Chiral hypervalent organo-iodine(III) compounds

Article abstract of DOI:10.1002/1099-0690(200104)2001:8<1569::AID-EJOC1569>3.0.CO;2-T

A series of ortho-substituted chiral hypervalent iodine reagents has been synthesized utilizing a zirconium-mediated iodoacylation reaction, which was followed by a stereoselective reduction, methylation, and an oxidation/ligand-exchange sequence. The evaluation of these new compounds as stereoselective electrophilic reagents towards alkenes and ketones is reported. Enantioselectivities as high as 65% have been achieved in the dioxytosylation of styrene and of up to 40% in the oxytosylation of propiophenone. X-ray structure analysis and ab initio calculations on a hypervalent iodine salt have been used to develop a model for rationalizing the stereoselectivities in these reactions with chiral hypervalent iodine reagents. In this model, high enantiomeric excess in the reaction correlates with the relative population of a conformation in which a methyl group on the asymmetric carbon atom is in the axial position. This work provides new opportunities for the synthesis of new and more efficient chiral hypervalent iodine reagents for stereoselective synthesis.

Full text of DOI:10.1002/1099-0690(200104)2001:8<1569::AID-EJOC1569>3.0.CO;2-T

FULL PAPER
Chiral Hypervalent Organo-Iodine(III) Compounds
Urs H. Hirt,[a] Martin F. H. Schuster,[a] Andrew N. French,[b] Olaf G. Wiest,[c] and
Thomas Wirth*[a]
Keywords: Alkenes / Computational chemistry / Hypervalent compounds / Iodine / Oxidations
A series of ortho-substituted chiral hypervalent iodine re-
agents has been synthesized utilizing a zirconium-mediated
analysis and ab initio calculations on a hypervalent iodine
salt have been used to develop a model for rationalizing the
iodoacylation reaction, which was followed by a stereoselec- stereoselectivities in these reactions with chiral hypervalent
tive reduction, methylation, and an oxidation/ligand-ex- iodine reagents. In this model, high enantiomeric excess in
change sequence. The evaluation of these new compounds
as stereoselective electrophilic reagents towards alkenes and
the reaction correlates with the relative population of a con-
formation in which a methyl group on the asymmetric carbon
ketones is reported. Enantioselectivities as high as 65% have atom is in the axial position. This work provides new oppor-
been achieved in the dioxytosylation of styrene and of up to
40% in the oxytosylation of propiophenone. X-ray structure
tunities for the synthesis of new and more efficient chiral hy-
pervalent iodine reagents for stereoselective synthesis.
Introduction
to give the highest degree of selectivity achieved to date and
therefore this substituent has also been utilized in the pre-
sent study. Likewise, the placement of a second substituent
ortho to the iodine atom was found to further increase the
selectivity in the additions of these reagents to alkenes.[20]
In order to explore the scope of this selectivity, a number
of ortho-alkyloxy-, ortho-alkyl-, and ortho-aryl-substituted
compounds have been synthesized.
Many details of the reaction mechanism, in particular
with respect to the chiral induction, are still unclear.
Herein, we report our progress in the synthesis and evalu-
ation of new reagents according to a generally applicable
procedure. In addition, we present ab initio calculations
aimed at rationalizing the chiral induction by reagents of
type 1. These results might be useful in the further optim-
ization of chiral reagents, leading to more efficient stereose-
lective reactions.
Hypervalent iodine compounds have found broad ap-
plication in organic chemistry and are frequently used in
synthesis.[1Ϫ5] The investigation of their efficacy as oxidants
and as electrophilic reagents, and the development of new
reactions of such species is of current interest. They are of
high synthetic potential by virtue of the fact that they are
nonmetallic oxidation and oxygenation reagents, thus cir-
cumventing the problem of toxicity associated with many
of the transition metals commonly used for carrying out
such reactions. Using the commercially available hydroxy-
(tosyloxy)iodobenzene (Koser’s reagent), alkenes can be di-
oxytosylated, ketones can be α-oxytosylated, and sulfides
can be converted into sulfoxides.[6Ϫ8] In some reactions em-
ploying hypervalent iodine reagents, products with new ste-
reocenters are generated. Until recently, only very few chiral
hypervalent iodine compounds had been reported and
hence reactions with these compounds are very rare.[9Ϫ18]
We have developed the synthesis of a series of chiral hyp-
ervalent iodine compounds of type 1 and have reported
their use in stereoselective reactions with alkenes and ke-
tones.[19,20] It was shown previously that the placement of a
chiral moiety ortho to the iodine atom on the aromatic ring
results in compounds that react selectively with alkenes.[19]
These investigations showed a 1-methoxyethyl substituent
[a]
Results and Discussion
Institut für Organische Chemie der Universität Basel,
St. Johanns-Ring 19, 4056 Basel, Switzerland
[b]
Chemistry Department, Albion College,
Synthesis
Albion, MI 49224, USA
[c]
Department of Chemistry and Biochemistry, University of
The synthetic strategy for obtaining the new chiral hyper-
valent iodine reagents described herein is based on a simple,
four-step sequence. The requisite aryl halide was subjected
to a zirconium-mediated reaction with acetonitrile and iod-
ine to give the corresponding iodoaryl methyl ketones. Ster-
eoselective reduction then generated the chiral alcohols,
which were easily methylated and oxidized to the required
Notre Dame,
Notre Dame, IN 46556-5670, USA
[d]
Department of Chemistry, Cardiff University,
Cardiff CF10 3TB, UK
Fax: (internat.) ϩ 44-29/2087-6968
E-mail: wirth@cf.ac.uk
Supporting information for this article is available on the
WWW under http://www.wiley-vch.de/home/eurjoc or from
the author.
Eur. J. Org. Chem. 2001, 1569Ϫ1579
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0408Ϫ1569 $ 17.50ϩ.50/0
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U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest, T. Wirth
FULL PAPER
iodine(III) compounds. This strategy proved very effective Debenzylation and re-protection[27] of the phenol as an
in generating a host of differently substituted compounds MOM ether, followed by stereoselective reduction with (Ϫ)-
in high yields and with excellent asymmetric induction.
(Ipc)2BCl, gave the enantiomerically pure chiral alcohol 3j
Hypervalent iodine reagents bearing an ortho substituent after recrystallization. After methylation, the MOM ether
were synthesized from the corresponding substituted hal- was cleaved using a catalytic amount of hydrochloric acid
ides as shown in Scheme 1. Lithiation of the bromobenzene and the resulting phenol derivative 8 was treated with so-
derivatives 2 and reaction with (isobutyl)zirconocene chlor- dium hydride and the appropriate alkyl halides to give the
ide,[21] followed by treatment with acetonitrile and iodine desired ortho-alkyloxy iodo compounds 5gϪ5j. The tert-bu-
gave the required acylation products 3 in good yields. tyl ether 5i was synthesized in low yield (36%) by reaction
Asymmetric reduction of the iodo ketones 3 with (Ϫ)-B- of 8 with tert-butyl 2,2,2-trichloroacetimidate and boron
chlorodiisopinocampheylborane [(Ϫ)-(Ipc)2BCl] [22Ϫ24] gave trifluorideϪdiethyl ether.[28]
excellent yields of the benzylic alcohols 4 with very high
enantioselectivities (94Ϫ99% ee). Subsequent methylation
of the resulting secondary alcohols with sodium hydride
and methyl iodide proved facile. This was followed by ox-
idation with sodium perborate tetrahydrate in glacial acetic
acid to give the diacetoxyiodo compounds 6.[25] Ligand ex-
change with toluenesulfonic acid monohydrate furnished
compounds 1aϪ1f in good yields. These compounds were
found to be unstable and were therefore generated in situ
prior to reaction with styrene or propiophenone. Addition-
ally, 1-bromonaphthalene (7) was subjected to the above re-
action sequence to give 1k in 26% overall yield (Scheme 2).
