infra). Following an empirical screen of
different Rh complexes, the tetra-trifluoroacetamide adduct,
1–2 mol%
SO3R
Rh2(L)4
stereospecific
O
O
R2
N
R2
+
S
aziridination
R1
PhI(OAc)2
MgO
R1
RO
NH2
Figure 1. Rh-catalyzed oxidation affords N-alkoxysulfonyl aziridines.
O
O
O
O
N
O
O
catalyst
yield
S
S
catalyst
H2N
2 mol% Rh2(oct)4
83%
PhI(OAc)2, MgO
1 mol% Rh2(NHCOCF3)4 84%
* Corresponding author. Tel.: +1 650 724 4557; fax: +1 650 725 0259;
e-mail: jdubois@stanford.edu
P. M. Wehn is currently employed as a senior research scientist at Amgen
1
2
y
Figure 2. Intramolecular aziridination gives a novel bicyclic heterocycle.
in South San Francisco, CA.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.099

11332
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
Table 2. Diastereoselective reactions of chiral sulfamates
Rh2(NHCOCF3)4, was found to be the catalyst of choice for
effecting aziridine reactions across a varied spectrum of
substituted starting materials.8 In most cases, as little as
1 mol % of catalyst is needed to mediate the intramolecular
aziridination event. Contemporaneous with these findings,
others have delineated analogous processes for sulfamate-
mediated aziridination using Cu- and Ru-based catalysts.3g,9
O
O
O
O
2 mol%
catalyst
O
O
S
R4
R3
S
S
R3
O
NH2
N
O
R1
R2
LnRh
N
O
R5
PhI(OAc)2
MgO
R4
R1
R1
R3
R2
R5
R4
R2
R2
Entrya
Substrate
Major product
Selectivityb
4:1
%
Yield
O
O
O
O
A number of differentially configured achiral and chiral
unsaturated sulfamates have been prepared to map the scope
of this aziridination process. Using standard conditions
that employ 1–2 mol % Rh2(NHCOCF3)4 and 1.1 equiv of
commercial PhI(OAc)2, substrates containing either E- or
Z-alkenyl units are oxidized smoothly (Table 1). A notable
feature of the Rh-catalyzed reaction follows from these col-
lective data: E-olefins afford exclusively trans aziridines;
conversely, Z-olefins give cis products. Stereospecificity is
an invariant property of this Rh-mediated p-bond oxidation
whether the reaction is performed in an intra- or intermolec-
ular fashion. As seen in Table 1, cis-substituted vinylsilanes,
a,b-unsaturated phosphonates, and conjugated enynes all
engage in this process, giving single diastereomeric products
(entry 2). These stable, heteroatom-substituted aziridines are
rather unusual structural motifs, access to which is not read-
ily apparent in the absence of this method.
S
S
H2N
O
N
O
1
84
Me
Me
H
O
O
O
O
S
S
Me
O
NH2
N
O
2
3
4:1
92
69
CO2Et
CO2Et
Me
O
O
O
O
O
O
S
S
Me3Si
H
H2N
N
15:1
H
Me3Si
OTBS
OTBS
O
O
O
O
O
O
S
S
tBuO2C
H2N
N
4
5
20:1
20:1
87
82
H
H
tBuO2C
OTBS
O
OTBS
O
O
O
O
S
S
Me
O
NH2
N
CO2Me
OMEM
CO2Me
OMEM
Me
Table 1. Intramolecular reactions of achiral sulfamates
Entrya
Substrate
Product
% Yield
72
O
O
O
O
S
S
N
H
H2N
O
O
O
O
O
S
O
S
6
20:1
10:1
61
Ph
H2N
O
N
O
H
1
O
tBu
O
O
Ph
Si
H
O
Si
tBu
tBu
H
tBu
O
O
O
O
O
H2N
O
O
O
N
O
O
S
S
R = SiPh3
= P(O)OEt2
= –C≡CSiiPr3
83
62
74
H
R
H
Me3Si
S
S
H2N
O
N
O
2
7
66c
H
H
Me3Si
TBSO
R
TBSO
a
All reactions conducted with 1–2 mol % Rh2(NHCOCF3)4 in
CH2Cl2 between 0 and 23 ꢀC.
a
Reactions conducted with 2 mol % Rh2(oct)4 in CH2Cl2 at 23 ꢀC.
Product diastereoselectivity determined by integration of the 1H NMR of
the unpurified reaction mixture.
b
c
Reaction performed with 2 mol % Rh2(NHCOCF3)4.
Our optimized conditions for intramolecular olefin aziridina-
tion can be employed with chiral sulfamate derivatives to
give products with satisfactory levels of diastereocontrol.
Several examplesof such reactions are highlighted in Table 2.
In these entries, product diastereoselectivities range from
modest to high across a number of structurally dissimilar
starting materials. While only moderate stereocontrol was
noted for sulfamates prepared from secondary alcohols (en-
tries 1 and 2, entry 3 being an exception), a sharp increase
in diastereoselectivity was recorded for substrates containing
a stereogenic element at the b-site (entries 4 and 5). These
studies, along with previous work from our lab, have led us
to propose a stereochemical model to account for the ob-
served sense of induction.5b In brief, the recorded data are
consistent with an aziridination event proceeding through
a chair-like transition state that minimizes gauche and
A1,3-type interactions. It is interesting to note, however,
that seven-membered ring oxathiazepane-fused aziridines
(entry 7) can also begenerated with useful levels of diastereo-
control. The scope of this latter finding has not been explored
in full.3f,10
Our ability to oxidize alkenes in an intramolecular process
with both high efficiency and chemoselectivity motivated
the advancement of a related intermolecular protocol.6 Iden-
tifying an N-functionalized starting material that itself would
not undergo intramolecular C–H insertion was a prerequisite
to the successful execution of this aim. In practice, use of the
terminal oxidant PhI(OAc)2 for aziridination offers a salient
advantage by enabling the choice of any number of sulfon-
amide and/or carbamate derivatives as the N-atom source.
This point is noteworthy, as previous aziridination methods
that rely on ArSO2N]IPh-type reagents are strictly limited
to a small number of sulfonamide materials.2,11 Accordingly,
after screening a collection of aryl- and alkylsulfonamides,
we identified 2,2,2-trichloroethylsulfamate (TcesNH2) as the
most effective reagent for Rh-catalyzed intermolecular ami-
nation reactions. The decision to utilize TcesNH2 followed
from a number of considerations, which included: (1) its
ease and low cost of preparation from trichloroethanol;12
(2) crystallinity and shelf-stability; and (3) the potential to

K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
11333
cleave the Tces-group from the product aziridine under mild
reducing conditions (i.e., Zn). Later studies have shown that
it is also the fastest nitrogen source to react under our condi-
tions, a fact that may be responsible for its superior
performance.13
as would be expected for an electrophilic oxidant, the isopro-
pylidene moiety in carvone is preferentially modified (entry
6). Although most styrenyl alkenes display exceptional per-
formance under the Rh-catalyzed conditions, electron-defi-
cient 2,6-dichlorostyrene (entry 5) presents a daunting test
and in this case the product yield is reduced. By employing
a larger number of equivalents of this alkene (i.e., 3 equiv),
however, the aziridine can be generated in 77% yield
(2 mol % catalyst). Finally, it should be noted that cyclopen-
tene and cyclohexene (entry 9) are problematic substrates
and fail to give even modest amounts of the corresponding
aziridines. Allylic C–H insertion is also found to be compet-
itive in these cases. Similar difficulties functionalizing both
alkenes have been encountered using other transition metal-
based aziridination methods.3a,14 The inability to form either
product in higher yield under our conditions is rather surpris-
ing, and lacks an obvious explanation at this time.
Initial experiments using trans-b-methylstyrene as a test
substrate in combination with TcesNH2, PhI(OAc)2, MgO,
and 1 mol % Rh2(NHCOCF3)4 afforded an 85% yield of
the desired aziridine (Table 3, entry 1). Importantly, no prod-
uct from competing allylic insertion, a problem encountered
with other Rh(II) catalysts, was obtained. A second distin-
guishing characteristic of this process is its efficacy with
only a single equivalent of the olefinic substrate. This feature
is of paramount importance in the context of complex
molecule synthesis, but is more the exception than the rule
for previously reported catalytic aziridination methods. We
have observed comparable results in reactions with a host
of different aryl- and aliphatic alkenes applied as the limiting
reagent. Of added note, the reactive nitrene-like oxidant can
discriminate between electronically dissimilar olefins and,
Knowledge of the scope of the Rh-mediated aziridination
process coupled with a desire to showcase further its utility
for synthesis gave us cause to explore reactions with gly-
cal-based substrates.15 Oxidation of such materials provides
direct entry into value-added 2-amino sugars masked with
a readily removable trichloroethoxysulfonyl (Tces) unit. By
using Zn deprotection under non- or mildly acidic conditions,
access to N-sulfated amino sugars, common structural units
in heparins and in complex cell-surface carbohydrates, is
also possible.16 Much to our satisfaction, when 1 equiv of
commercial tri-O-acetyl-D-glucal was subjected to oxidation
(2 mol % catalyst), complete formation of the C2-aminated
product occurred (Fig. 3). The product in this case is not
the fused bicycle, but instead the 1,2-acetoxy-Tces-amine,
presumed to result from in situ aziridine ring opening with
AcOH. Although MgO is needed as a scavenger for AcOH,
it is kinetically slow to remove the acid from solution; as
such, the labile aziridine is displaced to give the anomeric
acetate. We have observed similar patterns of reactivity
with electron-rich aryl and strained aziridines, such as those
derived from p-methoxystyrene and indene, respectively.
Ring opening of the aziridine aside, the efficiency of this re-
action to givethe alkoxysulfonamide product using a limiting
amount of triacetyl glucal is unprecedented, thus this method
should find application in carbohydrate synthesis.
