Catalytic enantioselective α-oxysulfonylation of ketones mediated by iodoarenes

Article abstract of DOI:10.1002/ejoc.200800741

The α-oxysulfonylation of ketones catalysed by enantio enriched iodoarenes using mCPBA as stoichiometric oxidant is reported to give useful synthetic intermediates in good yield and modest enantioselectivity. We believe this to be the first report of an enantioselective organocatalytic reaction involving hypervalent iodine reagents which should open up a new field for enantioselective organocatalysis of oxidation reactions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800741

FULL PAPER
DOI: 10.1002/ejoc.200800741
Catalytic Enantioselective α-Oxysulfonylation of Ketones Mediated by
Iodoarenes
Sabine M. Altermann,[a] Robert D. Richardson,[a] T. Keri Page,[a] Ruth K. Schmidt,[a,b]
Edward Holland,[a] Umal Mohammed,[a] Shauna M. Paradine,[a,c] Andrew N. French,[a,c]
Christine Richter,[a,d] A. Masih Bahar,[a,b] Bernhard Witulski,[a,e] and Thomas Wirth*[a]
Keywords: Hypervalent iodine reagents / Organocatalysis / Oxidation / Stereoselective synthesis
The α-oxysulfonylation of ketones catalysed by enantio
enriched iodoarenes using mCPBA as stoichiometric oxidant
is reported to give useful synthetic intermediates in good
yield and modest enantioselectivity. We believe this to be the
volving hypervalent iodine reagents which should open up
a new field for enantioselective organocatalysis of oxidation
reactions.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
first report of an enantioselective organocatalytic reaction in- Germany, 2008)
Introduction
The past three decades have revealed the use of hyperval-
ent iodine compounds as very versatile and mild oxidation
and oxygenation reagents[1–7] replacing toxic and heavy
metal-containing reagents, thus providing more environ-
mental friendly reaction conditions. They can also be em-
ployed as electrophilic reagents e.g. for functionalisations of
alkenes and subsequent halolactonisations,[8] dioxytosyla-
tions[9] or α-oxytosylations.[10] For these reactions, mostly
hypervalent iodine compounds bearing two heteroatom li-
gands on iodine(III) as well as their polymer-supported de-
rivatives are used. Due to the high interest in enantioselec-
tive reactions, employment of enantiomerically enriched hy-
pervalent iodine compounds has been investigated recently,
e.g. α-oxytosylation of ketones.[11–13] In this manner, syn-
thetically valuable tosylates such as 3 can be obtained in up
to 40% ee (Scheme 1).
Scheme 1. Enantioselective α-oxytosylation of propiophenone.
Recently, the catalytic use of iodine compounds has been
developed.[8,14–17] First investigations in iodocatalysis were
undertaken by Fujita and co-workers with anodic gem-di-
fluorination of thiodiketals mediated by aryl iodides.[18]
mCPBA is a potent oxidation reagent in the synthesis of
λ3-iodane compounds. Ochiai and co-workers successfully
employed mCPBA as stoichiometric chemical oxidant in
In this reaction, the Koser-type iodane 2 has to be used
in stoichiometric amounts. On the other hand, a range of
enantiomerically pure iodine compounds of various types
has been synthesized but remained untested, because oxi-
dation to the respective aryl λ3-iodanes has been unsuccess-
ful so far.
[a] Cardiff University, School of Chemistry, Park Place,
Cardiff CF10 3AT, UK
Fax: +44-29-2087-6968
E-mail: wirth@cf.ac.uk
[b] Universität Münster, Institut für Organische Chemie,
48149 Münster, Germany
Scheme 2. First catalytic reactions using iodoarene as catalysts. [A]
mCPBA (2 equiv.), BF3·OEt2 (3 equiv.), AcOH, room temp., 43–
[c] Chemistry Department, Albion College,
Albion, MI 49224, USA
63% yield, Nu
= OAc; [B] mCPBA (1.1 equiv.), p-TsOH
[d] Universität Kaiserslautern, Fachbereich Chemie,
67663 Kaiserslautern, Germany
[e] Universität Mainz, Institut für Organische Chemie,
55128 Mainz, Germany
(1.1 equiv.), MeCN, 50 °C, 63–88% yield, Nu = OTs; [C] mCPBA
(1.5 equiv.), CF3CO2H (1 equiv.), CH2Cl2, room temp., 66–91%
yield.
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T. Wirth et al.
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the first catalytic α-acetoxylation of phenones.[15] The reac- Table 1. Enantiomerically pure ethers as catalysts in the α-oxytosyl-
ation of propiophenone 1.
tion was conducted using iodobenzene as catalyst and ace-
tic acid as nucleophile in presence of BF3·Et2O and water
leading to functionalised ketones 4 (Scheme 2). Kita et al.
reported that only 5 mol-% iodotoluene[19] are used to-
gether with 1.5 equiv. mCPBA and 1 equiv. trifluoroacetic
acid to achieve the spirocyclization to lactones 5 in 66–91%
yield (Scheme 2).[16]
Based on these results, we recently reported the first cata-
lytic use of enantiomerically pure iodoarenes in asymmetric
reactions[20] which opened the possibility to employ a wide
range of enantiomerically pure iodoarenes with very dif-
ferent structural features as catalysts. Very recently, Kita et
al. reported a highly enantioselective spirocyclization using
an aryliodide with a spirobiindane moiety.[21]
Results and Discussion
We herein report the synthesis of enantiomerically en-
riched α-oxysulfonylated phenones using chiral iodoarenes
as catalysts. The reaction using stoichiometric iodanes can
usually be performed at –30 °C to maximise enantio-
selectivity,[11] but at this temperature the reactions em-
ploying catalytic amounts of iodoarenes and mCPBA as the
stoichiometric oxidant proceed very slowly, consistent with
the results of Togo.[17] This suggests that the formation of
the hydroxy(tosyloxy)iodoarene could be the rate-determin-
ing step in the catalytic cycle. Therefore, the reactions were
conducted at room temperature for 2–4 days using commer-
cial 70–77% wet mCPBA as the stoichiometric oxidant
since we found no difference in the reactivity compared to
dry mCBPA. Acetonitrile was used since we observed high-
est reaction rates and cleanest products with this solvent.[20]
Initially, p-toluenesulfonic acid was used as the nucleophile
and clean reactions with propiophenone 1 to give tosylate 3
were observed. Most of the reactions described herein were
conducted using small amounts of reagents (0.1–0.2 mmol),
leading to sometimes poor yields compared to conversions
achieved due to loss during work-up and purification.
Various chiral ethers bearing iodoarene moieties have
been synthesized and the results in the catalytic oxytosyl-
ation of propiophenone are summarised in Table 1.
[a] Determined by 1H NMR analysis of the crude reaction product.
Interesting trends regarding enantioselectivities were ob-
[b] Determined by HPLC. [c] Absolute configuration of iodoarene
unknown. n.d. = not determined.
served from these results. The addition of a substituent to
the 6-position of the aromatic ring resulted in an increase
in the enantioselectivity when catalysts 7–9 were employed,
an ethyl substituent yielding highest selectivities (entry 2).
We therefore synthesized the chiral esters 17–31 as a new
When the ether moiety was shifted further away from the class of iodine catalysts. Many of these compounds are
iodine, a decrease of enantioselectivity (entries 5 and 6) was available through simple esterifications using enantiomer-
observed, only the diether derivative 13 with a phenylethyl ically pure alcohols such as (–)-borneol, (–)-menthol and
ether moiety resulted in moderate selectivity (entry 8). (–)-fenchol as detailed in the experimental part. The results
Other ethers of 2-iodophenol with various terpene-derived of the catalytic reactions are shown in Table 2.
chiral moieties bearing no additional heteroatom resulted in
When terpene esters derived from 2-iodobenzoic acid
almost no enantioselectivity. The existence of an additional were used as catalysts, conversions and enantiomeric ex-
heteroatom in the chiral moiety, which is able to coordinate cesses were quite poor. Due to the close proximity of the
to the iodine atom, seems to be a very important feature of bulky ester moiety of 17–19 to the iodine atom, the iodine
these catalysts.
centre might be hindered for an approach of the oxidising
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Enantioselective α-Oxysulfonylation of Ketones
Table 2. Enantiomerically pure esters as catalysts in the α-oxytosyl-
ation of propiophenone 1.
Based on these results, methyl substituents were intro-
duced into esters 21–23 by alkylation. The resulting dia-
stereomers were separated by preparative HPLC. The abso-
lute configuration of ester 32 has been determined by ester
cleavage and comparison to literature.[22] Based on the ab-
solute configurations (S) of the products 3, the absolute
configurations of esters 31 and 33 are assumed to be iden-
tical to 32. When catalysts 28–33 were employed, an in-
crease of enantioselectivity up to 39% was observed for the
menthyl ester 32. On the other hand, its diastereomer 29
resulted in a product with only 15% ee. Without the ad-
ditional methyl substituent in the benzylic position, the es-
ter can rotate freely and no selectivity is observed. The
methyl substituent might then force the ester into a certain
conformation with the chiral terpene substituent leading to
additional interactions. This results in lower selectivities
(15% ee, entry 13), or in a matched scenario, to higher
selectivities (39% ee, entry 16) compared to the methyl ester
24 (24% ee, entry 8). These facts again demonstrate the im-
portance of a chiral moiety in the ortho-position to the
iodine.
In order to investigate the influence of a nitrogen atom
as potential coordination site to the iodine atom, several
amide catalysts were prepared. Binaphthyl derivative 34 re-
sulted in very poor yields and selectivities. The nitrogen
atom in nitrile 35 seems to coordinate less efficiently to the
iodine and is a reactive catalyst in the synthesis of 3 (95%
conversion), but the selectivity obtained is low (7% ee).
Compound 36, based on a chiral alcohol developed by
Helmchen and co-workers,[23] containing both, an ester
moiety as well as a nitrogen atom, failed as catalyst; no
conversion was observed (Figure 1).
[a] Determined by 1H NMR analysis of the crude reaction product.
[b] Determined by HPLC. n.d. = not determined.
agents which results in poor conversions. This assumption
is supported by the fact that esters 21–23, with an ad-
ditional carbon atom in the side chain, resulted in excellent
conversions. Here, the bulky terpene moiety is shifted fur-
ther away from the iodine atom. Secondly, methyl ester 20
also gave good conversions; the methyl moiety is too small
to interfere with the oxidation of the iodine atom.
However, an elongation of the side chain by one methyl-
ene moiety resulted in better conversions and yields, but
still poor selectivities when borneyl ester 21 (entry 5) was
employed and in racemic products when menthyl or fenchyl
esters 22 and 23 (entries 6 and 7) were used. The introduc-
Figure 1. Nitrogen-containing iodoarene catalysts.
The fact, that disubstituted esters and nitriles as catalysts
tion of stereogenic centres in the benzylic position of such result in poor enantiomeric excess, only confirms the crucial
reagents has already been successful as shown with the syn- influence of small substituents in the side chain, as observed
thesis and use of compound 2 (Scheme 1). Alkylation of the previously.[12]
prochiral benzylic carbon atom in 21–23 could achieve an
Several other naphthalene-derived iodine compounds
increase of the enantioselectivity in the α-oxytosylation, have been prepared and investigated. Iodoarenes 37–40 are
since the chiral centre would be closer to the iodine moiety. compounds we could not previously investigate in reactions
Different substituted methyl esters 24–27 were prepared in shown in Scheme 1 because they could not be converted to
order to determine the optimal nature of the substituent stable λ3-iodanes. Reaction using 37 as catalyst failed, the
(entries 8–11). Conversions achieved with these catalysts paracyclophane derivative 38 led to good conversion (75%),
were generally high. Highest enantioselectivities could be but only produced racemic 3. The reason for the synthetic
obtained using catalyst 24 with a methyl substituent. Esters efforts to prepare optically pure 38 was the impossibility to
25–27 equipped with more hindered substituents or with oxidize iodoparacyclophane to a hypervalent iodine deriva-
even two substituents resulted in lower enantioselectivities.
tive. A Heck-reaction of 4-bromo-[2.2]-paracyclophane[24]
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T. Wirth et al.
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with styrene produced 4-styryl-[2.2]-paracyclophane,[25] Table 4. α-Oxysulfonylation of propiophenone using different cata-
lysts.
which was then photochemically isomerised to 1,4-phen-
anthreno-[2.2]-paracyclophane,[24] brominated[26] and the
bromine finally excanged to iodine to give 38. The binaph-
thyl derivative 39 was less reactive than 40 (Figure 2), prob-
ably due to an intramolecular coordination with the car-
boxylic acid moiety. Catalyst 40 generated 3 in 79% yield
with 12% ee (S).
Entry
Catalyst % ee of 45[a] % Conv.[b] % ee of 46[a] % Conv.[b]
1
2
3
4
5
6
7
8
14
15
16
18
24
25
29
32
5
2
4
n.d.
23
18
15
31
85
13
89
0
33
5
0
0
2
n.d.
23
22
18
29
50
33
20
Ͻ5
89
98
n.d.
39
100
15
1
[a] Determined by HPLC. [b] Determined by H NMR analysis of
the crude reaction product. n.d. = not determined.
Mesitylenesulfonic acid was used as a sterically con-
gested nucleophile yielding ketone 47. Catalyst 18 failed to
give any product. In opposition to previous results, catalyst
29 led to a product with higher enantioselectivity alongside
moderate conversion whereas its diastereomer 32 showed
excellent conversion but low selectivity again suggesting the
cooperative effect of a chirally-matched catalyst. Also, re-
actions catalysed by the fenchyl-derived catalyst 30 were
conducted, resulting in only moderate selectivity and con-
version.
Chiral sulfonic acids such as camphorsulfonic acid could
lead to increased selectivities. As shown in Table 5, this was
indeed the case; the use of (1S)-(–)-10-camphorsulfonic acid
as nucleophile increased the diastereomeric excess of 48 to
up to 44% when the reaction was catalysed by catalyst 32
(entry 5). The diastereomer 29 as well as catalyst 30 resulted
in low selectivities. Catalysts 18 and 24 failed to give prod-
uct 48 (Figure 3).
Figure 2. Naphthalene- and phenanthrene-based iodoarene cata-
lysts.
A range of aryl alkyl ketones were investigated using
ether 7 as catalyst (Table 3). The reactions were conducted
under the reaction conditions described above. All selected
substrates gave good yields and similar selectivities, there-
fore propiophenone was used for all further investigations.
Table 3. α-Oxytosylation of aryl alkyl ketones using catalyst 7.
Table 5. α-Oxysulfonylation of propiophenone using bulky nucleo-
philes.
Entry
Catalyst % ee of 47[a]
% Conv.[b] % de of 48[a] % Conv.[b]
(% yield)
(% yield)
1
2
3
4
5
18
24
29
30
32
–
–
29
22
11
0
–
20
10
100 (33)
–
–
26
25
44
0
0
71
43
67 (24)
[a] Determined by HPLC, absolute configuration unknown. [b] De-
1
termined by H NMR analysis of the crude reaction product.
[a] Determined by HPLC.
In a next series of experiments, the nature of the nucleo-
phile was examined. A range of sterically variable sulfonic
acids was employed and some results are summarised in
Table 4. Methanesulfonic acid was used as the least steri-
cally hindered reagent to yield product 45. Conversions
Figure 3. Use of other sulfonic acids as nucleophiles. Mes: 2,4,6-
trimethylphenyl.