Scheme 3. Synthesis of chiral ortho-alkyloxy-substituted hyperval-
ent iodine compounds 1gϪ1j
Perborate oxidation of the ortho-alkyloxy iodo com-
pounds 5 in glacial acetic acid gave moderate to good yields
of the diacetoxyiodo compounds, which were converted
into the final hydroxy(tosyloxy)iodo compounds 1gϪ1j by
means of a ligand-exchange reaction with toluenesulfonic
acid monohydrate. These compounds also proved to be un-
stable and were thus generated in situ during the reactions
with styrene and propiophenone. NMR analysis of the
crude reaction mixtures indicated a 60Ϫ95% conversion
into the desired hydroxy(tosyloxy)iodine(III) reagents 1,
with the material balance being accounted for by un-
changed iodine(I) compound 5.
Scheme 1. Synthesis of chiral hypervalent iodine compounds of
type 1
Reactions
Reactions of the hypervalent iodine reagents 1aϪ1k with
alkenes and ketones were carried out using styrene and pro-
piophenone as representative substrates.[29] The results of
the enantioselective dioxytosylation of styrene and the α-
oxytosylation of propiophenone (Scheme 4) are given in
Table 1. This evaluation of the chiral hypervalent iodine re-
agents shows that increasing the size of the ortho substitu-
Scheme 2. Synthesis of chiral hypervalent iodine compound 1k
ent from R ϭ H through R ϭ Me (1a) to R ϭ Et (1b)
results in an increased selectivity in the dioxytosylation of
Hypervalent iodine reagents bearing an ortho-alkyloxy styrene. The unsubstituted reagent yielded the product 9
substituent were synthesized in a similar fashion from the with 33% ee,[19] whereas using 1a and 1b, 9 was obtained
corresponding protected ortho-hydroxy compound 3f, as with 47% and 65% ee, respectively. Likewise, the ortho-me-
shown in Scheme 3. 2-Bromophenol was protected as the thoxy compound gave an ee of 52% in the dioxytosylation
benzyl ether[26] and subjected to the reaction sequence with of styrene.[20] A similar trend is seen in the oxytosylation
acetonitrile and iodine to give iodo ketone 3f in good yield. of propiophenone, where an increase in selectivity is also
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Eur. J. Org. Chem. 2001, 1569Ϫ1579

Chiral Hypervalent Organo-Iodine(III) Compounds
FULL PAPER
Table 1. Enantioselectivity in the dioxytosylation of styrene and in Computational Studies
the α-oxytosylation of propiophenone
We performed computational studies on the hypervalent
iodine compounds in order to obtain further insight into
the origin of the observed stereoselectivities and to provide
a structural basis for further optimizations of these com-
pounds. We started our computational studies from the pre-
viously published X-ray structure of 1l.[20] The T-shaped
structure, which stems from the stereoelectronic require-
ments of a three-center four-electron system, is a typical
feature of hypervalent iodine compounds[30] and is also
found in 1l. In contrast to Koser’s reagent, the two oxygen
atoms nearest to the iodine atom in the present system are
Compound
R
9 [ee][a]
10 [ee][a]
[b]
1a
1b
1c
1d
1e
1f
Me
Et
47%
65%
48%
13%
52%
35%
30%
28%
34%
43%
36%
40%
[b]
iPr
[b]
Ph
OMe
OBn
OEt
28%
29%
14%
17%
11%
1g
1h
1i
OiPr
OtBu
OMOM
Naphthyl
1j
15%
[b]
1k
[a]
˚
All reactions were carried out at Ϫ30 °C. Enantiomeric excesses
the oxygen atom of the hydroxy group (IϪOH: 1.94 A) and
[b]
were determined by HPLC using a Chiralcel OD column. Ϫ
Not determined.
˚
the methoxy oxygen atom (IϪOMe: 2.47 A). Thus, the tos-
ylate oxygen atom of Koser’s reagent is replaced by the me-
thoxy oxygen atom of 1l. The three sulfonate oxygen atoms
˚
are even further away from the iodine atom (IϪOTs: 2.82 A,
observed on going from 1e to 1b (Table 1). This is suggest-
ive of a cooperative effect between the ortho substituent and
the chiral moiety. However, further increases in steric bulk
at the ortho position indicate a limit to the size/selectivity
trend. For example, in the ortho-alkyl series, maximum se-
lectivity is observed for the ortho-ethyl compound 1b, with
lower selectivity being observed for reagents 1 bearing both
smaller and larger substituents. The marked reduction in
selectivity seen with the phenyl-substituted compound 1d
can be attributed to unfavorable π-stacking interactions be-
˚
˚
3.40 A, 4.43 A). Because of the ionic character of com-
pounds 1, the interaction with the tosylate group can be
considered as being purely electrostatic and calculations
have been performed starting from the X-ray data of 1l neg-
lecting the tosylate counterion.[20]
Relatively few computational studies of hypervalent iod-
ine compounds have hitherto appeared in the
literature,[31Ϫ36] hence accounts of the performances of dif-
ferent computational methods and indications for the cho-
ice of basis sets are limited. We chose the B3LYP hybrid
density functional,[37] which has evolved in recent years as
an accurate and computationally efficient method for the
calculation of organic molecules.[38,39] For the basis set, we
used the LANL2DZ effective core potential.[40] All calcula-
tions were performed using the Gaussian 94 and Gaussian
98 series of programs.[41]
We started our studies with a validation of the computa-
tional methodology through comparison of the calculated
structure with the known X-ray structure of 1l. As shown
in Figure 1, the key geometrical parameters of the experi-
mental and computed structures are in good agreement.
Scheme 4. Reactions of chiral hypervalent iodine compounds 1
˚
The IϪOMe distance (X-ray: 2.47 A) is calculated as
˚
tween the substituent and the phenyl ring of the substrate.
2.39 A, while the I1ϪC2ϪC3 angle (X-ray: 116.1°) is calcu-
lated as 117.6°.
