New options for the reactivity of the burgess reagent with epoxides in both racemic and chiral auxiliary modes - Structural and mechanistic revisions, computational studies, and application to synthesis

Article abstract of DOI:10.1002/ejoc.200900159

The reaction of the chiral auxiliary version of the Burgess reagent with epoxides yields diastereomeric pairs of sulfamldates, which, lead, to cis and trans amino alcohols in each, enantiomeric series. Experimental and spectral, details are provided for a

Full text of DOI:10.1002/ejoc.200900159

FULL PAPER
DOI: 10.1002/ejoc.200900159
New Options for the Reactivity of the Burgess Reagent with Epoxides in Both
Racemic and Chiral Auxiliary Modes – Structural and Mechanistic Revisions,
Computational Studies, and Application to Synthesis
Hannes Leisch,[a] Bradford Sullivan,[a] Branden Fonovic,[a] Travis Dudding,[a] and
Tomas Hudlicky*[a]
Keywords: Burgess reagent / Chiral auxiliaries / Enantioselectivity / Amino alcohol derivatives / Sulfamidate synthesis /
Balanol / Density functional calculations / Structure revisions
The reaction of the chiral auxiliary version of the Burgess
reagent with epoxides yields diastereomeric pairs of sulfami-
dates, which lead to cis and trans amino alcohols in each
enantiomeric series. Experimental and spectral details are
provided for all new sulfamidates and the products derived
from them. Structure revisions have been made for several
previously reported products from the reactions of the Bur-
gess reagent with cyclic oxiranes and styrene diols. Con-
siderable revisions are also suggested for the possible
mechanisms operating in the reactions of the Burgess rea-
gent with 1,2-diols and epoxides. Finally, a Density Func-
tional Theory (DFT) study for the interaction of the achiral
version of the Burgess reagent with oxiranes is included
along with an explanation of the lack of asymmetric induc-
tion observed in reactions conducted in a catalytic mode with
C2-symmetric catalysts.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
closures feature the preparation of α- and β-glycosylamines
from carbohydrates,[11] sulfamidates from 1,2-diols,[12] disul-
fides from thiols,[13] sulfamidates from 2,3-epoxy
alcohols,[14] sulfamides from amino alcohols,[15] and five-
and seven-membered sulfamidates from epoxides.[16]
The reactivity of epoxides with the Burgess reagent is
especially noteworthy because they were believed to be inert
to the action of this reagent as recently as a decade ago.[2,17]
In 2003 we published the first report on the reactivity of
the Burgess reagent with aliphatic and benzylic epoxides to
yield five- and seven-membered sulfamidates, respec-
tively.[16,18] The sulfamidates can serve as precursors to both
cis and trans amino alcohols, which are commonly used in
the pharmaceutical sector.[19]
Introduction
The Burgess reagent (1), discovered almost four decades
ago,[1,2] has experienced renewed popularity over the past
few years in a number of creative synthetic ventures. Origi-
nally designed as a mild dehydrating agent for secondary
and tertiary alcohols, as shown in Figure 1, it has occasion-
ally been used in approaches to or for the total synthesis of
natural products and medicinal agents, for example, ced-
rene,[3] narciclasine,[4] taxol,[5] efrotomycin,[6] and pravasta-
tin.[7]
In the course of our initial investigations we were able to
propose a mechanism to account for the formation of
seven-membered sulfamidates from either epoxides[16] or
1,2-diols[12] and suggested that the latter compounds yield
in some cases seven-membered sulfamidates and not re-
gioisomeric pairs of five-membered sulfamidates as had
been reported.[12] The seven-membered sulfamidates consti-
tute minute amounts in the reaction mixtures derived from
aliphatic epoxides but become more prominent in the reac-
tion of benzylic or otherwise activated oxiranes, as shown
in Figure 2. In the case of 1,2-diols derived from various
styrenes, the seven-membered sulfamidates are minor prod-
ucts, but their proportion increases with deactivation of the
aromatic ring.[12] The discrepancies in the initial structural
assignments are shown in Figure 2.
Figure 1. Dehydration of alcohols with the Burgess reagent.
It is also the reagent of choice for the synthesis of ure-
thanes from primary alcohols[8] and dehydration of amides
to nitriles.[9] Its polymer-linked version has been employed
in the synthesis of oxazolines and thiazolines.[10] Recent dis-
[a] Department of Chemistry and Centre for Biotechnology, Brock
University,
500 Glenridge Ave., St. Catharines, Ontario, L2S 3A1, Canada
Fax: +1-905-984-4841
E-mail: thudlicky@brocku.ca
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
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Reactivity of Burgess Reagent with Epoxides
The investigations described in this paper have led to
considerable revisions of some previously reported struc-
tures as well as adjustments in the current mechanism of
the reaction of the Burgess reagent with epoxides and di-
ols.[22] One of the reasons for the erroneous structural as-
signments may be the fact that almost all reactions per-
formed to date on diols and epoxides were carried out on
conformationally flexible substrates (exceptions being cy-
clohexene oxide, some of the 2,3-hydroxyoxiranes,[14] and
carbohydrates[11]). The reactivity manifolds as well as iden-
tification of products and stereochemical assignments are
different in cyclic oxiranes, diols, and amino alcohols. In
this paper we report the details of the use of the first chiral
auxiliary version of the Burgess reagent in its interactions
with oxiranes and provide corrections regarding some of
the previously published structures. In addition, a computa-
tional rationale Density Functional Theory (DFT) is ad-
vanced for the clarification of the mechanistic options in
the reactions with oxiranes.[12,16,22]
Results and Discussion
Figure 2. Sulfamidate formation from oxiranes and 1,2-diols. As-
sumed (reported) and actual (correctly assigned) products.
Synthesis of Optically Pure Amino Alcohols
The original Burgess reagent, modelled after known syn
elimination protocols (acetate and xanthate pyrolysis, Cope
elimination, sulfoxide and selene oxide eliminations), was
prepared only in its methyl and ethyl carbamate versions.[1]
Four additional forms of the reagent, altered at the carb-
amate terminus, appeared in 2004 (benzyl, o-NO2-benzyl,
allyl, and β-trichloroethyl), and their use in milder depro-
tection schemes for carbamates has been suggested.[12] One
report described a Burgess type reagent with quinuclidine
instead of triethylamine.[23] In 2006 we published a prelimi-
nary report on the synthesis of enantiopure sulfamidates
and the corresponding trans amino alcohols in both enan-
tiomeric forms by employing a chiral auxiliary version of
the Burgess reagent, the menthyl carbamate 10, Figure 4.
Prior to this report we also prepared several other chiral
auxiliary versions such as the camphor-derived carbamate
11 and the two cyclic forms 12 and 13 prepared from the
diene diol 14;[24] however, the reactions of these reagents
with oxiranes proved erratic, and we therefore focused on
the investigations of reactions of the menthyl version.
Seven-membered sulfamidates may be derived from ep-
oxides as well as from diols. That epoxides formed in situ
may be the intermediates was supported by the results of
the reaction with optically active styrene oxide and with
the optically pure diol derived from styrene.[16] In each case
inversion of configuration occurred at the benzylic center
(see below for more details).
The reaction of the Burgess reagent with oxiranes derived
from cyclic compounds was of special interest to us because
it could serve as a source of both cis and trans amino
alcohols, as shown in Figure 3. As the reactive tendencies
of sulfamidates resemble those of cyclic sulfates,[20,21] we
reasoned that such a Scheme would provide the eventual
access to enantiopure amino alcohols in both dia-
stereomeric series by inverting the initially formed oxygen-
ated center with ammonium benzoate. These considerations
have led us to implement a chiral auxiliary version of
the Burgess reagent (possibly also a catalytic asymmetric
option) and its reactions with both cyclic and acyclic
oxiranes in order to validate the idea depicted in Figure 3
in a homochiral fashion.
Figure 3. Synthesis of cis- and trans amino alcohols from cyclic
sulfamidates.[16]
Figure 4. Chiral versions of the Burgess reagent.
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We prepared the menthyl carbamate version of the rea- Similarly, 19b was evaluated [α]2D2 = –7.4 (c = 1.0, EtOH),
gent 10 despite expectations that a freely rotating auxiliary ref.[26] –5.9 (c = 1.0, EtOH) and 19F NMR of its Mosher
group might not lead to significant levels of diastereoselec- amide indicated Ͼ93% ee (this lower value was likely
tion.[25] The menthol-containing reagent 10 was prepared due to an incomplete separation of the diastereomeric
easily by reacting menthol with chlorosulfonyl isocyanate benzoates 16). These were exciting results, especially in view
followed by triethylamine, Scheme 1. Reaction of 10 of the fact that we also obtained the allylic amine 17 in
(2.3 equiv.) with cyclohexene oxide produced a 1:1 mixture reasonable yield during the ammonium benzoate reac-
1
of diastereomers, identified by H- and 13C NMR, but in- tion.[27]
separable on a silica column, in a modest yield. As optimi-
It seemed prudent at this point to apply this protocol to
zation of reaction yields at this stage was not a priority, we several other epoxides in order to evaluate the generality of
decided first to evaluate the level of optical purity in the the process before choosing an auxiliary group that would
products after the removal of the auxiliary group. Sulfamid- permit full separation at the stage of sulfamidates such as
ates 15a and 15b were treated with ammonium benzoate in 15a and 15b. Table 1 shows the products and their enantio-
DMF to yield a separable mixture of diastereomeric carba- meric excess from the reactions of various oxiranes with the
mates 16a and 16b, which were hydrolyzed and converted menthyl Burgess reagent 10. In each case the diastereomeric
separately to oxazolidones 18a and 18b in excellent yields. pairs were separated at the stage of the protected trans
Optical rotations of 18a matched the literature value [α]2D2 amino benzoates. The diastereomeric excess was determined
= +7.5 (c = 1.0, EtOH), ref.[26] +6.0 (c = 1.0, EtOH) and by GC/MS. The absolute stereochemistry of 27a and 27b
Mosher’s amide analysis of 19a indicated Ͼ98% ee. were determined after hydrogenation to 16a and 16b.
Table 1. Reactions of oxiranes with menthyl version of the Burgess reagent.
[a] Yields are isolated and unoptimized. [b] Enantiomeric excess determined by Mosher’s amide formation of cyclic carbamates, derived
from the corresponding benzoates by hydrolysis and cyclization. [c] Diastereomeric excess determined by GC/MS of benzoates after
separation by flash column chromatography. [d] Not separable by flash column chromatography. [e] Diastereomeric excess determined by
GC/MS of separated benzoates after hydrogenation.
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Reactivity of Burgess Reagent with Epoxides
Attempted Asymmetric Catalysis in the Reaction of the
Burgess Reagent with Oxiranes
In order to study the extent of asymmetric induction, we
tested Jacobsen’s[29] salen (30) catalyst as well as the scan-
dium chelate of the C2-symmetric bipyridine[30] 31, reported
to act as an activating Lewis acid in reactions with epoxides.
The use of 0.1 equiv. of Jacobsen’s catalyst (30) along with
the Burgess reagent and cyclohexene oxide in THF or di-
ethyl ether at either room temperature or reflux led to low
yields (20%) of racemic sulfamidates with no sign of asym-
metric induction. Similar results were obtained when cyclo-
hexene oxide was treated with the Burgess reagent in the
presence of 0.1 equiv. of Bolm’s catalyst (31) in either THF
or dichloromethane at room temperature. In order to deter-
mine the enantiomeric excess of the products, cyclic sulfam-
idate 7 was treated with ammonium benzoate in DMF, fol-
lowed by acid hydrolysis to yield protected amino alcohol
9. Basic hydrolysis of the benzoate ester followed by 3-(3-
dimethylaminopropyl)-1-ethylcarbodiimide hydrochloride-
mediated esterification with (R)-Mosher’s acid gave a one-
to-one mixture of diastereomers as assessed by 19F NMR
Scheme 1. Reagents and conditions: a) 10 (2 equiv.), THF reflux,
–
1.5 h; b) PhCO2 NH4+, DMF, 45 °C, 12 h; c) THF, H2O, conc.