Table 3. A method for intermolecular olefin aziridination
1–2 mol%
R2
Tces
R3
R2
O
Rh2(NHCOCF3)4
R3
N
+
H2N S OCH2CCl3
O
R1
1.0 equiv
PhI(OAc)2, MgO
R1
Entrya
Substrate
Product
% Yield
85
Me
NTces
Me
1
2
NTces
85
91
Me
Me
NTces
3
4
F
F
NTces
71
40
O2N
O2N
Cl
Cl
NTces
5
6
2.2. Nucleophilic ring openings of alkoxysulfonyl
aziridines
Cl
Cl
O
O
In undertaking studies to advance our amination chemistry,
we wished to examine systematically the electrophilic reac-
tivity of these unusual alkoxysulfonylated strained hetero-
cycles. Prior work by Dauban and Dodd, in accord with
our own findings, indicated that the 6,3-bicyclic aziridines
formed through intramolecular reactions ring open to
favor the seven-membered oxathiazepane dioxide product
Me
Me
Me
Me
85b
70b
Me
Me
NTces
Me
NTces
7
8
Me
Me
Me
OH
OH
82
NTces
NHTces
OAc
OAc
2 mol%
Rh2(NHCOCF3)4
O
O
O
OAc
NTces
9
15c
NTces
H2NSO3CH2CCl3
PhI(OAc)2, MgO
C6H5Cl
AcO
AcO
NHTces
OAc
OAc
a
Reactions conducted with 1 mol % Rh2(NHCOCF3)4 in C6H5Cl from
–10 to 23 ꢀC.
Product isolated as a 1:1 diastereomeric mixture.
Isolated yield for each of the two products.
1.0 equiv
91%
1.0 M
b
c
Figure 3. Glycal oxidation gives a sulfated 2-amino sugar in protected form.

11334
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
O
O
O
O
O
O
explanation for the observed C5 regioselectivity follows
from frontier molecular orbital theory. Density functional
calculations (B3LYP/6-31G*) on the parent bicyclic aziri-
dine 2 indicate that the coefficient of the LUMO orbital is
substantially greater at C5 than at C4 (Fig. 6).18 Similar
observations are noted for the calculated structures of the
LUMO+ orbital on 2 and for related alkyl-substituted aziri-
dines of this type. Although the underlying factors biasing
the shape of the LUMO and LUMO+ orbitals are unclear,
such computational data are consistent with our experimen-
tal findings and the strong preference for these unusual
heterocycles to ring open at the C5 center.
O
O
S
S
R1
S
NaN3
HN
HN
4
R1
R2
N
O
R1
R2
+
4
5
DMF
5
R2
R3
R3
or aq. iPrOH
R3
N3
N3
C4 ring-opening
C5 ring-opening
favored
O
HN
O
O
O
O
O
O
O
O
O
O
O
S
S
S
S
HN
HN
HN
Ph
Et3Si
CO2Et
RO
Me
N3
70%
N3
N3 OR
N3
72%
89%
79%
R = SitBuMe2
Figure 4. Regioselective nucleophilic opening favors seven-membered ring
product.
Regioselective ring opening of bicyclic aziridines such as 3
is observed with nucleophiles other than azide ion (Fig. 7).
Oxygen- and sulfur-derived agents such as MeOH, H2O,
and PhSH are effective for the internal opening of alkoxysul-
fonyl aziridines to give oxathiazepane products, analogous
to the results of Dauban and Dodd.9 When H2O and PhSH
were employed, neither acid nor base was necessary for
the reactions to proceed to completion, a fact that is demon-
strative of the exceptional reactivity of these aziridinyl
heterocycles.
(Fig. 4).5b,9 We have found subsequently that substitution on
the bicyclic framework does not adversely affect regio-
selectivity in these SN2 processes. Regiocontrol in the ring
opening of alkoxysulfonylaziridines was investigated using
a small collection of differentially substituted starting mate-
rials and NaN3 as the nucleophile. As a general rule, azide
attack occurs with a strong preference to displace the C5–
N bond giving the corresponding oxathiazepane. Substrates
that displayed lower selectivity and afforded small amounts
of the 6-membered oxathiazinane contained groups that
strongly enhance electrophilicity at the C4 position (e.g.,
vinyl and alkynyl).
The product oxathiazepanes are valuable precursors to poly-
substituted amine derivatives. As with other cyclic sulfa-
mates, the seven-membered heterocycles are susceptible to
nucleophilic displacement of the C–O bond to give ring-
opened products.5a,19 Such reactions are possible using
N–H or N-alkyl derived starting materials; however, the
facility by which this SN2 process occurs can be greatly im-
proved if the N-center is first acylated (Fig. 8). This behavior
is analogous to that observed for six-membered oxathiazi-
nanes. Accordingly, N-Boc functionalization of 5 enables
the subsequent addition of NaCN to give the diastereochemi-
cally-pure acyclic amine 7. Thus, in four steps from a starting
homoallylic alcohol, access to diverse product libraries of
highly functionalized amines can be achieved.
X-ray crystallography has provided some insight for under-
standing the high regioselectivity observed in these SN2
reactions (Fig. 5).17 Analysis of the ORTEP diagram
of phenyl-substituted aziridine 3 shows only a very slight,
albeit statistically discernible, variation between the C4–N
˚
˚
(1.491 A) and the C5–N bond lengths (1.497 A). While
this difference is biased in a way that is consistent with the
observed regioselectivity for ring opening, it is so small
that we presume other factors must be at play. An X-ray
structure of the highly crystalline seven-membered azide
product has led us to consider an alternative proposal. In
comparing the starting material and product ORTEPs, it ap-
pears that minimal conformational reorganization occurs
upon C5–N bond cleavage. Alternatively, nucleophilic at-
tack at the C4 position would give the oxathiazinane product
in a twist boat-like arrangement with the benzyl substituent
aligned pseudo-axially. A large conformational change is
then needed for the product to interconvert into its preferred
chair-like structure. Presumably, such torsional strain energy
is manifest in the transition state for C4 attack, thus disfavor-
ing it as compared to azide addition at C5. A second possible
Given the marked electrophilic reactivity of the intramolec-
ular aziridine products, we expected that trichloroethoxy-
sulfonyl aziridines synthesized through intermolecular
olefin amination would display a similar propensity for ring
O
S
H
H
O5
O
H
N
H
4
H
H
H
large LUMO
coefficient at C5
2
Figure 6. B3LYP/6-31G* calculated LUMO of unsubstituted bicyclic azi-
ridine 2.
O
HN
O
O
O
N
O
S
PhSH,
H2O
R = SPh
= OH
= OMe
66%
85%
88%
S
Ph
H
O
Ph
or
MeOH
H
R
3
4
Figure 5. X-ray structures of bicyclic aziridine 3 and the azide-opened
product.
Figure 7. Ring opening occurs selectively with disparate nucleophiles.

K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
11335
O
HN
O
O
O
O
O
the corresponding aryl ketones. Both aryl- and alkyl-
substituted aziridines undergo smooth displacement by
DMSO solvent at temperatures ranging from 23–40 ꢀC. As
no additional reagents are required to effect this reaction,
the products may be easily obtained from a simple extractive
work-up; yields in all cases exceed 75%. Taking advantage
of this new protocol in combination with an effective aziri-
dination method, we have found that 1,3-cyclohexadiene
can be converted in a two-step sequence to a useful a-amino
enone derivative. The intermediate vinylaziridine is gener-
ated quantitatively, but is unstable to both chromatography
and crystallization. By simply stirring the unpurified aziri-
dine in DMSO, the easily isolable, aminated product is
obtained. Overall, the high performance of both reaction
steps and low catalyst load (2 mol %) has enabled this trans-
formation to be conducted with 5 mmol of cyclohexadiene,
furnishing >1 g of crystalline aminoketone product.
S
S
NHBoc
Boc2O
BocN
Et3Si
NaCN
Et3Si
aq. CH3CN
45 °C
76%
Et3Si
DMAP
95%
N3 CN
N3
N3
6
5
7
Figure 8. Activation and ring opening of seven-membered oxathiazepane.
opening. Nucleophiles such as PhSH, H2O, NaN3, and
BnNH2 do indeed react smoothly with these materials to
give 1,2-difunctionalized amine products (Eqs. 1 and 2).6
In the case of phenyl-substituted aziridines, a clear bias exists
for opening at the benzylic position, and a single diastereo-
meric alkoxysulfonamide is formed. Similarly, trisubstituted
aziridines are observed to open regioselectively and with ab-
solute stereocontrol. As demonstrated previously, the
trichloroethoxysulfonyl group may be removed from these
products with a mild reducing agent such as Zn/Cu couple
followed by acid treatment to cleave the sulfated amine. Con-
sequently, this aziridination protocol should enjoy use in
complex, multi-step synthesis due to the overall efficiency
of the process (i.e., limiting amounts of alkene) and the
ease by which the free amine can be liberated from the
ring-opened product.
R1
R2
H
H
H
Me
H
R3
H
H
H
H
yield
82
Ph
p-FC6H4
m-O2NC6H4
Ph
Tces
N
O
Me2SO
91
R3
NHTces
R2
R3
R1
23–40 °C
1–24 h
75
R2
R1
83
8
9
Ph
CO2Me 80
Et
H
Et
H
84
SPh
R1 = R2 = –(CH2)4–
NTces
92
Me
Me
PhSH
DMF
(1)
(2)
NHTces
O
2 mol%
Rh2(NHCOCF3)4
NTces
95%
NHTces
Me2SO
H2NSO3CH2CCl3
PhI(OAc)2, MgO
23 °C
1.0 equiv
5 mmol
Me
OH
73%
(2 steps)
H2O
NTces
nPr
Me
Me
nPr
NHTces
Me
dioxane
Figure 10. Tces-aziridines undergo facile ring opening with Me2SO.
80%
Selective oxidation of olefins to aziridines is a particularly
appealing strategy for assembling functionally complex
amines and amine derivatives. We have described a Rh-cata-
lyzed process for effecting such chemistry in both intra- and
intermolecular contexts. In the latter method, unparalleled
efficiency with limiting amounts of the starting alkene is
notedacross arange of dissimilar substrates. When combined
with the versatility of the alkoxysulfonylated azacycles for
subsequent ring opening reactions, these processes should
find great value in synthesis.
With the aim of employing an aziridination strategy in the
context of a natural product synthesis, we required a direct
method for converting N-alkoxysulfonyl aziridines to the
corresponding a-aminoketones. Hiyama has shown that
phenyl-substituted N-acylaziridines undergo oxidative ring
opening in DMSO to give N-acyl-a-aminoketones, albeit
at high temperatures (120 ꢀC) and under long reaction times
(Fig. 9).20,21 In addition, application of this process typically
leads to mixtures of regioisomeric products. Ring opening
by the solvent followed by intramolecular deprotonation
and elimination of Me2S has been postulated as the mecha-
nism for this transformation.