In the ortho-alkyloxy series, all the alkyloxy compounds
Having validated this computational method, we pro-
1eϪ1j give roughly the same selectivity in the reaction with ceeded to use it to calculate the structures 11 without the
styrene, with the methoxy substituent giving the best result. tosylate counterion. We found the oxygen atom of the chiral
No significant relationship between the size of the alkyloxy moiety to be oriented towards the iodine atom. Addition-
group and the selectivity can be seen. This could in part be ally, the T-shaped structure around the iodine atom was
due to the formation of a hydrogen bond between the ether found to be preserved in all these molecules. Despite the
oxygen atom and the hydroxy group on the iodine atom. presence of an additional methoxy group in 11m, the geo-
This would minimize the steric effect of the alkyloxy sub- metry around the iodine atom is virtually identical to that
stituent on the iodine atom by forcing the alkyloxy substitu- in 11l, which has no additional substituent, and no interfer-
ent away from the iodine atom. Such a hydrogen bond was ence with the chiral moiety is observed.
found in the structures of 1eϪ1j generated by the ab initio
For 11e, which bears a methoxy group in the second ortho
calculations described in the next section. Likewise, only a position, a hydrogen bond between the proton of the hy-
weak correlation is seen between the polarity of the ortho droxy group at the iodine atom and the oxygen atom of the
˚
substituent and the selectivity, with alkyl compounds being methoxy group with an OϪH distance of 1.8 A is calcu-
slightly more selective than the corresponding alkyloxy lated. Because of this additional attraction, the distance be-
compounds.
tween the oxygen atom of the chiral side chain (O5) and
Eur. J. Org. Chem. 2001, 1569Ϫ1579
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U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest, T. Wirth
FULL PAPER
Figure 1. X-ray structure of 1l and the calculated structure of the corresponding cation
˚
the iodine atom (I1) is greater (2.47 A) than that in 11m or position, the dihedral angle D1 is 103.1°. The optimization
˚
11l (2.39 A). Moreover, when compared to the situation in of 11l-eq with the methyl group in a pseudoequatorial posi-
11m or 11l, the stereogenic carbon atom of 11e is twisted tion did not show a new local minimum and 11l-ax was
out of the aromatic plane. This is reflected in a larger dihed- again obtained. However, compounds 11aϪ11e and 11k did
ral angle D1 (see Table 2). As a result of this torsion, the show local minima for both the pseudoequatorial (D1:
methyl group C7 resides in a pseudoaxial position in rela- 168.3Ϫ174.9°) and the pseudoaxial (D1: 81.5Ϫ85.3°) ori-
tion to the five-membered ring containing the iodine atom ented methyl group. In the case of 11k, this new equatorial
and the oxygen atom of the chiral side chain. In addition to conformation was in fact 2.1 kcal/mol lower in energy than
the electronic effects, the substituent R in the second ortho the starting axial conformation.
position to the iodine atom also exerts an influence on the
Optimization of 11b (R ϭ Et) and 11c (R ϭ iPr) gave
chiral moiety through steric interactions, leading to the two additional local minima as a result of the rotation of
higher selectivities seen in Table 1. Therefore, other sub- R. The energy differences between all these conformers are
stituents were introduced in this position. In all structures summarized in the Supporting Information. As shown in
with the second ortho position to the iodine atom occupied Figure 3, the facial discrimination of structure 11b is higher
by a substituent (11aϪ11d, Figure 2), the dihedral angle D1 with the methyl group in a pseudoaxial position than it is
is larger than that in 11l.
with this group in a pseudoequatorial position.
Table 2. Selected calculated distances and angles for structures 11
Structure
11a
11b
11e-ax
11l
11m
˚
˚
˚
˚
˚
I1ϪO5
I1ϪO8
2.42 A 2.40 A 2.47 A 2.39 A 2.39 A
˚
˚
˚
˚
˚
2.04 A 2.04 A 2.03 A 2.03 A 2.03 A
113.6° 112.7° 118.1° 117.5° 117.4°
I1ϪC2ϪC3
D1: C7ϪC4ϪO5ϪI1 83.2°
84.9°
84.3° 103.1° 103.7°
D2: O5ϪI1ϪC2ϪC3 Ϫ19.6° Ϫ16.1° Ϫ18.3° Ϫ7.7° Ϫ7.6°
Figure 3. Pseudoequatorial and pseudoaxial positions of the methyl
group C7 in 11b
In all the structures other than 11k, the pseudoaxial ori-
entation of the methyl group is energetically favored. The
reason for this can be deduced by analyzing the computed
Figure 2. Structures 11 without the tosylate counterion
structures of 11a-eqϪ11e-eq with
a pseudoequatorial
methyl group C7. The interatomic distance between C6 and
˚
The differences in geometry of the optimized structures C7 is only about 3.0 A, bringing the hydrogen atoms in
11aϪ11d with the methyl group C7 in a pseudoaxial posi- these positions into van der Waals contact. This steric re-
tion are too small to be meaningful and cannot be the pulsion might provide an explanation for the favored
reason for the observed difference in selectivity. Therefore, pseudoaxial orientation. Another reason might be the pre-
we focussed our attention on the structures and relative en- ferred arrangement of the T-shaped structure of hyperval-
ergy differences of low-energy conformers of 11aϪ11d and ent compounds.[30] The T-shaped structure of the molecule
11l having the methyl group C7 either in a pseudoaxial (11l- creates steric hindrance with the additional substituent R,
ax) or in a pseudoequatorial (11l-eq) orientation. The relat- which, in some cases, can lead to a lower energy conformer
ive energy difference between the conformers provides their with a pseudoequatorial methyl group C7, as seen with 11k.
relative population according to the Boltzmann distribu-
In the dioxytosylation of styrene with 1k, in which the
tion. In 11l-ax, with the methyl group C7 in a pseudoaxial methyl group is preferentially equatorial, an ee of just 36%
1572
Eur. J. Org. Chem. 2001, 1569Ϫ1579

Chiral Hypervalent Organo-Iodine(III) Compounds
FULL PAPER
derivative (12.0 mmol) was dissolved in THF (20 mL) and n-butyl-
lithium (12.0 mmol, 7.5 mL of a 1.6  solution in hexane) was ad-
ded at Ϫ78 °C. After the solution in the first flask had been reco-
oled to Ϫ78 °C, it was slowly transferred to the second flask by
means of a cannula. After 1 h at Ϫ50 °C, acetonitrile (0.53 mL,
10 mmol) was added, the flask was sealed, and the reaction mixture
was heated to 65 °C for 18 h. After cooling to room temperature,
a solution of iodine (6.35 g, 25 mmol) in THF (25 mL) was added
and the resulting mixture was stirred for a further 7 h. After hydro-
lysis with 1  HCl (20 mL) and stirring for 5 h, the mixture was
is observed, while with 1b, which has the most favored axial
position of C7, an ee of 65% is achieved (Table 1). This is
in good agreement with the preferred orientations of the
methyl group C7 calculated for 11k and 11b. However, com-
pound 1d gives only a low enantiomeric excess in the dioxy-
tosylation of styrene. This was surprising at first glance, but
the reaction with vinylcyclohexane to give 1-cyclohexyl-1,2-
ditosyloxyethane shows that 11d is indeed able to discrimin-
ate between the faces of double bonds quite well (44% ee).
The lower selectivity seen in the dioxytosylation of styrene extracted with saturated aq. Na2SO3 solution (5 ϫ 25 mL). The
organic phase was washed with water, dried with MgSO4, and con-
centrated in vacuo.
is probably due to an additional π-stacking interaction be-
tween the phenyl ring of the substrate and the phenyl sub-
stituent of 1d.
GP2: Chiral reductions of acetophenone derivatives with (Ϫ)-B-
chlorodiisopinocampheylborane were carried out as described pre-
viously.[22] A solution of the acetophenone derivative in THF was
added to a solution of 1.1 equiv. of (Ϫ)-B-chlorodiisopinocam-
pheylborane in THF (1.0 ) at Ϫ25 °C. After the reaction
(15Ϫ25 h), the solution was allowed to warm to room temperature
and the solvent was removed. The residue was dissolved in diethyl
ether and diethanolamine (2.2 equiv.) was added. After stirring for
2 h at room temperature, the mixture was filtered through Celite
and concentrated in vacuo.