H2SO4, room temp., 6 h; d) 1  NaOH in MeOH, 2 h; e) NaH,
THF reflux, 18 h, f) nBuLi, 0 °C, 30 min, (S)-(+)- Mosher’s acid and GC/MS analysis. An explanation for the lack of asym-
chloride, –78 °C to room temp.
metric induction may be the propensity of the Burgess rea-
gent acting as pseudo acid in activating the epoxide for nu-
cleophilic attack and in doing so preventing coordination
of the epoxide to the asymmetric catalyst. Some support
Application to the Enantiodivergent Formal Synthesis of
Balanol
for this view is provided by calculations (see the section on
computational studies).
Encouraged by the ease with which the trans amino
alcohol derivatives were obtained, we applied this method-
ology to the synthesis of both (–)- and (+)-balanol. Benzo-
ates 27a and 27b possess the absolute stereochemistry of
Structural and Mechanistic Revisions
During the course of this study we became concerned
about discrepancies in the 1H NMR spectra of cis-sulfamid-
(–)- and (+)-balanol, respectively, and only oxidative cleav-
ates 15a and 15b and those of the previously reported trans-
age of the olefin followed by reductive amination is required
sulfamidates 6 (Figure 2).[16] Especially troubling was the
to produce the balanol core. The conversions of 27a to (–)-
comparison of spectral properties of the protected cis
29a and hence to (–)-balanol and 27b to (+)-29b, the inter-
amino benzoate derived from the reaction of 6 with ammo-
mediate for (+)-balanol, have been completed and pub-
nium benzoate (reported in our 2003 publication as com-
lished recently,[28] and are shown in Scheme 2.
pound 9, Scheme 3)[16] with those of the products obtained
from treatment of sulfamidates 15 with ammonium benzo-
ate (Scheme 1). Results of the repetition of the synthesis of
6 and preparation of standards confirmed our suspicions
that our original assumption of the trans-epoxide opening
followed by rapid intramolecular sulfonation was incorrect
and that epoxides yield cis not trans-sulfamidates upon re-
action with the Burgess reagent. The synthesis and structure
revisions are shown in Scheme 4. The cis-sulfamidate 36
was prepared as shown from cis amino alcohol 33, gener-
ated from the commercially available trans-isomer 37 by Ja-
cobsen’s protocol.[31] Selective protection of the amine func-
tionality of 33 followed by treatment with thionyl chloride
in CH3CN furnished heterocycle 35 in 78% yield, which
upon ruthenium-mediated oxidation gave cis-sulfamidate
36. The trans-isomer, 41, was generated from commercial
Scheme 2. Reagents and conditions: a) 1  NaOH, MeOH; b)
NaH, THF, reflux; c) p-benzyloxy benzoyl chloride, NEt3, DMAP,
dichloromethane, 0 °C to room temp.; d) OsO4, NMO, H2O,
dichloromethane, room temp.; e) i) NaIO4, acetone, H2O, room
temp.; ii) BnNH2, MeOH, NaCNBH3, AcOH, mol. sieves (3 Å),
–78 °C to room temp.; f) 0.3  NaOH, MeOH, THF, –20 °C.
37 in a similar fashion. It became clear that 6 (Figure 2) is
identical to 41 and not 36; therefore, 7 (Figure 2) must be
the same as 36, a cis, not trans-isomer. This argument elim-
inates the possibility of direct intramolecular sulfonation,
which we have studied by dilution experiments and sub-
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H. Leisch, B. Sullivan, B. Fonovic, T. Dudding, T. Hudlicky
The mechanism for the conversions of 1,2-diols to sulfa-
FULL PAPER
strate-to-reagent ratios. In all cases, it is the cis-isomer of
sulfamidate that is formed from epoxides and not the ex- midates requires the participation of two equivalents of the
pected trans-isomer. Thus the mechanism operating on ep- Burgess reagent, only one of which remains in the product.
oxides is similar in concept but not procedure to that op- To date the published results reported the conversions of
erating on diols, as trans-cyclohexane diol yields exclusively diols on freely rotating side chains, and, with the exception
cis-sulfamidate 36. cis-Cyclohexane diol is unreactive be- of the carbohydrate-glycosylamine transformations, no ri-
cause the bis sulfonated intermediate cannot undergo a SN2 gid cyclic diols have been evaluated to determine which of
displacement.
the sulfonates in 44 becomes a leaving group. In the carbo-
hydrate cases, it is almost self-evident, although not unam-
biguously validated. An experiment on a cyclic trans-diol
with known absolute stereochemistry and labelled at one of
the hydroxylated sites with deuterium would be required to
confirm the exact course of events leading from 44 to either
7a or its regioisomer 7b, Figure 5. With epoxides, two
equivalents are also required but, unlike in the reactions
with diols, one returns unchanged into the reaction cycle.
The alkoxide 45, generated upon opening of the oxirane
ring, is sulfonated by the second equivalent faster than it
can undergo the intramolecular sulfonation to produce
trans-sulfamidate 41 (path a). There is little doubt that the
actual conversion to 46 (path b) is facilitated to some extent
by the energetically unfavourable formation of a trans-fused
five-membered ring as an alternative. Displacement of the
second Burgess reagent from 46 then leads to cis-fused 7
and not to trans-fused 41 as was assumed originally.[16]
–
Scheme 3. Reagents and conditions: a) THF, 48 h; b) PhCO2
NH4+, DMF, 45 °C, 12 h; c) THF, H2O, conc. H2SO4, room temp.,
6 h; d) 1  NaOH in MeOH, 2 h; e) (R)-(+)-Mosher’s acid, EDC,
DMAP, dichloromethane, 0 °C to room temp., 18 h.
Scheme 4. Reagents and conditions: a) methyl chloroformate,
NaHCO3, CHCl3/H2O; b) SOCl2, CH3CN, –40 °C; c) RuCl3·H2O,
–
NaIO4, CH3CN/H2O; d) Ac2O; e) SOCl2; f) 10% HCl; g) PhCO2
NH4+, DMF, 45 °C, 12 h; h) MeNH2, THF, CH3CN, H2O, room
temp., 18 h.
Two other observations are worth mentioning. First, the Figure 5. Mechanistic options for the reaction of the Burgess rea-
gent with cis or trans-cyclohexadiol or cyclohexene oxide.
trans-sulfamidate yields 42 on treatment with ammonium
benzoate and not the expected “inverted” cis-disposed ben-
zoate. Such mild hydrolysis conditions for a methyl carba-
The lack of reactivity of cis-diols is clear from stereoelec-
mate are interesting. Second, methylamine in acetonitrile tronic considerations; no SN2 displacement is possible from
also provides the free sulfamidate 42 under very mild condi- the doubly sulfonated compound 47. However, it should be
tions. Clearly, the hydrolysis (or reductive) conditions re- interesting to investigate possible single elimination path-
quire fine tuning in order to provide protected amino ways to allylic alcohols (path b) or double eliminations to
alcohols in either series of diastereomeric sulfamidates.
dienes at elevated temperatures.
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Reactivity of Burgess Reagent with Epoxides
With activated epoxides and diols, such as those that and b in option A. If pathway a occurred, sulfonation to
contain a benzylic carbon–oxygen bond, the formation of 49, deprotonation to 50, and displacement to 53a should be
both five- and seven-membered sulfamidates is possible, as the outcome. Path b assumes sulfonation of the primary
demonstrated in our preliminary publication.[16] The mech- alcohol, intramolecular deprotonation of 51 to 52, and the
anistic divergence regarding which of the two hybrids of the final closure to 53b. Reaction with the second equivalent of
amide resonance participates in the reaction may depend on the Burgess reagent then leads to 54, through the participa-
hard-soft matching of the polarized C–O bond with either tion of hybrid 1b, favored in these reactions on account of
nitrogen- or oxygen-centered anion. The more activated the hard–soft acid–base arguments. Ejection of triethyl-
benzylic position, the more the seven-membered sulfamid- amine completes the formation of 4a, in which the benzylic
ate predominates the reaction mixtures. It is not yet clear carbon configuration is opposite to that in 48. We have
that the seven-membered sulfamidates are formed from ep- demonstrated that indeed path b seems to be operating in
oxides and not from the intermediates of type 55. Again, this sequence and have isolated 48b by hydrolysis of 4a in
this question can only be answered by performing the syn- pure enantiomeric form, indicating that path a with the for-
thesis on diols (or epoxides) of known absolute stereochem- mation of 53a did not take place. These experiments sup-
istry and with the Burgess reagents containing two different port the intermediacy of epoxides in the formation of minor
carbamate groups. Neither parameter is sufficient to distin- products, seven-membered sulfamidates, from the reactions
guish between the two pathways, A and B, shown in Fig- of diols. However, the alternative, formation of 55 from 48a
ure 6.
and intramolecular displacement to 4a cannot be excluded.
We also performed an additional set of experiments in
which 20% of racemic styrene oxide was added to a reac-
tion of the Burgess reagent with racemic styrene diol and
in another experiment 20% of racemic styrene diol was
added to the reaction of racemic styrene oxide. In each case,
the ratio of the sulfamidates changed in favor of the minor
product: in the reaction of styrene oxide, the minor compo-
nent, five-membered sulfamidate, increased from 8% to
20% and in the reaction of styrene diol, the amount of the
minor component, the seven-membered sulfamidate, in-
creased from 10% to 23%. These experiments do not unam-
biguously exclude option B, Figure 6, but validate that ep-
oxides are potential intermediates in the reaction since the
formation of the diol from the epoxide cannot take place
under the reaction conditions. To exclude or validate the
existence of 55 a set of mixed Burgess reagents must be
used, with sequential sulfonation and determination
whether the transformation of 55 to 4a occurs. For the mo-
ment option A seems as the more reasonable.
Computational Studies
The apparent mechanistic complexity of the Burgess rea-
gent’s reactivity is attested to by a number of corrections
having appeared within the chemical literature over the last
several years.[16,25] Constitutional and stereochemical struc-
tural assignments have been corrected, and to date there
has not been a single computational study addressing the
Burgess reagent’s reactivity.[32] With this knowledge in
hand, our efforts next turned to the use of (GGA)-hybrid
Kohn–Sham density functional theory (KS-DFT) at the
B3LYP[33]-6-31G(d)[34] level in order to gain mechanistic in-
sight into this reaction dynamic. First we examined the
Figure 6. Mechanistic options for the reaction of the Burgess rea-
gent with styrene oxide.
We performed the reaction on optically pure diol 48a, mechanistic origin of chemoselective formation of five-
which can form an epoxide by two different pathways: a membered cis-sulfamidate (Table 1) formation from the re-
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Scheme 5. Mechanistic possibilities for reaction of the Burgess reagent (1) with cyclohexene oxide.
actions of meso cyclo[n.1.0]alkanes (n = 3–6). Second, we
attempted to explain why no discernible level of diastereose-
lection was found from reactions conducted using chiral
Burgess reagent 10 and cyclohexene oxide. Finally these re-
sults were extrapolated to rationalize the lack of observed
enantioinduction within ring-opening reactions of cyclo-
hexene oxide with achiral Burgess reagent 1 catalyzed by
C2-symmetric 2,2Ј-bipyridine·Sc(OTf)3 31 as well as Jacob-
sen’s [(salen)CrICl] complex 30.
Our attention turned towards conducting an initial set
of representative studies investigating reaction scenarios
comprising Burgess reagent 1 and cyclohexene oxide
(Scheme 5). In line with this reasoning, first-order saddle
Figure 7. Five-membered-TS1 corresponding to syn sulfamidate
points corresponding to backside SN2 addition of the Bur-
gess reagent to cyclohexene oxide were located by way of
an exhaustive scan of the potential energy surface
(PES)[35] using the Gaussian 03[36] suite of programs, Path-
way B, Scheme 5. However, all optimized geometries pos-
sessed activation barriers that were unrealistically large
(∆G‡ Ͼ 50 kcal/mol).[37] Accordingly a more extensive in-
vestigation of the reaction hypersurface was conducted,
from which front side attack [3+2] concerted asynchronous
(∆G‡ = 38.9 kcalmol–1) was located, Pathway A, Scheme 5
and Figure 7.[38] Regarding the specific metrics of five-
membered-TS1, contained within are multiple bond-form-
ing and bond-breaking events, namely one C···O bond of
the epoxide fragments at a distance of 2.10 Å, while the
C···N (2.62 Å) and O···S (1.84 Å) bonds are formed simul-
taneously. Of particular interest is the presence of multiple
hydrogen bonding interactions, which contribute to an
overall weak stabilization of the transition state. Specifi-
cally, there exists a S=Oδ–···H–C hydrogen bond identified
by atoms in molecules[39] (AIM) quantum theory (ٌ =
–0.0156) at 2.38 Å in length. using natural bond orbital[40]
(NBO) analysis to quantify the interaction yields a stabiliz-
ing interaction energy of 2.56 kcal/mol. Finally, two hydro-
gen bond contacts generated from the ester functionality
were identified: a C=Oδ–···H–C–N+ hydrogen bond contact
of 2.69 Å (ٌ = –0.00604, NBO = 1.43 kcal/mol) as well as
a C–Oδ–···H–C–Cδ+ contact at 2.46 Å (ٌ = –0.00865, NBO
= 1.52 kcal/mol).
formation.