3. Experimental
3.1. General
The ability of trichloroethoxysulfonyl aziridines to undergo
facile displacement with common nucleophiles suggested
that oxidative opening with DMSO would indeed be feasible
(Fig. 10). Remarkably, the reaction of 8 in DMSO ensued
with reasonable speed at 23 ꢀC to give a single ketone prod-
uct. As with other nucleophilic reactions of styrenyl-derived
aziridines, DMSO addition is regioselective and furnishes
All reagents were obtained commercially unless otherwise
noted. Reactions were performed using oven-dried glassware
under an atmosphere of dry nitrogen. Air- and moisture-
sensitive liquids and solutions were transferred via syringe
or stainless steel cannula. Organic solutions were con-
centrated under reduced pressure (w15 Torr) by rotary
evaporation. Dichloromethane, benzene, acetonitrile, N,N-
dimethylformamide (DMF), and dimethylsulfoxide
(DMSO) were dried by passage under 12 psi of N2 through
two columns containing activated alumina. In addition,
OEt
–O
H
CO2Et
N
O
Me2SO
Me
S
N
NHCO2Et
Me
Ph
120 °C
23 h
Ph
Me
Me
O
+
Me
Ph
˚
DMSO was also stored over 3 A molecular sieves. N,N-Di-
Figure 9. Hiyama’s DMSO-promoted oxidative ring opening affords an
a-aminoketone.20
˚
methyl acetamide (DMA) was dried over 4 A molecular

11336
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
sieves and used without further purification. All other sol-
vents (iPrOH and C6H5Cl) were used as received from com-
mercial suppliers. Chlorosulfonyl isocyanate was obtained
from Acros Chemicals, transferred via cannula to a Schlenk
flask, and stored at –20 ꢀC. Triethylamine was distilled from
CaH2 prior to use. Light magnesium oxide was flame dried
under reduced pressure (w15 Torr). (Diacetoxy)iodobenzene
was recrystallized from CHCl3 and dried in vacuo (w1 Torr).
Chromatographic purification of products was accomplished
using forced-flow chromatography on EM Science Geduran
silica gel 60 (40–63 mm). Thin layer chromatography was
performed on EM Science silica gel 60 F254 plates (250 mm).
Visualization of the developed chromatogram was accom-
plished by fluorescence quenching and by staining with
ethanolic anisaldehyde, aqueous potassium permanganate,
or aqueous ceric ammonium molybdate (CAM) solution.
afforded the desired sulfamate ester. Product yields range
from 75–90%.
3.3.2. Intramolecular aziridination. To a solution of sulfa-
mate (4.96 mmol) in 50 mL of CH2Cl2 were added sequen-
tially MgO (460 mg, 11.4 mmol, 2.3 equiv) and 1–2 mol %
Rh2(NHCOCF3)4.22 The mixture was cooled to 0 ꢀC and a
single portion of PhI(OAc)2 (2.08 g, 6.45 mmol, 1.3 equiv)
was added. The orange suspension was allowed to warm
slowly to 23 ꢀC over 2 h. After 6 h at 23 ꢀC, during which
time the colored mixture faded to a pale yellow, the reac-
tion was filtered through a small pad of Celite. The flask
and filter cake were washed thoroughly with CH2Cl2 and
the combined filtrates were concentrated under reduced
pressure. Purification by chromatography on silica gel
(conditions given below) afforded the desired bicyclic
aziridine product.
3.2. Instrumentation
3.3.3. Intermolecular aziridination. To a solution of
Cl3CCH2OSO2NH2 (251 mg, 1.1 mmol, 1.1 equiv) in
2.0 mL of C6H5Cl were added sequentially olefin
(1.0 mmol, 1.0 equiv), MgO (93 mg, 2.3 mmol, 2.3 equiv),
and Rh2(NHCOCF3)4 (6 mg, 10 mmol, 0.01 equiv).22 The
resulting purple mixture was cooled to ꢂ10 ꢀC (s-CO2/ethyl-
ene glycol bath) and a single portion of PhI(OAc)2 (420 mg,
1.3 mmol, 1.3 equiv) was added. Immediately following the
addition of PhI(OAc)2, the suspension turned orange. This
mixture was allowed to warm slowly to 23 ꢀC over 3 h. After
5 h at 23 ꢀC, during which time the colored mixture faded to
pale yellow, the reaction was diluted with 10 mL of CH2Cl2
and filtered through a small pad of Celite. The flask and filter
cakewerewashed thoroughly with CH2Cl2 and the combined
filtrates were concentrated under reduced pressure. The iso-
lated material was purified by chromatography on silica gel
(conditions given below) to afford the desired aziridine.
Nuclear magnetic resonance (NMR) spectra were acquired
on a Varian Mercury-400 operating at 400 and 100 MHz or
a Varian Inova-500 operating at 500 and 125 MHz for H
1
and 13C, respectively, and are referenced internally according
to residual solvent signals. Data for 1H NMR are recorded as
follows: chemical shift (d, ppm), multiplicity (s, singlet; d,
doublet; t, triplet; q, quartet; quint, quintet; dd, doublet of
doublets; dt, doublet of triplets; td, triplet of doublets; m,
multiplet), integration, and coupling constant (Hz). Data
for 13C NMR are reported in terms of chemical shift (d,
ppm). Infrared spectra were recorded on a Thermo-Nicolet
IR300 spectrometer using NaCl salt plates and are reported
in terms of frequency of absorption. High-resolution mass
spectra were obtained from the Mass Spectrometry Facility,
University of California at San Francisco, supported by the
NIH Division of Research and Resources, the High-Resolu-
tion Mass Spectrometry Facility, University of California at
Riverside, and the Vincent Coates Foundation Mass Spec-
trometry Laboratory, Stanford University. Diffraction data
were collected at the UC Berkeley CHEXRAY facility
on Bruker-Siemens SMART and APEX diffractometers
3.4. Characterization data for substrates and products
3.4.1. Compounds from Table 1.
3.4.1.1. Entry 1, trans-styrenyl sulfamate. Purified by
chromatography on silica gel (3:2 hexanes/EtOAc); white
solid: TLC Rf¼0.45 (1:1 hexanes/EtOAc); 1H NMR
(CDCl3, 500 MHz) d 7.40–7.30 (m, 4H), 7.28–7.24 (m, 1H),
6.53 (d, 1H, J¼16.0 Hz), 6.19 (dt, 1H, J¼16.0, 7.0 Hz),
5.02 (br s, 2H), 4.32 (t, 2H, J¼6.5 Hz), 2.68 (qd, 2H,
J¼6.5, 2.5 Hz) ppm; 13C NMR (CDCl3, 125 MHz) d 136.8,
133.3, 128.6, 127.5, 126.1, 124.0, 70.4, 32.4 ppm; IR (thin
film) n 3415, 3315, 1536, 1362, 1181, 933 cmꢂ1; HRMS
(ES+) calcd for C10H13NO3S 227.0616 found 250.0516
(MNa+).
˚
(l¼0.71073 A, graphite monochromator). The structures
were solved by direct methods (SIR-2002) and refined using
Fourier techniques (SHELXL-97).
3.3. General procedures
3.3.1. Alcohol sulfamoylation. Formic acid (0.70 mL,
18 mmol, 1.5 equiv) was added dropwise to neat ClSO2NCO
(1.6 mL, 18 mmol, 1.5 equiv) at 0 ꢀC with rapid stirring.
Vigorous gas evolution was observed during the addition
process and within 5 min the mixture solidified. To the solid
mass was then added 9.2 mL of CH3CN, and the resulting
solution was stirred for 1 h at 0 ꢀC and 8 h at 23 ꢀC. The
reaction was cooled to 0 ꢀC and a solution of the alcohol
(12.3 mmol) and pyridine (1.1 mL, 13.5 mmol, 1.1 equiv)
in DMA was added dropwise via cannula. After stirring for
3 h at 23 ꢀC, the solution was diluted with 25 mL of Et2O
and transferred to a separatory funnel with 25 mL of H2O.
The ethereal layer was collected washed successively with
1ꢁ25 mL of H2O and 1ꢁ25 mL of saturated aqueous
NaCl. The organic layer was dried over MgSO4, filtered,
and concentrated under reduced pressure. Purification by
chromatography on silica gel (conditions given below)
3.4.1.2. Entry 1, trans-phenyl aziridine. Reaction per-
formed with 1 mol % Rh2(NHCOCF3)4. Purified by chroma-
tography on silica gel (90:10:1 CH2Cl2/EtOAc/Et3N); white
solid (72%): TLC Rf¼0.42 (1:1 hexanes/EtOAc); 1H NMR
(CDCl3, 500 MHz) d 7.40–7.30 (m, 5H), 4.77 (ddd, 1H,
J¼12.5, 7.5, 6.0 Hz), 4.55 (ddd, 1H, J¼12.5, 6.5, 6.5 Hz),
3.90 (d, 1H, J¼4.0 Hz), 3.28 (ddd, 1H, J¼6.5, 4.5, 2.5 Hz),
2.51 (dq, 1H, J¼15.0, 6.0 Hz), 2.41 (dtd, 1H, J¼17.0, 7.0,
2.0 Hz) ppm; 13C NMR (CDCl3, 125 MHz) d 134.1, 128.7
(2), 126.2, 68.9, 50.5, 47.6, 18.7 ppm; IR (thin film)
n 1366, 1186, 1051, 878, 783 cmꢂ1; HRMS (ES+) calcd
for C10H11NO3S 225.0460 found 248.0352 (MNa+).

K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
11337
3.4.1.3. Entry 2, cis-triphenylsilyl sulfamate. Purified
by chromatography on silica gel (3:1 hexanes/EtOAc); white
solid: TLC Rf¼0.32 (7:3 hexanes/EtOAc); 1H NMR
(CDCl3, 400 MHz) d 7.61–7.57 (m, 6H), 7.45–7.36 (m,
9H), 6.69 (dt, 1H, J¼14.4, 7.2 Hz), 6.21 (dt, 1H, J¼14.0,
1.4 Hz), 4.52 (br s, 2H), 3.96 (t, 2H, J¼6.6 Hz), 2.36 (qd,
2H, J¼6.8, 1.2 Hz) ppm; 13C NMR (CDCl3, 100 MHz)
d 146.4, 135.7, 134.8, 129.6, 128.0, 127.9, 69.7, 33.3 ppm;
IR (thin film) n 3391, 3291, 3067, 1607, 1427, 1365, 1182,
5.15 (m, 1H), 5.13 (t, 1H, J¼1.2 Hz), 4.98 (br s, 2H), 4.73
(sext, 1H, J¼6.2 Hz), 2.48 (dddt, 1H, J¼14.4, 7.2, 6.0,
1.2 Hz), 2.41 (dddt, 1H, J¼14.4, 7.2, 6.0, 1.2 Hz), 1.41 (d,
3H, J¼6.4 Hz) ppm; 13C NMR (CDCl3, 100 MHz) d 132.5,
118.9, 80.3, 40.7, 20.1 ppm; IR (thin film) n 3378, 3289,
3082, 2982, 2938, 1644, 1558, 1359, 1181, 918 cmꢂ1
;
HRMS (ES+) calcd for C5H11NO3S 165.0460 found
183.0800 (MNH4 ).