Conclusion
In summary, we have presented a new, rapid synthesis for
the generation of a large number of new chiral hypervalent
iodine reagents. Evaluation of these new reagents by their
reactions with styrene and propiophenone has indicated
that enantioselectivities are improved by the presence of an
ortho substituent, but that there is a limit to this improve-
ment. Additionally, we have been able to show that B3LYP
calculations on structures 11 can be used to rationalize the
observed stereoselectivities in the dioxytosylation of styrene
with the corresponding reagents 1. Therefore, such calcula-
tions could be used in the future for the development of
new chiral hypervalent iodine compounds. However, the
proposed model is still limited because only structures of
type 11 have been calculated and compared. In future, cal-
culations on the intermediates and the transition states will
have to be performed. Until new calculations and addi-
tional experimental efforts aimed at elucidating the mech-
anism of the dioxytosylation of alkenes are provided, the
proposed model offers a powerful tool for the evaluation of
these reagents and may be refined with new experimental
data. Further investigations aimed at probing the effects of
substituents on the selectivities of these reagents are ongo-
ing.
GP3: Sodium hydride (10 mmol) (55Ϫ65% in oil) was washed with
pentane (4 ϫ) and then suspended in DMF (12 mL). After cooling
to 0 °C, a solution of the alcohol or phenol (2.5 mmol) in DMF (6
mL) was added. After stirring for 15 min at room temperature, the
mixture was cooled to 0 °C and methyl iodide (355 mg, 2.5 mmol)
was added. After a further 3 h at room temperature, water was
carefully added. The resulting mixture was extracted with tert-butyl
methyl ether (2 ϫ), and the combined organic phases were washed
with brine (3 ϫ), dried with MgSO4, and concentrated in vacuo.
GP4:[25] A 0.1  solution of an aryl iodide in glacial acetic acid
was heated to 50Ϫ75 °C and then sodium perborate tetrahydrate
(10 equiv.) was slowly added. The reaction mixture was stirred for
3Ϫ4 h. The conversion was monitored by TLC. After completion
of the reaction, the mixture was quickly extracted with a small
volume of dichloromethane (2 ϫ). The combined extracts were
dried with MgSO4 and the solvent was removed in vacuo. The di-
acetoxyiodo derivatives could be purified either by washing with
pentane or by dissolving the crude product in acetonitrile and
washing with pentane.
GP5: The (diacetoxyiodo)benzene derivative was dissolved in ace-
tonitrile (ca. 0.9 ). To this solution, exactly 1 equiv. of para-tolu-
enesulfonic acid monohydrate in acetonitrile (0.4 ) was added.
After stirring for 1 h, the solvent was removed in vacuo. Some of
the products were found to be unstable and were therefore charac-
terized only by NMR spectroscopy.
Experimental Section
General Remarks: All reactions were performed under argon in an-
hydrous solvents. Ϫ 1H and 13C NMR spectra were recorded at
300 and 75 MHz, respectively, with samples in CDCl3 solution us-
ing TMS as an internal standard. Melting points are uncorrected.
Ϫ All starting materials (2a, 2b, 2c, 2d, 2e, 7) are commercially
available and were used without further purification. Compound
2f[26] was synthesized according to the literature procedure.
(S)-(Hydroxy)[2-(1-methoxyethyl)-6-methylphenyl](4-methylphenyl-
sulfonato-κO)iodine (1a): GP5; 90% (62 mg) yield; purification not
possible. Ϫ 1H NMR (CDCl3): δ ϭ 1.47 (d, 3 H, J ϭ 6.3 Hz), 2.35
(s, 3 H), 2.77 (s, 3 H), 3.21 (s, 3 H), 4.76 (q, 1 H, J ϭ 5.8 Hz), 7.1
(m, 1 H), 7.1 (m, 2 H), 7.38 (m, 2 H), 7.54 (m, 2 H).
General Procedures
GP1:[21] In a 200-mL Schlenk flask, zirconocene dichloride (3.51 g,
12 mmol) was dissolved in THF (70 mL) and tert-butyllithium
(10.5 mmol, 6.55 mL of a 1.6  solution in hexane) was added at
Ϫ78 °C. The brown solution was allowed to warm to room temper-
(S)-(Hydroxy)[2-ethylphenyl-6-(1-methoxyethyl)](4-methylphenyl-
sulfonato-κO)iodine (1b): GP5; purification not possible. Ϫ 1H
NMR (CDCl3): δ ϭ 1.20Ϫ1.50 (m, 6 H), 2.35 (s, 3 H), 3.04 (q, J ϭ
7.4 Hz, 2 H), 3.25 (s, 3 H), 4.70Ϫ4.80 (m, 1 H), 7.17 (d, J ϭ 7.8 Hz,
ature; the yellow precipitate dissolved and after 1 h the solution was 2 H), 7.20Ϫ7.45 (m, 3 H), 7.62 (d, J ϭ 8.2 Hz, 2 H), 9.37 (s, 1
cooled to Ϫ78 °C once more. In a second flask, the bromobenzene
Eur. J. Org. Chem. 2001, 1569Ϫ1579
H, OH).
1573

U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest, T. Wirth
FULL PAPER
(S)-(Hydroxy)[2-(1-methoxyethyl)-6-(1-methylethyl)phenyl](4-
arom.), 7.3 (t, 1 H, J ϭ 7.5 Hz, 4-H arom.). Ϫ 13C NMR (CDCl3):
δ ϭ 23.0 [q, CH(CH3)2], 30.5 (d, CHMe2), 38.0 (q, COCH3), 96.3
sible. Ϫ H NMR (CDCl3): δ ϭ 1.10Ϫ1.50 (m, 9 H), 2.34 (s, 3 H), (s, arom. C-2), 124.1 (d, arom. C), 126.9 (d, arom. C), 128.5 (d,
methylphenylsulfonato-κO)iodine (1c): GP5; purification not pos-
1
3.25 (s, 3 H), 3.35 (m, 1 H), 4.80 (m, 1 H), 7.10Ϫ7.60 (m, 7 H).
arom. C), 148.1 (s, arom. C-1 or C-3), 151.6 (s, arom. C-1 or C-3),
204.7 (s, COMe). Ϫ IR (KBr): ν˜ ϭ 3056, 2963, 2867, 1704, 1465,
1352, 1273, 1182, 1106, 1005, 793, 726 cmϪ1. Ϫ MS (EI, 70 eV):
m/z (%) ϭ 288 (74), 273 (100), 217 (11), 147 (9), 131 (11), 117 (12).
Ϫ HRMS: calcd. for C10H13IO 288.0011; found 288.0011 [Mϩ].
(S)-[3-(1-Methoxyethyl)-1,1Ј-biphenyl-2-yl)]hydroxy(4-
methylphenylsulfonato-κO)iodine (1d): GP5; purification not pos-
1
sible. Ϫ H NMR (CDCl3): δ ϭ 1.49 (d, J ϭ 6.4 Hz, 3 H), 2.37 (s,
3 H), 3.05Ϫ3.30 (m, 3 H), 4.60Ϫ4.75 (m, 1 H), 7.18 (d, J ϭ 8 Hz,
2 H), 7.20Ϫ7.80 (m, 8 H), 7.64 (d, J ϭ 8.2 Hz, 2 H), 10.06 (s, 1
H, OH).
2-Iodo-3-phenylacetophenone (3d): GP1; 56% (1.80 g) yield; puri-
fication by flash chromatography on silica gel (tert-butyl methyl
ether/pentane, 1:50 Ǟ 1:10); colorless crystals, m.p. 103Ϫ106 °C.