[3+2] concerted asynchronous bond-forming event,[41] the
direct product of which is a local minimum for cis five-
membered sulfamidate 7,[42] a finding which is consistent
with experiment.
The absence of diastereoselection for the case of 15 may
be understood as being an artefact of remote chiral induc-
tion. To support this supposition a refined frozen-core
(TS)-MCMM conformational search conducted at the
semi-empirical PM3 level of theory was performed by me-
ans of 10 and cyclohexene oxide. This search revealed low
energy conformers wherein the heavy atoms of the chiral
auxiliary resided far from the site of oxirane opening.[43]
Regarding the addition of chiral Lewis-acid reagents for
stereoinduction, it is readily apparent that during asynchro-
nous concerted five-membered-TS1 the Burgess reagent oc-
cupies a large volume of space surrounding the oxirane
moiety. According to these results it is impossible for a
Lewis acid to be bound to the oxirane during this transition
state.[44] Last, it should also be noted that, in the presence
of a Lewis acid co-catalyst such as CrI or ScIII, the Burgess
reagent 1 is thought to undergo rapid degradation and in
doing so generates an excess of achiral species capable of
competitively catalyzing these reactions.[45]
Conclusions
Irrespective of the highlighted metrics and stereoelec-
tronic attributes of 5-mem-TS1 noted above, it is of perhaps
The reactivity of the Burgess reagent with epoxides and
even greater significance that 5-mem-TS1 corresponds to a 1,2-diols was examined for possible mechanistic duality.
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Reactivity of Burgess Reagent with Epoxides
4-Methoxy-6-phenyl-2,26,7-dihydro-1,5,2,3-dioxathiazepine 2,2-Di-
oxide (4): Colorless crystals; m.p. 100–105 °C (ethyl acetate/hex-
Several structural assignments previously reported in the
literature were corrected and a computational study (DFT)
was performed to rationalize the lack of asymmetric induc-
tion in the reactions of meso epoxides with the Burgess rea-
gent in the presence of C2-symmetric catalysts. The mecha-
nisms by which the Burgess reagent reacts with epoxides
and diols may proceed through common intermediates as
the experimental evidence seems to suggest. The DFT stud-
ies revealed that the formation of syn sulfonamidate 15
from the reaction of cyclohexene oxide and the Burgess rea-
gent proceeds via a concerted asynchronous [3+2] transi-
tion state. In addition, this transition state provided a struc-
tural basis for rationalizing the lack of diastereo- and
enantioselectivities observed when a chiral Lewis acid, or a
chiral version of the Burgess reagent was used within a reac-
tion with cyclohexene oxide. The chiral auxiliary version of
the Burgess reagent was exploited in the synthesis of cis and
trans amino alcohol derivatives and in the total synthesis of
balanol. Future work in this area will address design of new
Burgess reagents and exploitations of catalytic asymmetric
versions in the reactions with epoxides and diols.
anes); R = 0.50 (hexanes/ethyl acetate, 3:1). IR (film): νmax = 2959,
˜
f
1603, 1305 cm–1. H NMR (300 MHz, CDCl3): δ = 7.36–7.47 (m,
1
5 H), 6.15 (dd, J = 3.6, 10.7 Hz, 1 H), 4.62 (dd, J = 10.5, 12.6 Hz,
1 H), 4.52 (dd, J = 3.6, 12.6 Hz, 1 H), 3.93 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 158.6, 132.1, 130.5, 129.6, 126.8, 82.8, 72.9,
58.9 ppm. HRMS (EI): calcd. for C10H11NO5S: 257.0358; found
257.0352. C10H11NO5S (257): calcd. C 46.23, H 4.31; found C
46.23, H 4.51.
Methyl cis-Hexahydro-3H-1,2,3-benzoxathiazole-3-carboxylate 2,2-
Dioxide (7): Compound 7 was prepared in 64% yield (604 mg) as
colorless crystals following the general procedure for reactions of
oxiranes with the Burgess reagent (1), using cyclohexene oxide as
starting material; m.p. 97–98 °C (ethyl acetate/hexanes); Rf = 0.49
(hexanes/ethyl acetate, 1:1). IR (film): ν
= 2943, 1743, 1385,
˜
max
1183 cm–1. 1H NMR (300 MHz, CDCl3): δ = 5.00 (br. s, 1 H), 4.22
(br. s, 1 H), 3.90 (br. s, 3 H), 2.33 (br. s, 2 H), 1.45–1.85 (m, 4 H),
1.16–1.33 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.4,
80.0, 58.3, 54.7, 27.4, 27.2, 22.0, 19.1 ppm. HRMS (FAB) [M +
H+]: calcd. for C8H14O5NS: 236.0593; found 236.0608. C8H13NO5S
(235): calcd. C 40.84, H 5.70; found C 40.98, H 5.70.
Alternatively, compound 7 was prepared by the following pro-
cedure. Ruthenium(III) chloride hydrate (catalytic amount), so-
dium periodate (439 mg, 2.05 mmol) and water (5 mL) were added
sequentially, at 0 °C to a solution of oxathiazolidine 35 (300 mg,
1.37 mmol) in CH3CN (5 mL). The reaction mixture was warmed
to room temperature and was stirred at ambient temperature for
an additional 3 h. The reaction mixture was extracted three times
with Et2O. The organic layers were combined, washed with water,
then brine, and dried with anhydrous magnesium sulfate. Filtration,
evaporation of the solvent, and purification by flash column
chromatography (hexanes/ethyl acetate, 4:1) afforded 287 mg (82%)
of compound 36 as white solid after recrystallization from hexanes/
ethyl acetate. The analytical data obtained for compound 36 is
identical to data of compound 7.
Experimental Section
All non-aqueous reactions were carried out in under argon using
standard Schlenk techniques for the exclusion of moisture and air.
Dichloromethane was distilled from calcium hydride. THF and
benzene were dried with potassium/benzophenone. Analytical thin-
layer chromatography was performed on Silicycle 60 Å 250 µm
TLC plates with F-254 indicator. Flash column chromatography
was performed using Natland 200–400 mesh silica gel. Melting
points were recorded with a Hoover Unimelt apparatus and are
uncorrected. IR spectra were obtained with a PerkinElmer One FT-
IR spectrometer. Optical rotation was measured on a Perkin–Elmer
341 polarimeter. 1H-, 19F- and 13C-NMR spectra were recorded on
a Bruker (300 MHz or 600 MHz) spectrometer. All chemical shifts
are referenced to TMS or residual undeuterated solvent (CHCl3,
CH2Cl2). Combustion analyses were performed by Atlantic Micro-
labs, Norcross, GA. Mass spectra were recorded with Kratos/MsI
Concept 1S mass spectrometer at Brock University.
trans-2-(Methoxcarbonylamino)cyclohexyl Benzoate (9): Ammo-
nium benzoate (651 mg, 4.68 mmol) was added to a solution of
benzoxathiazole 7 (550 mg, 2.34 mmol) in dry DMF (10 mL). The
solution was heated to 55 °C until TLC analysis indicated full con-
version of the starting material (18 h). The solvent was evaporated,
and the residue was dissolved in THF (6 mL), three drops of water
and three drops of hydrosulfuric acid were added. The reaction
mixture was stirred at room temperature for 3 h, before the pH was
adjusted to 8 with saturated aqueous NaHCO3 solution. The layers
were separated, and the aqueous layer was extracted three times
with dichloromethane. The organic layers were combined and
washed with H2O and brine. After the solvent was evaporated un-
der reduced pressure, the residue was purified by flash column
chromatography (hexanes/ethyl acetate, 9:1) affording 265 mg of
colorless oil (41%). Rf = 0.55 (hexanes/ethyl acetate, 2:1). IR (film):
General Procedure for Reactions Between Oxiranes and the Burgess
Reagent: (Methoxycarbonylsulfamoyl)triethylammonium hydrox-
ide, inner salt (2.38 g, 9.2 mmol) was added to a stirred solution of
the oxirane (4.0 mmol) in THF (20 mL) at room temperature in a
single portion. The resulting reaction mixture was brought to reflux
immediately by submerging it into a preheated oil bath (70 °C).
The reaction was stirred until complete consumption of the oxirane
(TLC), then cooled to room temperature and filtered through a
plug of silica to remove salts formed during the reaction. The reac-
tion mixture was concentrated, and the resulting residue was puri-
fied by flash column chromatography using an appropriate solvent
gradient to yield the sulfamidate product(s).
ν
max = 3339, 3064, 2940, 2861, 1714, 1538, 1452, 1320, 1279, 1235,
˜
1115, 713 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.04 (d, J =
7.5 Hz, 2 H), 7.55 (m, 1 H), 7.43 (t, J = 7.5 Hz, 2 H), 4.83 (m, 2
H), 3.71–3.88 (m, 1 H), 3.53 (s, 3 H), 2.02–2.24 (m, 2 H), 1.69–2.02
(m, 2 H), 1.49–1.68 (m, 1 H), 1.18–1.48 (m, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 167.0, 156.8, 133.2, 130.3, 129.9, 128.5, 75.9,
54.5, 52.2, 32.6, 31.3, 24.6, 24.2 ppm. HRMS (FAB): calcd. for
C15H20NO4: 278.1392; found 278.1382.
Methyl 4-Phenyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-Dioxide
(3): Colorless oil; Rf = 0.44 (hexanes/ethyl acetate, 3:1). IR (film):
ν
˜
max = 2962, 1746, 1321, 1192 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 7.38–7.47 (m, 5 H), 6.15 (dd, J = 3.3, 10.5 Hz, 1 H), 4.68–4.51
(m, 2 H), 3.94 (s, 3 H) ppm. NMR (75 MHz, CDCl3): δ = 158.6,
N,N-Diethyl-N-{[({[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl]-
132.1, 130.4, 129.4, 126.7, 82.7, 72.8, 58.8 ppm. HRMS (EI): calcd. oxy}carbonyl)amino]sulfonyl}ethanaminium, Inner Salt (10): A solu-
for C10H11NO5S: 257.0358; found 257.0357. tion of (–)-menthol (5.00 g, 32 mmol) in benzene (15 mL) was
Eur. J. Org. Chem. 2009, 2806–2819
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2813

H. Leisch, B. Sullivan, B. Fonovic, T. Dudding, T. Hudlicky
FULL PAPER
added dropwise to a stirred solution of chlorosulfonyl isocyanate
(5.21 g, 36.8 mmol) in benzene (15 mL) over 30 min while keeping
the internal temperature between 25 and 30 °C in an ice-water bath.
The reaction mixture was stirred at room temperature for an ad-
ditional 30 min, before ice-cold hexane (40 mL) was added while
cooling the reaction mixture to 0–5 °C. The product was filtered
and washed with ice-cold hexanes (2ϫ20 mL) and dried under re-
duced pressure to yield 8.29 g (87%) of (–)-mentholsulfamoyl chlo-
23.4, 22.30, 22.25, 21.3, 21.2, 19.3, 16.4, 16.3 ppm. HRMS (EI):
calcd. for C17H29NO5S: 359.1766; found 359,1761. C17H29NO5S
(359): calcd. C 56.80, H 8.12; found C 57.12, H 8.30.