Also (1R)-(+)-10-camphorsulfonic acid was used as a nu-
were generally much lower than conversions of reactions cleophile with 29 and 32 as catalysts in order to investigate
using pTsOH, whereas enantioselectivities decreased only the influence of the opposite enantiomer nucleophile. The
little. Surprisingly, menthyl ester 18 was not active as a cata- conversions are high, but the diastereoselectivies obtained
lyst. The use of benzenesulfonic acid in these reactions led are 18% (for 29) and 34% (for 32) and therefore lower than
to similar results as obtained with p-toluenesulfonic acid.
with (–)-camphorsulfonic acid.
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Enantioselective α-Oxysulfonylation of Ketones
Based on the results obtained so far, menthyl ester cata- forms the driving force for this reaction.[32,33] Another
lyst 32 achieved highest enantioselectivities was employed mechanistic possibility is the hypervalent iodine atom to be
in reactions with (–)-camphorsulfonic acid using other attacked by the double bond electrons of the enol tautomer
promising ketones such as 43 and 44 under the conditions to form 53 with subsequent SN2-type replacement by the
described above. Unexpectedly, enantioselectivities and tosylate (path B). The chiral moiety in this reaction path is
yields were inferior to the results achieved with propiophen- closer to the newly formed stereocentre than in 52. This
one and the compounds 49 and 50 only obtained with 16% might suggest path B to take place; concordant to the
and 26% de, respectively (Figure 4).
mechanism proposed by Moriarty.[34]
In this reaction, substitution of the hyper-leaving group
by m-chlorobenzoate rather than by the tosylate does not
occur in our work as well as that of Togo.[17] Also, enolis-
ation of product 3 resulting in racemisation, which is vital
take place in reagent 1 in order to proceed the reaction, has
not been monitored. To ensure this fact, enriched product
3 was resubmitted to the reaction conditions described
above; no change of enantioenrichment was observed. The
results obtained fortify the suggestion that a rigid five-mem-
bered ring is formed in the intermediate hypervalent species
based on oxygen-containing catalysts. The chiral centre is
fixed in position due to coordination to the iodine atom,
yielding in high enantioselectivities. If this interaction can-
not be achieved, free rotation of the chiral moiety is pos-
sible resulting in poor enantioselectivities.
Figure 4. α-Oxytosylation using (–)-camphorsulfonic acid as nu-
cleophile.
In all reactions described above the iodine atom was al-
ways covalently bound to an aromatic moiety in the cata-
lyst. To our best knowledge, the only alkyl iodides, which
can be oxidised to λ3-iodanes are fluorinated iodine com-
pounds.[27–31] Iodoalkanes containing a very small alkane
moiety cannot be isolated as hypervalent compounds due
to their instability. We investigated methyliodide and
iodoacetonitrile as possible catalysts. The reaction using
methyl iodide as catalyst gave only a conversion of 18%
and iodoacetonitrile none at all. On the other hand, both
compounds were also used in catalytic amounts in the re-
spective acetoxylation reaction using the reaction condi-
tions established by Ochiai and co-workers,[15] resulting in
99% conversion for both compounds.
Two possible mechanisms are discussed (Scheme 3). The
enol tautomer of propiophenone reacts with the Koser-type
iodane 51 generated in situ from the iodoarene (path A)
and a subsequent SN2Ј-type attack of the tosylate to 52 re-
places the iodine moiety. The facile reduction of λ3-iodane
to an iodine(I) compound in the reductive elimination step
Conclusions
In conclusion, we have established and improved the
enantioselective oxysulfonylation of ketones catalysed by
enantiomerically pure iodoarenes. α-Sulfonyloxylated
ketones are obtained in good yields as well as in promising
enantiomeric excesses. Best results were achieved, when es-
ters containing two chiral centres were used as catalysts and
(–)-camphorsulfonic acid as a chiral sulfonic acid used as
nucleophile.
Experimental Section
1
General: H and 13C NMR spectra were recorded in CDCl3 on a
Bruker Avance 400 or Bruker Avance 500BB against an internal
deuterium lock. Melting points are uncorrected. IR measurements
were taken using a Perkin–Elmer 1600 FTIR spectrometer or on a
Bruker Alpha-E FTIR Spectrometer as a liquid film. Low resolu-
tion mass spectrometry was carried out using a Varian Saturn 2
GC-MS. Flash chromatography was carried out using Fisher Silica
Gel (35–70 mesh). Preparative thin-layer chromatography was car-
ried out using Merck silica gel 60 F254 on glass plates. All solvents
used were dried and purified by standard methods. Reactions re-
quiring the exclusion of air were carried out under an atmosphere
of argon in oven dried glassware.
General Procedures (GP)
GP1. Etherification of 1-Fluoro-2-nitrobenzene:[35] In a dry flask
2.2 equiv. of sodium hydride (60% in mineral oil) were washed with
hexane to remove the mineral oil and then dried by flushing with
argon. The resulting powder was suspended in dry THF. Then
1.0 equiv. of 1-fluoro-2-nitrobenzene in THF were added drop wise
at 0 °C. Subsequently, 2.2 equiv. of an alcohol were added and the
mixture was refluxed overnight. The mixture was washed with
NH4Cl solution (aqueous, satd.), extracted with CH2Cl2 and dried
Scheme 3. Possible mechanisms of the α-oxytosylation of propio-
phenone.
Eur. J. Org. Chem. 2008, 5315–5328
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T. Wirth et al.
FULL PAPER
with MgSO4. After evaporation of the solvents, the product was
purified by column chromatography.
1 H, arom.), 7.49–7.42 (m, 2 H, arom.), 7.28–7.25 (m, 2 H, arom.),
5.79 (q, J = 6.9 Hz, 1 H, 2-CH), 2.41 (s, 3 H, 16-CH3), 1.60 (d, J
= 6.9 Hz, 3 H, 1-CH3) ppm. HPLC conditions: Chiracel OB-H
GP2. Hydrogenation of Nitroarenes:[36] In a flask under argon at-
mosphere, the respective nitroaryl ether was dissolved in MeOH.
Then Pd/C (10%) was then added and the mixture was stirred vig-
orously in a hydrogen atmosphere until the reaction was completed.
The mixture was then filtered through SiO2 and the solvent was
evaporated; the crude product was used without further purifica-
tion.
GP3. Iodination of Amines:[37] To a mixture of an amine (1 equiv.)
in water and H2SO4 a solution of sodium nitrite (1.2 equiv.) was
added slowly at 0 °C and the mixture was stirred for 3 d. After
reaction completion the excess nitrous acid was quenched by the
addition of urea. An aqueous solution of KI (1.2 equiv.) was added
and the mixture was stirred for 3 h at 50 °C. To the resulting mix-
ture an aqueous solution of Na2S2O3 was added. The mixture was
extracted with diethyl ether, washed with 1 NaOH to pH 5,
washed with brine and dried with MgSO4. Evaporation of the sol-
vent afforded the crude product.
column, hexane/2-propanol, 40:60, 0.5 mL/min, 40 °C, tR
=
18.1 min (R), 21.6 min (S).[39]
1-(2-Iodophenyl)-2-propanol: Synthesized from 1-(2-iodophenyl)-
propan-2-one.[40] Methylmagnesium iodide (372 mg, 2.24 mmol)
was added dropwise over 5 min to a solution of 2-iodophenyl acet-
aldehyde (550 mg, 2.24 mmol) in dry diethyl ether (4 mL) under Ar
at –10 °C. After 1.5 h, aq. satd. ammonium chloride (5 mL) was
added to the stirred solution. The aqueous phase was washed with
dichloromethane (2ϫ10 mL) and the organic layers combined and
dried with MgSO4. The solvent was removed under vacuum to
yield a light yellow oil. The product was purified by column
chromatography, (petroleum ether/diethyl ether, 1:1). Yield 97%
(568 mg, 2.18 mmol) HPLC conditions: Chiracel OD column, hex-
ane/2-propanol, 99:1, 3 mL/min, 10 °C, tR = 145.1 min (–)-enantio-
mer, 165.5 min (+)-enantiomer. Enantiomer 2 (Rf = 165.5 min):
1
[α]D = 21.3 (c = 0.19, CHCl3). H NMR (CDCl3, 250 MHz): δ =
7.78 (dd, J = 1.2, 8.0 Hz, 1 H, arom. H), 7.39 (m, 2 H, arom. H),
6.96 (dt, J = 1.2, 7.9 Hz, 1 H, arom. H), 4.14 (m, 1 H, CHOH),
2.92 (m, 2 H, CH2), 1.55 (s, 1 H, OH), 1.34 (d, J = 6.2 Hz, 3 H,
CH3) ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 141.4 (C-2), 139.8
(C-6), 130.9 (C-5), 128.4 (C-3), 128.4 (C-4), 101.2 (C-1), 67.7 (C-
GP4. Synthesis of Esters: 2-Iodobenzoyl chloride (1 equiv.) and an
alcohol (1.5 equiv.) were stirred together with p-TsOH (5 mol-%) in
acetonitrile at 80 °C for 1–3 d. After reaction completion, the mix-
ture was cooled to room temperature and poured into aqueous
saturated NaHCO3 and extracted with CH2Cl2 (3ϫ). The com-
bined organic layers were dried with MgSO4 and solvent was re-
moved. The crude product was purified by flash chromatography
(petroleum ether:diethyl ether, 4:1).
8), 49.9 (C-7), 23.0 (C-9) ppm. IR (neat): ν = 3199 (OH), 1124
˜
(CO) cm–1. MS (ES+): m/z (%) = 262 (4) [M]+, 218 (45), 105 (5), 91
+
(100), 45 (47). HRMS: calcd. for C9H11IO·NH4 280.0193, found
280.0195.
GP5. Synthesis of Esters: 2-Iodophenylacetic acid (1 equiv.), an
alcohol (1.5 equiv.) and p-TsOH (5 mol-%) were stirred at room
temperature in CH2Cl2 for 1–3 d. After reaction completion, the
mixture was poured into aqueous saturated NaHCO3 and extracted
with CH2Cl2 (3ϫ). The combined organic layers were dried with
MgSO4 and solvent was removed. The crude product was purified
by flash chromatography (petroleum ether/diethyl ether, 4:1).
GP6. Alkylation of Esters and Nitriles:[38] To a freshly prepared
LDA solution was added dropwise a solution of the respective ester
or nitrile (1 equiv.) in dry THF at –78 °C and stirred for 30 min at
this temperature. The alkylhalogenide (1.2 equiv.) was added drop-
wise and the mixture was stirred at room temperature for 2–3 h.
After reaction completion, the mixture was poured into aqueous
saturated NH4Cl and extracted with CH2Cl2 (3ϫ). The combined
organic layers were dried with MgSO4 and solvent was removed.
The crude product was purified by flash chromatography (petro-
leum ether/diethyl ether, 4:1).
(+)-1-Iodo-2-(2-methoxypropyl)benzene (10): Sodium hydride
(53 mg, 2.22 mmol) (55–65% in oil) was washed with pentane
(4ϫ1 mL) and then suspended in dimethylformamide (3 mL). Af-
ter cooling to 0 °C, a solution of (+)-1-(2-iodophenyl)-2-propanol
(193 mg, 0.74 mmol) in dimethylformamide (2 mL) was added. Af-
ter stirring for 15 minutes at room temperature, the mixture was
cooled to 0 °C and methyl iodide (355 mg, 2.5 mmol) was added.
After a further 3 hours at room temperature, water (5 mL) was
carefully added. The resulting mixture was extracted with tert-butyl
methyl ether (2ϫ5 mL), and the combined organic phases were
washed with brine (3ϫ5 mL), dried with MgSO4, and concentrated
under reduced pressure to yield a yellow oil. The product was puri-
fied by column chromatography (hexane/ethyl acetate, 4:1). Yield
97% (198 mg, 0.72 mmol). HPLC conditions: Chiracel OD-H col-
umn, hexane/2-propanol, 99:1, 0.5 mL/min, 22 °C, tR = 8.4 min
(–)-enantiomer, 9.9 min (+)-enantiomer. [α]D = 41.2 (c = 0.12,
CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 7.74 (dd, J = 1.2,
7.6 Hz, 1 H, arom. H), 7.18 (m, 2 H, arom. H), 6.81 (dt, J = 7.9,
1.2 Hz, 1 H, arom. H), 3.55 (m, 1 H, CHOCH3), 3.28 (s, 3 H,
OCH3), 2.98 (dd, J = 13.6, 6.5 Hz, 1 H, ArCHH), 2.67 (dd, J =
13.5, 6.6 Hz, 2 H, ArCHH), 1.10 (d, J = 6.1 Hz, 3 H, CH3) ppm.
13C NMR (CDCl3, 62.5 MHz): δ = 140.7 (C-2), 138.4 (C-6), 130.1
(C-5), 127.1 (C-3), 127.0 (C-4), 100.3 (C-1), 55.5 (C-8), 49.1 (C-10),
GP7. α-Oxysulfonylation of Ketones: A ketone (1 equiv.), an organ-
oiodine catalyst (10 mol-%), mCBPA (2.3–3 equiv.) and a sulfonic
acid (3 equiv.) were stirred at room temperature for 2–4 d. After
reaction completion, the mixture was poured into aqueous satu-
rated Na2S2O3 and extracted with CH2Cl2 (3ϫ). Then, the organic
layers were poured into aqueous saturated NaHCO3 and extracted
with CH2Cl2 (3ϫ). The combined organic layers were dried with
Na2SO4 and solvent was removed. The crude product was purified
by flash chromatography (petroleum ether/diethyl ether, 4:1) or pre-
parative TLC (petroleum ether/diethyl ether, 2:1).
28.7 (C-7), 18.0 (C-9) ppm. IR (neat): ν = 2820, 1469, 1366, 1169,
˜
1122, 1089, 1010, 907, 751, 717 cm–1. MS (ES+): m/z (%) = 276
(16) [M]+, 217 (34), 105 (9), 91 (100), 58 (37). HRMS: calcd. for
C10H13IO 276.112, found 276.1115 [M + H]+.