+
1109, 928, 700 cmꢂ1
;
HRMS (ESꢂ) calcd for
3.4.2.2. Entry 1, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Purified by chroma-
tography on silica gel (1:1 hexanes/EtOAc); white solid
(84%, 4:1 ds). Major diastereomer: TLC Rf¼0.28 (1:1 hex-
anes/EtOAc); 1H NMR (CDCl3, 400 MHz) d 5.07 (dqd,
1H, J¼11.0, 6.5, 4.5 Hz), 3.19 (dddd, 1H, J¼5.0, 3.2 Hz),
2.57 (dd, 1H, J¼5.4, 0.6 Hz), 2.43–2.40 (m, 1H), 2.30
(ddd, 1H, J¼14.4, 8.2, 4.6 Hz), 1.93 (ddd, 1H, J¼14.4,
10.8, 3.2 Hz), 1.42 (d, 3H, J¼6.4 Hz) ppm; 13C NMR
(CDCl3, 100 MHz) d 79.6, 40.8, 35.8, 26.3, 21.3 ppm; IR
C22H23NO3SSi 409.1168 found 408.1102 (M+ꢂH).
3.4.1.4. Entry 2, cis-triphenylsilyl aziridine. Reaction
performed with 2 mol % Rh2(NHCOCF3)4. Purified by chro-
matography on silica gel (7:3 hexanes/EtOAc); white solid
(83%): TLC Rf¼0.13 (4:1 hexanes/EtOAc); 1H NMR
(CDCl3, 400 MHz) d 7.73–7.67 (m, 6H), 7.35–7.18 (m,
9H), 4.51 (td, 1H, J¼11.6, 4.4 Hz), 3.72 (ddd, 1H, J¼8.4,
6.8, 4.0 Hz), 3.64 (ddd, 1H, J¼11.6, 7.0, 2.0 Hz), 2.88 (d,
1H, J¼6.8 Hz), 2.39–2.28 (m, 1H), 2.13–2.05 (m, 1H)
ppm; 13C NMR (CDCl3, 100 MHz) d 136.2, 132.2, 130.1,
127.8, 69.4, 43.6, 37.0, 18.7 ppm; IR (thin film) n 3070,
3050, 3014, 1428, 1370, 1182, 1110, 1049, 973, 895,
(thin film) n 2988, 2931, 1366, 1187, 971, 863, 798 cmꢂ1
;
HRMS (ES+) calcd for C5H9NO3S 163.0303 found
+
181.0653 (MNH4 ). Minor diastereomer: TLC Rf¼0.21
1
(1:1 hexanes/EtOAc); H NMR (CDCl3, 400 MHz) d 4.59
796 cmꢂ1
;
HRMS (ESꢂ) calcd for C22H21NO3SSi
(dqd, 1H, J¼11.4, 6.2, 4.3 Hz), 3.13 (dddd, 1H, J¼5.2,
1.5 Hz), 2.86 (dd, 1H, J¼5.0, 1.8 Hz), 2.61 (ddd, 1H,
J¼5.4, 2.0, 0.6 Hz), 2.43 (ddd, 1H, J¼15.4, 11.4, 4.0 Hz),
2.29 (ddd, 1H, J¼15.4, 4.2, 1.6 Hz), 1.46 (d, 3H,
J¼6.0 Hz) ppm; 13C NMR (CDCl3, 100 MHz) d 76.2, 40.9,
32.8, 26.1, 21.4 ppm; IR (thin film) n 2923, 2851, 1361,
407.1011 found 406.0938 (M+ꢂH).
3.4.1.5. Entry 2, cis-diethoxyphosphoryl sulfamate.
Purified by chromatography on silica gel (98:2 Et2O/
MeOH); colorless oil: TLC Rf¼0.34 (97:3 Et2O/MeOH);
1H NMR (CDCl3, 400 MHz) d 6.60 (ddt, 1H, JHP¼52.2 Hz,
1184, 1023, 870, 800 cmꢂ1
.
JHH¼13.0, 3.8 Hz), 5.92 (br s, 2H), 5.76 (ddt, 1H, JHP
¼
18.0 Hz, JHH¼12.8, 1.2 Hz), 4.31 (t, 2H, J¼6.2 Hz), 4.08
(dq, 4H, JHP¼7.2 Hz, JHH¼7.2 Hz), 3.04–2.97 (m, 2H),
1.32 (t, 6H, J¼7.2 Hz) ppm; 13C NMR (CDCl3, 100 MHz)
d 148.0 (d, JCP¼3.8 Hz), 119.9 (d, JCP¼182.0 Hz), 68.8 (d,
JCP¼3.0 Hz), 62.0 (d, JCP¼5.4 Hz), 30.1 (d, JCP¼8.4 Hz),
16.3 (d, JCP¼6.8 Hz) ppm; IR (thin film) n 3337, 2985,
3.4.2.3. Entry 2, ethylpentenoate sulfamate. Purifiedby
chromatography on silica gel (97:3 CH2Cl2/EtOAc); col-
1
orless oil: TLC Rf¼0.22 (97:3 CH2Cl2/EtOAc); H NMR
(CDCl3, 400 MHz) d 5.49 (br s, 2H), 5.01 (t, 1H, J¼
6.5 Hz), 4.87 (s, 1H), 4.81 (s, 1H), 4.22 (q, 2H, J¼7.1 Hz),
2.57 (d, 2H, J¼6.7 Hz), 1.76 (s, 3H), 1.27 (t, 3H, J¼
7.1 Hz) ppm; 13C NMR (CDCl3, 100 MHz) d 169.9, 138.9,
115.0, 77.5, 62.2, 40.0, 22.1, 14.0 ppm; IR (thin film)
n 3374, 3280, 3082, 2984, 1741, 1654, 1560, 1376, 1186,
1054, 929, 781 cmꢂ1; HRMS (EI) calcd for C8H15NO5S
237.0671 found 237.0676 (M+).
1629, 1574, 1367, 1226, 1178, 1021, 968, 775 cmꢂ1
;
HRMS (ES+) calcd for C8H18NO6PS 287.0592 found
310.0478 (MNa+).
3.4.1.6. Entry 2, cis-diethoxyphosphoryl aziridine. Re-
action performed with 2 mol % Rh2(NHCOCF3)4. Purified
by chromatography on silica gel (24:1 Et2O/MeOH); color-
less oil (62%): TLC Rf¼0.21 (24:1 Et2O/MeOH); 1H NMR
(CDCl3, 400 MHz) d 4.80 (ddd, 1H, J¼11.6, 10.6, 4.6 Hz),
4.70 (ddd, 1H, J¼11.6, 7.0, 3.2 Hz), 4.35–4.25 (m, 2H),
4.18 (dq, 2H, J¼8.0, 7.2 Hz), 3.47 (dtd, 1H, J¼8.0, 6.4,
4.0 Hz), 2.89–2.79 (m, 1H), 2.74 (t, 1H, J¼5.8 Hz), 2.17
(dddd, 1H, J¼14.8, 8.2, 4.6, 3.2 Hz), 1.39–1.33 (m, 6H)
ppm; 13C NMR (CDCl3, 100 MHz) d 70.6, 64.4 (d,
JCP¼6.1 Hz), 62.4 (d, JCP¼6.8 Hz), 43.0, 38.8 (d,
JCP¼184.3 Hz), 16.4 (d, JCP¼6.1 Hz), 16.3 (d, JCP¼6.0 Hz),
16.2 (d, JCP¼3.0 Hz) ppm; IR (thin film) n 2986, 2915,
1376, 1256, 1187, 1053, 1025, 937, 804 cmꢂ1; HRMS
(ESꢂ) calcd for C8H16NO6PS 285.0436 found 284.0349
(M+ꢂH).
3.4.2.4. Entry 2, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Purified by chroma-
tography on silica gel (7:3 hexanes/EtOAc); white solid
(92%, 4:1). Major diastereomer: TLC Rf¼0.46 (1:1 hex-
1
anes/EtOAc); H NMR (CDCl3, 400 MHz) d 5.14 (t, 1H,
J¼7.4 Hz), 4.26 (q, 2H, J¼7.1 Hz), 2.76 (s, 1H), 2.48 (dd,
1H, J¼15.0, 7.0 Hz), 2.41 (dd, 1H, J¼15.1, 8.0 Hz), 2.38
(s, 1H), 1.47 (s, 3H), 1.29 (t, 3H, J¼7.1 Hz) ppm; 13C
NMR (CDCl3, 100 MHz) d 166.8, 76.0, 62.7, 48.2, 41.3,
25.9, 25.2, 14.0 ppm; IR (thin film) n 2985, 1755, 1446,
1379, 1302, 1191, 1085, 1026, 946, 892, 830 cmꢂ1; HRMS
(EI) calcd for C8H13NO5S 235.0514 found 235.0546 (M+).
Minor diastereomer: TLC Rf¼0.29 (1:1 hexanes/EtOAc);
1H NMR (CDCl3, 400 MHz) d 4.84 (dd, 1H, J¼10.8,
6.4 Hz), 4.28 (q, 2H, J¼7.1 Hz), 2.95 (d, 1H, J¼2.1 Hz),
2.65–2.48 (m, 3H), 1.46 (s, 3H), 1.29 (t, 3H, J¼7.2 Hz)
ppm; 13C NMR (CDCl3, 100 MHz) d 166.6, 74.2, 62.6, 47.6,
39.2, 26.2, 24.4, 14.0 ppm; IR (thin film) n 2985, 1758,
1371, 1306, 1185, 1076, 1029, 890, 784 cmꢂ1; HRMS
(EI) calcd for C8H13NO5S 235.0514 found 235.0518 (M+).