5-Methyl-2-(1-methylethyl)cyclohexyl (3aR,6aS)-rel-Tetrahydrocy-
clopenta[d][1,2,3]oxathiazole-3(3aH)-carboxylate 2,2-Dioxide (20a
and 20b): The general procedure for the reaction of oxiranes with
compound 10 and cyclopentene oxide (168 mg, 2.00 mmol) as
starting material gave 305 mg (37 %) of a 1:1 mixture of dia-
stereomers after purification by flash column chromatography
(hexanes/ethyl acetate, 15:1 to 3:1). Colorless oil; Rf = 0.81 (hex-
anes/ethyl acetate, 2:1). [α]2D3 = –79.2 (c = 1.02, CHCl3). IR (film):
ride as colorless crystals (87%); m.p. 86–88 °C (hexanes). [α]2D3
=
64.5 (c = 0.8, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 8.38–8.55
(br. s, 1 H), 4.81 (td, J = 11.2, 4.6 Hz, 1 H), 2.07–2.16 (m, 1 H),
1.83–2.01 (m, 1 H), 1.61–1.77 (m, 2 H), 1.39–1.58 (m, 2 H), 1.04–
1.22 (m, 2 H), 0.93 (t, J = 6.8 Hz, 6 H), 0.83 (d, J = 6.8 Hz, 3
H) ppm. (–)-Mentholsulfamoyl chloride was used without further
purification for the next step.
ν
max = 3400, 3019, 2962, 2400, 1731, 1522, 1423, 1383, 1307, 1030,
˜
669 cm–1. H NMR (300 MHz, CDCl3): δ = 5.21 (t, J = 5.3 Hz, 1
H), 4.74 (dt, J = 10.9, 4.4 Hz, 1 H), 4.55 –4.63 (m, 1 H), 2.08–2.15
(m, 5 H), 1.81–1.89 (m, 2 H), 1.66–1.74 (m, 2 H), 1.42–1.50 (m, 2
H), 1.10–1.18 (m, 2 H), 0.88–0.95 (m, 7 H), 0.76–0.85 (m, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 150.1, 83.8, 79.1, 78.3, 71.2,
61.4, 61.3, 46.7, 40.6, 40.5, 33.9, 32.75, 32.7, 32.3, 31.4, 31.4, 26.2,
26.0, 25.6, 23.3, 23.2, 22.9, 22.6, 21.9, 20.8, 20.8 ppm. HRMS
(FAB) [M + H+]: calcd. for C16H27NO5S: 346.1688; found
346.1659.
1
A solution of (–)-mentholsulfamoyl chloride (7.00 g, 23.5 mmol)
in benzene (40 mL) was added dropwise to a stirred solution of
triethylamine (6.53 mL, 47.0 mmol) in benzene (20 mL) over 1 h,
keeping the internal temperature between 10 and 15 °C in an ice-
water bath. The reaction mixture was stirred at room temperature
for an additional 30 min and then filtered to remove the triethyl-
amine hydrochloride salt. The filtrate was evaporated under re-
duced pressure, then dissolved in THF (50 mL) at 30 °C and cooled
to 0–5 °C and treated with hexanes (50 mL) to precipitate out the
title compound 10 (7.24 g, 85%) as a colorless solid; m.p. 87–89 °C
5-Methyl-2-(1-Methylethyl)cyclohexyl (3aR,8aS)-rel-Hexahydrocy-
clohepta[d][1,2,3]oxathiazole-3(3aH)-carboxylate 2,2-Dioxide (22a
and 22b): The general procedure for the reaction of oxiranes with
compound 10 and cycloheptene oxide (224 mg, 2.00 mmol) as
starting material gave 211 mg (35 %) of a 1:1 mixture of dia-
stereomers after purification by flash column chromatography
(hexanes/ethyl acetate, 15:1 to 4:1). Colorless oil; Rf = 0.57 (hex-
anes/ethyl acetate, 4:1). [α]2D3 = –60.5 (c = 0.75, CHCl3). IR (film):
(THF/hexanes). [α]2D3 = –48.7 (c = 0.48, CHCl ). IR (film): ν
=
˜
3
max
3426, 3020, 2958, 2872, 1682, 1457, 1389, 1369, 1340, 1285, 1253,
1
1216, 1105, 982, 922, 891 cm–1. H NMR (300 MHz, CDCl3): δ =
4.51 (td, J = 11.0, 4.6 Hz, 1 H), 3.45 (q, J = 7.7 Hz, 6 H), 3.14–
3.26 (m, 1 H), 1.93–2.08 (m, 2 H), 1.65 (d, J = 11.9 Hz, 2 H), 1.30–
1.44 (m, 11 H), 0.92–1.03 (m, 2 H), 0.87 (t, J = 7.7 Hz, 6 H), 0.76
(d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.7,
76.4, 50.7, 47.3, 46.7, 41.3, 34.6, 31.8, 26.4, 23.7, 21.2, 16.6, 9.8,
8.8 ppm.
ν
= 2958, 2931, 1729, 1457, 1381, 1332, 1307, 1190 cm–1. 1H
˜
max
NMR (300 MHz, CDCl3): δ = 5.00–5.17 (m, 1 H), 4.72 (dt, J =
11.0, 4.5 Hz, 1 H), 4.21–4.36 (m, 1 H), 2.20–2.37 (m, 1 H), 1.63–
2.18 (m, 10 H), 1.35–1.58 (m, 4 H), 1.03–1.33 (m, 3 H), 0.85–1.00
(m, 8 H), 0.71–0.84 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 149.8, 149.8, 81.6, 81.6, 79.1, 79.0, 63.1, 63.0, 46.8, 46.7, 40.6,
40.5, 33.9, 31.5, 31.4, 30.2, 30.2, 29.2, 28.6, 28.5, 26.0, 25.9, 25.6,
23.3, 22.9, 22.6, 21.9, 21.6, 20.9, 20.8, 15.8 ppm. MS (FAB): m/z
(%) = 374 (52) [M + H+]: 139, 137 (22), 97 (19), 95 (44), 83 (100),
81 (37), 79 (11), 77 (12), 69 (46), 67 (21), 57 (36), 55 (62), 53 (14).
HRMS (FAB) [M + H+] Calcd for C18H33NO5S: 374.2001; found
374.2018.
General Procedure for the Synthesis of Sulfamidates from Oxiranes
with the Menthyl Version of the Burgess Reagent: Compound 10
(4.60 mmol) was added to a stirred solution of oxirane (2.0 mmol)
in THF (5 mL) at room temperature in a single portion. The re-
sulting reaction mixture was brought to reflux immediately by sub-
merging it into a preheated oil bath (70 °C). The reaction mixture
was stirred until complete consumption of the oxirane (TLC), then
cooled to room temperature and filtered through a plug of silica to
remove salts formed during the reaction. Following concentration
of the reaction mixture, the residue was purified by flash column
chromatography using an appropriate solvent gradient (hexanes/
ethyl aceate) to afford a 1:1 mixture of diastereomers.
5-Methyl-2-(1-methylethyl)cyclohexyl 5-Butyl-1,2,3-oxathiazolidine-
3-carboxylate 2,2-Dioxide (24a and 24b): The general procedure for
the reaction of oxiranes with 10 and 2-butyloxirane (200 mg,
2.00 mmol) as starting material gave 159 mg (22%) of a 1:1 mixture
of diastereomers 24a and 24b after purification by flash column
chromatography (hexanes/ethyl acetate, 20:1 to 5:1). Colorless oil;
Rf = 0.68 (hexanes/ethyl acetate, 5:1). [α]2D3 = –51.7 (c = 2.3,
5-Methyl-2-(1-Methylethyl)cyclohexyl (3aR,7aS)-rel-Hexahydro-
1,2,3-benzoxathiazole-3(3aH)-carboxylate 2,2-Dioxide (15a and
15b): The general procedure for the reaction of oxiranes with com-
pound 10 and cyclohexene oxide (196 mg, 2.00 mmol) as starting
material gave 215 mg (30%) of a 1:1 mixture of diastereomers 15a
and 15b after purification by flash column chromatography (hex-
anes/ethyl acetate, 15:1 to 3:1) as colorless oil. Rf = 0.65 (hexanes/
CHCl ). IR (film): νmax = 3019, 2961, 2400, 1730, 1384, 1316, 1215,
˜
3
1046, 928, 724, 669 cm–1. H NMR (300 MHz, CDCl3): δ = 4.71–
1
4.84 (m, 1 H), 4.58–4.71 (m, 1 H), 3.90–4.09 (m, 1 H), 3.57–3.71
(m, 1 H), 2.10 (m, 3 H), 1.52–1.77 (m, 4 H), 1.25–1.53 (m, 6 H),
1.16–1.23 (s, 3 H), 0.92–1.12 (m, 2 H), 0.85–0.91 (m, 6 H), 0.70–
0.74 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 149.8, 79.9,
79.2, 50.6, 46.7, 40.5, 33.9, 32.1, 31.4, 29.7, 26.6, 25.8, 23.1, 22.1,
21.9, 20.8, 16.0, 13.7 ppm. MS (EI): m/z (%) = 361 (1), 176 (44),
83 (88), 42 (60), 43 (39), 54 (31), 55 (61). HRMS (EI): calcd. for
C17H31NO5S: 361.1923; found 361.1920.
ethyl acetate, 3:1). [α]2D3 = –52.2 (c = 1.00, CHCl ). IR (film): ν
˜
3
max
= 3401, 2958, 2873, 2254, 1728, 1457, 1383, 1314, 908, 738 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.98–5.04 (br. s, 1 H), 4.73 (dt,
J = 10.7, 4.5 Hz, 1 H), 4.15–4.27 (m, 1 H), 2.28–2.40 (m, 2 H),
1.97–2.17 (m, 2 H), 1.43–1.89 (m, 9 H), 1.02–1.37 (m, 4 H), 0.94
(d, J = 3.1 Hz, 3 H), 0.92 (d, J = 3.1 Hz, 3 H), 0.80 (d, J = 6.6 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 149.9, 79.7, 79.3, 58.2,
58.1, 47.2, 47.1, 41.0, 40.9, 34.3, 31.8, 27.6, 27.5, 27.4, 26.1, 23.5,
5-Methyl-2-(1-methylethyl)cyclohexyl (3aR,7aS)-rel-3a,6,7,7a-
Tetrahydro-2λ6-1,2,3-benzoxathiazole-3-carboxylate 2,2-Dioxide
(26a and 26b): The general procedure for the reaction of oxiranes
with compound 10 and cyclohexadiene oxide (192 mg, 2.00 mmol)
2814
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2806–2819

Reactivity of Burgess Reagent with Epoxides
as starting material gave 257 mg (36%) of a 1:1 mixture of dia-
stereomers 26a and 26b after purification by flash column
chromatography (hexanes/ethyl acetate, 15:1 to 3:1). White solid;
m.p. 115–118 °C (hexanes/ethyl acetate); Rf = 0.55 (hexanes/ethyl
20.7, 16.3 ppm. HRMS (EI): calcd. for C24H35NO4: 401.2566;
found 401.2575. C24H35NO4 (401): calcd. C 71.79, H 8.79; found
C 71.84, H 8.76.
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl trans-2-(Benzo-
yloxy)cyclopentylcarbamate (21a and 21b): The general procedure
for the syntheses of benzoates using a mixture of 20a and 20b
(433 mg, 1.25 mmol) as starting material gave a mixture of two
diastereomers (252 mg, 52%), which were separated by flash col-
umn chromatography (CH2Cl2/MeOH, 200:1). Diastereomer 1:
M.p. 85–86 °C (ethyl acetate/hexanes); Rf = 0.73 (CH2Cl2/MeOH,
acetate, 4:1). [α]2D3 = –54.5 (c = 1.25, CHCl ). IR (film): ν
=
˜
3
max
3443, 3031, 2959, 2930, 2873, 1731, 1599, 1457, 1432, 1371, 1331,
1307, 1241, 1217, 1189, 1170, 1125 cm–1 1H NMR (300 MHz,
.
CDCl3) (two rotamers): δ = 6.02–6.28 (m, 1 H), 5.56–5.85 (m, 1
H), 5.13–5.33 (m, 1 H), 4.66–4.84 (m, 2 H), 1.82–2.44 (m, 5 H),
1.39–1.75 (m, 5 H), 1.00–1.31 (m, 3 H), 0.87–0.96 (m, 6 H), 0.74–
0.85 (m, 3 H), ppm. 13C NMR (75 MHz, CDCl3) (two rotamers):
δ = 147.9, 135.0, 129.5, 119.0, 117.9, 81.7, 81.6, 79.2, 75.5, 75.3,
75.1, 74.6, 72.9, 72.8, 53.2, 53.2, 51.5, 45.2, 44.9, 44.8, 44.7, 38.6,
37.9, 37.7, 32.0, 29.5, 29.3, 29.3, 24.2, 23.9, 23.7, 22.6, 22.1, 21.2,
20.3, 19.9, 18.9 18.8, 18.7 ppm. HRMS (EI): calcd. for
C17H27NO5S: 357.1610; found 357.1593.