(S)-(Hydroxy)[2-(1-methoxyethyl)-6-methoxyphenyl](4-
methylphenylsulfonato-κO)iodine (1e): Described in ref.[20]
Ϫ
1H NMR (CDCl3): δ ϭ 2.64 (s, 3 H, COCH3), 7.21 (dd, 1 H,
J ϭ 1.9 Hz, J ϭ 7.4 Hz, H arom.), 7.30 (m, 3 H, H arom.), 7.42
(m, 4 H, H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 30.3 (q, COCH3),
94.4 (s, arom. C-2), 125.4 (d), 127.9 (d), 128.0 (d, 2 C), 128.1 (d),
129.4 (d, 2 C), 130.8 (d), 144.1 (s), 147.9 (s, arom. C-1), 148.3 (s,
arom. C-3), 204.2 (s, COCH3). Ϫ IR (KBr): ν˜ ϭ 3052, 1706, 1442,
(S)-[2-(Benzyloxy)-6-(1-methoxyethyl)phenyl](hydroxy)(4-
methylphenylsulfonato-κO)iodine (1f): GP5; generation in situ.
(S)-[2-Ethoxy-6-(1-methoxyethyl)phenyl](hydroxy)(4-methylphenyl-
sulfonato-κO)iodine (1g): GP5; generation in situ.
1413, 1396, 1352, 1298, 1276, 1183, 1124, 1010, 809, 765, 701 cmϪ1
.
Ϫ MS (EI, 70 eV): m/z (%) ϭ 323 (21), 322 (91), 308 (22), 307
(100), 165 (12), 153 (25), 152 (77), 151 (22), 126 (10), 76 (19). Ϫ
HRMS: calcd. for C14H11IO 321.9855; found 321.9857 [Mϩ].
(S)-(Hydroxy)[2-(1-methoxyethyl)-6-(1-methylethyloxy)phenyl](4-
methylphenylsulfonato-κO)iodine (1h): GP5; generation in situ.
(S)-[2-(1,1-Dimethylethoxy)-6-(1-methoxyethyl)phenyl](hydroxy)(4-
methylphenylsulfonato-κO)iodine (1i): GP5; generation in situ.
3-(Benzyloxy)-2-iodoacetophenone (3f): GP1; 65% (2.38 g) yield;
purification by flash chromatography on silica gel (tert-butyl
methyl ether/pentane, 1:10); brown crystals, m.p. 53Ϫ55 °C. Ϫ H
1
(S)-(Hydroxy)[2-(1-methoxyethyl)-6-(methoxymethoxy)phenyl](4-
methylphenylsulfonato-κO)iodine (1j): GP5; generation in situ.
NMR (CDCl3): δ ϭ 2.60 (s, 3 H, COCH3), 5.18 (s, 2 H, CH2),
6.87Ϫ6.93 (m, 2 H, H arom.), 7.25Ϫ7.42 (m, 4 H, H arom.),
7.49Ϫ7.51 (m, 2 H, H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 30.1 (q,
COCH3), 71.2 (t, CH2), 83.8 (s, arom. C-2), 113.6 (d), 119.7 (d),
127.0 (d, 2 C), 128.0 (d), 128.6 (d, 2 C), 129.5 (d), 136.1 (s), 148.0
(s), 157.3 (s), 203.3 (s, COCH3). Ϫ IR (KBr): ν˜ ϭ 3060, 3029, 2913,
2867, 1696, 1560, 1498, 1449, 1423, 1387, 1272, 1240, 1044, 1029,
785, 751, 737, 697 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 353 [Mϩ ϩ
H] (4), 352 (19), 225 (3), 181 (2), 119 (3), 91 (100), 65 (13), 43 (13),
39 (4). Ϫ C15H13IO2 (352.17): calcd. C 51.16, H 3.72, O 9.09; found
C 50.89, H 3.93, O 8.94.
(S)-(Hydroxy)[2-(1-methoxyethyl)naphthalen-1-yl](4-methylphenyl-
sulfonato-κO)iodine (1k): GP5; generation in situ.
2-Iodo-3-methylacetophenone (3a): GP1; 39% (1.02 g) yield; puri-
fication by flash chromatography on silica gel (tert-butyl methyl
1
ether/pentane, 1:10); yellow oil. Ϫ H NMR (CDCl3): δ ϭ 2.48 (s,
3 H, COCH3), 2.85 (s, 3 H, CH3), 7.06 (m, 1 H, 4-H arom.), 7.27
(dd, 2 H, J ϭ 1.3 Hz, J ϭ 5.3 Hz, 3-, 5-H arom.). Ϫ 13C NMR
(CDCl3): δ ϭ 29.0 (q, CH3), 30.1 (q, COCH3), 96.8 (s, arom. C-2),
124.1 (d, arom. C), 128.0 (d, arom. C), 130.8 (d, arom. C), 142.9
(s, arom. C-1 or C-3), 147.2 (s, arom. C-1 or C-3), 204.0 (s,
COCH3). Ϫ IR (KBr): ν˜ ϭ 3045, 2976, 2961, 1704, 1567, 1433,
1396, 1652, 1275, 1174, 1126, 1012, 783, 718 cmϪ1. Ϫ MS (EI,
70 eV): m/z (%) ϭ 260 (66), 245 (100), 217 (28), 90 (35), 63 (14). Ϫ
HRMS: calcd. for C9H9IO 259.9698; found 259.9704 [Mϩ].
(S)-1-[2-Iodo-3-(methoxymethoxy)phenyl]ethanol (3j): GP2; 58%
(1.65 g) yield, 95% ee;[42] after recrystallization (tert-butyl methyl
ether/pentane) 99% ee; colorless crystals, m.p. 50Ϫ51 °C. Ϫ 1H
NMR (CDCl3): δ ϭ 1.45 [d, 3 H, J ϭ 6.3 Hz, CH(OH)CH3], 2.25
(d, 1 H, J ϭ 3.0 Hz, OH), 3.51 (s, 3 H, OCH3), 5.17 [dq, 1 H, J ϭ
6.4 Hz, J ϭ 3.1 Hz, CH(OH)Me], 5.24 (s, 2 H, CH2), 6.96 (dd, 1
H, J ϭ 7.8 Hz, J ϭ 1.7 Hz, 3- or 5-H arom.), 7.22 (dd, 1 H, J ϭ
7.7 Hz, J ϭ 1.7 Hz, 3- or 5-H arom.), 7.29 (t, 1 H, J ϭ 7.8 Hz, 4-
H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 23.5 [q, CH(OH)CH3], 56.4
(q, OCH3), 73.9 [d, CH(OH)Me], 90.9 (s, arom. C-2), 95.1 (t, CH2),
113.6 (d, arom. C-6), 119.7 (d, arom. C-4), 129.5 (d, arom. C-5),
149.6 (s, arom. C-3), 155.5 (s, arom. C-1). Ϫ IR (KBr): ν˜ ϭ 3332,
3070, 2975, 2929, 2897, 2824, 1932, 1850, 1773, 1590, 1566, 1468,
1453, 1444, 1425, 1369, 1253, 1150, 1073, 1026, 916, 784, 716, 737
cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 309 [Mϩ ϩ H] (5), 308 (36),
277 (4), 263 (5), 246 (54), 136 (5), 91 (6), 77 (5), 65 (7), 63 (6), 45
(100), 43 (12), 39 (6).