2-{[(4-Methylphenyl)sulfonyl]oxy}-1-phenyl-1-propanone (3): Syn-
thesis according to GP7 from propiophenone (45 mg, 0.33 mmol),
catalyst 32 (12 mg, 0.03 mmol, 10 mol-%), mCPBA (172 mg,
1 mmol) and p-toluenesulfonic acid (190 mg, 1 mmol); purification
by preparative TLC (diethyl ether/petroleum ether, 1:2). Yield 42%
4-(2-Iodophenyl)-2-butanone:[41] Synthesized according to ref.[40]: A
mixture of 2-iodobenzyl chloride (3.0 g, 11.9 mmol), 2,4-pentane-
dione (1.35 mL, 13.1 mmol) and potassium carbonate (1.65 g,
12 mmol) in ethanol (30 mL) was heated to reflux and stirred for
24 hours. The solvent was removed under vacuum and the residue
(43 mg, 0.14 mmol). 1H NMR (250 MHz, CDCl3): δ = 7.90–7.85 partitioned between diethyl ether (10 mL) and water (10 mL). The
(m, 2 H, arom.), 7.78–7.73 (m, 2 H, arom.), 7.59 (tt, J = 2.2, 7.4 Hz, organic layer was dried with MgSO4 and concentrated under vac-
5320
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5315–5328

Enantioselective α-Oxysulfonylation of Ketones
uum to yield a brown oil. Purification by column chromatography
(petroleum ether/diethyl ether, 4:1) to give a pale yellow oil. Yield
84%, (4.41 g, 16.1 mmol). H NMR (CDCl3, 250 MHz): δ = 7.84
11), 56.4 (C-9), 37.5 (C-7), 37.0 (C-8), 19.4 (C-10) ppm. IR (neat):
ν
= (= 3059), 2924, 2819, 1586, 1465, 1434, 1372, 1169, 1137,
˜
max
1094, 1010, 911, 747, 716 cm–1. MS (ES+): m/z (%) = 291 (31) [M+],
1
(d, J = 7.7 Hz, 1 H, arom. H), 7.29 (m, 2 H, arom. H), 6.93 (dt, J
290 (100), 278 (64), 217 (67), 107 (79), 91 (100), 58 (37), 258 (21),
= 1.3, 6.9 Hz, 1 H, arom. H), 3.03 (t, J = 7.7 Hz, 2 H, ArCH2), 217 (9), 131 (20), 104, (7), 91 (23), 59 (100). HRMS: calcd. for
2.78 (t, J = 7.7 Hz, 2 H, O =CCH2), 2.20 (s, 3 H, CH3) ppm. 13C
NMR (CDCl3, 62.5 MHz): δ = 207.5 (C-9), 143.6 (C-2), 139.6 (C-
6), 129.7 (C-5), 128.6 (C-5), 128.1 (C-4), 100.3 (C-1), 43.7 (C-7),
34.8 (C-8), 30.1 (C-10) ppm.
C11H15IO·H+: 291.0240, found 291.0239.
(S)-1-(2-Iodophenoxy)-2-propanol:[43] K2CO3 (1.70 g, 12 mmol) and
2-iodophenol (660 mg, 3 mmol) were dissolved in DMF (5 mL),
and the mixture was refluxed for 1 hour. (S)-(–)-Propylene oxide
(240 µL, 3.3 mmol) was added and the reaction was allowed to pro-
ceed at 60 °C until completion (48 h). The reaction was quenched
with aqueous NH4Cl (30 mL) and extracted with diethyl ether
(2ϫ30 mL). The aqueous layer was acidified with 10% HCl (5 mL)
and extracted with diethyl ether (2ϫ30 mL). The combined or-
ganic layers were dried with anhydrous MgSO4, filtered, and con-
centrated in vacuo. The product was purified by flash column
chromatography through silica (hexane/ethyl acetate, 6:1). The
product (pale yellow oil) was obtained in 70% yield (584 mg,
2.1 mmol) with Ͻ5% of the minor regioisomer [(S)-1-(2-iodo-
phenoxy)-1-propanol, determined by 1H NMR]. 1H NMR (CDCl3,
400 MHz): δ = 7.59 (dd, J = 1.6, 7.8 Hz, 1 H), 7.11 (dt, J = 1.6,
7.8 Hz, 1 H), 6.62 (dd, J = 1.2, 8.2 Hz, 1 H), 6.56 (dt, J = 1.3,
7.6 Hz, 1 H), 4.09 (m, 1 H, CHOH), 3.79 (dd, J = 3.7, 9.1 Hz, 1
H, CHH), 3.67 (dd, J = 7.0, 9.1 Hz, 1 H, CHH), 3.10 (s, 1 H, OH),
1.19 (d, J = 6.5 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 157.0, 139.3, 129.7, 123.1, 112.7, 87.0, 74.6, 66.1, 19.1 ppm.
4-(2-Iodophenyl)-2-butanol: 1-(2-Iodophenyl)butan-3-one (2.00 g,
7.30 mmol) was added dropwise over 2 min to a stirred suspension
of sodium borohydride (152 mg, 4.02 mmol) in ethanol (20 mL) un-
der argon at room temperature. The resulting solution was heated
to reflux with stirring. After 3 hours, the solution was removed
from the oil bath, cooled to room temperature and quenched with
water (10 mL) and acetic acid (3 mL). The resulting mixture was
concentrated under vacuum, and the residue partitioned between
ether (10 mL) and water (10 mL). The aqueous layer was extracted
with diethyl ether (3ϫ10 mL), the organic fractions combined,
dried with MgSO4 and the solvent removed under reduced pres-
sure, to yield the alcohol as a yellow oil. Purification was performed
using column chromatography (petroleum ether/diethyl ether, 3:1)
to give a pale yellow oil. Yield 97% (1.96 g, 7.1 mmol). The race-
mate has been reported.[42] HPLC conditions: Chiracel OD semi-
preparative column, hexane/2-propanol, 93:7, 4.5 mL/min, 15 °C,
tR = 25.1 min (–)-enantiomer, 32.5 min (+)-enantiomer. [α]D
=
+9.25 (c = 1.8, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 7.74 (dd,
J = 1.1, 7.6 Hz, 1 H, arom. H), 7.19 (m, 2 H, arom. H), 6.92 (dt,
J = 1.3, 6.6 Hz, 1 H, arom. H), 3.81 (m, 1 H, CH2CHOMe), 2.80
(ddd, J = 6.9, 9.6, 13.7 Hz, 1 H, ArCH2), 2.70 (ddd, J = 6.9, 9.6,
13.7 Hz, 1 H, ArCH2), 1.67 (m, 2 H, CHCH2), 1.43 (s, 1 H, OH),
1.20 (d, J = 6.2 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3, 62.5 MHz):
δ = 144.6 (C-2), 139.5 (C-6), 127.8 (C-4), 129.5 (C-3), 128.5 (C-5),
100.6 (C-1), 67.5 (C-9), 39.6 (C-7), 37.1 (C-8), 23.6 (C-10) ppm. IR
(S)-2-Iodo-1-(2-methoxypropoxy)benzene (12): NaH (60% disper-
sion in oil, 300 mg, 7.5 mmol) was washed with hexane (3ϫ10 mL)
and suspended in DMF (5 mL). (S)-1-(2-Iodophenoxy)-2-propanol
(2.0 mmol) was dissolved in 2 mL of DMF and added dropwise.
The reaction mixture was allowed to stir at room temperature for
45 min. Methyl iodide (380 µL, 6.0 mmol) was added and the reac-
tion was allowed to proceed until completion (3–4 h). Water was
added dropwise to the flask until effervescence ceased (2–5 mL),
then excess was added (10–15 mL total). The crude product was
extracted with diethyl ether (3ϫ20 mL). The organic layers were
combined and dried with anhydrous MgSO4, filtered, and concen-
trated in vacuo. The product was purified by flash column
chromatography through silica, using hexane/ethyl acetate, 10:1.
The pure product, a pale yellow oil, was obtained in 90% yield
(525 mg, 1.8 mmol). [α]D = –5.69 (c = 27.4, CHCl3). 1H NMR
(CDCl3, 400 MHz): δ = 7.74 (dd, J = 8.0, 1.5 Hz, 1 H, 9-CH), 7.27
(dt, J = 7.4,4 Hz, 1 H, 7-CH), 6.80 (dd, J = 7.0, 1.1 Hz, 1 H, 5-
CH), 6.70 (dt, J = 7.5, 1.4 Hz, 1 H, 6-CH), 4.03 (dd, J = 5.9,
5.5 Hz, 1 H, 3-CHb), 3.88 (dd, J = 5.1, 4.8 Hz, 1 H, 3-CHa), 3.79
(m, 1 H, J = 6.3, 1.5, 2-CH), 3.50 (s, 3 H, OCH3), 1.31 (d, J =
6.2 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 157.1,
(neat): ν = 3371, 2922, 1463, 1377, 1155, 1010, 741, 720 cm–1. MS
˜
(ES+): m/z (%) = 276 (16) [M+], 258 (52), 231 (12), 217 (67), 107
+
(79), 91 (100), 58 (37). HRMS: calcd. for C10H13IO·NH4
294.0349, found 294.0353.
(+)-1-Iodo-2-(3-methoxybutyl)benzene (11): Sodium hydride
(261 mg, 10.9 mmol) (55–65% in oil) was washed with pentane
(4ϫ2 mL) and then suspended in dimethylformamide (10 mL). Af-
ter cooling to 0 °C, a solution of (+)-4-(2-iodophenyl)-2-butanol
(1.00 g, 3.62 mmol) in dimethylformamide (5 mL) was added. After
stirring for 15 min at room temperature, the mixture was cooled to
0 °C and methyl iodide (514 mg, 3.62 mmol) was added. After a
further 3 h at room temperature, water (20 mL) was carefully
added. The resulting mixture was extracted with tert-butyl methyl
ether (2ϫ15 mL), and the combined organic phases were washed
with brine (3ϫ10 mL), dried with MgSO4, and concentrated under
reduced pressure to yield a yellow coloured oil. Purification was
performed using column chromatography (hexane/ethyl acetate,
3:1) to give a pale yellow oil. Yield 96% (1.01 g, 3.48 mmol). HPLC
conditions: Chiracel OD-H column, hexane/2-propanol, 95:5,
0.5 mL/min, 20 °C, tR = 8.9 min (–)-enantiomer, 13.0 min (+)-en-
antiomer. [α]D = +53 (c = 0.4, CHCl3). 1H NMR (CDCl3,
500 MHz): δ = 7.74 (dd, J = 1.2, 7.9 Hz, 1 H, arom. H), 7.20 (dt,
J = 1.8, 7.6 Hz, 1 H, arom. H), 7.15 (dd, J = 1.8, 7.6 Hz, 1 H,
arom. H), 6.80 (dt, J = 1.2, 7.9 Hz, 1 H, arom. H), 3.38 (s, 3 H,
OCH3), 3.19 (dq, J = 6.4, 12.4 Hz, 1 H, CH), 2.73 (ddd, J = 6.4,
10.0, 13.4 Hz, 1 H, ArCH2), 2.69 (ddd, J = 5.6, 10.2, 13.4 Hz, 1 H,
139.2, 129.4, 122.4, 112.1, 86.3, 72.6, 75.2, 57.4, 17.0 ppm. IR: ν =
˜
2974, 2929, 2877, 2822, 1581, 1467, 1437, 1242, 1116, 745 cm–1.
MS (EI): m/z (%) = 283 (82), 255 (100), 225 (43), 199 (49), 171
(15), 159 (9), 127 (60), 89 (12). HRMS: calcd. for C10H14IO2
293.0039, found 293.0034.
1-{[(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl]oxy}-2-nitro-
benzene: Following GP1, sodium hydride (496 mg, 15.9 mmol) in
THF (10 mL) were stirred with 1-fluoro-2-nitrobenzene (1.02 g,
762 µL, 7.22 mmol) and -menthol (2.48 g, 15.9 mmol). Yield 94%
1
(1.9 g, 6.86 mmol), yellow oil. [α]D = –69.9 (c = 2.89, CHCl3). H
NMR (250 MHz, CDCl3): δ = 7.76 (dd, J = 8.1, 1.7 Hz, 1 H, 2-
CH), 7.51–7.44 (m, 1 H, 3-CH), 7.08 (d, J = 8.3 Hz, 1 H, 4-CH),
ArCH2), 1.72–1.60 (m, 2 H, CHCH2), 1.14 (d, J = 6.2 Hz, 3 H, 6.99–6.92 (m, 1 H, 5-CH), 4.20 (dt, J = 4.1, 10.5 Hz, 1 H, 7-CH),
CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 145.3 (C-2), 139.9 2.25–2.17 (m, 1 H, 13-CH), 2.14–2.09 (m, 1 H, menthyl), 1.77–1.69
(C-6), 129.9 (C-3), 128.7 (C-5), 128.1 (C-4), 100.9 (C-1), 76.4 (C- (m, 2 H, menthyl), 1.64–1.57 (m, 1 H, menthyl), 1.53–1.43 (m, 1
Eur. J. Org. Chem. 2008, 5315–5328
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5321

T. Wirth et al.
FULL PAPER
H, menthyl), 1.16–1.04 (m, 2 H, menthyl), 1.03–0.95 (m, 1 H, men-
thyl), 0.92 (d, J = 7.2 Hz, 3 H, 14Ј-CH3), 0.91 (d, J = 6.4 Hz, 3 H,
(400 MHz, CDCl3): δ = 7.83 (dd, J = 8.1, 1.6 Hz, 1 H, 2-CH),
7.49–7.45 (m, 1 H, arom.), 6.96 (t, J = 7.7 Hz, 1 H, arom.), 6.92
14-CH3), 0.74 (d, J = 6.8 Hz, 3 H, 15-CH3) ppm. 13C NMR (d, J = 8.7 Hz, 1 H, 5-CH), 4.45–4.40 (m, 1 H, 7-CH), 2.44–2.37
(62.5 MHz, CDCl3): δ = 151.9, 133.9, 125.8, 119.9, 115.4, 79.6,
(m, 1 H, bornyl), 2.32–2.25 (m, 1 H, bornyl), 1.82–1.73 (m, 2 H,
bornyl), 1.41–1.25 (m, 2 H, borneyl), 1.16 (dd, J = 13.4, 3.2 Hz, 1
H, bornyl), 0.95 (s, 6 H, 13,13Ј-CH3), 0.93 (s, 3 H, 14-CH3) ppm.
13C NMR (125 MHz, CDCl3): δ = 152.5, 133.9, 125.6, 119.5, 115.4,
85.1, 49.9, 47.6, 45.2, 36.7, 27.8, 26.8, 19.7, 19.0, 13.6 ppm. IR
47.9, 40.0, 34.6, 31.8, 26.1, 23.8, 22.4, 21.1, 16.7 ppm. IR (KBr): ν
˜
= 2955 (s), 2861 (w), 1608 (m), 1525 (s), 1478 (w), 1349 (m), 1279
(m), 1249 (w), 744 (w) cm–1. MS (EI): m/z (%) = 277 (1), 153 (7),
139 (27), 138 (50), 97 (16), 83 (100), 81 (26), 55 (37). HRMS: calcd.
for C16H23NO3 277.1672, found 277.1672.
(KBr): ν = 2947 (m), 2873 (m), 1609 (s), 1578 (m), 1522 (s), 1356
˜
(s), 1281 (s), 1164 (m), 1115 (m), 1022 (m), 991 (m), 868 (m), 831
(m), 738 (s) cm–1. MS (EI): m/z (%) = 275 (3), 153 (5), 138 (10),
137 (100), 95 (32), 81 (71), 69 (14), 41 (10). HRMS: calcd. for
C16H21NO3 275.1516, found 275.1518.