400:1). [α]2D3 = –99.6 (c = 1.00, CHCl ). IR (film): ν
= 3684,
˜
3
max
3019, 2961, 2400, 1711, 1512, 1424, 1031, 929, 669, 627 cm–1. H
NMR (300 MHz, CDCl3): δ = 8.03 (d, J = 7.2 Hz, 2 H), 7.42–7.52
(m, 3 H), 5.16 (q, J = 5.8 Hz, 1 H), 4.91 (br. s, 1 H), 4.40–4.48 (m,
1 H), 4.03–4.12 (m, 1 H), 2.19–2.23 (m, 2 H), 1.73–1.85 (m, 5 H),
1.51–1.58 (m, 7 H), 1.20–1.25 (m, 2 H), 0.67–0.85 (m, 7 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 156.0, 132.9, 130.2, 129.7, 128.3,
80.4, 75.0, 47.3, 41.3, 34.2, 31.3, 26.2, 22.0, 20.8 ppm. HRMS
(FAB) [M + H+]: calcd. for C23H33NO4: 388.2488; found 388.2474.
Diastereomer 2: M.p. 86–89 °C (ethyl acetate/hexanes); Rf = 0.70
(CH2Cl2/MeOH, 400:1). [α]2D3 = –5.59 (c = 1.05, CHCl3). IR (film):
1
General Procedure for the Synthesis of Benzoates: Ammonium ben-
zoate (346 mg, 2.49 mmol) was added to a stirred solution of sulfa-
midate diastereomers (1.25 mmol) in dry DMF (5 mL). The solu-
tion was heated to 55 °C and stirred for 18 h before the solvent was
evaporated, and the resulting residue was dissolved in THF (3 mL).
Three drops of H2O and three drops of concentrated H2SO4 were
added, and the reaction mixture was stirred at room temperature
for 12 h. The reaction mixture was diluted with H2O and the pH
adjusted to 9 (satd. aq. NaHCO3) before the layers were separated.
The aqueous layer was extracted with dichloromethane (3ϫ5 mL),
then the organic layers were combined and washed with brine
(1ϫ5 mL), dried with Na2SO4, and the solvents evaporated. The
ν
˜
max = 3436, 3019, 2960, 2400, 1711, 1512, 1037, 929, 669 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 6.9 Hz, 2 H), 7.50–7.57
(m, 3 H) 5.11–5.19 (m, 1 H), 4.78–4.82 (m, 1 H), 4.52–4.57 (m, 1
H), 4.11–4.14 (m, 1 H), 2.11–2.21 (m, 2 H), 1.80–1.83 (m, 1 H),
1.72–1.79 (m, 4 H), 1.46–1.58 (m, 6 H), 1.38–1.45 (m, 4 H), 0.80–
1.25 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 156.0, 132.9,
130.2, 129.7, 128.3, 80.1, 74.7, 47.3, 41.4, 34.2, 31.3, 29.7, 26.2,
diastereomers were separated via flash column chromatography 23.5, 22.0, 20.7, 16.3 ppm. HRMS (FAB) [M + H+]: calcd. for
using the appropriate solvent system (CH2Cl2/MeOH).
C23H33NO4: 388.2488; found 388.2481.
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl [(1R,2R)-2-(Ben-
zoyloxy)cyclohexyl]carbamate (16a) and (1R,2S,5R)-5-Methyl-2-(1-
methylethyl)cyclohexyl[(1S,2S)-2-(benzoyloxy)cyclohexyl]carbamate
(16b): The general procedure for the syntheses of benzoates using
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl trans-2-(Benzo-
yloxy)cycloheptylcarbamate (23a and 23b): The general procedure
for the syntheses of benzoates with a mixture of 22a and 22b
(468 mg, 1.25 mmol) as starting material gave a mixture of two
a mixture of 15a and 15b (449 mg, 1.25 mmol) as starting materials diastereomers 23a and 23b 389 mg (75%), which were separated by
gave a mixture of two diastereomers (246 mg, 49%), which were
separated by flash column chromatography (CH2Cl2/MeOH,
200:1). Compound 16a: M.p. 111–113 °C (ethyl acetate/hexanes); Rf
= 0.50 (CH2Cl2/methanol, 100:1). [α]2D0 = –77.8 (c = 1.05, CHCl3).
flash column chromatography (CH2Cl2/MeOH, 200:1). Dia-
stereomer 1: M.p. 89–91 °C (ethyl acetate/hexanes); Rf = 0.55
(CH2Cl2/MeOH, 100:1). [α]2D3 = –105.1 (c = 0.8, CHCl3). IR (film):
ν
max = 3363, 2930, 2867, 1714, 1602, 1585, 1526, 1452, 1370, 1316,
˜
IR (film): ν
= 3434, 3368, 3019, 2954, 2868, 1711, 1603, 1585,
1279, 1239, 1179, 1117, 1070, 1028 cm–1 1H NMR (600 MHz,
.
˜
max
1513, 1452, 1370, 1318, 1279, 1216, 1115, 1038, 1028, 757, 712, 668
CDCl3): δ = 7.98 (d, J = 7.5 Hz, 2 H), 7.46 (t, J = 7.5 Hz, 1 H),
7.35 (t, J = 7.5 Hz, 2 H), 4.91 (dt, J = 9.0, 3.4 Hz, 1 H), 4.63 (d, J
= 9.2 Hz, 1 H), 4.28–4.36 (m, 1 H), 3.83–3.93 (m, 1 H), 1.85–1.94
1
cm–1. H NMR (300 MHz, CDCl3): δ = 8.07 (d, J = 7.7 Hz, 2 H),
7.55 (t, J = 7.2 Hz, 1 H), 7.43 (t, J = 7.7 Hz, 2 H), 4.83 (dt, J =
10.6, 4.5 Hz, 1 H), 4.59 (d, J = 9.3 Hz, 1 H), 4.34–4.46 (m, 1 H), (m, 2 H), 1.74–1.93 (m, 2 H), 1.47–1.71 (m, 10 H), 1.36–1.44 (m,
3.76–3.90 (m, 1 H), 2.07–2.19 (m, 2 H), 1.73–1.93 (m, 3 H), 1.13– 1 H), 1.16–1.27 (m, 1 H), 0.89–1.02 (m, 1 H), 0.81–0.88 (m, 2 H),
1.69 (m, 10 H), 0.91–1.06 (m, 1 H), 0.86 (d, J = 10.0 Hz, 3 H), 0.75 0.77 (d, J = 7.0 Hz, 3 H), 0.67 (d, J = 6.8 Hz, 3 H), 0.56–0.61 (m,
(d, J = 6.6 Hz, 3 H), 0.46–0.68 (m, 4 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 167.1, 156.5, 133.4, 130.6, 130.2, 128.7, 76.6, 74.7,
54.3, 47.5, 41.2, 34.6, 32.8, 31.5, 26.6, 25.0, 24.5, 23.8, 22.2, 21.1,
16.8 ppm. HRMS (EI): calcd. for C24H35NO4: 401.2566; found
401.2579. C24H35NO4 (401): calcd. C 71.79, H 8.79; found C 71.82,
H 8.80. Compound 16b: M.p. 138–141 °C (ethyl acetate/hexanes);
Rf = 0.45 (CH2Cl2/MeOH, 100:1). [α]2D0 = –15.8 (c = 1.05, CHCl3).
3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 166.5, 155.9, 132.9,
130.3, 129.8, 128.3, 127.8, 78.4, 74.4, 56.2, 47.2, 40.9, 34.2, 32.0,
31.2, 26.2, 25.9, 23.9, 23.5, 22.4, 21.9, 20.7, 16.5 ppm. MS (EI): m/z
(%) = 415 (1), 137 (13), 123 (11), 111 (20), 105 (100), 97 (11), 95
(27), 83 (44), 82 (11), 81 (20), 77 (23), 71 (25), 69 (26), 67 (10), 57
(29), 56 (26), 55 (30). HRMS (EI): calcd. for C25H37NO4: 415.2723;
found 415.2715. Diastereomer 2: M.p. 121–124 °C (ethyl acetate/
hexanes); Rf 0.50 (CH2Cl2/MeOH, 100:1). [α]2D3 = –37.6 (c = 0.75,
IR (film): ν
= 3685, 3435, 3020, 2956, 2869, 1711, 1515, 1452,
˜
max
1318, 1279, 1216, 1115, 1039, 929, 759, 714, 669 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 8.05 (d, J = 7.7 Hz, 2 H), 7.55 (t, J =
7.1 Hz, 1 H), 7.43 (t, J = 7.7 Hz, 2 H), 4.86 (dt, J = 10.6, 4.5 Hz,
CHCl ). IR (film): νmax = 3369, 2928, 2866, 1714, 1524, 1452, 1369,
˜
3
1315, 1279, 1180, 1116, 1070, 1028 cm–1
.
1H NMR (600 MHz,
CDCl3): δ = 7.96 (d, J = 7.4 Hz, 2 H), 7.47 (t, J = 7.4 Hz, 1 H),
1 H), 4.69 (d, J = 9.3 Hz, 1 H), 4.35–4.49 (m, 1 H), 3.73–3.90 (m, 7.35 (t, J = 7.4 Hz, 2 H), 4.93 (dt, J = 8.7, 3.7 Hz, 1 H), 4.69–4.77
1 H), 2.12 (d, J = 12.5 Hz, 2 H), 1.98 (d, J = 11.9 Hz, 1 H), 1.73– (m, 1 H), 4.29–4.40 (m, 1 H), 3.85–3.94 (m, 1 H), 1.77–1.93 (m, 4
1.88 (m, 2 H), 1.08–1.68 (m, 10 H), 0.79–0.97 (m, 5 H), 0.55 (d, J H), 1.64–1.74 (m, 2 H), 1.43–1.62 (m, 8 H), 1.31–1.41 (m, 1 H),
= 6.4 Hz, 3 H), 0.30 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR (75 MHz, 1.04–1.11 (m, 1 H), 0.76–0.88 (m, 5 H), 0.66–0.73 (m, 1 H), 0.49
CDCl3): δ = 167.2, 156.3, 133.3, 130.4, 130.1, 128.7, 76.0, 74.6,
54.4, 47.6, 41.8, 34.6, 33.2, 31.7, 31.6, 26.5, 24.9, 24.5, 23.9, 22.4,
(d, J = 5.3 Hz, 3 H), 0.27 (d, J = 0.48 Hz, 3 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 166.6, 155.8, 132.9, 130.3, 129.7, 128.3,
Eur. J. Org. Chem. 2009, 2806–2819
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2815

H. Leisch, B. Sullivan, B. Fonovic, T. Dudding, T. Hudlicky
127.8, 78.2, 74.3, 56.5, 47.3, 41.5, 34.3, 32.2, 31.3, 27.5, 26.2, 24.0, (3aR,7aR)-3H-Hexahydrobenzoxazolidin-2-one (18a): 2-(Menthyl-
FULL PAPER
23.6, 22.4, 22.0, 20.4, 16.1 ppm. MS (EI): m/z (%) = 415 (1), 155
(10), 138 (18), 137 (14), 123 (16), 111 (20), 105 (100), 97 (11), 96
carbonylamino)cyclohexyl benzoate 16a (260 mg, 0.65 mmol) was
dissolved in 1  NaOH in MeOH (30 mL), and the reaction mix-
(12), 95 (43), 94 (10), 83 (47), 82 (16), 81 (31), 77 (23), 71 (28), ture was stirred at room temperature for 10 h. The reaction mixture
69 (34), 67 (14), 57 (32), 56 (25), 55 (37). HRMS (EI): calcd. for
C25H37NO4: 415.2723; found 415.2720.