3-Ethyl-2-iodoacetophenone (3b): GP1; 52% (1.42 g) yield; purifica-
tion by flash chromatography on silica gel (tert-butyl methyl ether/
1
pentane, 1:10); yellow solid. Ϫ H NMR (CDCl3): δ ϭ 1.22 (t, 3
H, J ϭ 7.5 Hz, CH2CH3), 2.59 (s, 3 H, COCH3), 2.80 (q, 2 H, J ϭ
7.5 Hz, CH2CH3), 7.05 (dd, 1 H, J ϭ 1.9 Hz, J ϭ 7.1 Hz, 3- or 5-
H arom.), 7.25 (dd, 1 H, J ϭ 1.9 Hz, J ϭ 7.7 Hz, 3- or 5-H arom.),
7.31 (t, 1 H, J ϭ 7.4 Hz, 4-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ
14.5 (q, CH2CH3), 30.3 (q, COCH3), 34.5 (t, CH2CH3), 95.8 (s,
arom. C-2), 124.1 (d, arom. C-6), 128.3 (d, arom. C-5), 129.5 (d,
arom. C-4), 147.7 (s, arom. C-1 or C-3), 147.8 (s, arom. C-1 or C-
3), 204.3 (s, COCH3). Ϫ IR (KBr): ν˜ ϭ 3062, 2967, 2931, 2872,
1704, 1568, 1455, 1407, 1352, 1269, 1175, 1128, 1098, 1009, 796,
722 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 274 (72), 259 (100), 104
(41), 103 (13), 77 (12). Ϫ HRMS: calcd. for C10H11IO 273.9855;
found 273.9861 [Mϩ].
(S)-1-(2-Iodo-3-methylphenyl)ethanol (4a): GP2; 72% (400 mg)
yield, 94% ee;[43] purification by flash chromatography on silica gel
(dichloromethane); colorless oil. Ϫ 1H NMR (CDCl3): δ ϭ 1.44 [d,
3 H, J ϭ 6.4 Hz, CH(OH)CH3], 2.47 (s, 3 H, CH3), 5.17 [q, 1 H,
2-Iodo-3-(1-methylethyl)acetophenone (3c): GP1; 31% (580 mg)
yield; purification by flash chromatography on silica gel (tert-butyl J ϭ 6.3 Hz, CH(OH)Me], 7.15 (dd, 1 H, J ϭ 1.2 Hz, J ϭ 7.4 Hz,
1
methyl ether/pentane, 1:10); yellow oil. Ϫ H NMR (CDCl3): δ ϭ
1.24 [d, 6 H, J ϭ 6.8 Hz, CH(CH3)2], 2.59 (s, 3 H, COCH3), 3.5 H, J ϭ 1.3 Hz, J ϭ 7.6 Hz, 3- or 5-H arom.). Ϫ 13C NMR (CDCl3):
(q, 1 H, J ϭ 6.8 Hz, CHMe2), 7.03 (dd, 1 H, J ϭ 1.9 Hz, J ϭ δ ϭ 23.6 [q, CH(OH)CH3], 26.9 (q, CH3), 74.3 [d, CH(OH)Me],
7.2 Hz, 5-H arom.), 7.27 (dd, 1 H, J ϭ 1.9 Hz, J ϭ 7.8 Hz, 3-H 104.7 (s, arom. C-2), 123.4 (d, arom. C), 128.2 (d, arom. C), 128.8
3- or 5-H arom.), 7.24 (t, 1 H, J ϭ 7.5 Hz, 4-H arom.), 7.34 (dd, 1
1574
Eur. J. Org. Chem. 2001, 1569Ϫ1579

Chiral Hypervalent Organo-Iodine(III) Compounds
(d, arom. C), 141.9 (s, arom. C-3), 148.2 (s, arom. C-1). Ϫ IR m.p. 71Ϫ72 °C. Ϫ 1H NMR (CDCl3): δ ϭ 1.45 [d, 3 H, J ϭ 6.4 Hz,
FULL PAPER
(KBr): ν˜ ϭ 3334, 3046, 2972, 2923, 1459, 1402, 1367, 1113, 1068,
CH(OH)CH3], 2.23 (d, 1 H, J ϭ 2.8 Hz, OH), 5.13 (s, 2 H), 5.18
[dq, 1 H, J ϭ 6.3 Hz, J ϭ 2.9 Hz, CH(OH)Me], 6.75 (dd, 1 H, J ϭ
1003, 783 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 262 (47), 247 (100),
119 (16), 92 (70), 91 (35), 65 (11). Ϫ HRMS: calcd. for C9H11IO 7.9 Hz, J ϭ 1.5 Hz, H arom.), 7.18 (dd, 1 H, J ϭ 7.7 Hz, J ϭ
261.9855; found 261.9860 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ46.4 (c ϭ 1.205,
CHCl3).
1.4 Hz, H arom.), 7.24Ϫ7.52 (m, 6 H, H arom.). Ϫ 13C NMR
(CDCl3): δ ϭ 23.5 [q, CH(OH)CH3], 71.1 (t, CH2), 73.9 [d,
CH(OH)Me], 90.5 (s, arom. C-2), 111.5 (d, arom. C-6), 118.9 (d,
arom. C-4), 127.0 (d, 2 C), 127.8 (d), 128.5 (d, 2 C), 129.4 (d, arom.
C-5), 136.5 (s), 149.6 (s, arom. C-3), 156.6 (s, arom. C-1). Ϫ IR
(KBr): ν˜ ϭ 3294, 3063, 3034, 2970, 1587, 1564, 1497, 1469, 1450,
1371, 1262, 1047, 1028, 1014, 779, 745, 730, 713 cmϪ1. Ϫ MS (EI,
70 eV): m/z (%) ϭ 355 [Mϩ ϩ H] (8), 354 (35), 246 (9), 227 (3), 91
(100), 77 (4), 65 (17), 45 (1), 37 (4).
(S)-1-(3-Ethyl-2-iodophenyl)ethanol (4b): GP2; 86% (950 mg) yield,
95% ee;[44] purification by flash chromatography on silica gel
(dichloromethane); colorless oil. Ϫ 1H NMR (CDCl3): δ ϭ 1.21 (t,
3
H, J ϭ 7.5 Hz, CH2CH3), 1.45 [d, 3 H, J ϭ 6.3 Hz,
CH(OH)CH3], 2.27 (br., 1 H, OH), 3.37 (q, 2 H, J ϭ 7.5 Hz,
CH2CH3), 5.20 [dq, 1 H, J ϭ 2.2 Hz, J ϭ 6.3 Hz, CH(OH)CH3],
7.13 (dd, 1 H, J ϭ 1.7 Hz, J ϭ 7.4 Hz, 3- or 5-H arom.), 7.27 (t, 1
H, J ϭ 7.4 Hz, 4-H arom.), 7.36 (dd, 1 H, J ϭ 1.7 Hz, J ϭ 7.7 Hz,
3- or 5-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 14.6 (q, CH2CH3),
23.7 [q, CH(OH)CH3], 35.3 (t, CH2CH3), 74.5 [d, CH(OH)CH3],
104.1 (s, arom. C-2), 123.8 (d, arom. C), 127.7 (d, arom. C), 128.5
(d, arom. C), 146.9 (s, arom. C), 148.3 (s, arom. C). Ϫ IR (KBr):
ν˜ ϭ 3346, 3061, 2968, 2929, 2871, 1572, 1456, 1413, 1368, 1338,
1110, 1070, 1004, 910, 839, 796, 724 cmϪ1. Ϫ MS (EI, 70 eV): m/z
(%) ϭ 276 (58), 262 (15), 261 (100), 106 (52), 105 (14), 91 (27), 77
(14). Ϫ HRMS: calcd. for C10H13IO 276.0011; found 276.0018
[Mϩ]. Ϫ [α]2D5 ϭ Ϫ43.5 (c ϭ 1.135, CHCl3).