2-Amino-1-{[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl]-
oxy}benzene: According to GP2, 1-{[(1R,2S,5R)-5-methyl-2-(1-
methylethyl)cyclohexyl]oxy}-2-nitrobenzene (250 mg, 0.90 mmol)
was dissolved in methanol (40 mL). After the addition of Pd/C
(10%) catalyst (8 mg) the mixture was stirred under the atmosphere
of hydrogen for 5.5 h. After filtration, the crude product (207 mg,
(1R,2S,4S)-2-[(2-Aminophenyl)oxy]-1,7,7-trimethylbicyclo[2.2.1]-
heptane: According to GP2, (1R,2S,4S)-1,7,7-trimethyl-2-[(2-ni-
trophenyl)oxy]bicyclo[2.2.1]heptane (250 mg, 0.91 mmol) was dis-
solved in methanol (40 mL). After the addition of Pd/C catalyst
0.84 mmol, 93 %) was used without further purification. [α]D
=
–90.4 (c = 0.35, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 6.84 (d,
J = 7.5 Hz, 1 H, 5-CH), 6.81–6.70 (m, 3 H, arom.), 4.09 (dt, J = (8 mg) the mixture was stirred under the hydrogen atmosphere for
10.5, 3.9 Hz, 1 H, 7-CH), 3.81 (s, 2 H, NH2), 2.34–2.25 (m, 1 H, 5.5 h. After filtration the crude product (213 mg, 0.87 mmol, 96%)
menthyl), 2.23–2.17 (m, 1 H, menthyl), 1.80–1.72 (m, 2 H, men-
thyl), 1.60–1.53 (m, 1 H, menthyl), 1.51–1.41 (m, 1 H, menthyl),
1.19–1.08 (m, 1 H, menthyl), 1.06–1.00 (m, 1 H, menthyl), 0.95 (d,
was used without further purification. 1H NMR (400 MHz,
CDCl3): δ = 6.76–6.71 (m, 2 H, arom.), 6.69–6.65 (m, 2 H, arom.),
4.36–4.32 (m, 1 H, 7-CH), 2.42–2.33 (m, 1 H, bornyl), 2.24–2.17
J = 7.0 Hz, 3 H, 14Ј-CH3), 0.93 (d, J = 6.5 Hz, 3 H, 14-CH3), 0.95– (m, 1 H, bornyl), 1.82–1.71 (m, 2 H, bornyl), 1.44–1.35 (m, 1 H,
0.91 (m, 1 H, menthyl), 0.83 (d, J = 6.9 Hz, 3 H, 15-CH3) ppm. bornyl), 1.32–1.25 (m, 1 H, borneyl), 1.16 (dd, J = 13.4, 3.2 Hz, 1
13C NMR (100 MHz, CDCl3): δ = 145.9, 137.8, 121.2, 118.8, 115.8,
113.5, 78.2, 48.5, 40.9, 35.0, 31.8, 26.5, 24.0, 22.6, 21.3, 17.1 ppm.
H, bornyl), 0.95 (s, 6 H, 15,15Ј-CH3), 0.92 (s, 3 H, 13-CH3) ppm.
13C NMR (125 MHz, CDCl3): δ = 146.6, 136.6, 120.7, 118.5, 115.1,
112.5, 83.1, 49.7, 47.6, 45.2, 37.1, 28.0, 27.2, 19.8, 19.0, 13.9 ppm.
IR (KBr): ν = 3473 (w), 3376 (w), 2955 (w), 1603 (s), 1501 (s), 1453
˜
(m), 1280 (m), 1016 (m), 741 (s) cm–1. MS (EI): m/z (%) = 248 (1),
110 (9), 109 (100), 108 (12), 81 (13), 80 (40), 55 (32), 43 (53).
HRMS: calcd. for C16H24NO·H+ 248.2009, found 248.2011.
IR (neat): ν = 3466 (w), 3379 (w), 2984 (w), 3872 (w), 1602 (s),
˜
1503.8 (s), 1454 (s), 1387 (m), 1362 (m), 1283 (w), 1275 (s), 1220
(s), 1146 (s), 1108 (m), 1016 (m), 738 (s) cm–1. MS (ESI): m/z (%)
= 254 (4), 137 (7), 109 (46), 108 (25), 95 (19), 81 (52), 80 (100), 69
(21), 67 (26), 65 (20), 53 (43), 43 (25), 41 (78). HRMS: calcd. for
C16H23NO·H+ 246.1852, found 246.1852.
2-Iodo-1-{[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl]-
oxy}benzene (14): GP3: To a suspension of 2-amino-1-
{[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl]oxy}benzene
(280 mg, 1.13 mmol) in H2O and concd. H2SO4 (1 mL), a solution
of NaNO2 (94 mg, 1.36 mmol) was added at 0 °C. This mixture was
stirred for 90 hours; ensuring temperature was maintained below
0 °C. Finally, an aqueous solution of KI (226 mg, 1.36 mmol) was
added and stirred at 50 °C for 2 hours. The reaction was then
quenched with satd. NH4Cl (10 mL), extracted with CH2Cl2 and
dried with Na2SO4 to give a brown oil. Yield 54 % (219 mg,
(1R,2S,4S)-2-[(2-Iodophenyl)oxy]-1,7,7-trimethylbicyclo[2.2.1]hep-
tane (15): According to GP3 (1R,2S,4S)-1,7,7-trimethyl-2-[(2-
aminophenyl)oxy]bicyclo[2.2.1]heptane (280 mg, 1.02 mmol) was
stirred with NaNO2 (84 mg, 1.22 mmol) and KI (203 mg,
1.36 mmol). After work-up, (317.0 mg, 0.71 mmol) product were
obtained (70% yield) as a red-brown oil. [α]D = –25.0 (c = 0.11,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.63 (dd, J = 8.2,
1.6 Hz, 1 H, 2-CH), 7.28–7.22 (m, 1 H, arom.), 6.65 (d, J = 7.8 Hz,
1
0.61 mmol). [α]D = –69.0 (c = 0.58, CHCl3). H NMR (500 MHz,
CDCl3): δ = 7.77 (dd, J = 6.2, 1.6 Hz, 1 H, 2-CH), 7.30–7.24 (m, 1 H, 5-CH), 4.38–4.32 (m, 1 H, 7-CH), 2.52–2.44 (m, 1 H, bornyl),
1 H, 4-CH), 6.82 (dd, J = 8.3, 0.7 Hz, 1 H, 3-CH), 6.58 (dt, J =
7.5, 1.2 Hz, 1 H, 5-CH), 4.09 (dt, J = 10.0, 5.0 Hz, 1 H, 7-CH),
2.42–2.34 (m, 1 H, bornyl), 1.83–1.73 (m, 2 H, bornyl), 1.43–1.36
(m, 1 H, bornyl), 1.33–1.28 (m, 1 H, bornyl), 1.13 (dd, J = 13.4,
2.28–2.35 (m, 1 H, menthyl), 2.14–2.10 (m, 1 H, menthyl), 1.77– 3.2 Hz, 1 H, bornyl), 0.98 (s, 3 H, 14-CH3), 0.94 (s, 3 H, 13Ј-CH3),
1.71 (m, 2 H, menthyl), 1.67–1.61 (m, 1 H, menthyl), 1.51–1.43 (m,
1 H, menthyl), 1.16–1.05 (m, 2 H, menthyl), 0.93 (d, J = 7.1 Hz, 3
0.93 (s, 3 H, 13-CH3) ppm. 13C NMR (62.5 MHz, CDCl3): δ =
157.7, 139.6, 129.6, 122.2, 113.2, 87.5, 84.7, 50.2, 47.8, 45.5, 36.9,
H, 14Ј-CH3), 0.93 (d, J = 6.6 Hz, 3 H, 14-CH3), 0.95–0.88 (m, 1 28.2, 27.6, 20.1, 19.3, 14.2 ppm. IR (neat): ν = 3059 (w), 2947 (s),
˜
H, menthyl), 0.76 (d, J = 7.0 Hz, 3 H, 15-CH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 157.2, 139.9, 129.6, 122.3, 113.3, 88.3, 79.2,
2877 (m), 1576 (m), 1464 (s), 1389 (w), 1369 (w), 1278. (m), 1248
(s), 1137 (m), 1111 (w), 1049 (m), 1023 (m), 891 (w), 846 (w), 744
(s) cm–1. MS (EI): m/z (%) = 356 (21), 220 (14), 153 (9), 138 (12),
137 (100), 136 (27), 121 (7), 81 (84), 77 (21), 69 (18), 44 (10), 41
(15). HRMS: calcd. for C16H21IO 356.0632, found 356.0630.
48.2, 40.5, 34.8, 31.8, 26.4, 23.9, 22.5, 21.2, 16.9 ppm. IR (neat): ν
˜
= 2950 (s), 2869 (s), 1582 (m), 1465 (s), 1379 (w), 1277 (m), 1237
(s), 1181 (w), 1155 (w), 1115 (w), 1100 (w), 1039 (w), 1013 (m), 744
(m) cm–1. MS (EI): m/z (%) = 358 (29), 220 (74), 151 (9), 138 (100),
123 (17), 95 (42), 83 (50), 81 (46), 55 (34). HRMS: calcd. for
C16H23IO 358.0788, found 358.0788.
2-Nitrophenyl (R)-1-Phenylethyl Ether:[44] 1-Fluoro-2-nitrobenzene
(526 mg, 3.72 mmol) and (R)-1-phenylethanol (500 mg, 4.09 mmol)
were dissolved in dry THF (10 mL) under argon and cooled to
(1R,2S,4S)-1,7,7-Trimethyl-2-[(2-nitrophenyl)oxy]bicyclo[2.2.1]hep- 0 °C. A solution of potassium bis(trimethylsilyl)amide (0.5  in tol-
tane: According to GP1 NaH (224 mg, 5.59 mmol) was stirred with
1-fluoro-2-nitrobenzene (358 mg, 2.54 mmol) and (–)-borneol
(862 mg, 5.6 mmol). After purification by flash column chromatog-
raphy, the product was obtained as a yellow oil in 90 % yield
uene, 8.19 mL, 4.09 mmol) was added dropwise. The mixture was
stirred for 4 h and warmed up to room temp. The reaction was
quenched with satd. NH4Cl, extracted with CH2Cl2 and dried with
MgSO4. Evaporation of the solvents afforded 862 mg (3.54 mmol,
(630 mg, 2.3 mmol). [α]D = –93.4 (c = 1.85, CHCl3). 1H NMR 95%) of the product as a yellow oil. [α]D = –86.2 (c = 0.48, CHCl3).
5322
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5315–5328

Enantioselective α-Oxysulfonylation of Ketones
1H NMR (400 MHz, CDCl3): δ = 7.61 (dd, J = 8.1, 1.7 Hz, 1 H,
2-CH), 7.25–7.10 (m, 6 H, arom.), 6.82–6.73 (m, 2 H, arom.), 5.28
(q, J = 6.4 Hz, 1 H, 7-CH), 1.53 (d, J = 6.4 Hz, 3 H, 8-CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 149.3, 140.0, 131.7, 127.0, 125.1,
(EI): m/z (%) = 384 (13), 231 (100), 203 (31), 136 (68), 109 (55), 93
(47), 76 (25). HRMS: calcd. for C17H21IO2 384.0581, found
384.0576.
(2R,4R,7S)-Menthyl 2-Iodobenzoate (18): Synthesis according to
GP4 from commercially available 2-iodobenzoyl chloride (2.46 g,
9.24 mmol) and -menthol (2.17 g, 13.85 mmol). The product was
purified by flash column chromatography (petroleum ether:diethyl
124.8, 123.7, 123.5, 118.4, 114.5, 76.1, 21.9 ppm. IR (neat): ν =
˜
3568 (w), 3435 (w), 3035 (m), 2975 (m), 2928 (m), 1955 (w), 1889
(w), 1816 (w), 1604 (s), 1526 (s), 1483 (s), 1447 (m), 1356 (s), 1278
(s), 1254 (s), 1163 (m), 745 (s), 697 (s), 667 (m), 606 (m) cm–1. MS
(ES): m/z (%) = 261 (11), 231 (2), 214 (100), 198 (3), 138 (5), 122
(55), 110 (65), 94 (16), 80 (6), 52 (12), 44 (10). HRMS: calcd. for
ether, 4:1). Yield 98% (3.5 g, 9.06 mmol), colourless oil. [α]D
=
–45.4 (c = 0.48, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.98
(dd, J = 7.9, 1.1 Hz, 1 H, 15-C), 7.74 (dd, J = 7.8, 1.7 Hz, 1 H, 12-
C), 7.40 (td, J = 7.6, 1.2 Hz, 1 H, 13-C), 7.14 (td, J = 7.5, 1.7 Hz,
1 H, 14-C), 4.97 (td, J = 10.9, 4.4 Hz, 1 H, 2-CH), 2.21–2.15 (m,
1 H, menthyl), 2.06–1.96 (m, 1 H, menthyl), 1.76–1.69 (m, 2 H,
menthyl), 1.59–1.51 (m, 2 H, menthyl), 1.19–1.07 (m, 2 H, men-
thyl), 0.95 (d, J = 6.9 Hz, 3 H,9Ј-CH3), 0.92 (d, J = 7.0 Hz, 3 H,
9-CH3), 0.97–0.88 (m, 1 H, menthyl), 0.82 (d, J = 6.9 Hz, 3 H, 10-
CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.6, 141.5, 136.4,
132.6, 130.8, 128.2, 94.2, 76.3, 47.5, 41.2, 34.6, 31.9, 26.7, 23.7,
+
C14H13NO3·NH4 261.1234, found 261.1232.
2-Aminophenyl (R)-1-Phenylethyl Ether: According to GP2, 2-ni-
trophenyl (R)-1-phenylethyl ether (943 mg, 3.88 mmol) was dis-
solved in MeOH (50 mL). After addition of Pd/C (10%) catalyst
(8 mg) the mixture was stirred under hydrogen atmosphere for 4 h.
After filtration the crude product (784 mg, 3.68 mmol, 95%) was
used without further purification. [α]D = –7.3 (c = 0.13, CHCl3).
1H NMR (250 MHz, CDCl3): δ = 7.32–7.15 (m, 5 H, arom.), 6.66–
6.45 (m, 4 H, arom.), 5.22 (q, J = 6.4 Hz, 1 H, 7-CH), 1.58 (d, J
22.4, 21.2, 16.6 ppm. IR (neat): ν = 2954 (s), 2860 (m), 1719 (s),
˜
= 6.4 Hz, 3 H, 8-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 1284 (s), 1249 (s), 1126 (m), 1090 (m), 1038 (w), 1008 (m), 955 (w),
145.9, 143.6, 137.1, 128.9, 127.8, 125.8, 121.6, 118.7, 115.6, 114.2,
76.8, 24.7 ppm. IR (KBr): ν = 1599 (s), 1500 (s), 1453 (s), 1366
738 (s) cm–1. MS (EI): m/z (%) = 386 (100), 380 (5), 371 (4), 330
(10), 321 (12), 305 (3), 293 (3), 274 (3). HRMS: calcd. for
˜
(m), 1267 (s), 1215 (s), 1139 (m), 1081 (s), 1005 (m), 738 (s), 697 C17H23IO2 386.0737, found 386.0737.
(s) cm–1. MS (EI): m/z (%) = 214 (88), 196 (3), 122 (34), 109 (43),
(2R)-endo-Fenchyl 2-Iodobenzoate (19): Synthesis according to GP4
from commercially available 2-iodobenzoyl chloride (325 mg,
1.22 mmol) and (+)-(1R)-endo-fenchyl alcohol (125 mg,
94 (100), 84 (38), 72 (53). HRMS: calcd. for C14H15NO·H+
214.1226, found 214.1223.
2-Iodophenyl (R)-1-Phenylethyl Ether (16): 2-Aminophenyl (R)-1-
phenylethyl ether (75 mg, 0.31 mmol) in H2O (0.5 mL) and concd.