was diluted with water (30 mL) and extracted three times with
dichloromethane. The organic layers were combined, washed with
brine, dried with anhydrous magnesium sulfate, filtered and the sol-
vent was evaporated. Flash column chromatography (hexanes/ethyl
acetate, 4:1) of the residue afforded menthol [(1R,2R)-2-hydroxycy-
clohexyl]carbamate as colorless solid (152 mg, 79 %); m.p. 130–
132 °C (hexanes/ethyl acetate); Rf = 0.15 (hexanes/ethyl acetate,
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl [2-(Benzoyloxy)-
hexyl]carbamate (25a and 25b): The general procedure for the syn-
theses of benzoates with a mixture of 24a and 24b (451 mg,
1.25 mmol) as starting materials gave a mixture of two dia-
stereomers (181 mg, 36%), which were inseparable by flash column
chromatography. Mixture of two Diastereomers: Colorless solid;
M.p. 121–124 °C (ethyl acetate/hexanes); Rf = 0.50 (CH2Cl2/
1:1). [α]2D0 = –53.7 (c = 1.35, CHCl ). IR (film): νmax = 3685, 3620,
˜
3
3020, 2870, 2401, 1693, 1510, 1477, 1451, 1423, 1215, 1046, 1024,
929 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.60–4.79 (br. s, 1 H),
4.53 (dt, J = 11.2, 4.0 Hz, 1 H), 3.21–3.44 (m, 2 H), 3.00–3.21 (br.
s, 1 H), 1.79–2.09 (m, 4 H), 1.54–1.75 (m, 2 H), 1.38–1.53 (m, 2
H), 0.66–1–38 (m, 17 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
158.1, 75.8, 75.4, 57.2, 47.7, 41.7, 34.6, 34.5, 32.2, 31.7, 26.6, 25.0,
24.4, 23.8, 22.4, 21.2, 16.8 ppm. MS (EI): m/z (%) = 297 (1), 158
(10), 139 (27), 138 (17), 115 (19), 114 (28), 98 (100), 97 (21), 96
(19), 95 (23), 83 (90), 82 (14), 81 (43), 71 (21), 70 (10), 69 (46), 67
(13). HRMS (EI): calcd. for C17H31NO3: 279.2304; found 297.2298.
C17H31NO3 (297.44): calcd. C 68.65, H 10.51; found C 68.65, H
10.81.
MeOH, 100:1). [α]2D3 = –37.6 (c = 0.75, CHCl ). IR (film): ν
=
˜
3
max
3684, 3401, 3019, 2961, 2400, 1713, 1517, 1423, 1215, 1046, 929,
1
641, 669, 627 cm–1. H NMR (300 MHz, CDCl3): δ = 7.97 (d, J =
7.3 Hz, 2 H), 7.46–7.54 (m, 1 H), 7.33–7.43 (m, 2 H), 5.03–5.20 (m,
1 H), 4.70–4.86 (m, 1 H), 4.35–4.54 (m, 1 H), 3.33–3.49 (m, 2 H),
1.88–2.01 (m, 1 H), 1.72–1.88 (m, 2 H), 1.46–1.73 (m, 6 H), 1.23–
1.44 (m, 6 H), 1.08–1.22 (m, 2 H), 0.90–1.06 (m, 2 H), 0.77–0.88
(m, 3 H), 0.64–0.75 (m, 4 H), 0.58 (d, J = 6.9 Hz, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 163.9, 154.0, 130.6, 127.2, 125.9, 72.2,
71.7, 44.9, 41.9, 38.9, 31.8, 29.0, 28.9, 28.8, 24.9, 23.8, 21.1, 20.1,
19.6, 18.3, 13.9, 13.9, 11.5 ppm. MS (EI): m/z (%) = 403 (1), 221
(15), 176 (13), 55 (61), 54 (31), 43 (37). HRMS (EI): calcd. for
C24H37NO4: 403.2723; found 403.2720.
Menthyl [(1R,2R)-2-Hydroxycyclohexyl]carbamate (140 mg,
0.47 mmol) was dissolved in THF (5 mL) and sodium hydride
(42 mg, 1.04 mmol) was added in one portion. The reaction mix-
ture was heated at reflux for 12 h until TLC indicated complete
conversion of starting material. The reaction mixture was quenched
by the addition of an aqueous saturated solution of NH4Cl. The
aqueous layer was extracted three times with ethyl acetate. The or-
ganic layers were combined, washed with brine, dried with anhy-
drous magnesium sulfate, filtered, and the solvent was evaporated.
Flash column chromatography (hexanes/ethyl acetate, 2:1 to 1:1) of
the residue afforded (+)-18 as colorless solid (55 mg, 83%); m.p.
133–134 °C (hexanes/ethyl actate). [α]2D2 = +7.5 (c = 1.0, EtOH); Rf
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl [(1S,6R)-2-(Ben-
zoyloxy)cyclohex-2-enyl]carbamate (27a) and (1R,2S,5R)-5-Methyl-
2-(1-methylethyl)cyclohexyl [(1R,6S)-2-(Benzoyloxy)cyclohex-2-en-
yl]carbamate (27b): The general procedure for the syntheses of ben-
zoates using a mixture of 26a and 26b (446 mg, 1.25 mmol) as start-
ing materials gave a mixture of two diastereomers (254 mg, 51%),
which were separated by flash column chromatography (CH2Cl2/
MeOH, 400:1). Compound 27a: M.p. 103–105 °C (ethyl acetate/hex-
anes); Rf = 0.67 (CH2Cl2/MeOH, 400:1). [α]2D3 = –100.8 (c = 0.25,
CHCl ). IR (film): νmax = 3436, 3019, 2962, 1713, 1602, 1511, 1424,
˜
3
= 0.45 (hexanes/ethyl acetate, 1:1). IR (film): ν
= 3684, 3622,
˜
1277, 1117, 1048, 1028 cm–1. 1H NMR (300 MHz, CDCl3): δ =
8.07 (d, J = 7.4 Hz, 2 H), 7.56 (t, J = 7.4 Hz, 1 H), 7.44 (t, J =
7.8 Hz, 2 H), 5.85 (d, J = 10.2 Hz, 1 H), 5.69 (dd, J = 9.5, 1.5 Hz,
1 H), 5.04–5.11 (m, 1 H), 4.66 (d, J = 9.2 Hz, 1 H), 4.52–4.62 (m,
1 H), 4.46 (dt, J = 10.7, 3.9 Hz, 1 H), 2.25–2.28 (m, 2 H), 2.08–
2.11 (m, 1 H), 1.96–2.00 (m, 1 H), 1.88–1.93 (m, 1 H), 1.59–1.72
(m, 4 H), 1.26–1.42 (m, 2 H), 1.21–1.25 (m, 1 H), 0.98–1.04 (m, 1
H), 0.87 (d, J = 7.1 Hz, 3 H), 0.78 (d, J = 6.6 Hz, 3 H), 0.72 (d, J
= 5.8 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.5, 156.2,
133.0, 130.2, 129.8, 129.5, 128.4, 128.3, 126.8, 77.2, 74.8, 73.9, 51.7,
47.2, 41.0, 34.2, 31.2, 26.4, 26.3, 24.0, 23.5, 21.9, 20.8, 16.5 ppm.
HRMS (EI): calcd. for C24H33NO4: 399.2410; found 399.2403.
C24H33NO4 (399): calcd. C 72.15, H 8.33; found C 72.42, H 8.44.
Compound 27b: M.p. 107–109 °C (ethyl acetate/hexanes); Rf = 0.62
(CH2Cl2/MeOH, 400:1). [α]2D3 = +16.2 (c = 0.4, CHCl3). IR (film):
max
3020, 1757, 1521, 1476, 1423, 1215, 1034, 929 cm–1 1H NMR
.
(300 MHz, CDCl3): δ = 5.96–6.19 (br. s, 1 H), 3.81 (dt, J = 11.1,
4.3 Hz, 1 H), 3.16–3.33 (m, 1 H), 2.05–2.20 (m, 1 H), 1.93–2.05 (m,
1 H), 1.67–1.90 (m, 2 H), 1.49–1.65 (m, 1 H), 1.14–1.47 (m, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 161.2, 84.2, 61.3, 29.5, 28.9,
24.1, 23.9 ppm. MS (EI): m/z (%) = 141 (32), 140 (11), 99 (6), 96
(5), 69 (42), 57 (15), 56 (100), 54 (8), 43 (40). HRMS (EI): calcd.
for C7H11NO2: 141.0790; found 141.0788.
(3aS,7aS)-3H-Hexahydrobenzoxazolidin-2-one (18b): 2-(Menthyl-
carbonylamino)cyclohexyl Benzoate 16b (270 mg, 0.67 mmol) was
dissolved in 1  NaOH in MeOH (30 mL), and the reaction mix-
ture was stirred at room temperature for 10 h, then diluted with
water (30 mL) and extracted three times with dichloromethane. The
organic layers were combined, washed with brine, dried with anhy-
drous magnesium sulfate and the solvent was evaporated. Flash
ν
max = 3369, 3033, 2954, 2928, 2869, 1714, 1523, 1277, 1241, 1116,
˜
1
1027 cm–1. H NMR (600 MHz, CDCl3): δ = 8.06 (d, J = 7.2 Hz, column chromatography (hexanes/ethyl acetate, 4:1) of the residue
2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.8 Hz, 2 H), 5.84 (d,
J = 8.6 Hz, 1 H), 5.59 (dq, J = 9.8, 2.2 Hz, 1 H), 5.04–5.12 (m, 1
H), 4.70 (d, J = 9.5 Hz, 1 H), 4.55–4.61 (m, 1 H), 4.49 (td, J =
10.8, 3.7 Hz, 1 H), 2.23–2.29 (m, 2 H), 2.06–2.13 (m, 1 H), 1.91–
afforded menthol [(1S,2S)-2-hydroxycyclohexyl]carbamate as col-
orless solid (179 mg, 89 %); m.p. 151–153 °C (hexanes/ethyl ace-
tate); Rf = 0.15 (hexanes/ethyl acetate, 1:1). [α]2D0 = –58.2 (c = 1.2,
CHCl ). IR (film): νmax = 3684, 3621, 3437, 3020, 2939, 2869, 2400,
˜
3
2.03 (m, 2 H), 1.54–1.71 (m, 3 H), 1.41–1.49 (m, 1 H), 1.21 (t, J = 1693, 1510, 1477, 1451, 1424, 1389, 1215, 1046, 1023, 929 cm–1. 1H
11.5 Hz, 1 H), 0.85–0.97 (m, 6 H), 0.65 (d, J = 6.6 Hz, 3 H), 0.42
NMR (300 MHz, CDCl3): δ = 4.62–4.85 (br. s, 1 H), 4.55 (dt, J =
(d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.5 11.1, 4.2 Hz, 1 H), 3.21–3.42 (m, 2 H), 2.98–3.21 (br. s, 1 H), 1.81–
156.0, 132.9, 130.1, 129.8, 129.3, 128.3, 127.0, 74.5, 73.7, 51.7, 47.3,
41.4, 34.2, 31.3, 26.6, 26.2, 24.0, 23.5, 22.0, 20.5, 16.1 ppm. HRMS
(EI): calcd. for C24H33NO4: 399.2410; found 399.2410.
2.14 (m, 4 H), 1.56–1.80 (m, 2 H), 1.39–1.55 (m, 2 H), 0.60–1.39
(m, 17 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.2, 75.8, 75.5,
57.3, 47.9, 41.8, 34.6, 34.5, 32.1, 31.8, 26.6, 25.0, 24.4, 23.8, 22.4,
2816
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2806–2819

Reactivity of Burgess Reagent with Epoxides
21.2, 16.8 ppm. MS (EI): m/z (%) = 297 (1), 160 (8), 159 (8), 158
and brine. The organic layer was dried with MgSO4, filtered, then
(9), 139 (24), 138 (17), 115 (19), 114 (28), 98 (100), 97 (22), 96 (23), the solvent was evaporated at reduced pressure. Flash column
95 (30), 83 (96), 82 (18), 81 (49), 71 (29), 70 (13), 69 (54), 67 (17). chromatography (hexanes/ethyl acetate, 2:1) of the residue afforded
HRMS (EI): calcd. for C17H31NO3: 279.2304; found 297.2303.