(S)-2-Iodo-1-(1-methoxyethyl)-3-methylbenzene (5a): GP3; 92%
(303 mg) yield; no purification necessary; colorless oil. Ϫ 1H NMR
(CDCl3): δ ϭ 1.37 [d, 3 H, J ϭ 6.3 Hz, CH(OMe)CH3], 2.47 (s, 3
H, CH3), 3.24 (s, 3 H, OCH3), 4.68 [q, 1 H, J ϭ 6.4 Hz, CH(O-
Me)Me], 7.15 (m, 1 H, H arom.), 7.24 (m, 2 H, H arom.). Ϫ 13C
NMR (CDCl3): δ ϭ 22.6 [q, CH(OMe)CH3], 29.6 (q, CH3), 56.6
(q, OCH3), 83.5 [d, CH(OMe)Me], 105.5 (s, arom. C-2), 123.6 (d,
arom. C), 128.3 (d, arom. C), 128.8 (d, arom. C), 141.9 (s, arom.
C-3), 146.1 (s, arom. C-1). Ϫ IR (KBr): ν˜ ϭ 3046, 2976, 2926, 2819,
1447, 1403, 1369, 1342, 1312, 1240, 1205, 1114, 1061, 1005, 840,
784, 745, 719 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 276 (16), 261
(100), 245 (9), 118 (10), 91 (16). Ϫ HRMS: calcd. for C10H13IO
276.0011; found 276.0021 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ76.1 (c ϭ 1.50,
CHCl3).
(S)-1-[2-Iodo-3-(1-methylethyl)phenyl]ethanol (4c): GP2; 68%
(238 mg) yield, Ͼ 99% ee;[44] purification by flash chromatography
on silica gel (tert-butyl methyl ether/pentane, 1:10); colorless oil. Ϫ
1H NMR (CDCl3): δ ϭ 1.23 [t, 6 H, J ϭ 6.5 Hz, CH(CH3)2], 1.44
[d, 3 H, J ϭ 6.3 Hz, CH(OH)CH3], 2.57 (br., 1 H, OH), 3.37 (sept,
1 H, J ϭ 6.8 Hz, CHMe2), 5.21 [q, 1 H, J ϭ 6.3 Hz, CH(OH)Me],
7.14 (dd, 1 H, J ϭ 1.8 Hz, J ϭ 7.6 Hz, 3- or 5-H arom.), 7.29 (t, 1
H, J ϭ 7.6 Hz, 4-H arom.), 7.39 (dd, 1 H, J ϭ 1.9 Hz, J ϭ 7.7 Hz,
3- or 5-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 23.1 (q, CH3), 23.4
(q, CH3), 23.7 (q, CH3), 38.6 (d, CHMe2), 74.8 [d, CH(OH)Me],
104.9 (s, arom. C-2), 124.3 (d, arom. C), 125.2 (d, arom. C), 128.6
(d, arom. C), 148.4 (s, arom. C-1 or C-3), 150.7 (s, arom. C-1 or
C-3). Ϫ IR (KBr): ν˜ ϭ 3347, 3063, 2964, 2929, 2863, 1456, 1409,
1365, 1103, 1069, 1001, 794, 726 cmϪ1. Ϫ MS (EI, 70 eV): m/z
(%) ϭ 290 (61), 275 (100), 257 (12), 233 (11), 130 (16), 105 (14), 91
(17), 77 (14), 43 (53). Ϫ HRMS: calcd. for C11H15IO 290.0168;
found 290.0167 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ44.0 (c ϭ 0.835, CHCl3).
(S)-1-Ethyl-2-iodo-3-(1-methoxyethyl)benzene (5b): GP3; quant.
(725 mg) yield; no purification necessary; colorless oil. Ϫ 1H NMR
(CDCl3): δ ϭ 1.22 (t, 3 H, J ϭ 7.5 Hz, CH2CH3), 1.38 [d, 3 H, J ϭ
6.3 Hz, CH(OCH3)CH3], 2.80 (q, 2 H, J ϭ 7.5 Hz, CH2CH3), 3.24
(s, 3 H, OCH3), 4.69 [q, 1 H, J ϭ 6.3 Hz, CH(OMe)Me], 7.13 (dd,
1 H, J ϭ 2.6 Hz, J ϭ 6.7 Hz, 3- or 5-H arom.), 7.24Ϫ7.28 (m, 2
H, 4-H and 3- or 5-H arom.)]. Ϫ 13C NMR (CDCl3): δ ϭ 14.6
(q, CH2CH3), 22.7 [q, CH(OMe)CH3], 35.2 (t, CH2CH3), 56.6 (q,
OCH3), 83.7 [d, CH(OMe)Me], 104.9 (s, arom. C-2), 123.9 (d,
arom. C-4), 127.6 (d, arom. C-5), 128.5 (d, arom. C-6), 146.2 (s,
arom. C-1 or C-3), 146.9 (s, arom. C-1 or C-3). Ϫ IR (KBr): ν˜ ϭ
3061, 2971, 2930, 2820, 1572, 1455, 1413, 1370, 1346, 1113, 1062,
1004, 797, 726 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 290 (24), 276
(19), 275 (100), 259 (10), 105 (11), 91 (9). Ϫ HRMS: calcd. for
C11H15IO 290.0168; found 290.0168 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ82.3 (c ϭ
1.72, CHCl3).
(S)-1-(2-Iodo-1,1Ј-biphenyl-3-yl)ethanol (4d): GP2; 81% (1.135 g)
yield, 95% ee;[45] purification by flash chromatography on silica gel
(dichloromethane); colorless crystals, m.p. 108Ϫ110 °C. Ϫ 1H
NMR (CDCl3): δ ϭ 1.50 [d, 3 H, J ϭ 6.3 Hz, CH(OH)CH3], 2.35
(br., 1 H, OH), 5.23 [dq, 1 H, J ϭ 1.9 Hz, J ϭ 6.3 Hz, CH(OH)Me],
7.18 (dd, 1 H, J ϭ 1.8 Hz, J ϭ 7.4 Hz, 5-H arom.), 7.25 (m, 2 H,
H arom.), 7.39 (m, 4 H, H arom.), 7.54 (dd, 1 H, J ϭ 1.7 Hz, J ϭ
(S)-2-Iodo-1-(1-methoxyethyl)-3-(1-methylethyl)benzene (5c): GP3;
83% (156 mg) yield; purification by flash chromatography on silica
gel (tert-butyl methyl ether/pentane, 1:20); colorless oil. Ϫ 1H
NMR (CDCl3): δ ϭ 1.23 [dd, 6 H, J ϭ 1.9 Hz, J ϭ 6.9 Hz,
CH(CH3)2], 1.38 [d, 3 H, J ϭ 6.3 Hz, CH(OMe)CH3], 3.25 (s, 3 H,
OCH3), 3.38 (sept, 1 H, J ϭ 6.8 Hz, CHMe2), 4.71 [q, 1 H, J ϭ
6.3 Hz, CH(OMe)Me], 7.15 (dd, 1 H, J ϭ 2.4 Hz, J ϭ 6.9 Hz, H
arom.), 7.28 (m, 2 H, H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 22.7
(q, CH3), 23.2 (q, CH3), 23.3 (q, CH3), 38.6 (d, CHMe2), 56.7 (q,
OCH3), 84.0 [d, CH(OMe)Me], 105.8 (s, arom. C-2), 124.4 (d,
arom. C), 125.2 (d, arom. C), 128.6 (d, arom. C), 146.2 (s, arom.