HCl (0.11 mL) was treated with a solution of NaNO2 (25 mg,
0.36 mmol) in H2O (0.1 mL) at 0 °C for 40 min. The reaction mix-
0.81 mmol). The product was purified by flash column chromatog-
raphy (petroleum ether:diethyl ether, 4:1). Yield 88% (274 mg,
0.71 mmol), colourless oil. [α]D = 16.3 (c = 2.46, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.90 (d, J = 7.9 Hz, 1 H, 15-CH), 7.81 (dd,
ture was slowly transferred into a solution of KI (61 mg) in H2O J = 7.8, 1.7 Hz, 1 H, 12-CH), 7.39 (td, J = 7.6, 0.8 Hz, 1 H, 13-
(0.15 mL) at 0 °C. The reaction mixture was then stirred 5 min at
room temp., 15 min at 45 °C and 15 min at 80 °C. Then the mixture
was cooled to 0 °C and quenched with aqueous Na2S2O3 (1 ). The
aqueous phase was extracted with ethyl acetate, washed with brine
and the solvent was evaporated under reduced pressure to yield the
product in 54% (62 mg, 0.19 mmol) as a deep red oil. [α]D = –37.2
CH), 7.14 (td, J = 7.6, 1.3 Hz, 1 H, 14-CH), 4.62 (d, J = 1.9 Hz, 1
H, 2-CH), 1.90–1.84 (m, 1 H, fenchyl), 1.76–1.74 (m, 1 H, fenchyl),
1.74–1.70 (m, 1 H, fenchyl), 1.66–1.63 (m, 1 H, fenchyl), 1.53–1.43
(m, 1 H, fenchyl), 1.23 (dd, J = 10.4, 1.1 Hz, 1 H, fenchyl), 1.20 (s,
3 H, 10Ј-CH3), 1.14 (s, 3 H, 10-CH3), 1.18–1.10 (m, 1 H, fenchyl),
0.87 (s, 3 H, 8-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.1,
(c = 0.04, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 7.71–7.63 (m, 141.6, 135.9, 132.6, 130.9, 128.1, 94.4, 88.0, 48.8, 48.7, 41.8, 40.1,
1 H, 13-CH), 7.41–7.15 (m, 5 H, arom.), 7.13–6.82 (m, 2 H, arom.), 30.0, 27.1, 26.1, 20.7, 19.9 ppm. IR (neat): ν = 3413 (m), 2935 (m),
˜
6.73–6.52 (m, 1 H, arom.), 5.28 (q, J = 6.4 Hz, 1 H, 7-CH), 1.61
2869 (m), 2358 (w), 1713 (s), 1579 (w), 1463 (m), 1291 (s), 1269 (s),
(d, J = 6.4 Hz, 3 H, 8-CH3) ppm. 13C NMR (62.5 MHz, CDCl3): 1135 (m), 1108 (m), 1030 (w), 985 (w), 780 (m), 741 (s) cm–1. MS
δ = 139.5, 129.7, 129.1, 127.6, 125.7, 122.5, 120.9, 115.9, 114.2,
(EI): m/z (%) = 384 (6), 231 (100), 203 (31), 153 (37), 136 (70), 81
87.7, 39.9, 24.5 ppm. IR (neat): ν = 3062 (w), 3011 (w), 2980 (m),
(71). HRMS: calcd. for C17H21IO2 384. 0581, found 384.0578.
˜
2920 (w), 1582 (m), 1470 (s), 136 (w), 1241 (s), 1071 (m), 1016 (m),
(3S)-endo-Bornyl 2-(2-Iodophenyl)acetate (21): Synthesis according
to GP5 from 2-iodophenylacetic acid (1.04 g, 3.98 mmol) and (–)-
borneol (0.92 g, 5.97 mmol). The product was purified by flash col-
umn chromatography (petroleum ether:diethyl ether, 4:1). Yield
99% (1.57 g, 3.94 mmol), colourless oil. [α]D = –24.2 (c = 0.53,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.85 (dd, J = 8.5,
0.9 Hz, 1 H, 16-CH), 7.35–7.28 (m, 2 H, arom.), 7.00–6.92 (m, 1
H, arom.), 4.89 (ddd, J = 9.9, 5.5, 1.3 Hz, 1 H, 3-CH), 3.81 (s, 2
H, 1-CH2), 2.40–2.27 (m, 1 H, bornyl), 1.80–1.61 (m, 3 H, bornyl),
930 (w), 823 (w), 752 (s), 699 (m) cm–1.
(2S)-endo-Bornyl 2-Iodobenzoate (17): Synthesis according to GP4
from 2-iodobenzoyl chloride (138 mg, 0.9 mmol) and (–)-borneol
(358 mg, 1.34 mmol). The product was purified by flash column
chromatography (petroleum ether:diethyl ether, 4:1). Yield 94%
(324 mg, 0.84 mmol), colourless oil. [α]D = –22.1 (c = 2.72, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.99 (dd, J = 7.9, 1.1 Hz, 1 H,
15-CH), 7.79 (dd, J = 7.8, 1.7 Hz, 1 H, 12-CH), 7.41 (td, J = 7.6,
1.2 Hz, 1 H, 13-CH), 7.17–7.13 (m, 1 H, 14-CH), 5.14 (ddd, J = 1.28–1.09 (m, 2 H, bornyl), 1.02 (dd, J = 13.8, 3.4 Hz, 1 H, bornyl),
9.9, 5.7, 1.3 Hz, 1 H, 2-CH), 2.53–2.47 (m, 1 H, bornyl), 2.13–2.07 0.88 (s, 3 H, 11Ј-CH3), 0.84 (s, 3 H, 11-CH3), 0.79 (s, 3 H, 9-CH3)
(m, 1 H, bornyl), 1.83–1.77 (m, 1 H, bornyl), 1.74 (t, J = 4.6 Hz,
1 H, bornyl), 1.41–1.27 (m, 2 H, bornyl), 1.19 (dd, J = 13.9, 3.5 Hz,
ppm. 13C NMR (125 MHz, CDCl3): δ = 171.0, 139.8, 138.6, 130.9,
129.1, 128.7, 101.4, 81.1, 49.2, 48.1, 47.1, 45.2, 37.0, 28.3, 27.3,
1 H, bornyl), 0.96 (s, 3 H, 10Ј-CH3), 0.94 (s, 3 H, 8-CH3), 0.91 (s, 20.0, 19.2, 13.9 ppm. IR (neat): ν = 3059 (w), 2956 (s), 2871 (m),
˜
3 H, 10-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.3, 141.6, 1730 (s), 1467 (m), 1448 (m), 1434 (m), 1335 (m), 1303 (w), 1251
136.2, 132.7, 131.1, 128.2, 94.3, 82.2, 49.4, 48.4, 45.3, 37.1, 28.4,
(s), 1218 (s), 1152 (s), 1110 (m), 1016 (s), 738 (m) cm–1. MS (EI):
m/z (%) = 417 (14), 416 (100), 290 (41), 154 (16), 137 (84), 121 (15),
108 (45), 95 (55), 81 (32). HRMS: calcd. for C18H27INO2 416.1081,
27.8, 20.1, 19.3, 14.1 ppm. IR (neat): ν = 2956 (s), 2873 (m), 2342
˜
(w), 1722 (s), 1580 (m), 1457 (m), 1427 (m), 1374 (w), 1291 (s),
1244 (s), 1131 (s), 1043 (m), 1000 (m), 973 (w), 738 (s) cm–1. MS found 416.1084.
Eur. J. Org. Chem. 2008, 5315–5328
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5323

T. Wirth et al.
FULL PAPER
(3R,5R,8S)-Menthyl 2-(2-Iodophenyl)acetate (22): Synthesis ac-
cording to GP5 from 2-iodophenylacetic acid (2.92 g, 11.13 mmol)
and -menthol (2.61g, 16.7 mmol). The product was purified by
flash column chromatography (petroleum ether:diethyl ether, 4:1).
Yield 95% (4.24 g, 10.6 mmol), colourless oil. [α]D = –42.1 (c =
1.17, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J =
7.8 Hz, 1 H, 16-CH), 7.36–7.21 (m, 2 H, arom.), 6.99–6.92 (m, 1
H, arom.), 4.71 (td, J = 4.4, 10.9 Hz, 1 H, 3-CH), 3.77 (s, 2 H, 1-
CH2), 1.99–2.10 (m, 1 H, menthyl), 1.91–1.77 (m, 1 H, menthyl),
1.74–1.60 (m, 2 H, menthyl), 1.53–1.43 (m, 1 H, menthyl), 1.42–
1.25 (m, 2 H, menthyl), 1.01 (t, J = 11.9 Hz, 2 H, menthyl), 0.90
(d, J = 6.6 Hz, 3 H, 10Ј-CH3), 0.86 (d, J = 6.9 Hz, 3 H, 10-CH3),
0.73 (d, J = 6.9 Hz, 3 H, 11-CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.9, 139.8, 138.4, 130.9, 129.1, 128.7, 101.4, 75.3,
50.6, 47.0, 41.1, 34.6, 31.8, 26.6, 23.8, 22.4, 21.2, 16.8 ppm. IR
163 (99), 104 (100), 103 (70), 77 (44), 59 (64). HRMS: calcd. for
C10H11O2I·NH4 308.0142, found 308.0142. HPLC conditions:
Chiracel OD-H column, hexane/2-propanol, 99:1, 0.5 mL/min,
10 °C, tR = 24.5 min (–)-enantiomer, 27.5 min (+)-enantiomer.
+
Methyl 2-(2-Iodophenyl)butyrate (25): Synthesis according to GP6
from methyl 2-iodophenylacetate (3.2 g, 11.61 mmol) and ethyl
iodide (2.35 mg, 15.1 mmol). The product was purified by flash col-
umn chromatography (petroleum ether:diethyl ether, 4:1). Yield
95% (3.35 g, 11 mmol), yellow oil. Enantiomer 1 (Rf = 24.5 min):
1
[α]D = –58.5 (c = 0.94, CHCl3). H NMR (400 MHz, CDCl3): δ =
7.91 (d, J = 7.9 Hz, 1 H, 10-CH), 7.40–7.19 (m, 2 H, arom.), 7.00–
6.83 (m, 1 H, arom.), 3.95 (t, J = 7.8 Hz, 1 H, 3-CH), 3.65 (s, 3 H,
1-CH3), 2.13–1.91 (m, 1 H, 4-CHB), 1.87–1.65 (m, 1 H, 4-CHA),
0.91 (t, J = 7.4 Hz, 3 H, 5-CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 177.9, 144.4, 140.1, 129.1, 128.9, 128.1, 102.2, 56.7,
(neat): ν = 3376 (m), 2929 (s), 2861 (s), 2346 (w), 1729 (s), 1585
˜
52.4, 27.2, 12.4 ppm. IR (neat): ν = 3433 (br), 2936 (w), 2350 (w),
˜
(w), 1452 (s), 1370 (m), 1248 (m), 1219 (m), 1166 (m), 1038 (m),
1021 (m), 986 (m) cm–1. MS (EI): m/z (%) = 418 (22), 292 (63), 273
(29), 156 (45), 136 (70), 108 (22), 91 (100), 81 (87), 58 (49). HRMS:
calcd. for C18H29INO2 418.1237, found 418.1241.
1729 (s), 1464 (m), 1430 (m), 1345 (w), 1306 (w), 1261 (w), 1199
(m), 1165 (m), 1007 (m), 742 (m) cm–1. MS (EI): m/z (%) = 322
(48), 196 (100), 194 (23), 168 (63) 52 (74). HRMS: calcd. for
+
C11H13O2I·NH4 322.0298, found 322.0300. HPLC conditions:
(3R)-endo-Fenchyl 2-(2-Iodophenyl)acetate (23): Synthesis accord-
ing to GP5 from 2-iodophenylacetic acid (1.01 g, 3.86 mmol) and
(1R)-endo-(+)-fenchyl alcohol (0.89 g, 5.79 mmol). The product
was purified by flash column chromatography (petroleum ether:die-
thyl ether, 4:1). Yield 60% (0.914 g, 2.3 mmol), colourless oil. [α]D
Chiracel OD column, hexane/2-propanol, 99:1, 0.5 mL/min, 10 °C,
tR = 21.6 min (–)-enantiomer, 24.9 min (+)-enantiomer.
Methyl 2-Benzyl-2-(2-iodophenyl)acetate (26): Synthesis according
to GP6 from methyl 2-iodophenylacetate (278 mg, 1 mmol) and
benzyl bromide (206 mg, 1.21 mmol). The product was purified by
flash column chromatography (petroleum ether:diethyl ether, 4:1).
Yield 91% (332 mg, 0.91 mmol), yellow oil. Enantiomer 1 (Rf =
36.2 min): [α]D = –72.1 (c = 0.72, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 7.88 (dd, J = 1.2, 7.9 Hz, 1 H, 15-CH), 7.47 (dd, J =
1.6, 7.8 Hz, 1 H, 12-CH), 7.28 (td, J = 1.2, 7.5 Hz, 1 H, 13-CH),
7.27–7.08 (m, 5 H, 6,7,8,9,10-CH), 6.88 (td, J = 1.6, 7.5 Hz, 1 H,
14-CH), 4.39 (dd, J = 5.8, 9.4 Hz, 1 H, 3-CH), 3.63 (s, 3 H, 1-
CH3), 3.32 (dd, J = 9.3, 13.7 Hz, 1 H, 4-CHB), 3.03 (dd, J = 5.7,
13.7 Hz, 1 H, 4-CHA) ppm. 13C NMR (100 MHz, CDCl3): δ =
173.6, 141.8, 140.2, 138.9, 128.7, 129.5, 129.4, 129.1, 128.2, 126.8,
1
= 13.9 (c = 0.53, CHCl3). H NMR (500 MHz, CDCl3): δ = 7.84
(d, J = 7.9 Hz, 1 H, 16-CH), 7.35–7.29 (m, 2 H, arom.), 7.01–6.91
(m, 1 H, arom.), 4.38 (d, J = 1.9 Hz, 1 H, 3-CH), 3.85 (s, 2 H, 1-
CH2), 1.68 (d, J = 3.7 Hz, 1 H, fenchyl), 1.62–1.52 (m, 3 H, fen-
chyl), 1.46–1.35 (m, 1 H, fenchyl), 1.15 (dd, J = 1.3, 10.1 Hz, 1 H,
fenchyl), 1.07 (s, 3 H, 10Ј-CH3), 1.02 (s, 3 H, 10-CH3), 0.92–1.03
(m, 1 H, fenchyl), 0.72 (s, 3 H, 9-CH3) ppm. 13C NMR (500 MHz,
CDCl3): δ = 171.2, 139.8, 138.5, 131.0, 129.1, 128.7, 101.4, 87.3,
48.7, 48.6, 46.9, 41.7, 39.9, 30.0, 26.9, 26.1, 20.6, 19.8 ppm. IR
(neat): ν = 3424 (w), 3057 (w), 2857 (s), 2868 (m), 2358 (w), 1729
˜
(s), 1585 (w), 1563 (w), 1468 (m), 1335 (m), 1252 (s), 1213 (s), 1157
(s), 1102 (w), 1035 (s), 1007 (s), 802 (w) cm–1. MS (EI): m/z (%) =
416 (14), 290 (100), 154 (30), 137 (73), 106 (27). HRMS: calcd. for
C18H27INO2 416.1081, found 416.1080.