3.4.2. Compounds from Table 2.
3.4.2.1. Entry 1, pentenyl sulfamate. Purified by chro-
matography on silica gel (3:1 hexanes/EtOAc); colorless oil:
TLC Rf¼0.30 (7:3 hexanes/EtOAc); 1H NMR (CDCl3,
400 MHz) d 5.79 (ddt, 1H, J¼16.4, 10.8, 7.2 Hz), 5.18–

11338
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
3.4.2.5. Entry 3, pentenylsilane sulfamate. Purified by
film) n 2933, 1773, 1387, 1196, 1024, 828, 690 cmꢂ1
;
HRMS (EI) calcd for C11H19NO8S 325.0831 found
chromatography on silica gel (13% EtOAc/hexanes); white
solid: TLC Rf¼0.40 (4:1 hexanes/EtOAc); 1H NMR
(CDCl3, 500 MHz) d 6.31 (dt, 1H, J¼14.5, 7.0 Hz), 5.74
(d, 1H, J¼14.0 Hz), 4.97 (br s, 2H), 4.69 (ddd, 1H, J¼12.8,
6.3, 4.5 Hz), 3.85–3.80 (m, 2H), 2.61–2.50 (m, 2H), 0.93
(s, 9H), 0.16 (s, 9H), 0.14 (s, 3H), 0.12 (s, 3H) ppm; 13C
NMR (CDCl3, 125 MHz) d 141.2, 133.8, 84.3, 65.2, 34.9,
25.8, 18.3, 0.1, ꢂ5.4, ꢂ5.5 ppm; IR (thin film) n 3368,
3290, 2955, 2931, 2858, 1609, 1363, 1251, 1186, 1128,
933, 837, 779 cmꢂ1; HRMS (ESꢂ) calcd for C14H33NO4SSi2
367.1669 found 366.1591 (M+ꢂH).
250.0389 (M+ꢂO(CH2)OCH3).
3.4.2.10. Entry 6, dioxasilylcycloheptene sulfamate.
Purified by chromatography on silica gel (4:1 hexanes/
EtOAc); white solid: TLC Rf¼0.22 (4:1 hexanes/EtOAc);
1H NMR (CDCl3, 400 MHz) d 5.79–5.72 (m, 1H), 5.61
(ddt, 1H, J¼12.0, 3.6, 1.8 Hz), 5.12–5.08 (m, 1H), 4.84 (br
s, 2H), 4.71 (dq, 1H, J¼17.2, 2.8 Hz), 4.51 (ddt, 1H,
J¼17.2, 4.0, 2.0 Hz), 4.24 (dd, 1H, J¼10.2, 5.8 Hz), 4.21
(dd, 1H, J¼9.8, 5.0 Hz), 1.04 (s, 9H), 1.03 (s, 9H) ppm;
13C NMR (CDCl3, 100 MHz) d 133.1, 128.0, 73.9, 69.4,
64.2, 27.7, 21.3, 21.0 ppm; IR (thin film) n 3370, 3291,
2935, 2859, 1560, 1473, 1364, 1185, 1116, 1000,
3.4.2.6. Entry 3, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Reaction performed with
2 mol % Rh2(oct)4. Purified by chromatography on silica
gel (13% EtOAc/hexanes); white solid (69%, 15:1 ds):
TLC Rf¼0.33 (4:1 hexanes/EtOAc); 1H NMR (CDCl3,
400 MHz) d 4.88 (ddt, 1H, J¼9.8, 5.4, 4.4 Hz), 3.79 (dd,
1H, J¼11.4, 4.2 Hz), 3.75 (dd, 1H, J¼11.6, 4.0 Hz), 3.46 (q,
1H, J¼6.8 Hz), 2.18–2.10 (m, 2H), 1.95 (d, 1H, J¼7.2 Hz),
0.89 (s, 9H), 0.27 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H) ppm;
13C NMR (CDCl3, 100 MHz) d 82.2, 64.1, 43.7, 40.3, 25.8,
21.6, 18.3, ꢂ0.8, ꢂ5.4, ꢂ5.5 ppm; IR (thin film) n 2950,
826 cmꢂ1
;
HRMS (ESꢂ) calcd for C13H27NO5SSi
337.1379 found 336.1301 (M+ꢂH).
3.4.2.11. Entry 6, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Purified by chroma-
tography on silica gel (15% EtOAc/hexanes); white solid
1
(61%, 20:1 ds): TLC Rf¼0.42 (4:1 hexanes/EtOAc); H
NMR (CDCl3, 400 MHz) d 4.92–4.86 (m, 2H), 4.55 (dd,
1H, J¼12.8, 1.6 Hz), 4.47 (dd, 1H, J¼12.0, 10.8 Hz), 4.37
(dd, 1H, J¼12.2, 6.2 Hz), 3.56 (t, 1H, J¼6.4 Hz), 3.21 (dt,
1H, J¼10.6, 6.2 Hz), 1.06 (s, 9H), 1.00 (s, 9H) ppm; 13C
NMR (CDCl3, 100 MHz) d 77.8, 63.2, 58.9, 48.3, 45.3,
27.2, 27.0, 21.4, 20.8 ppm; IR (thin film) n 2930, 2858,
2929, 2858, 1360, 1256, 1174, 972, 843, 776 cmꢂ1
.
3.4.2.7. Entry 4, tert-butyl ester sulfamate. Purified by
chromatography on silica gel (5:14:1 hexanes/CH2Cl2/
Et2O); colorless oil: TLC Rf¼0.25 (5:14:1 hexanes/
1472, 1371, 1257, 1182, 1063, 1010, 900, 787 cmꢂ1
;
1
CH2Cl2/Et2O); H NMR (CDCl3, 400 MHz) d 6.06 (dd,
HRMS (ESꢂ) calcd for C13H25NO5SSi 335.1223 found
1H, J¼11.6, 3.6 Hz), 5.80 (dd, 1H, J¼11.6, 1.6 Hz), 5.56
(dddd, 1H, J¼7.6, 6.0, 3.6, 1.6 Hz), 5.03 (br s, 2H), 4.28
(dd, 1H, J¼11.0, 3.6 Hz), 4.19 (dd, 1H, J¼10.8, 6.0 Hz),
1.48 (s, 9H), 0.89 (s, 9H), 0.10 (s, 3H), 0.07 (s, 3H) ppm;
13C NMR (CDCl3, 100 MHz) d 165.2, 146.3, 123.0, 81.5,
73.8, 67.7, 28.0, 25.7, 18.1, ꢂ4.8, ꢂ4.9 ppm; IR (thin
film) n 3369, 3284, 2955, 2931, 2858, 1710, 1369, 1254,
1186, 1113, 1001, 836 cmꢂ1; HRMS (ES+) calcd for
C15H31NO6SSi 381.1641 found 404.1539 (MNa+).
358.1119 (M+ꢂH).
3.4.2.12. Entry 7, bicyclic aziridine. Reactionperformed
with 2 mol % Rh2(NHCOCF3)4 at 23 ꢀC. Purified by chro-
matography on silica gel (9:1 hexanes/Et2O); white solid
(66%, 10:1 ds): TLC Rf¼0.48 (4:1 hexanes/Et2O); 1H
NMR (CDCl3, 400 MHz) d 4.44 (td, 1H, J¼12.2, 1.8 Hz),
4.33 (ddd, 1H, J¼12.2, 4.0, 3.0 Hz), 4.18 (ddd, 1H,
J¼10.2, 8.4, 2.4 Hz), 2.80 (dd, 1H, J¼8.8, 3.2 Hz), 2.30 (d,
1H, J¼7.2 Hz), 2.31–2.22 (m, 1H), 1.97 (dq, 1H, J¼14.8,
2.2 Hz), 0.89 (s, 9H), 0.29 (s, 9H), 0.11 (s, 6H) ppm; 13C
NMR (CDCl3, 100 MHz) d 69.5, 69.2, 49.1, 43.9, 38.7,
25.6, 17.8, ꢂ0.7, ꢂ3.6, ꢂ3.9 ppm; IR (thin film) n 2953,
3.4.2.8. Entry 4, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Purified by chroma-
tography on silica gel (7% EtOAc/hexanes); white solid
1
(87%, 20:1 ds): TLC Rf¼0.20 (19:1 hexanes/EtOAc); H
2931, 2857, 1355, 1253, 1165, 1105, 954, 837 cmꢂ1
;
NMR (CDCl3, 400 MHz) d 4.82–4.77 (m, 1H), 4.58 (dd,
1H, J¼11.4, 9.0 Hz), 4.41 (dd, 1H, J¼11.4, 6.6 Hz), 3.25–
3.21 (m, 2H), 1.51 (s, 9H), 0.89 (s, 9H), 0.11 (s, 3H), 0.10
(s, 3H) ppm; 13C NMR (CDCl3, 100 MHz) d 163.0, 84.4,
73.6, 56.1, 50.9, 42.2, 27.7, 25.5, 17.9, ꢂ4.9, ꢂ5.0 ppm; IR
(thin film) n 2955, 2859, 1737, 1385, 1257, 1192, 1111,
995, 842, 788 cmꢂ1; HRMS (ES+) calcd for C15H29NO6SSi
379.1485 found 402.1363 (MNa+).
HRMS (ESꢂ) calcd for C14H31NO4SSi2 365.1512 found
364.1432 (M+ꢂH).
3.4.3. Products from Table 3.
3.4.3.1. Entry 3, p-fluorophenyl aziridine. Purified by
chromatography on silica gel (9:1 hexanes/EtOAc); white
solid (91%): TLC Rf¼0.52 (4:1 hexanes/EtOAc); 1H NMR
(CDCl3, 500 MHz) d 7.33–7.28 (m, 2H), 7.12–7.07 (m,
2H), 4.89 (d, 1H, J¼11.0 Hz), 4.83 (d, 1H, J¼11.0 Hz),
3.88 (dd, 1H, J¼7.0, 4.5 Hz), 3.11 (d, 1H, J¼7.5 Hz), 2.62
(d, 1H, J¼4.5 Hz) ppm; 13C NMR (CDCl3, 125 MHz)
d 163.2 (d, JCF¼248.8 Hz), 129.9 (d, JCF¼3.1 Hz), 128.6
(d, JCF¼8.0 Hz), 116.2 (d, JCF¼22.1 Hz), 93.0, 79.9, 42.4,
37.8 ppm; IR (thin film) n 1515, 1382, 1182, 1011, 841,
3.4.2.9. Entry 5, bicyclic aziridine. Reaction performed
with 2 mol % Rh2(oct)4 at 23 ꢀC. Purified by chroma-
tography on silica gel (11:9 hexanes/EtOAc); white solid
1
(82%, 20:1 ds): TLC Rf¼0.16 (1:1 hexanes/EtOAc); H
NMR (CDCl3, 400 MHz) d 5.30 (d, 1H, J¼2.7 Hz), 4.78
(d, 1H, J¼7.3 Hz), 4.73 (d, 1H, J¼7.3 Hz), 4.39 (d, 1H,
J¼2.8 Hz), 3.83 (s, 3H), 3.68–3.60 (m, 2H), 3.60–3.48 (m,
2H), 3.37 (s, 3H), 2.88 (s, 1H), 2.42 (s, 1H), 1.64 (s, 3H)
ppm; 13C NMR (CDCl3, 100 MHz) d 164.5, 95.0, 79.9,
71.3, 69.5, 68.0, 59.0, 54.6, 53.1, 38.6, 24.0 ppm; IR (thin
784 cmꢂ1
;
HRMS (ES+) calcd for C10H9Cl3FNO3S
346.9353 found 346.9353 (MNa+).