C17H31NO3 (297.44): calcd. C 68.65, H 10.51; found C 68.82, H
10.79.
compound 32 as colorless oil 31 mg (40%). 1H NMR (300 MHz,
CDCl3): δ = 7.47–7.56 (m, 2 H), 7.34–7.42 (m, 3 H), 4.53–4.97 (m,
2 H), 3.43–3.78 (m, 7 H), 1.91–2.17 (m, 2 H), 1.17–1.86 (m, 6 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 156.6, 156.5, 132.6, 129.93,
129.90, 128.8, 127.6, 125.5, 55.7, 54.2, 52.5, 52.3, 33.0, 32.8, 31.3,
30.9, 30.1, 29.3, 24.4, 24.2, 24.1 ppm. 19F NMR (282 MHz,
CDCl3): δ = –72.08 (1 F), –72.42 (1 F) ppm. The results were con-
firmed by GC/MS analysis.
Following the same procedure as for the preparation of compound
(+)-18a using menthol [(1S,2S)-2-hydroxycyclohexyl]carbamate
(160 mg, 0.54 mmol) and sodium hydride (32 mg, 1.33 mmol) as
starting materials, gave 62 mg (82%) of compound (–)-18b as color-
less crystals; m.p. 131–133 °C (hexanes/ethyl acetate). [α]2D2 = –7.4
(c = 1.1, EtOH). HRMS (EI): calcd. for C7H11NO2: 141.0790;
found 141.0785.
Methyl cis-Hexahydro-3H-1,2,3-benzoxathiazole-3-carboxylate 2-
Oxide (35): A solution of methyl carbamate 34 (0.79 g, 4.56 mmol)
in CH3CN (20 mL) was added dropwise to a solution of thionyl
chloride (0.83 mL, 11.41 mmol) in CH3CN (60 mL) at –35 °C over
10 min. The reaction mixture was stirred at –35 °C for 5 min, before
pyridine (1.84 mL, 22.82 mmol) was added dropwise. The reaction
mixture was warmed to room temperature over 3 h. The solvent
was evaporated, and the residue was triturated with Et2O. The sus-
pension was filtered, and the filtrate was concentrated under re-
duced pressure. Purification of the residue by flash column
chromatography (hexanes/ethyl acetate, 5:1) afforded 0.63 g (63%)
of compound 35 as colorless oil. Rf = 0.75 (hexanes/ethyl acetate,
(3aR,7aR)-3-[(S)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyl]hex-
ahydrobenzo[d]oxazol-2(3H)-one (19a): nBuLi (2  in THF, 78 µL,
0.16 mmol) was added to a solution of cyclic carbamate 18a
(20 mg, 0.14 mmol) in THF (2 mL) at 0 °C. The reaction mixture
was stirred at the same temperature for 1 h then cooled to –78 °C.
(S)-(+)-Mosher’s chloride (43 mg, 0.17 mmol) was added, and the
reaction mixture was warmed to room temperature over 14 h. The
reaction was quenched by the addition of a saturated aqueous solu-
tion of NH4Cl. The aqueous layer was extracted three times with
ethyl acetate. The organic layers were combined, washed with brine
and dried with anhydrous sodium sulfate. The organic layer was
filtered and the solvent was evaporated. The crude residue was ana-
lyzed by 19F NMR (282 MHz, CDCl3): δ = –72.61 (not detected),
–69.30 (1 F) ppm. Compound 19b as well as a racemic standard
were prepared in the same manner, using 18b and a racemate of 18
as starting materials. Compound 19b: 19F NMR (282 MHz, CDCl3):
δ = –72.61 (1 F), –69.31 (0.035 F) ppm. Compound 19: –72.61 (1 F),
–69.30 (1 F) ppm. The results were confirmed by GC/MS analysis.
1:1). IR (film): ν
= 2943, 2867, 1730, 1442, 1359, 1328, 1288,
˜
max
1187, 1148 cm–1. 1H NMR (300 MHz, CDCl3) (two rotamers): δ =
5.24–5.31 (br. s, 0.66 H), 4.66 (q, J = 4.0 Hz, 0.33 H), 3.94–4.12
(m, 1 H), 3.84 (s, 1 H), 3.82 (s, 2 H), 2.09–2.34 (m, 2 H), 1.54–2.45
(m, 4 H), 1.33–1.52 (m, 1 H), 1.08–1.31 (m, 1 H) ppm. 13C NMR
(75 MHz, CDCl3) (two rotamers): δ = 152.9, 85.0, 80.0, 55.6, 54.1,
53.7, 53.6, 28.8, 28.4, 27.9, 26.8, 22.6, 22.2, 19.6, 19.5 ppm. MS
(EI): m/z (%) = 219 (12), 171 (16), 155 (29), 154 (26), 140 (65), 127
(44), 126 (13), 124 (16), 77 (100), 75 (16), 64 (33). HRMS (EI):
calcd. for C8H13NO4S: 219.0565; found 219.0561.
(1R,2R)-2-[(S)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyloxy]cy-
clohexylmethylcarbamate (32): 2-(Methylcarbonylamino)cyclohexyl
benzoate (9) (220 mg, 0.80 mmol) was dissolved in 1  NaOH in
MeOH (20 mL), and the reaction mixture was stirred at room tem-
perature for 8 h. It was diluted with water (30 mL) and extracted
three times with dichloromethane. The organic layers were com-
bined, washed with brine, dried with anhydrous magnesium sulfate
then the solvent was evaporated. Flash column chromatography
(hexanes/ethyl acetate, 4:1) of the residue afforded methyl 2-hy-
droxycyclohexylcarbamate as colorless solid (132 mg, 95%); m.p.
Methyl trans(2-Hydroxycyclohexyl)carbamate (39): Methyl chloro-
formate (0.3 mL, 3.94 mmol) was added dropwise to a vigorously
stirred solution of trans-2-aminocyclohexanol hydrochloride (0.5 g,
3.3 mmol) and NaHCO3 (0.83 g, 9.9 mmol) in a 1:1 mixture of
CHCl3 and H2O (30 mL). The mixture was allowed to stir at room
temperature for 1 h, before the reaction mixture was neutralized
with 1  aq. HCl. The aqueous layer was extracted three times with
dichloromethane. The combined organic layers were washed with
brine, dried with MgSO4 and evaporation of the solvent and
recrystallization from hexanes/ethyl acetate furnished the title com-
pound as colorless solid (498 mg, 87%); m.p. 109–111 °C (hexanes/
109–111 °C (hexanes/ethyl acetate). IR (film): ν
= 3436, 3156,
˜
max
2942, 2863, 2253, 1708, 1517, 1452, 1517, 1452, 1384 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 4.75–5.15 (br. s, 1 H), 3.66 (s, 3 H),
3.21–3.46 (m, 1 H), 2.98–3.18 (br. s, 1 H), 1.91–2.12 (m, 2 H), 1.60–
1.79 (m, 2 H), 1.05–1.41 (m, 4 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 158.4, 75.6, 57.5, 52.9, 34.6, 32.2, 25.1, 24.5 ppm. MS
(EI): m/z (%) = 173 (1), 141 (18), 114 (75), 112 (22), 102 (12), 98
(100), 88 (42), 69 (26), 56 (51), 51 (66). HRMS (EI): calcd. for
C8H15NO3: 173.1052; found 173.1053. C8H15NO3 (173): calcd. C
55.47, H 8.73; found C 55.16, H 8.73.
ethyl acetate). IR (film): νmax = 3436, 3156, 2942, 2863, 2253, 1708,
˜
1
1517, 1452, 1517, 1452, 1384 cm–1. H NMR (300 MHz, CDCl3):
δ = 4.75–5.15 (br. s, 1 H), 3.66 (s, 3 H), 3.21–3.46 (m, 1 H), 2.98–
3.18 (br. s, 1 H), 1.91–2.12 (m, 2 H), 1.60–1.79 (m, 2 H), 1.05–1.41
(m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.4, 75.6, 57.5,
52.9, 34.6, 32.2, 25.1, 24.5 ppm. MS (EI): m/z (%) = 173, 141 (18),
114 (75), 112 (22), 102 (12), 98 (100), 88 (42), 69 (26), 56 (51), 51
(66). HRMS (EI): calcd. for C8H15NO3: 173.1052; found, 173.1053.
C8H15NO3 (173): calcd. C 55.47, H 8.73; found C 55.16, H 8.73.
To a solution of methyl carbamate prepared as described (40 mg,
0.23 mmol) dissolved in dry dichloromethane (3 mL) were added
Methyl (3aR,7aR)-Hexahydro-3H-1,2,3-benzoxathiazole-3-carbox-
ylate 2-Oxide (40): A solution of methyl [(1R,2R)-2-hydroxycyclo-
hexyl]carbamate (0.8 g, 4.62 mmol) in CH3CN (20 mL) was added
dropwise to a solution of thionyl chloride (0.84 mL, 11.6 mmol) in
CH3CN (60 mL) at –35 °C over 10 min. The reaction mixture was
stirred at the same temperature for 5 min before pyridine (1.8 mL,
23.11 mmol) was added dropwise. The reaction mixture was
warmed to room temperature over 3 h. The solvent was evaporated,
and the residue was triturated with Et2O. After filtration, the mix-
sequentially
1-ethyl-3-[3Ј-(dimethylamino)propyl]carbodiimide·
HCl (49 mg, 0.25 mmol), 4-(dimethylamino)pyridine (3 mg,
0.023 mmol), and Mosher’s acid (54 mg, 0.23 mmol) at 0 °C. The
reaction mixture was kept at 0 °C for 1 h, then stirred at room
temperature for 2 d. TLC analysis indicated no further consump-
tion of starting material. The reaction mixture was diluted with
dichloromethane and washed with NH4Cl, aq. saturated NaHCO3,
Eur. J. Org. Chem. 2009, 2806–2819
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2817

H. Leisch, B. Sullivan, B. Fonovic, T. Dudding, T. Hudlicky
FULL PAPER
ture was concentrated under reduced pressure. Flash column
chromatography (hexanes/ethyl acetate, 5:1) of the residue afforded
the product as colorless solid (0.79 g, 78%); m.p.51–54 °C; Rf 0.5
Acknowledgments
For financial support of this work, the authors are indebted to the
Natural Sciences and Engineering Research Council of Canada,
Canadian Foundation for Innovation, Ontario Innovation Trust,
Petroleum Research Fund administered by the American Chemical
Society, Research corporation, and Brock University. TDC Re-
search, Inc. and TDC Research Foundation are acknowledged for
fellowships for B. S.
(hexanes/ethyl acetate, 2:1). IR (film): ν
= 3368, 2954, 2254,
˜
max
1733, 1572, 1444, 1384, 1328, 1300 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 4.71 (dt, J = 11, 4 Hz, 1 H), 3.83 (s, 3 H), 3.13 (dt, J
= 13, 3 Hz, 1 H), 2.61–2.74 (m, 1 H), 2.20–2.34 (m, 1 H), 1.79–
2.02 (m, 2 H), 1.69 (dq, J = 12, 4 Hz, 1 H), 1.19–1.54 (m, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 154.7, 86.8, 63.2, 54.0, 29.8,
29.5, 24.3, 23.9 ppm. MS (EI): m/z (%) = 219 (5), 140 (10), 114
(100), 81 (12), 59 (24), 44 (17). HRMS (EI): calcd. for C8H13NO4S:
219.0565; found , 219.0565. C8H13NO4S (219): calcd. C 43.82, H
5.98; found C 44.12, H 6.05.
[1] a) G. M. Atkins, E. M. Burgess, J. Am. Chem. Soc. 1968, 90,
4744–4745; b) E. M. Burgess, H. R. Penton, E. A. Taylor, J.
Am. Chem. Soc. 1970, 92, 5224–5226; c) G. M. Atkins, E. M.
Burgess, J. Am. Chem. Soc. 1972, 94, 6135–6141; d) E. M. Bur-
gess, H. R. Penton, E. A. Taylor, J. Org. Chem. 1973, 38, 26–
31.
[2] For reviews of applications of the Burgess Reagent in synthesis
see: a) S. Burckhardt, Synlett 2000, 559; b) C. Lamberth, J.
Prakt. Chem./Chem.-Ztg. 2000, 342, 518–522; c) P. Taibe, S.
Mobashery, in Encyclopedia of Reagents in Organic Synthesis
(Ed.: L. A. Paquette), vol. 5, Wiley, Chichester, 1995, p. 3345.
[3] J. H. Rigby, M. Kirova-Snover, Tetrahedron Lett. 1997, 38,
8153–8156.