101.8, 57.2, 52.5, 39.9 ppm. IR (neat): ν = 3037 (w), 2943 (w), 1731
˜
(s), 14956 (w), 1455 (w), 1431 (m), 1349 (w), 1214 (m), 1161 (m),
1008 (m), 750 (m), 691 (m) cm–1. MS (EI): m/z (%) = 384 (10), 258
(100), 256 (65), 108 (73), 91 (97). HRMS: calcd. for
Methyl (2-Iodophenyl)acetate:[45] Synthesis according to GP5 from
2-iodophenylacetic acid (8.4 g, 32.1 mmol). The product was puri-
fied by flash column chromatography (petroleum ether:diethyl
ether, 4:1). Yield 91% (8.1 g, 29.3 mmol), yellow oil. 1H NMR
(500 MHz, CDCl3): δ = 7.74 (dd, J = 7.9, 1.0 Hz, 1 H, 2-CH), 7.19
(m, 2 H, 4-, 5-CH), 6.86 (td, J = 7.5, 1.8 Hz, 1 H, 3-CH), 3.71 (s,
2 H, 7-CH2), 3.61 (s, 3 H, 9-CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 171.1, 139.7, 137.9, 130.8, 129.1, 128.6, 101.2, 52.4,
46.3 ppm.
C16H15O2I·NH4 384.0455, found 384.0459. HPLC conditions:
+
semi-preparative Chiracel OD column, hexane/2-propanol, 99:1,
3 mL/min, 10 °C, tR = 36.2 min (–)-enantiomer, 39.8 min (+)-
enantiomer.
Methyl 2-(2-Iodophenyl)-2-propylpropionate (27): Synthesis accord-
ing to GP6 from 24 (2.75 g, 9.5 mmol) and 1-propyl iodide (2.1 g,
12.4 mmol). The product was purified by flash column chromatog-
raphy (petroleum ether:diethyl ether, 4:1). Yield 54% (1.71 g,
5.13 mmol), yellow oil. Enantiomer 2 (Rf = 33.5 min): [α]D = 8.1 (c
= 0.85, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.86 (dd, J =
1.1, 7.8 Hz, 1 H, 12-CH), 7.36–7.31 (m, 2 H, arom.), 6.94–6.90 (m,
1 H, arom.), 3.70 (s, 3 H, 1-CH3), 2.35–2.29 (m, 1 H, 4-CHB), 1.98–
1.90 (m, 1 H, 4-CHA), 1.62 (s, 3 H, 7-CH3), 1.23–1.15 (m, 1 H,
5-CHB), 0.92–0.82 (m, 4 H, 5-CHA and 6-CH3) ppm. 13C NMR
Methyl 2-(2-Iodophenyl)propionate (24): Synthesis according to
GP6 from methyl 2-iodophenylacetate (3.51 g, 12.63 mmol). The
product was purified by flash column chromatography (petroleum
ether:diethyl ether, 4:1). Yield 75% (2.78 g, 9.5 mmol), yellow oil.
1
Enantiomer 1 (Rf = 24.5 min): [α]D = –70.7 (c = 0.65, CHCl3). H
NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 7.9, 1.1 Hz, 1 H, 9- (125 MHz, CDCl3): δ = 177.2, 145.5, 142.3, 128.6, 128.4, 128.2,
CH), 7.31 (td, J = 7.5, 0.9 Hz, 1 H, 7-CH), 7.20 (dd, J = 7.8,
1.4 Hz, 1 H, 6-CH), 6.95 (td, J = 7.7, 1.9 Hz, 1 H, 8-CH), 4.11 (q,
98.6, 53.6, 52.8, 39.6, 25.1, 18.0, 14.9 ppm. IR (neat): ν = 3440 (br),
˜
2933 (m), 1729 (s), 1644 (w), 1459 (m), 1430 (m), 1374 (w), 1233
J = 7.1 Hz, 1 H, 3-CH), 3.68 (s, 3 H, 1-CH3), 1.45 (d, J = 7.1 Hz, (m), 1132 (m), 1008 cm–1. (m), 743 (m) cm–1. MS (EI): m/z (%) =
3 H, 4-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 174.8, 143.9, 350 (35), 224 (62), 222 (32), 182 (100), 58 (19). HRMS: calcd. for
+
140.1, 129.1, 129.1, 127.8, 101.3, 52.5, 49.9, 18.6 ppm. IR (neat): ν C13H17O2I·NH4 350.0611, found 350.0614. HPLC conditions:
˜
= 3436 (br), 2966 (w), 2919 (w), 2343 (w), 1737 (s), 1649 (m), 1549 semi-preparative Chiracel OD column, hexane/2-propanol, 99:1,
(m), 1467 (m), 1431 (m), 1331 (w), 1261 (m), 1202 (w), 1085 (m),
3 mL/min, 10 °C, tR = 28.1 min (–)-enantiomer, 33.5 min (+)-
1008 (m), 7901 (m) cm–1. MS (EI): m/z (%) = 290 (2), 231 (28), enantiomer.
5324
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5315–5328

Enantioselective α-Oxysulfonylation of Ketones
(4S)-endo-Bornyl (2R)-2-(2-Iodophenyl)propionate (28): Synthesis
according to GP6 from 21 (649.0 mg, 1.63 mmol). The product was
purified by flash column chromatography (petroleum ether:diethyl
HPLC conditions: semi-preparative Chiracel OD column, hexane/
2-propanol, 98:2, 3 mL/min, 10 °C, tR = 24.5 min.
(4S)-endo-Bornyl (2S)-2-(2-Iodophenyl)propionate (31): [α]D = 16.5
(c = 0.66, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.86 (dd, J =
1.3, 7.8 Hz, 1 H, 17-CH), 7.33–7.27 (m, 2 H, arom.), 6.93–6.90 (m,
1 H, arom.), 4.86–4.82 (ddd, J = 1.0, 5.6, 9.8 Hz, 1 H, 4-CH), 4.13
(q, J = 7.2 Hz, 1 H, 2-CH), 2.39–2.28 (m, 1 H, bornyl), 1.76–1.70
(m, 1 H, bornyl), 1.66–1.59 (m, 2 H, bornyl), 1.49 (d, J = 7.2 Hz,
3 H, 1-CH3), 1.22–1.16 (m, 2 H, bornyl), 1.01–0.95 (dd, J = 3.4,
13.7 Hz, 1 H, bornyl), 0.87 (s, 3 H, 10-CH3), 0.83 (s, 3 H, 12Ј-CH3),
0.82 (s, 3 H, 12-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
174.1, 143.9, 139.7, 128.9, 128.7, 127.6, 102.1, 80.6, 49.7, 48.9, 47.8,
44.9, 36.6, 27.9, 27.2, 19.7, 18.9, 17.9, 13.5 ppm. HPLC conditions:
semi-preparative Chiracel OD column, hexane/2-propanol, 98:2,
3 mL/min, 10 °C, tR = 24.9 min.
ether, 4:1). Yield 41% (276 mg, 0.67 mmol), colourless oil. [α]D
=
–24.1 (c = 2.26, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.86
(dd, J = 1.2, 7.9 Hz, 1 H, 17-CH), 7.33–7.27 (m, 2 H, arom.), 6.95–
6.92 (m, 1 H, arom.), 4.86 (ddd, J = 1.2, 5.5, 9.9 Hz, 1 H, 4-CH),
4.14 (q, J = 7.2 Hz, 1 H, 2-CH), 2.36–2.25 (m, 1 H, bornyl), 1.69–
1.64 (m, 2 H, bornyl), 1.49 (d, J = 7.2 Hz, 3 H, 1-CH3), 1.21–1.10
(m, 2 H, bornyl), 1.01 (dd, J = 3.4, 13.7 Hz, 1 H, bornyl), 0.86 (s,
3 H, 12Ј-CH3), 0.81 (s, 3 H, 12-CH3), 0.83–0.80 (m, 1 H, bornyl),
0.63 (s, 3 H, 10-CH3) ppm. 13C NMR (62.5 MHz, CDCl3): δ =
174.1, 143.9, 139.7, 128.9, 128.7, 127.6, 101.5, 80.6, 49.8, 48.9, 47.8,
44.9, 36.6, 28.0, 27.1, 19.7, 18.9, 17.9, 13.5 ppm. IR (Neat): ν =
˜
2930 (m), 2852 (w), 2354 (w), 1702 (m), 1594 (m), 1448 (m), 1359
(m), 1218 (m), 1195 (s), 1181 (s), 1120 (w), 1099 (w), 1067 (w), 1016
(m), 922 (m), 814 (m), 757 (m) cm–1. MS (EI): m/z (%) = 430 (34),
(4R,6R,9S)-Menthyl (2S)-2-(2-Iodophenyl)propionate (32): [α]2D3
=
–20.9 (c = 3.04, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.85
(dd, J = 1.2, 7.9 Hz, 1 H, 17-CH), 7.34–7.27 (m, 2 H, 14-,15-CH),
6.95–6.90 (m, 1 H, 16-CH), 4.68 (td, J = 4.4, 10.9 Hz, 1 H, 4-CH),
4.12 (q, J = 7.2 Hz, 1 H, 2-CH), 1.94–1.88 (m, 1 H, menthyl), 1.88–
1.83 (m, 1 H, menthyl), 1.69–1.56 (m, 2 H, menthyl), 1.47 (d, J =
6.4 Hz, 3 H, 1-CH3), 1.35–1.24 (m, 1 H, menthyl), 1.04–0.92 (m, 2
H, menthyl), 0.88 (d, J = 8.3 Hz, 3 H, 11Ј-CH3), 0.86 (d, J =
7.8 Hz, 3 H, 11-CH3), 0.88–0.79 (m, 2 H, menthyl), 0.76 (d, J =
6.8 Hz, 3 H, 12-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
173.9, 144.1, 139.9, 129.0, 128.8, 127.8, 101.6, 75.2, 50.1, 47.3, 41.1,
34.6, 31.7, 26.1, 23.6, 22.4, 20.9, 18.2, 16.4 ppm. HPLC conditions:
semi-preparative Chiracel OD column, hexane/2-propanol, 98:2,
3 mL/min, 10 °C, tR = 19.5 min.
+
318 (35), 304 (53), 137 (100). HRMS: calcd. for C19H25IO2·NH4
430.1237, found 430.1241. HPLC conditions: preparative Chiracel
OD column, 98/1 hexane/2-propanol, 3 mL/min, 10 °C, tR
=
29.0 min.
(4R,6R,9S)-Menthyl (2R)-2-(2-Iodophenyl)propionate (29): Synthe-
sis according to GP6 from 22 (317.6 mg, 0.793 mmol) and methyl
iodide (146.5 mg, 1.03 mmol). The product was purified by flash
column chromatography (petroleum ether/diethyl ether, 4:1). Yield
90% (297 mg, 0.71 mmol), colourless oil. [α]D = –73.4 (c = 2.53,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.85 (dd, J = 0.9,
7.6 Hz, 1 H, 17-CH), 7.32–7.27 (m, 2 H, 14-, 15-CH), 6.94–6.91
(m, 1 H, 16-CH), 4.61 (td, J = 4.4, 10.9 Hz, 1 H, 4-CH), 4.08 (q,
J = 7.1 Hz, 1 H, 2-CH), 2.07–2.00 (m, 1 H, menthyl), 1.69–1.62
(m, 1 H, menthyl), 1.62–1.57 (m, 1 H, menthyl), 1.46 (d, J = 7.2 Hz,
3 H, 1-CH3), 1.35–1.24 (m, 2 H, menthyl), 1.04–0.92 (m, 2 H, men-
thyl), 0.90 (d, J = 6.5 Hz, 3 H, 12-CH3), 0.88–0.79 (m, 2 H, men-
thyl), 0.71 (d, J = 7.0 Hz, 3 H, 11Ј-CH3), 0.56 (d, J = 6.9 Hz, 3 H,
11-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 173.9, 144.1,
139.9, 129.0, 128.8, 127.8, 101.7, 75.2, 50.1, 47.3, 41.1, 34.6, 31.7,
(4R)-endo-Fenchyl (2S)-2-(2-Iodophenyl)propionate (33): [α]D = 34.4
(c = 1.43, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.85 (dd, J =
1.1, 7.7 Hz, 1 H,17-CH), 7.35–7.28 (m, 2 H, arom.), 6.96–6.93 (m,
1 H, arom.), 4.35 (d, J = 1.9 Hz, 1 H, 4-CH), 4.22 (q, J = 7.2 Hz,
1 H, 2-CH), 1.69–1.56 (m, 3 H, fenchyl), 1.55–1.53 (m, 1 H, fen-
chyl), 1.52 (d, J = 7.2 Hz, 3 H, 1-CH3), 1.42–1.33 (m, 1 H, fenchyl),
1.13 (dd, J = 1.4, 10.2 Hz, 1 H, fenchyl), 1.09 (s, 3 H, 10-CH3),
0.96–0.90 (m, 1 H, fenchyl), 0.83 (s, 3 H, 11Ј-CH3), 0.78 (s, 3 H,
11-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 174.7, 139.9,
128.9, 128.7, 127.9, 101.6, 87.1, 50.1, 48.7, 48.6, 41.6, 39.7, 29.9,
26.9, 26.1, 20.7, 19.6, 18.2 ppm. HPLC conditions: semi-prepara-
tive Chiracel OD column, hexane/2-propanol, 98:2, 3 mL/min,
10 °C, tR = 22.5 min.
26.1, 23.6, 22.4, 20.9, 18.2, 16.4 ppm. IR (neat): ν = 2952 (m), 2920
˜
(s), 2849 (m), 2356 (w), 1728 (s), 1462 (m), 1371 (w), 1258 (m),
1203 (w), 1174 (m), 1086 (m) cm–1. MS (EI): m/z (%) = 432 (4),
307 (18), 306 (100), 287 (74), 105 (10). HRMS: calcd. for
+
C19H27IO2·NH4 432.1394, found 432.1393. HPLC conditions:
semi-preparative Chiracel OD column, hexane/2-propanol, 98:2,
3 mL/min, 10 °C, tR = 23.2 min.