3.4.3.2. Entry 5, 2,6-dichlorophenyl aziridine. Purified
by chromatography on silica gel (9:1 hexanes/EtOAc);

K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
11339
1
white solid (40%): TLC Rf¼0.51 (4:1 hexanes/EtOAc); H
NMR (CDCl3, 500 MHz) d 7.38–7.35 (m, 2H), 7.28 (dd,
1H, J¼7.0, 8.5 Hz), 4.94 (d, 1H, J¼11.0 Hz), 4.90 (d, 1H,
J¼11.0 Hz), 4.02 (dd, 1H, J¼7.5, 5.0 Hz), 3.26 (dd, 1H,
J¼7.5, 1.0 Hz), 2.84 (dd, 1H, J¼5.0, 1.0 Hz) ppm; 13C
NMR (CDCl3, 125 MHz) d 136.2, 130.4, 129.5, 128.8,
92.9, 79.7, 41.3, 36.7 ppm; IR (thin film) n 1433, 1385,
by chromatography on silica gel (2:1 hexanes/EtOAc); white
solid (91%): TLC Rf¼0.43 (1:1 hexanes/EtOAc); 1H NMR
(CDCl3, 500 MHz) d 6.19 (d, 1H, J¼9.5 Hz), 5.71 (d, 1H, J¼
8.5 Hz), 5.21(t, 1H, J¼9.5 Hz), 5.07 (t, 1H, J¼10.0 Hz), 4.62
(d, 1H, J¼11.5 Hz), 4.58 (d, 1H, J¼11.0 Hz), 4.26 (dd, 1H,
J¼12.5, 4.5 Hz), 4.09 (dd, 1H, J¼12.5, 2.0 Hz), 3.88 (ddd,
1H, J¼10.0, 4.5, 2.0 Hz), 3.76 (q, 1H, J¼9.5 Hz), 2.19 (s,
3H), 2.12 (s, 3H), 2.06 (s, 3H), 2.03 (s, 3H) ppm; 13C NMR
(CDCl3, 125 MHz) d 171.7, 170.7, 169.7, 169.4, 93.2, 91.9,
78.5, 72.5, 72.4, 67.9, 61.4, 57.8, 21.0, 20.8, 20.7,
20.5 ppm; IR (thin film) n 3262, 1755, 1369, 1218, 1079,
1043 cmꢂ1; HRMS (ES+) calcd for C16H22Cl3NO12S
556.9928 found 579.9823 (MNa+).
1184, 1011, 781 cmꢂ1
;
HRMS (ES+) calcd for
C10H8Cl5NO3S 396.8667 found 419.8576 (MNa+).
3.4.3.3. Entry 6, carvone aziridine. Reactionperformed
with 2 mol % Rh2(NHCOCF3)4. Purified by chromatography
on silica gel (4:1 hexanes/EtOAc); white solid (85%, 1:1 ds):
TLC Rf¼0.21 (3:1 hexanes/EtOAc). Higher Rf diastereomer:
1H NMR (CDCl3, 500 MHz) d 6.75 (d, 1H, J¼6.0 Hz), 4.78
(s, 2H), 2.72 (s, 1H), 2.58–2.49 (m, 1H), 2.49 (s, 1H), 2.42
(dt, 1H, J¼18.5, 5.0 Hz), 2.36–2.27 (m, 2H), 2.11–2.03
(m, 1H), 1.78 (s, 3H), 1.62 (s, 3H) ppm; 13C NMR (CDCl3,
125 MHz) d 197.9, 143.6, 135.7, 93.0, 79.4, 50.9, 42.5,
41.9, 40.1, 27.7, 15.6, 14.8 ppm; IR (thin film) n 1672,
1366, 1179, 1012, 853, 781 cmꢂ1; HRMS (ES+) calcd for
C12H16Cl3NO4S 374.9866 found 397.9758 (MNa+).
3.4.4.2. trans-5-Azido-4-phenyl-[1,2,3]-oxathiazepane-
2,2-dioxide. To a solution of 7-phenyl-3-oxa-2-thia-1-
azabicyclo[4.1.0]heptane-2,2-dioxide (53 mg, 0.25 mmol)
in 1.25 mL of DMF was added NaN3 (20 mg, 0.31 mmol,
1.2 equiv). The solution was stirred for 35 min then trans-
ferred to a separatory funnel containing 10 mL of EtOAc
and 10 mL of H2O. The organic phase was collected and
washed with an additional 1ꢁ10 mL of H2O. The aqueous
portions were combined and extracted with 1ꢁ10 mL of
EtOAc. The collective organic extracts were washed with
1ꢁ10 mL of saturated aqueous NaCl, dried over MgSO4, fil-
tered, and concentrated under reduced pressure. Purification
of the oily residue by chromatography on silica gel (2:1 hex-
anes/EtOAc) afforded the desired product as a white solid
(47 mg, 70%): TLC Rf¼0.57 (1:1 hexanes/EtOAc); 1H
NMR (CD3CN, 500 MHz) d 7.45–7.35 (m, 5H), 6.57 (br s,
1H), 4.46–4.34 (m, 2H), 4.24 (d, 1H, J¼10.5 Hz), 3.99 (td,
1H, J¼10.5, 4.5 Hz), 2.41 (dtd, 1H, J¼15.5, 4.5, 1.0 Hz),
2.17–2.10 (m, 1H); 13C NMR (CD3CN, 125 MHz) d 139.2,
129.8, 129.4, 128.3, 68.1, 64.5, 61.2, 35.3 ppm; IR (thin
film) n 3284, 2104, 1338, 1174, 758 cmꢂ1; HRMS (ES+)
calcd for C10H12N4O3S 268.0630 found 291.0526 (MNa+).
3.4.3.4. Entry 7, citronellol aziridine. Purified by chro-
matography on silica gel (9:1 CH2Cl2/EtOAc); colorless oil
(70%, 1:1 ds): TLC Rf¼0.33 (9:1 CH2Cl2/EtOAc). Data re-
1
ported for the mixture of diastereomers: H NMR (CDCl3,
500 MHz) d 4.77–4.70 (m, 4H), 3.72–3.60 (m, 4H), 2.84–
2.82 (m, 2H), 1.62 (s, 6H), 1.66–1.24 (m, 14H), 1.32 (s,
6H), 0.90 (d, 3H, J¼6.4 Hz), 0.89 (d, 3H, J¼6.4 Hz) ppm;
13C NMR (CDCl3, 125 MHz) d 93.14, 93.13, 79.1, 60.64,
60.57, 55.02, 54.90, 51.9, 51.7, 39.45, 39.39, 34.1, 34.0,
29.1, 28.9, 25.2, 25.1, 21.0, 20.5, 20.4, 19.4 ppm; IR (thin
film) n 3315, 1364, 1177, 1016, 868, 777 cmꢂ1; HRMS
(ES+) calcd for C12H22Cl3NO4S 381.0335 found 404.0248
(MNa+).
3.4.3.5. Entry 9, cyclohexene aziridine. Purified by
chromatography on silica gel (10:1 hexanes/EtOAc); white
solid (15%): TLC Rf¼0.61 (4:1 hexanes/EtOAc); 1H NMR
(CDCl3, 400 MHz) d 4.80 (s, 2H), 3.14–3.09 (m, 2H),
2.02–1.84 (m, 4H), 1.51–1.39 (m, 2H), 1.35–1.24 (m, 2H)
ppm; 13C NMR (CDCl3, 100 MHz) d 93.1, 79.3, 42.0,
22.6, 19.2 ppm; IR (thin film) n 2943, 1367, 1181, 1016,
3.4.4.3. 4-Phenyl-5-(phenylthio)-[1,2,3]-oxathiazepane-
2,2-dioxide. To a solution of aziridine 3 (53 mg,
0.25 mmol) in 2.5 mL of DMF was added neat PhSH
(27 mL, 0.26 mmol, 1.05 equiv). The solution was stirred
for 2 h then transferred to a separatory funnel with 10 mL
of EtOAc and 10 mL of H2O. The organic layer was col-
lected and washed with 1ꢁ10 mL of H2O. The aqueous
layers were combined and extracted with 1ꢁ10 mL of
EtOAc. The collective organic fractions were then washed
with 1ꢁ10 mL of saturated aqueous NaCl, dried over
MgSO4, filtered, and concentrated under reduced pressure.
Purification of the oily residue by chromatography on silica
gel (3:1 hexanes/EtOAc) furnished the desired product as
a white solid (55 mg, 66%): TLC Rf¼0.70 (1:1 hexanes/
EtOAc); 1H NMR (CDCl3, 500 MHz) d 7.36–7.29 (m,
5H), 7.25–7.19 (m, 3H), 7.18–7.14 (m, 2H), 5.30 (br d,
1H, J¼8.5 Hz), 4.47–4.34 (m, 3H), 3.71 (td, 1H, J¼10.5,
4.0 Hz), 2.46 (dt, 1H, J¼16.0, 4.0 Hz), 2.39–2.30 (m, 1H)
ppm; 13C NMR (CDCl3, 125 MHz) d 138.3, 133.5, 132.5,
129.1, 129.0, 128.7, 128.1, 127.2, 69.2, 61.4, 52.7,
36.2 ppm; IR (thin film) n 3284, 1346, 1178, 944,
752 cmꢂ1; HRMS (ES+) calcd for C16H17NO3S2 335.0650
found 358.0547 (MNa+).
784 cmꢂ1
;
HRMS (ES+) calcd for C8H12Cl3NO3S
306.9603 found 329.9506 (MNa+).
3.4.3.6. Entry 9, cyclohexenyl amine. Purified by chro-
matography on silica gel (10:1 hexanes/EtOAc); white solid
(15%): TLC Rf¼0.54 (4:1 hexanes/EtOAc); 1H NMR
(CDCl3, 400 MHz) d 5.93 (dtd, 1H, J¼10.0, 3.6, 1.6 Hz),
5.72 (ddt, 1H, J¼10.0, 4.4, 2.4 Hz), 4.70 (br d, 1H,
J¼8.0 Hz), 4.63 (s, 2H), 4.14–4.06 (m, 1H), 2.10–1.94 (m,
3H), 1.80–1.60 (m, 3H) ppm; 13C NMR (CDCl3,
125 MHz) d 132.7, 126.0, 93.4, 78.1, 50.4, 29.7, 24.5,
19.1 ppm; IR (thin film) n 3304, 2945, 1431, 1364, 1183,
855 cmꢂ1
;
HRMS (ES+) calcd for C8H12Cl3NO3S
306.9603 found 329.9503 (MNa+).