Methyl trans-2,2-Hexahydro-3H-1,2,3-benzoxathiazole-3-carboxyl-
ate 2,2-Dioxide (41): Ruthenium(III) chloride hydrate (catalytic
amount), sodium periodate (205 mg, 0.96 mmol), and H2O (3 mL)
were added at 0 °C to a solution of oxathiazolidine 40 (140 mg,
0.64 mmol) in CH3CN (3 mL). The reaction mixture was warmed
to room temperature and was stirred for 3 h. The reaction mixture
was extracted three times with Et2O. The organic layers were com-
bined and washed with H2O and brine, then dried with anhydrous
MgSO4. Filtration, evaporation of the solvent and purification by
flash column chromatography (hexanes/ethyl aceate) afforded
130 mg (87%) of colorless oil. Rf = 0.55 (2:1, hexanes/ethyl aceate).
[4] J. H. Rigby, M. E. Mateo, J. Am. Chem. Soc. 1997, 119, 12655–
12656.
[5] R. A. Holton, H. B. Kim, C. Sonoza, F. Liang, R. J. Biediger,
P. D. Boatman, M. Shindo, C. C. Smith, S. Kim, H. Nadiza-
deh, Y. Suzuki, C. Tao, P. Vu, S. Tang, P. Zhang, K. K. Murthi,
L. N. Gentile, J. H. Liu, J. Am. Chem. Soc. 1994, 116, 1599–
1600.
IR (film): ν
= 3367, 2958, 2870, 2255, 1746, 1444, 1384, 1329,
˜
max
1299, 1193 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.39 (dt, J =
11, 4 Hz, 1 H), 3.88 (s, 3 H), 3.73–3.84 (m, 1 H), 2.59–2.73 (m, 1
H), 2.19–2.31 (m, 1 H), 1.81–2.05 (m, 2 H), 2.05 (dq, J = 12, 4 Hz,
1 H), 1.30–1.58 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
151.6, 84.6, 64.7, 54.9, 29.0, 28.3, 23.7, 23.5 ppm. MS (EI): m/z (%)
= 235, 155 (37), 150 (100), 140 (12), 124 (13), 114 (19), 101 (52),
98 (26), 95 (22), 81 (24), 69 (44), 59 (53). HRMS (EI): calcd. for
C8H13NO5S: 235.0514; found , 235.0519. C8H13NO5S (235): calcd.
C 40.84, H 5.57; found C 41.18, H 5.84.
[6] R. E. Dolle, K. C. Nicolaou, J. Am. Chem. Soc. 1985, 107,
1691–1694.
[7] A. R. Daniewski, P. M. Wovkulich, M. R. Uskokovic, J. Org.
Chem. 1992, 57, 7133–7139.
[8] E. M. Burgess, H. R. Penton, E. A. Taylor, W. M. Williams,
Org. Synth. 1977, 56, 40–44.
[9] a) D. A. Claremon, B. T. Phillips, Tetrahedron Lett. 1988, 29,
2155–2158; b) H. Nemoto, Y. Kubota, Y. Yamamoto, J. Org.
Chem. 1990, 55, 4515–4516.
[10] a) P. Wipf, S. Venkatraman, Tetrahedron Lett. 1996, 37, 4659–
4662; b) P. Wipf, S. Venkatraman, Synlett 1997, 1–10.
[11] K. C. Nicolaou, S. A. Snyder, A. Z. Nalbandian, D. A. Long-
bottom, J. Am. Chem. Soc. 2004, 126, 6234–6235.
[12] K. C. Nicolaou, X. Huang, S. A. Snyder, P. B. Rao, M. Bella,
M. V. Reddy, Angew. Chem. Int. Ed. 2002, 41, 834–838.
[13] S. C. Banfield, A. T. Omori, H. Leisch, T. Hudlicky, J. Org.
Chem. 2007, 72, 4989–4992.
[14] K. C. Nicolaou, S. A. Snyder, D. A. Longbottom, A. Z. Nal-
bandian, X. Huang, Chem. Eur. J. 2004, 10, 5581–5606.
[15] K. C. Nicolaou, D. A. Longbottom, S. A. Snyder, A. Z. Nal-
bandian, X. Huang, Angew. Chem. Int. Ed. 2002, 41, 3866–
3870.
trans-Hexahydro-3H-1,2,3-benzoxathiazole 2,2-Dioxide (42): Am-
monium benzoate (757 mg, 5.44 mmol) was added to a solution of
benzoxathiazole 41 (640 mg, 2.72 mmol) in dry DMF (5 mL) in
one portion. The reaction mixture was heated at 75 °C until full
conversion of starting material was indicated by TLC (24 h). The
solvent was evaporated and the residue was dissolved in THF
(3 mL). Three drops of water and concentrated H2SO4 were added,
and the reaction mixture was allowed to stir at 60 °C. After 3 h the
mixture was cooled to room temperature, and its pH was adjusted
to pH 9 (saturated aq. NaHCO3). The reaction mixture was ex-
tracted 3 times with dichloromethane. The organic layer was
washed with brine and dried with anhydrous MgSO4. The solvent
was evaporated under reduced pressure and the residue was puri-
fied by flash column chromatography (hexanes/ethyl acetate, 4:1)
affording 440 mg (91%) of the title compound 42; m.p. 94–97 °C
(hexanes/ethyl acetate); Rf = 0.6 (hexanes/ethyl acetate, 1:1). IR
[16] U. Rinner, D. R. Adams, M. L. dos Santos, K. A. Abboud, T.
Hudlicky, Synlett 2003, 1247–1252.
[17] The following statement appeared in a review (ref.[2b]) pub-
lished in 2000: “The compatibility of the Burgess reagent with
many functionalities, e.g. halogens, epoxides, alkenes, alkynes,
aldehydes, ketones, acetals, esters, secondary amides, makes it
an attractive technique for the introduction of C–C double
bonds into highly functionalized molecules.”
(film): νmax = 3256, 2953, 2869, 1794, 1642, 1458, 1448, 1406, 1364,
˜
1342, 1331, 1278, 1231, 1192, 1138, 1101, 1074, 1052, 1001, 950,
868, 865, 786, 650 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.91 (d,
J = 9.0 Hz, 1 H), 4.30 (dq, J = 10.0, 5.2 Hz, 1 H), 3.45 (m, 1 H),
2.24 (m, 1 H), 2.14 (m, 1 H), 1.91 (m, 2 H), 1.70 (dq, J = 12.0,
4.0 Hz, 1 H), 1.41 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 90.1, 63.2, 28.5, 27.7, 23.8, 23.4. HRMS: calcd. for C6H11NO3S:
177.0456; found 177.0454.
[18] Cyclic epoxides proximal to alcohols react with the Burgess
reagent to form sulfamidates (ref. 14). Distally located epoxides
appear inert provided excess reagent is not used. See A. A. Na-
gel, J. DiBrino, L. A. Vincent, J. A. Retsema, J. Med. Chem.
1982, 25, 881–884. It was likely this report that led to the belief
in inertness of epoxides.
[19] For reviews on the synthesis and utility of 1,2-amino alcohols
see: a) G. Shaw, in Comprhensive Heterocyclic Chemistry II
(Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven), Pergamon,
Supporting Information (see also the footnote on the first page of
this article): Details of the computational studies as well as copies
1
of H and 13C NMR spectra.
2818
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2806–2819

Reactivity of Burgess Reagent with Epoxides
New York, 1996, pp. 397; b) S. Wallbaum, J. Martens, Tetrahe-
dron: Asymmetry 1992, 3, 1475–1504; c) R. Noyori, M. Kita-
mura, Angew. Chem. Int. Ed. Engl. 1991, 193, 34–48; d) V. K.
Singh, Synthesis 1992, 605–617.
Pople, M. A. Ratner, T. L. Windus, J. Chem. Phys. 1998, 109,
1223–1229.
[35] For additional details regarding the procedural details associ-
ated with these PES scans, see SI.
[20] For reviews on synthesis and reaction of cyclic sulfates see: a)
B. B. Lohray, Synthesis 1992, 1035–1052; b) B. B. Lohray, V.
Bhushan, Adv. Heterocycl. Chem. 1997, 68, 89–180; c) H.-S.
Byun, L. He, R. Bittman, Tetrahedron 2000, 56, 7051–7091.
[21] G. R. Pettit, N. Melody, D. L. Herald, J. Org. Chem. 2001, 66,
2583–2587.
[36] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.
Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pom-
elli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P.
Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich,
A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui,
A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J.
Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, Gaussian 03, revision C.02,
Gaussian, Inc., Wallingford CT, 2004.
[22] The structures reported as minor products in ref.[12] (Table 1)
assigned as regioisomeric sulfamidates 5 are all the correspond-
ing seven-membered sulfamidates, as proven by comparison of
reaction mixtures obtained from both diols and the corre-
sponding epoxides (ref.[16]), and as was subsequently also re-
ported in a later publication (ref.[14]).
[23] U. Jaeger, W. Sundermeyer, H. Pritzkow, Chem. Ber. 1987, 120,
1191–1195.
[24] K. Finn, T. Hudlicky, unpublished observations.
[25] H. Leisch, R. Saxon, B. Sullivan, T. Hudlicky, Synlett 2006, 3,
445–449.
[26] C. A. de Parrodi, E. Juaristi, L. Quintero, A. Clara-Sosa, Tetra-
hedron: Asymmetry 1997, 8, 1075–1082.
[27] Similar reaction was observed in the racemic series. Sulfamid-
ate i was hydrolyzed to ii in 95% yield using conditions de-
scribed in the literature for mild hydrolysis of sulfamidates
(ref.[14]).
[37] See Supporting Information for calculated transition states.
Owing to their higher activation barrier subsequent steps along
this pathway were not considered.
[38] Although even this reaction barrier is slightly too high, it was
by far the lowest out of all the mechanistic possibilities consid-
ered.
[39] Atoms in Molecules: A Quantum Theory (Ed.: R. F. W. Bader),
Oxford Press, 1990. As implemented within the AIM program,
2000.
[40] E. D. Glendening, A. E. Reed, J. E. Carpenter, F. Weinhold,
NBO, version 3.1.
[41] a) K. B. Wiberg, Tetrahedron 1968, 24, 1083–1096; b) Wiberg
bond indices for pertinent bond forming/breaking distances
during 5-mem-TS1: C···N: 0.1588, C···O: 0.3007, and O···S:
0.4358.
[42] An Intrinsic Reaction Coordinate (IRC) calculation confirmed
that cis-5-mem sulfamidate was the immediate product of 5-
mem-TS1.
[43] See Supporting Information for details regarding these
searches.
[28] a) B. Sullivan, J. Gilmet, H. Leisch, T. Hudlicky, J. Nat. Prod.
2008, 71, 346–350; b) J. Gilmet, B. Sullivan, T. Hudlicky, Tetra-
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J. Am. Chem. Soc. 1995, 117, 5897–5898.
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1992, 125, 1169–1190.
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62, 4197–4199.
[32] To the best of our knowledge, as of this report, there have
been no previous computational studies addressing the Burgess
reagent’s reactivity.
[44] Multiple attempts were made to locate 5-mem-TS1 in the pres-
ence of an epoxide bound Lewis acid, none of these attempts
were successful in locating energetically feasible transition
states.
[45] For example a reaction dynamic involving Brønsted acidic tri-
methylammonium (a likely degradation product of Burgess rea-
gent) was computed and shown to have a reduced barrier to
cyclohexene oxide ring opening as compared with that of the
uncatalyzed processes (i.e. 5-mem-TS1).
[33] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652; b) C. Lee,
W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785–789.
[34] a) W. J. Hehre, R. Ditchfield, J. A. Pople, J. Chem. Phys. 1972,
56, 2257–2261; b) P. C. Hariharan, J. A. Pople, Theor. Chim.
Acta 1973, 28, 213–222; c) P. C. Hariharan, J. A. Pople, Mol.
Phys. 1974, 27, 209–214; d) M. M. Francl, W. J. Pietro, W. J.
Hehre, J. S. Binkley, M. S. Gordon, D. J. DeFrees, J. A. Pople,
J. Chem. Phys. 1982, 77, 3654–3665; e) V. A. Rassolov, J. A.
Received: February 14, 2009
Published Online: April 27, 2009
Eur. J. Org. Chem. 2009, 2806–2819
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2819