N,NЈ-(1S)-[1,1Ј-Binaphthalene]-2,2Ј-diylbis(2-iodobenzamide) (34):
(4R)-endo-Fenchyl (2R)-2-(2-Iodophenyl)propionate (30): Synthesis 2-Iodobenzoyl chloride (308 mg, 1.16 mmol) and (S)-(–)-1,1Ј-bi-
according to GP6 from 23 (542 mg, 1.36 mmol). The product was naphthyl-2,2Ј-diamine (110 mg, 0.39 mmol) were stirred in CH2Cl2
purified by flash column chromatography (petroleum ether/diethyl
ether, 4:1). Yield 89% (497 mg, 1.21 mmol), colourless oil. [α]D
(6 mL) at room temperature for 2 d. After completion of the reac-
tion, the mixture was poured into aqueous saturated NaHCO3
=
–41.1 (c = 0.93, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.85 (20 mL) and extracted with CH2Cl2 (3ϫ10 mL). The combined or-
(dd, J = 1.1, 7.7 Hz, 1 H, 17-CH), 7.35–7.29 (m, 2 H, arom.), 6.95–
6.91 (m, 1 H, arom.), 4.33 (d, J = 1.9 Hz, 1 H, 4-CH), 4.20 (q, J
= 7.2 Hz, 1 H, 2-CH), 1.65–1.62 (m, 2 H, fenchyl), 1.62–1.56 (m,
1 H, fenchyl), 1.55–1.53 (m, 1 H, fenchyl), 1.51 (d, J = 7.2 Hz, 3
H, 1-CH3), 1.40–1.33 (m, 1 H, fenchyl), 1.13 (dd, J = 1.4, 10.2 Hz,
1 H,fenchyl), 1.04 (s, 3 H, 11Ј-CH3), 1.03 (s, 3 H, 11-CH3), 1.01–
0.97 (m, 1 H, fenchyl), 0.46 (s, 3 H, 10-CH3) ppm. 13C NMR
ganic layers were dried with MgSO4 and solvent was removed. The
crude product was purified by flash chromatography (petroleum
ether/diethyl ether, 4:1). Yield 92% (264 mg, 0.36 mmol), white
powder. [α]D = 8.1 (c = 0.85, CHCl3). 1H NMR (500 MHz, CDCl3):
δ = 8.56 (d, J = 8.9 Hz, 2 H, arom.), 8.10 (d, J = 9.0 Hz, 2 H,
arom.), 7.97 (d, J = 8.2 Hz, 2 H, arom.), 7.70 (d, J = 7.9 Hz, 2 H,
arom.), 7.49–7.46 (m, 2 H, arom.), 7.36–7.30 (m, 2 H, arom.), 7.20–
(125 MHz, CDCl3): δ = 174.5, 139.9, 129.0, 128.8, 128.1, 127.9, 7.15 (m, 4 H, arom.), 6.97 (td, J = 1.6, 7.6 Hz, 2 H, arom.), 6.92
101.9, 87.0, 50.1, 48.8, 48.7, 41.6, 39.9, 30.0, 27.0, 26.1, 20.3, 19.8, (dd, J = 1.5, 7.6 Hz, 2 H, arom.) ppm. 13C NMR (125 MHz,
18.3 ppm. IR (neat): ν = 3056 (w), 2959 (s), 2919 (s), 2868 (m),
CDCl3): δ = 168.5, 141.5, 140.3, 135.1, 132.9, 132.1, 131.8, 130.5,
˜
1731 (s), 1585 (w), 1563 (w), 1469 (m), 1433 (w), 1242 (w), 1206 128.8, 128.6, 128.5, 127.9, 126.3, 125.7, 122.6, 110.4, 92.6 ppm. IR
(m), 1180 (m), 1125 (w), 1083 (w) cm–1. MS (EI): m/z (%) = 431 (neat): ν = 3456 (m), 3078 (w), 3021 (m), 2357 (w), 1818 (w), 1668
˜
(6), 430 (32), 305 (11), 304 (61), 154 (56), 137 (100), 81 (28).
(w), 1595 (m), 1490 (s), 1452 (s), 1332 (w), 1158 (m), 1073 (s), 1029
HRMS: calcd. for C19H25IO2·NH4 430.1237, found 430.1240. (m), 983 (m), 961 (s) cm–1. MS (EI): m/z (%) = 745 (100), 686 (15),
+
Eur. J. Org. Chem. 2008, 5315–5328
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5325

T. Wirth et al.
FULL PAPER
680 (9). HRMS: calcd. for C34H23I2N2O2 744.9849, found
744.9877.
benzenesulfonamide (110 mg, 0.27 mmol), 2-iodophenylacetic acid
(202 mg, 0.8 mmol), 1,3-dicyclohexylcarbodiimide (165 mg,
0.81 mmol) and 4-(dimethylamino)pyridine (98 mg, 0.81 mmol)
with acetonitrile (10 mL) was stirred for 2 d at 60–80 °C. After
work-up using aq. satd. NaHCO3 and CH2Cl2 (4ϫ20 mL) and
drying over MgSO4, the product was purified by column
chromatography (petroleum ether/diethyl ether, 4:1) to give a white
cloudy/green solid. Yield 61% (108 mg, 0.16 mmol). 1H NMR
(500 MHz, CDCl3): δ = 7.85 (dd, J = 1.1, 7.9 Hz, 1 H, 2-CH), 7.60
(tt, J = 1.2, 7.4 Hz, 1 H, 28-CH), 7.52–7.50 (m, 2 H, 26-, 30-CH),
7.46–7.42 (m, 2 H, 27-, 29-CH), 7.32 (dt, J = 1.1, 7.4 Hz, 1 H, 4-
CH), 7.24 (dd, J = 1.7, 7.6 Hz, 1 H, 5-CH), 6.99 (s, 1 H, 20-CH),
6.97 (dt, J = 1.6, 7.6 Hz, 1 H, 3-CH), 6.90 (s, 1 H, 22- or 18-CH),
5.84 (s, 1 H, 18- or 22-CH), 3.98 (s, 2 H, 7-CH2), 3.76 (d, J =
2.7 Hz, 1 H, 9-CH), 3.54 (d, J = 6.2 Hz, 1 H, 14-CH), 2.28 (s, 3 H,
24-CH3), 2.10 (s, 3 H, 23-CH3), 1.64–1.59 (m, 2 H, CH2), 1.51–
1.45 (m, 1 H, CH2), 1.23–1.16 (m, 1 H, CH2), 0.99 (s, 3 H, 16Ј-
CH3), 0.97 (s, 3 H, 16-CH3), 0.97–0.92 (m, 1 H, CH), 0.57 (s, 3 H,
15-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 139.9, 139.2,
138.3, 137.1, 135.9, 133.4, 132.2, 131.4, 130.1, 129.3, 129.2, 128.8,
128.6, 128.3, 101.7, 82.9, 69.6, 54.9, 50.2, 49.3, 47.3, 33.5, 28.3,
2-(2-Iodophenyl)propionitrile: Synthesis according to GP6 from 2-
iodophenylacetonitrile (8.21 g, 33.8 mmol) and methyl iodide
(7.19 g, 50.7 mmol). The product was purified by flash column
chromatography (petroleum ether/diethyl ether, 4:1). Yield 97%
(8.43 g, 32.8 mmol), yellow oil. Enantiomer 1 (Rf = 50.9 min): [α]D
1
= –31.2 (c = 2.33, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.85
(dd, J = 1.5, 8.0 Hz, 1 H, 8-CH), 7.61 (dd, J = 1.7, 7.6 Hz, 1 H, 5-
CH), 7.42 (td, J = 1.1, 7.5 Hz, 1 H, 6-CH), 7.03 (td, J = 1.5, 7.6 Hz,
1 H, 7-CH), 4.24 (q, J = 7.5 Hz, 1 H, 2-CH), 1.60 (d, J = 7.1 Hz,
3 H, 3-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.4, 130.2,
129.7, 128.0, 123.5, 121.6, 98.8, 36.6, 21.0 ppm. IR (neat): ν = 2938
˜
(s), 2925 (s), 2840 (s), 2352 (w), 1731 (m), 1465 (s), 1434 (m), 1375
(w), 1269 (w), 1009 (s), 755 (s) cm–1. MS (EI): m/z (%) = 257 (100),
242 (39), 128 (53), 103 (32). HRMS: calcd. for C9H8IN 256.9702,
found 256.9690. HPLC conditions: semi-preparative Chiracel OD
column, hexane/2-propanol, 98:2, 3 mL/min, 10 °C, tR = 50.9 min
(–)-enantiomer, 54.5 min (+)-enantiomer.
2-Benzyl-2-(2-iodophenyl)propionitrile (35): Synthesis according to
GP6 from 2-iodophenyl-methylacetonitrile (685 mg, 2.67 mmol)
and benzyl bromide (684 mg, 4 mmol). The product was purified by
flash column chromatography (petroleum ether/diethyl ether, 4:1).
Yield 91% (839 mg, 2.43 mmol), yellow oil. Enantiomer 2 (Rf =
80.9 min): [α]D = 8.5 (c = 0.30, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 7.97 (d, J = 7.9 Hz, 1 H, 15-CH), 7.20–7.15 (m, 2 H,
arom.), 7.14–7.10 (m, 3 H, arom.), 7.06–7.02 (m, 2 H, arom.), 6.91–
6.84 (m, 1 H, arom.), 3.60 (d, J = 13.6 Hz, 1 H, 4-CHB), 3.17 (d,
J = 13.6 Hz, 1 H, 4-CHA), 1.78 (s, 3 H, 3-CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 143.6, 138.9, 135.2, 130.6, 129.9, 129.1,
22.1, 21.4, 12.2 ppm. IR (KBr): ν = 2355, 2332 cm–1.
˜
13-Iodo-[2.2](1,4)phenanthrenoparacyclophane (38):[46,47] 5-Bromo-
[2.2](1,4)phenanthrenoparacyclophane (310 mg, 0.71 mmol) was
dissolved in dry DMF (20 mL) and iodine (1.8 g, 7.1 mmol), potas-
sium iodide (1.1 g, 7.02 mmol) and nickel-powder (412 mg,
7.1 mmol) were added to the solution and refluxed in argon atmo-
sphere. After 4 h the mixture was separated from unused nickel,
and diluted with water and the phases were separated. The aqueous
phase was extracted several times with CH2Cl2 and the combined
organic phases were washed with a small portion of brine and dried
with MgSO4 and purified by flash column chromatography to give
the product in 96% yield (295 mg, 0.68 mmol). 1H NMR
(500 MHz, CDCl3): δ = 8.42 (dd, J = 1.3, 8.0 Hz, 1 H, 8-CH), 8.31
(s, 1 H, 14-CH), 8.20 (dd, J = 1.5, 8.2 Hz, 1 H, 11-CH), 7.63–7.56
(m, 2 H, 9-CH, 10-CH), 6.98 (d, J = 7.5 Hz, 1 H, 17-CH), 6.78 (d,
J = 7.4 Hz, 1 H, 18-CH), 6.57 (dd, J = 1.7, 7.9 Hz, 2 H, 21-CH),
6.53 (dd, J = 1.7, 7.9 Hz, 1 H, 20-CH), 5.93 (dd, J = 1.8, 7.8 Hz,
1 H, 23-CH), 5.29 (dd, J = 1.6, 7.8 Hz, 1 H, 24-CH), 4.27 (ddd, J
= 4.8, 8.5, 14.0 Hz, 1 H, 1-CHAH), 3.82–3.76 (m, 1 H, 4-CHAH),
3.40 (ddd, J = 6.5, 8.6, 14.8 Hz, 1 H, 1-CHHB), 3.29–3.22 (m, 1 H,
3-CHHB), 3.04 (ddd, J = 7.1, 14.5, 17.7 Hz, 2 H, 3-CHAH, 4-
CHHB), 2.92 (ddd, J = 4.8, 8.8, 13.5 Hz, 1 H, 2-CHHB), 2.74 (ddd,
J = 6.3, 8.5, 14.3 Hz, 1 H, 2-CHAH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 139.1, 138.2, 136.8, 136.4, 136.3, 135.4, 135.2, 133.5,
132.8, 132.5, 132.4, 131.5, 132.0, 133.0, 128.8, 128.7, 127.5, 126.7,
130.0, 98.0, 38.8, 35.1 34.9, 33.6 ppm. MS (EI): m/z (%) = 434 (3),
329 (20), 307 (9), 203 (100), 202 (85), 104 (48), 78 (21). HRMS:
calcd. for C24H19I 434.0526, found 434.0529. HPLC conditions:
Chiracel OD column, hexane/2-propanol, 90:10, 0.5 mL/min,
128.8, 128.4, 127.6, 122.6, 95.7, 45.2, 43.6, 25.4 ppm. IR (neat): ν
˜
= 3318 (m), 2926 (s), 2360 (w), 2246 (w), 1693 (w), 1495 (m), 1454
(s), 1375 (w), 1078 (w), 1009 (w), 855 (m), 824 (m) cm–1. MS (EI):
m/z (%) = 365 (96), 347 (2), 315 (4), 254 (5), 237 (100), 222 (3), 108
(6). HRMS: calcd. for C16H18IN2 365.0509, found 365.0509. HPLC
conditions: semi-preparative Chiracel OD column, hexane/2-propa-
nol, 99:1, 3 mL/min, 10 °C, tR = 75.3 min, 80.9 min.
N-(3,5-Dimethylphenyl)-N-[(1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethyl-
bicyclo[2.2.1]hept-2-yl]benzenesulfonamide:[22] 3-[(3,5-Dimethyl-
phenyl)amino]isoborneol was synthesized according to litera-
ture.[22] A mixture of 3-[(3,5-dimethylphenyl)amino]isoborneol
(2.00 g, 7.3 mmol), benzenesulfonic acid chloride (3.90 g,
21.9 mmol) and pyridine (1.73 g, 2.1 mmol) in acetonitrile was
stirred for 3 d at room temperature. The reaction mixture was
quenched in aq. satd. NaHCO3, then extracted with CH2Cl2
(3ϫ20 mL), dried with MgSO4 to give a white powder. Yield 65%
1
(1.96 g, 4.75 mmol). H NMR (500 MHz, CDCl3): δ = 7.60 (tt, J
= 1.1, 7.3 Hz, 1 H, 20-CH), 7.51–7.50 (m, 2 H, 18-CH, 22-CH),
7.46–7.43 (m, 2 H, 19-CH, 21-CH), 6.98 (s, 1 H, 12-CH), 6.90 (s,
1 H, 14- or 10-CH), 5.83 (s, 1 H, 10- or 14-CH), 3.76 (d, J = 2.7 Hz,
1 H, 1-CH), 3.54 (d, J = 6.2 Hz, 1 H, 6-CH), 2.28 (s, 3 H, 16-CH3),
2.10 (s, 3 H, 15-CH3), 1.64–1.58 (m, 2 H, cyclohexyl), 1.51–1.45
(m, 1 H, CH2), 1.22–1.17 (m, 1 H, CH2), 0.99 (s, 3 H, 8Ј-CH3),
0.97 (s, 3 H, 8-CH3), 0.97–0.92 (m, 1 H, CH2), 0.57 (s, 3 H, 7-CH3)
ppm. 13C NMR (125 MHz, CDCl3): δ = 140.0, 139.2, 135.9, 133.4,
132.1, 130.1, 129.3, 128.6, 82.9, 69.6, 50.2, 49.3, 47.3, 33.5, 28.3,
22.1, 21.4, 12.2 ppm. MS (EI): m/z (%) = 414 (69), 274 (100), 160
(23), 122 (28). HRMS: calcd. for C24H32NO3S 414.2097, found
414.2100.
254 nm, 22 °C, tR = 12.4 min, 17.3 min. Enantiomer 1 (tR
12.4 min): [α]2D2 = –180 (c = 0.245, CHCl3). Enantiomer 2 (tR
17.3 min): [α]2D2 = 187 (c = 0.205, CHCl3).