3.4.4. Experimental protocols from Figures 3, 4, 7, and 8.
3.4.4.1. b-1,3,4,6-Tetraacetyl-2-N-trichloroethoxysul-
fonyl glucosamine. Reaction performed with 2 mol %
Rh2(NHCOCF3)4 at 1.0 M substrate concentration. Purified
3.4.4.4. 5-Hydroxy-4-phenyl-[1,2,3]-oxathiazepane-2,2-
dioxide. To a solution of aziridine 3 (53 mg, 0.25 mmol)

11340
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
in 1.67 mL of DMF was added 0.8 mL of H2O. The solution
was stirred for 60 h then all volatiles were removed in vacuo
(w1 Torr). Purification of the solid residue by chromato-
graphy on silica gel (3:2 EtOAc/hexanes) afforded the de-
sired product as a white solid (52 mg, 85%): TLC Rf¼0.14
(1:1 hexanes/EtOAc); 1H NMR (CH3CN, 500 MHz)
d 7.44–7.33 (m, 5H), 6.40 (br d, 1H, J¼10.4 Hz), 4.46–
4.30 (m, 2H), 4.13 (t, 1H, J¼10.4 Hz), 4.00 (dddd, 1H,
J¼9.6, 9.6, 5.2, 5.2 Hz), 3.01 (d, 1H, J¼5.6 Hz), 2.32 (dtd,
1H, J¼15.2, 4.4, 1.2 Hz), 2.14–2.02 (m, 1H) ppm; 13C
NMR (CD3CN, 125 MHz) d 140.0, 129.4, 128.7, 128.5,
72.8, 68.2, 62.8, 38.3 ppm; IR (thin film) n 3456, 3279,
1341, 1177, 1051, 759 cmꢂ1; HRMS (ES+) calcd for
C10H13NO4S 243.0565 found 266.0471 (MNa+).
3.5. General protocol for oxidative ring opening
of Tces-aziridines
Aziridine (0.25 mmol) was dissolved in DMSO and stirred
until TLC analysis indicated the complete consumption of
starting material (1–24 h). The solution was transferred to
a separatory funnel with 10 mL of EtOAc and washed with
2ꢁ10 mL of H2O. The aqueous layers were combined and
extracted with 1ꢁ10 mL of EtOAc. The collective organic
fractions were then washed with 1ꢁ10 mL of saturated
aqueous NaCl, dried over MgSO4, filtered, and concentrated
under reduced pressure. Purification by chromatography on
silica gel (as indicated below) furnished the desired ketone.
3.5.1. Characterization data for products from Figure 10.
3.5.1.1. (2-Oxo-2-phenylethyl)sulfamic acid 2,2,2-tri-
chloroethyl ester. Purified by chromatography on silica
gel (4:1 hexanes/EtOAc); white solid (82%): TLC Rf¼0.23
3.4.4.5. 5-Methoxy-4-phenyl-[1,2,3]-oxathiazepane-2,2-
dioxide. To a solution of aziridine 3 (53 mg, 0.25 mmol) in
2.5 mL of MeOH was added p-toluenesulfonic acid mono-
hydrate (2 mg, 10 mmol, 0.04 equiv). The contents were
stirred for 5 h, transferred to a separatory funnel with
10 mL of EtOAc, and washed with 2ꢁ10 mL of H2O. The
aqueous layers were combined and extracted with
1ꢁ10 mL of EtOAc. The collective organic fractions were
washed with 1ꢁ10 mL of saturated aqueous NaCl, dried
over MgSO4, filtered, and concentrated under reduced pres-
sure. Purification of the oily residue by chromatography on
silica gel (3:1 hexanes/EtOAc) gave the desired product as
a white solid (46 mg, 72%): TLC Rf¼0.70 (1:1 hexanes/
EtOAc); 1H NMR (CDCl3, 500 MHz) d 7.45–7.40 (m, 2H),
7.39–7.34 (m, 1H), 7.33–7.28 (m, 2H), 4.72 (d, 1H,
J¼11.0 Hz), 4.55 (td, 1H, J¼11.5, 2.5 Hz), 4.49 (ddd, 1H, J¼
11.5, 5.5, 1.5 Hz), 4.46 (d, 1H, J¼3.0 Hz), 3.87 (tt, 1H, J¼
11.0, 3.0 Hz), 3.38 (s, 3H), 2.11–2.01 (m, 1H), 1.33–1.27
(m, 1H) ppm; 13C NMR (CDCl3, 125 MHz) d 136.3, 128.8,
128.4, 126.4, 83.3, 71.7, 60.3, 57.7, 22.1 ppm; IR (thin
film) n 3255, 1410, 1359, 1190, 780 cmꢂ1; HRMS (ES+)
calcd for C11H15NO4S 257.0722 found 280.0622 (MNa+).
1
(4:1 hexanes/EtOAc); H NMR (CDCl3, 400 MHz) d 7.94
(dd, 2H, J¼6.4, 1.5 Hz), 7.67 (tt, 1H, J¼7.2, 1.2 Hz),
7.55–7.50 (m, 2H), 6.05 (br t, 1H, J¼4.4 Hz), 4.72 (d, 2H,
J¼4.4 Hz), 4.67 (s, 2H) ppm; 13C NMR (CDCl3,
100 MHz) d 192.0, 134.8, 133.4, 129.2, 128.0, 93.2, 78.3,
49.2 ppm; IR (thin film) n 3285, 1694, 1371, 1183,
857 cmꢂ1
;
HRMS (ES+) calcd for C10H10Cl3NO4S
344.9396 found 367.9292 (MNa+).
3.5.1.2. [2-(4-Fluorophenyl)-2-oxo-ethyl]sulfamic acid
2,2,2-trichloroethyl ester. Purified by chromatography on
silica gel (4:1 hexanes/EtOAc); white solid (91%): TLC Rf¼
0.31 (4:1 hexanes/EtOAc); 1H NMR (CDCl3, 400 MHz)
d 8.02–7.96 (m, 2H), 7.24–7.18 (m, 2H), 5.99 (t, 1H,
J¼4.0 Hz), 4.69 (d, 2H, J¼4.4 Hz), 4.67 (s, 2H) ppm; 13C
NMR (CDCl3, 100 MHz) d 190.5, 166.6 (d, JCF¼258.7 Hz),
130.8 (d, JCF¼10.0 Hz), 129.9 (d, JCF¼3.0 Hz), 116.5 (d,
JCF¼22.1 Hz), 93.2, 78.4, 49.1 ppm; IR (thin film) n 3270,
1687, 1597, 1408, 1236, 1181, 861 cmꢂ1; HRMS (ES+) calcd
for C10H9Cl3FNO4S 362.9302 found 385.9196 (MNa+).
3.4.4.6. N-(tert-Butoxycarbonyl)-2-azido-4-cyano-1-tri-
ethylsilylbutanamine. To a solution of N-Boc oxathiaze-
pane (800 mg, 1.96 mmol) in 14 mL of CH3CN was added
an aqueous solution of NaCN (193 mg, 3.92 mmol,
2.0 equiv) in 6 mL of H2O. The flask was sealed and the con-
tents heated at 45 ꢀC for 36 h. The reaction mixture was
cooled to 23 ꢀC and poured into a separatory funnel contain-
ing 50 mL of H2O and 5 mL of aqueous 1 M HCl (note: ap-
propriate caution must be taken when working up the
reaction as HCN is generated). The aqueous layer was ex-
tracted with 4ꢁ25 mL of EtOAc. The combined organic ex-
tracts were washed with 1ꢁ30 mL of saturated aqueous
NaCl, dried over MgSO4, and concentrated under reduced
pressure. Purification of the solid residue by chromatography
on silica gel (14:1 hexanes/EtOAc) gave the desired product
as a white solid (530 mg, 76%). TLC Rf¼0.32 (7:1 hexanes/
3.5.1.3. [2-(3-Nitrophenyl)-2-oxo-ethyl]sulfamic acid
2,2,2-trichloroethyl ester. Reaction performed at 0.1 M
in olefin substrate. Purified by chromatography on silica
gel (2:1 hexanes/EtOAc); yellow solid (75%): TLC Rf¼
0.22 (2:1 hexanes/EtOAc); 1H NMR (CDCl3, 500 MHz)
d 8.78 (t, 1H, J¼2.0 Hz), 8.53 (ddd, 1H, J¼8.0, 2.0,
1.0 Hz), 8.28 (ddd, 1H, J¼7.5, 2.5, 1.5 Hz), 7.78 (t, 1H,
J¼7.5 Hz), 5.90 (t, 1H, J¼4.5 Hz), 4.78 (d, 2H, J¼4.5 Hz),
4.70 (s, 2H) ppm; 13C NMR (CDCl3, 125 MHz) d 190.4,
148.6, 134.6, 133.4, 130.6, 128.9, 122.9, 93.2, 78.5,
49.6 ppm; IR (thin film) n 3303, 1705, 1534, 1353, 1183,
1086, 858 cmꢂ1; HRMS (ES+) calcd for C10H9Cl3N2O6S
389.9247 found 412.9153 (MNa+).
3.5.1.4. (1-Methyl-2-oxo-2-phenylethyl)sulfamic acid
2,2,2-trichloroethyl ester. Reaction performed at 40 ꢀC.
Purified by chromatography on silica gel (5:1 hexanes/
EtOAc); white solid (83%): TLC Rf¼0.24 (4:1 hexanes/
EtOAc); 1H NMR (CDCl3, 400 MHz) d 7.97–7.94 (m, 2H),
7.64 (tt, 1H, J¼6.8, 1.2 Hz), 7.54–7.49 (m, 2H), 6.27 (br d,
1H, J¼7.6 Hz), 5.20 (quint, 1H, J¼7.2 Hz), 4.68 (d, 1H, J¼
10.8 Hz), 4.54 (d, 1H, J¼10.8 Hz), 1.55 (d, 3H, J¼7.2 Hz)
ppm; 13C NMR (CDCl3, 100 MHz) d 197.5, 134.5, 132.9,
129.1, 128.8, 93.1, 78.1, 54.4, 20.5 ppm; IR (thin film) n
1
EtOAc); H NMR (CDCl3, 400 MHz) d 4.46 (br d, 1H,
J¼10.4 Hz), 3.60 (td, 1H, J¼7.2, 1.7 Hz), 3.40 (dd, 1H,
J¼10.4, 2.0 Hz), 2.65 (dt, 1H, J¼17.2, 7.4 Hz), 2.58 (dt,
1H, J¼17.2, 6.6 Hz), 2.04–1.88 (m, 2H), 1.42 (s, 9H), 0.99
(t, 9H, J¼7.8 Hz), 0.67 (q, 6H, J¼7.8 Hz) ppm; 13C NMR
(CDCl3, 100 MHz) d 156.4, 118.7, 79.8, 62.8, 40.7, 28.2,
27.0, 14.2, 7.3, 2.4 ppm; IR (thin film) n 2957, 2878, 2100,
1703, 1494, 1366, 1243, 1167, 1011 cmꢂ1; HRMS (ES+)
calcd for C16H31N5O2Si 353.2247 found 376.2148 (MNa+).

K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
11341
3290, 1687, 1369, 1186, 973, 854 cmꢂ1; HRMS (ES+) calcd
for C11H12Cl3NO4S 358.9553 found 381.9462 (MNa+).
with 1ꢁ100 mL of EtOAc. The collective organic fractions
were washed with 1ꢁ50 mL of saturated aqueous NaCl,
dried over MgSO4, filtered, and concentrated under reduced
pressure. Purification of the oily residue by chromatography
on silica gel (3:1 hexanes/EtOAc) yielded the desired prod-
uct as a white solid (1.29 g, 73%). TLC Rf¼0.54 (1:1 hex-
anes/EtOAc); 1H NMR (CDCl3, 500 MHz) d 7.10–7.05
(m, 1H), 6.14 (ddd, 1H, J¼10.0, 3.0, 1.0 Hz), 6.08 (br d,
1H, J¼3.0 Hz), 4.66 (d, 1H, J¼11.0 Hz), 4.62 (d, 1H,
J¼10.5 Hz), 4.19 (ddd, 1H, J¼14.0, 5.0, 3.5 Hz), 2.73–
2.67 (m, 1H), 2.66–2.51 (m, 2H), 2.01–1.92 (m, 1H) ppm;
13C NMR (CDCl3, 125 MHz) d 193.9, 152.4, 127.2, 93.2,
78.3, 58.7, 30.3, 25.6 ppm; IR (thin film) n 3291, 1687,
1389, 1185, 1020, 859 cmꢂ1; HRMS (ES+) calcd for
C8H10Cl3NO4S 320.9396 found 343.9288 (MNa+).
3.5.1.5. 3-Oxo-3-phenyl-2-(2,2,2-trichloroethoxysulfo-
nylamino)propionic acid methyl ester. Purified by chro-
matography on silica gel (3:1 hexanes/EtOAc); white solid
(80%): TLC Rf¼0.49 (2:1 hexanes/EtOAc); 1H NMR
(CDCl3, 400 MHz) d 8.10–8.06 (m, 2H), 7.68 (tt, 1H, J¼
7.2, 1.2 Hz), 7.56–7.51 (m, 2H), 6.48 (d, 1H, J¼8.8 Hz),
5.84 (d, 1H, J¼8.4 Hz), 4.69 (d, 1H, J¼10.8 Hz), 4.64 (d,
1H, J¼10.8 Hz), 3.76 (s, 3H) ppm; 13C NMR (CDCl3,
100 MHz) d 189.4, 166.1, 135.2, 133.0, 129.6, 129.1, 93.0,
78.4, 60.5, 53.8 ppm; IR (thin film) n 3276, 1753, 1690,
1449, 1377, 1242, 1187, 858 cmꢂ1; HRMS (ES+) calcd for
C12H12Cl3NO6S 402.9451 found 425.9340 (MNa+).
3.5.1.6. (1-Ethyl-2-oxo-butyl)sulfamic acid 2,2,2-tri-
chloroethyl ester. Purified by chromatography on silica
gel (6:1 hexanes/EtOAc); colorless oil (84%): TLC Rf¼
Acknowledgements
We are grateful to both the National Science Foundation and
National Institutes of Health for support of our program.
Additional funding from Amgen, Boehringer Ingelheim,
Bristol Myers Squibb, GlaxoSmithKline, Merck, and Pfizer
is gratefully acknowledged. B.J.C. was the recipient of a
Pfizer Undergraduate Summer Research Fellowship (2005).
1
0.17 (9:1 hexanes/EtOAc); H NMR (CDCl3, 500 MHz)
d 5.89 (d, 1H, J¼7.5 Hz), 4.64 (d, 1H, J¼10.5 Hz), 4.57 (d,
1H, J¼10.5 Hz), 4.29 (ddd, 1H, J¼6.0, 6.0, 4.5 Hz), 2.63
(dq, 1H, J¼18.0, 7.5 Hz), 2.51 (dq, 1H, J¼18.0, 7.5 Hz),
2.04 (dddd, 1H, J¼15.0, 15.0, 7.5, 5.0 Hz), 1.74 (sept, 1H,
7.0 Hz), 1.13 (t, 3H, J¼7.0 Hz), 0.96 (t, 3H, J¼7.5 Hz)
ppm; 13C NMR (CDCl3, 125 MHz) d 207.9, 93.2, 78.0,
62.8, 32.8, 25.2, 8.7, 7.5 ppm; IR (thin film) n 3285, 2978,
1721, 1373, 1188, 1008, 858 cmꢂ1; HRMS (ES+) calcd for
C8H14Cl3NO4S 324.9709 found 347.9613 (MNa+).
References and notes
1. For general reviews on aziridines, see: (a) Pearson, W. H.;
Lian, B. W.; Bergmeier, S. C. Comprehensive Heterocyclic
Chemistry, II; Katritzky, A. R., Ress, C. W., Scrive, E. F. V.,
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Murphree, S. S.; Padwa, A. Prog. Heterocycl. Chem. 2001,
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1347–1365; (d) Zwanenburg, B.; Holte, P. T. Top. Curr. Chem.
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M€uller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905–2920;
(b) Dauban, P.; Dodd, R. H. Synlett 2003, 1571–1586;
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Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res.
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K.; Lectard, S. Pure Appl. Chem. 2006, 78, 363–375.
3. Representative methods include: (a) Evans, D. A.; Bilodeau,
M. T.; Faul, M. M. J. Am. Chem. Soc. 1994, 116, 2742–2753;
(b) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc.
1993, 115, 5326–5327; (c) Dauban, P.; Saniere, L.; Tarrade,
A.; Dodd, R. H. J. Am. Chem. Soc. 2001, 123, 7707–7708;
(d) Liang, J.-L.; Yuan, S.-X.; Chan, P. W. H.; Che, C.-M.
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3.5.1.7. (2-Oxo-cyclohexyl)sulfamic acid 2,2,2-tri-
chloroethyl ester. Purified by chromatography on silica
gel (4:1 hexanes/EtOAc); white solid (92%): TLC
Rf¼0.22 (4:1 hexanes/EtOAc); 1H NMR (CDCl3,
500 MHz) d 5.98 (br d, 1H, J¼4.5 Hz), 4.62 (d, 1H,
J¼11.0 Hz), 4.58 (d, 1H, J¼11.0 Hz), 4.18–4.12 (m, 1H),
2.73–2.67 (m, 1H), 2.62 (ddddd, 1H, J¼14.0, 2.5, 2.5, 2.5,
2.5 Hz), 2.40 (ddd, 1H, J¼13.5, 6.5, 1.0 Hz), 2.20–2.13
(m, 1H), 1.98–1.92 (m, 1H), 1.82–1.72 (m, 1H), 1.71–1.54
(m, 2H) ppm; 13C NMR (CDCl3, 125 MHz) d 205.3, 93.2,
78.2, 61.4, 40.7, 35.9, 27.4, 23.8 ppm; IR (thin film) n
3302.86, 2918, 1720, 1374, 1184, 1020, 858 cmꢂ1; HRMS
(ES+) calcd for C8H12Cl3NO4S 322.9553 found 345.9445
(MNa+).
3.5.1.8. 5-(2,2,2-Trichloroethoxysulfonylamino)cyclo-
hex-2-enone. To
a solution of Cl3CCH2OSO2NH2
(1.25 g, 5.5 mmol, 1.1 equiv) in 10.0 mL of C6H5Cl were
added sequentially 1,3-cyclohexadiene (5.0 mmol), MgO
(460 mg, 11.5 mmol, 2.3 equiv), and Rh2(NHCOCF3)4
(64 mg, 0.10 mmol, 0.02 equiv). The purple mixture was
cooled to ꢂ10 ꢀC (s-CO2/ethylene glycol bath) and
PhI(OAc)2 (210 mg, 0.65 mmol, 1.3 equiv) was added in
a single portion. After 40 min of stirring at ꢂ10 ꢀC, the
reaction was warmed to 23 ꢀC. The reaction was stirred for
1 h then diluted with 30 mL of CH2Cl2 and filtered through
a pad of Celite. The flask and filter cake were washed
thoroughly with CH2Cl2 and the combined filtrates were
concentrated under reduced pressure. The isolated material
was dissolved in 25 mL of DMSO and the mixture was
stirred for 12 h. The solution was transferred to a separatory
funnel with 100 mL of EtOAc and washed with 2ꢁ100 mL
of H2O. The aqueous washes were combined and extracted

11342
K. Guthikonda et al. / Tetrahedron 62 (2006) 11331–11342
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€
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17. Crystallographic data (excluding structure factors) for the
structures shown in Figure 5 have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication nos. CCDC 614129 and 614130 (azide and aziri-
dine, respectively). Copies of the data can be obtained, free
of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
6. Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 124,
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7. We and others have observed that allylic carbamates react with
Rh-catalysts and PhI(OAc)2 to give cyclized products. In most
cases, the intermediate aziridine is opened by AcOH under the
reaction conditions to give the oxazolidin-2-one product, see:
(a) Levites-Agababa, E.; Menhaji, E.; Perlson, L. N.; Rojas,
C. M. Org. Lett. 2002, 4, 863–865; (b) Padwa, A.; Stengel, T.
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Modern Rhodium-Catalyzed Organic Reactions, Evans, P. A.,
Ed.; Wiley-VCH: Weinheim, 2005; pp 379–416; For a related
method employing unsaturated N-tosyloxycarbamates that
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see: Lebel, H.; Huard, K.; Lectard, S. J. Am. Chem. Soc.
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ꢀ
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12. 2,2,2-Trichloroethylsulfamate (TcesNH2) is now sold by
Aldrich Chemical Co.
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21. Trost and Dong have recently demonstrated that In(OTf)3 can
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idine at reduced temperatures (80 ꢀC); see Ref. 4e.
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submitted for publication.