=
=
1-Oxo-1-phenylbutan-2-yl 4-Methylbenzenesulfonate (41): Synthesis
according to GP7 from butyrophenone (74 mg, 0.5 mmol), catalyst
7 (15 mg, 0.05 mmol), mCBPA (77%, 356 mg, 1.5 mmol) and p-
toluenesulfonic acid (300 mg, 1.5 mmol) yielding 105 mg
(0.33 mmol, 66%) 41 as colorless solid. m.p. 79–85 °C. [α]D = 3.69
1
(c = 1.73, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.78 (d, J =
7.8 Hz, 2 H), 7.66 (d, J = 8.3 Hz, 2 H), 7.51 (t, J = 7.4 Hz, 1 H),
7.47 (t, J = 8.1 Hz, 2 H), 7.17 (d, J = 8.1 Hz, 2 H), 5.48 (dd, J =
5.0, 7.9 Hz, 1 H), 2.32 (s, 3 H), 1.93–1.85 (m, 2 H), 0.90 (t, J =
7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.9, 144.0,
N-Phenylsulfonylamino-N-(3,5-dimethylphenyl)-N-isobornyl 2-Iodo-
phenylacetate (36): A mixture of N-(3,5-dimethylphenyl)-N-
[(1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-
5326
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5315–5328

Enantioselective α-Oxysulfonylation of Ketones
133.1, 132.7, 132.1, 128.7, 127.7, 127.6, 127.0, 81.5, 25.2, 20.6,
2-(Phenylsulfonyl)propiophenone (46): Synthesis according to GP7
8.5 ppm. IR (NaCl): ν = 1699, 1386, 1158, 828, 763, 661 cm–1. from propiophenone (50 mg, 0.37 mmol), an organoiodine catalyst
˜
HRMS (ESI-H+): calcd. for C17H19O4S 319.1004, found 319.0990.
HPLC conditions: Chiracel OB-H, 40 °C, 0.5 mL/min, hexane/2-
propanol, 60:40, tR = 15.1 minutes (major), 17.9 (minor).
(10 mol-%), mCPBA (77%, 193 mg, 0.86 mmol) and benzenesul-
fonic acid (177 mg, 1.12 mmol); purification by preparative TLC
1
(diethyl ether/petroleum ether, 1:2). H NMR (250 MHz, CDCl3):
δ = 7.90–7.86 (m, 4 H, arom.), 7.65–7.56 (m, 2 H, arom.), 7.52–
7.43 (m, 4 H, arom.), 5.83 (q, J = 6.9 Hz, 1 H, 2-CH), 1.61 (d, J
= 6.9 Hz, 3 H, 1-CH3) ppm. HPLC conditions: Chiracel OB-H
1-Oxo-1-phenyloctan-2-yl 4-Methylbenzenesulfonate (42):[48] Syn-
thesis according to GP7 from 1-phenyl-1-octanone (102 mg,
0.5 mmol), catalyst 7 (15 mg, 0.05 mmol), mCBPA (77%, 356 mg,
1.5 mmol) and p-toluenesulfonic acid (300 mg, 1.5 mmol) yielding
160 mg (0.43 mmol, 86%) 42 as colorless solid. m.p. 56–59 °C.
column, hexane/2-propanol, 40:60, 0.5 mL/min, 40 °C, tR
=
15.8 min, 18.8 min.
2-(Mesitylsulfonyl)propiophenone (47): Synthesis according to GP7
from propiophenone (46 mg, 0.34 mmol), an organoiodine catalyst
(10 mol-%), mCPBA (77%, 178 mg, 0.79 mmol) and 2-mesity-
lenesulfonic acid (243 mg, 1.03 mmol); purification by preparative
TLC (diethyl ether/petroleum ether, 1:2). 1H NMR (250 MHz,
CDCl3): δ = 7.90–7.85 (m, 2 H, 3-CH), 7.58 (tt, J = 1.3, 7.4 Hz, 1
H, 5-CH), 7.48–7.41 (m, 2 H, 4-CH), 6.90 (s, 2 H, 7-CH), 5.74 (q,
J = 6.9 Hz, 1 H, 2-CH), 2.59 (s, 6 H, 6-CH3), 2.27 (s, 3 H, 8-CH3),
1.59 (d, J = 6.9 Hz, 3 H, 1-CH3) ppm. HPLC conditions: Chiracel
1
[α]D = 13.71 (c = 1.62, CHCl3). H NMR (400 MHz, CDCl3): δ =
7.77 (dd, J = 1.2, 7.9 Hz, 2 H), 7.66 (d, J = 8.2 Hz, 2 H), 7.51 (t,
J = 8.0 Hz, 1 H), 7.37 (t, J = 8.0 Hz, 2 H), 7.17 (d, J = 7.8 Hz, 2
H), 5.51 (dd, J = 5.6, 7.6 Hz, 1 H), 2.32 (s, 3 H), 1.83–1.77 (m, 2
H), 1.48–1.32 (m, 1 H), 1.30–1.18 (m, 1 H), 1.17–1.04 (m, 6 H),
0.79 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ =
195.1, 145.0, 134.1, 133.8, 133.3, 129.7, 128.8, 128.7, 128.6, 81.4,
32.7, 31.4, 28.5, 25.0, 22.5, 21.7, 14.1 ppm. HPLC conditions: Chir-
acel OB-H, 40 °C, 0.5 mL/min, hexane/2-propanol, 60:40, tR = 13.2
minutes (major), 15.8 (minor).
AD column, hexane/2-propanol, 70:30, 0.5 mL/min, 10 °C, tR
=
10.9 min, 12.6 min.
1-[3-(Trifluoromethyl)phenyl]-1-oxobutan-2-yl 4-Methylbenzenesul-
fonate (43): Synthesis according to GP7 from 1-[3-(trifluorometh-
2-(Camphorsulfonyl)propiophenone (48):[51] Synthesis according to
GP7 from propiophenone (33 mg, 0.25 mmol), an organoiodine
catalyst (10 mol-%), mCPBA (77%, 128 mg, 0.57 mmol) and (1S)-
(+)- or (1R)-(–)-10-camphorsulfonic acid (173 mg, 0.74 mmol); pu-
rification by preparative TLC (diethyl ether/petroleum ether, 1:2).
1H NMR (250 MHz, CDCl3): δ = 7.98–7.96 (m, 1 H, 3-CH, arom.),
7.94 (t, J = 1.5 Hz, 1 H, arom.), 7.62 (tt, J = 1.3, 7.4 Hz, 1 H, 15-
CH), 7.54–7.47 (m, 2 H, 14,16-CH), 6.06 (q, J = 6.9 Hz, 1 H 2-
yl)phenyl]-1-butanone (101 mg, 0.5 mmol), catalyst
7 (15 mg,
0.05 mmol), mCBPA (77%, 356 mg, 1.5 mmol) and p-toluenesul-
fonic acid (300 mg, 1.5 mmol) yielding 130 mg (0.35 mmol, 70%)
43 as colorless solid. m.p. 92–94 °C. [α]D = 6.83 (c = 2.53, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.8 Hz, 1 H), 8.02
(s, 1 H), 7.76 (d, J = 7.6 Hz, 1 H), 7.65 (d, J = 6.8 Hz, 2 H), 7.54
(t, J = 7.8 Hz, 1 H), 6.99 (d, J = 7.0 Hz, 2 H), 5.63 (q, J = 7.0 Hz, CH), 6.07 (q, J = 6.9 Hz, 1 H, 2-CH for other diastereomer), 3.75
1 H), 2.34 (s, 3 H), 1.55 (s, 3 H) ppm. 13C NMR (100 MHz,
(d, J = 15.0 Hz, 1 H, 3-CHB) (3.67, J = 15.1 Hz for other dia-
CDCl3): δ = 193.1, 144.3, 133.2, 132.0, 131.0, 130.0 (q, J = 33 Hz), stereomer), 3.21 (d, J = 15.0 Hz, 1 H, 3-CHA) (δ =3.19 ppm, J =
129.1, 128.8, 128.4, 126.9, 124.7, 122.5 (q, J = 272 Hz), 76.6, 20.6, 15.1 Hz for other diastereomer), 2.35–2.32 (m, 2 H, camphor),
17.5 ppm. IR (NaCl): ν = 1704, 1385, 1156, 829, 762, 665 cm–1. 2.13–2.01 (m, 2 H, camphor), 1.97 (d, 2 H, J = 4.5 Hz, camphor)
˜
LRMS (EI+): m/z (%) = 372 (2) [M·+], 328 (5), 281 (2), 199 (22),
174 (100), 155 (20), 119 (10), 91 (21). HRMS (EI+) calcd. for
C17H15F3O4S 372.0643, found 372.0633. HPLC conditions: Chira-
cel OB-H, 40 °C, 0.5 mL/min, hexane/2-propanol, 60:40, tR = 15.3
minutes (major), 16.8 (minor).
(δ =1.90 ppm, J = 4.6 Hz for other diastereomer), 1.68 (d, 3 H, J
= 7.0 Hz, 1-CH3) (δ =1.66 ppm for other diastereomer), 1.47–1.38
(m, 1 H, camphor), 1.08 (s, 3 H, 11Ј-CH3) (δ =1.12 ppm for other
diastereomer), 0.87 (s, 3 H, 11-CH3) ppm. HPLC conditions: Chir-
acel AD column, hexane/2-propanol 70:30, 0.5 mL/min, 10 °C, tR
= 21.8 min, 28.0 min.
2,3-Dihydro-1-oxo-1H-inden-2-yl 4-Methylbenzenesulfonate (44):[49]
Synthesis according to GP7 from 1-indanone (66 mg, 0.5 mmol),
catalyst 7 (15 mg, 0.05 mmol), mCBPA (77%, 356 mg, 1.5 mmol)
and p-toluenesulfonic acid (300 mg, 1.5 mmol) yielding 120 mg
2-(Camphorsulfonyl)octaphenone (49): Synthesis according to GP7
from octanophenone (82 mg, 0.4 mmol), catalyst 32 (16.6 mg,
0.04 mmol), mCPBA (77%, 208 mg, 0.92 mmol) and (1S)-(+)-10-
camphorsulfonic acid (280 mg, 1.2 mmol); purification by prepara-
tive TLC (diethyl ether/petroleum ether, 1:2). The diastereomers
could not be separated by TLC. Yield 23% (40 mg, 0.09 mmol).
(0.39 mmol, 79%) 44 as colorless solid. m.p. 97–102 °C. [α]D
=
31.58 (c = 1.21, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.85 (d,
J = 8.3 Hz, 2 H), 7.76 (d, J = 8.3 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 1
H), 7.41–7.32 (m, 4 H), 5.05 (dd, J = 4.6, 8.0 Hz, 1 H), 3.57 (dd,
J = 8.0, 17.2 Hz, 1 H), 3.19 (dd, J = 4.6, 17.2 Hz, 1 H), 2.39 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 198.0, 150.3, 145.7,
136.8, 134.0, 133.5, 130.3, 128.8, 128.6, 127.1, 125.1, 78.6, 34.3,
22.1 ppm. HPLC conditions: Chiracel OB-H, 40 °C, 0.5 mL/min,
hexane/2-propanol, 60:40, tR = 27.4 minutes (minor), 30.5 (major).
1
[α]D = 17.0 (c = 1.75, CHCl3). H NMR (250 MHz, CDCl3): δ =
7.97–7.93 (m, 2 H, 16,20-CH), 7.64–7.50 (m, 3 H, 17,18,19-CH),
5.98–5.90 (m, 1 H, 7-CH), 3.66 (d, J = 15.1 Hz, 1 H, 8-CHB), 3.22
(d, J = 15.1 Hz, 1 H, 8-CHA), 2.58–0.83 (m, 26 H, 12-CH,
2,3,4,5,6,11,13,14-CH2, 1,16,16Ј-CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 214.3, 195.7, 134.8, 134.3, 129.3, 128.9, 128.8, 58.5,
49.4, 48.3, 43.2, 42.8, 33.0, 32.9, 31.8, 28.9, 27.3, 25.2, 22.8, 20.2,
2-(Methylsulfonyl)propiophenone (45):[50] Synthesis according to
GP7 from propiophenone (107 mg, 0.8 mmol), an organoiodine
catalyst (10 mol-%), mCPBA (77%, 413 mg, 1.84 mmol) and 2-
methanesulfonic acid (230 mg, 2.39 mmol); purification by prepar-
ative TLC (diethyl ether/petroleum ether, 1:2). 1H NMR (250 MHz,
CDCl3): δ = 7.96–7.92 (m, 2 H, 3-CH), 7.67–7.60 (m, 1 H, 5-CH),
7.54–7.48 (m, 2 H, 4-CH), 6.06 (q, J = 7.0 Hz, 1 H, 2-CH), 3.14
(s, 3 H, 6-CH3), 1.67 (d, J = 7.0 Hz, 3 H, 1-CH3) ppm. HPLC
conditions: Chiracel OB-H column, hexane/2-propanol, 40:60,
0.5 mL/min, 40 °C, tR = 22.5 min, 24.9 min.
20.0 ppm. IR (neat): ν = 3427 (s), 2960 (s), 2923 (s), 2860 (m), 2360
˜
(w), 1741 (s), 1697 (s), 1597 (w), 1447 (m), 1358 (s), 1252 (w), 1225
(m), 1175 (s), 930 (m), 769 (m), 697 (m) cm–1. MS (nano-ES): m/z
(%) = 250 (2), 222 (100), 170 (25), 120 (15), 105 (32), 94 (13), 72
(11), 58 (35), 44 (57). HRMS: calcd. for C24H34O5·NH4+ 452.2465,
found 452.2465. HPLC conditions: Chiracel AD column, hexane/
2-propanol, 70:30, 0.5 mL/min, 10 °C, tR = 19.7 min (minor),
21.5 min (major).
2-(Camphorsulfonyl)-m-(trifluoromethyl)propiophenone (50): Syn-
thesis according to GP7 from m-trifluoromethylpropiophenone
Eur. J. Org. Chem. 2008, 5315–5328
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5327

T. Wirth et al.
FULL PAPER
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(269 mg, 1.6 mmol); purification by preparative TLC (diethyl ether/
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1
(c = 1.2, CHCl3). H NMR (250 MHz, CDCl3): δ = 8.22 (s, 1 H,
3-CH), 8.15 (d, J = 7.8 Hz, 1 H, 7-CH), 7.88 (d, J = 7.4 Hz, 1 H,
5-CH), 7.66 (t, J = 7.8 Hz, 1 H, 6-CH), 6.01 (q, J = 6.9 Hz, 1 H,
2-CH) (6.02, J = 6.9 Hz for other diastereomer), 3.68 (d, J =
14.9 Hz, 1 H, 8-CHB), 3.18 (d, J = 15.2 Hz, 1 H, 8-CHA), 2.52–
2.32 (m, 2 H, camphor), 2.14–2.02 (m, 2 H, camphor), 1.68 (d, J
= 6.9 Hz, 3 H, 1-CH3), 1.97–1.47 (m, 3 H, camphor), 1.12 (s, 3 H,
16Ј-CH3), 1.09 (s, 3 H, 16-CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 213.1, 193.3, 133.5, 130.9, 130.8, 129.3, 128.6, 124.5,
57.1, 48.0, 47.0, 41.8, 41.5, 28.7, 25.9, 24.0, 18.7, 18.6, 17.5 ppm.
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IR (neat): ν = 3475 (m), 2968 (s), 2921 (s), 2354 (w), 1747 (s), 1711
˜
(s), 1605 (m), 1440 (m), 1363 (s), 1328 (s), 1257 (m), 1210 (s), 1169
(s), 1128 (s), 1074 (s), 1016 (m), 927 (s), 809 (m) cm–1. MS (nano-
ES): m/z (%) = 450 (7), 202 (12), 173 (37), 153 (15), 108 (14), 72
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450.1557, found 450.1561. HPLC conditions: Chiracel AD column,
hexane/2-propanol, 70:30, 0.5 mL/min, 10 °C, tR
= 16.4 min
(major), 20.6 min (minor).
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Sciences Research Council (EPSRC), National Mass Spectrometry
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Spectrometry Services for mass spectrometric data and EPSRC for
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Received: July 25, 2008
Published Online: September 16, 2008
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