C-1 or C-3), 150.8 (s, arom. C-1 or C-3). Ϫ IR (KBr): ν˜ ϭ 3057,
2964, 2927, 2820, 1574, 1455, 1410, 1369, 1329, 1205, 1110, 1061,
1002, 866, 795, 728 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 304 (12),
290 (18), 289 (100), 273 (6), 147 (9), 131 (7), 130 (6), 119 (8), 117
(9), 115 (9), 91 (11). Ϫ HRMS: calcd. for C12H17IO 304.0324;
found 304.0323 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ80.3 (c ϭ 0.93, CHCl3).
7.7 Hz, 3-H arom.).
Ϫ δ ϭ 23.8 [q,
13C NMR (CDCl3):
CH(OH)CH3], 74.6 [d, CH(OH)Me], 102.4 (s, arom. C-2), 125.0
(d, arom. C), 127.5 (d, arom. C), 127.8 (d, 2 C, arom. C), 128.2 (d,
arom. C), 129.0 (d, 2 C, arom. C), 129.4 (d, arom. C), 145.4 (s,
arom. C), 147.7 (s, arom. C-1 or C-3), 148.7 (s, arom. C-1 or C-3).
Ϫ IR (KBr): ν˜ ϭ 3585, 3437, 2977, 1450, 1360, 1334, 1278, 1243,
1171, 1124, 1098, 1065, 1000, 904, 806, 756, 731, 697 cmϪ1. Ϫ MS
(EI, 70 eV): m/z (%) ϭ 325 (17), 324 (85), 310 (20), 309 (100), 182
(43), 181 (34), 180 (13), 179 (16), 178 (19), 155 (15), 154 (67), 153
(34), 152 (55), 151 (17), 76 (17). Ϫ HRMS: calcd. for C14H13IO
324.0011; found 324.0009 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ 47.4 (c ϭ 0.99,
CHCl3).
(S)-1-[3-(Benzyloxy)-2-iodophenyl]ethanol (4f): GP2; 67% (856 mg)
yield, 99% ee[46] after recrystallization (pentane); colorless crystals,
(S)-2-Iodo-3-(1-methoxyethyl)-1,1Ј-biphenyl (5d): GP3; 95%
(843 mg) yield; no purification necessary; colorless crystals, m.p.
Eur. J. Org. Chem. 2001, 1569Ϫ1579
1575

U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest, T. Wirth
C-4), 129.2 (d, arom. C-5), 147.7 (s, arom. C-3), 156.3 (s, arom. C-
FULL PAPER
75Ϫ78 °C. Ϫ 1H NMR (CDCl3): δ ϭ 1.42 [d, 3 H, J ϭ 6.4 Hz,
˜ ϭ 2981, 2932, 2825, 1584, 1566, 1457, 1385,
CH(OMe)CH3], 3.30 (s, 3 H, OCH3), 4.72 [q, 1 H, J ϭ 6.3 Hz, 1). Ϫ IR (KBr): ν
CH(OMe)Me], 7.19 (dd, 1 H, J ϭ 2.3 Hz, J ϭ 6.9 Hz, 5-H arom.), 1373, 1345, 1315, 1281, 1262, 1114, 1060, 1009, 980, 897, 855, 834,
7.28 (dd, 1 H, J ϭ 2.1 Hz, J ϭ 7.8 Hz, 3-H arom.), 7.28 (m, 1 H,
821, 690 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 321 [Mϩ ϩ H] (5),
320 (39), 305 (2), 278 (31), 263 (100), 248 (8), 247 (10), 120 (16),
H arom.), 7.40 (m, 5 H, H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 22.7
[q, CH(OMe)CH3], 56.8 (q, OCH3), 83.8 [d, CH(OMe)Me], 103.1 91 (10), 77 (6), 65 (7), 59 (15), 43 (18), 39 (5).
(s, arom. C-2), 125.1 (d, arom. C), 127.5 (d, arom. C), 127.8 (d,
(S)-1-(1,1-Dimethylethoxy)-2-iodo-3-(1-methoxyethyl)benzene (5i):
2 C, arom. C), 128.2 (d, arom. C), 129.0 (d, arom. C), 129.4 (d,
2 C, arom. C), 145.4 (s, arom. C), 146.9 (s, arom. C-1 or C-3), 147.7
(s, arom. C-1 or C-3). Ϫ IR (KBr): ν˜ ϭ 3056, 2972, 2927, 2820,
1451, 1399, 1366, 1228, 1207, 1109, 1056, 1003, 802, 762, 731, 703
cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 338 (33.4), 324 (25), 232 (100),
180 (16), 178 (14), 165 (16), 152 (24). Ϫ HRMS: calcd. for
C15H15IO 338.0168; found 338.0174 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ82.6 (c ϭ
1.20, CHCl3).
Starting material: 8; synthesized according to ref.[28]; 36% (71 mg)
yield; colorless oil. Ϫ 1H NMR (CDCl3): δ ϭ 1.37 [d, 3 H, J ϭ
6.4 Hz, CH(OCH3)CH3], 1.49 [s, 9 H, C(CH3)3], 3.24 (s, 3 H,
OCH3), 4.67 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 7.00 (dd, 1 H,
J ϭ 7.9 Hz, J ϭ 1.6 Hz, 3- or 5-H arom.), 7.11 (dd, 1 H, J ϭ
7.7 Hz, J ϭ 1.4 Hz, 3- or 5-H arom.), 7.24 (t, 1 H, J ϭ 7.9 Hz, 4-
H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 22.5 [q, CH(OMe)CH3], 29.2
[q, C(CH3)3], 56.6 (q, OCH3), 81.3 (s, CMe3), 83.4 [d, CH(O-
Me)Me], 99.2 (s, arom. C-2), 119.8 (d, arom. C-4 or C-6), 120.5 (d,
arom. C-4 or C-6), 128.7 (d, arom. C-5), 147.6 (s, arom. C-1), 155.7
(s, arom. C-3). Ϫ IR (CHCl3): ν˜ ϭ 2983, 2932, 2825, 1567, 1455,
1415, 1392, 1369, 1344, 1315, 1264, 1162, 1113, 1059, 1012, 957,
919, 895, 862, 834, 821, 689 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ
334 [Mϩ] (4), 319 (8), 278 (60), 263 (100), 248 (8), 247 (12), 231
(13), 152 (3), 137 (6), 120 (14), 91 (9), 77 (6), 65 (6), 59 (13), 57
(22), 41 (11), 39 (6).
(S)-1-(Benzyloxy)-2-iodo-3-(1-methoxyethyl)benzene (5f): GP3; 80%
(696 mg) yield; purification by flash chromatography on silica gel
1
(dichloromethane); colorless crystals, m.p. 67Ϫ70 °C. Ϫ H NMR
(CDCl3): δ ϭ 1.38 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3], 3.24 (s, 3
H, OCH3), 4.70 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 5.14 (s, 2 H,
CH2), 6.76 (dd, 1 H, J ϭ 8.1 Hz, J ϭ 1.3 Hz, H arom.), 7.07 (dd,
1 H, J ϭ 7.7 Hz, J ϭ 1.3 Hz, H arom.), 7.22Ϫ7.42 (m, 4 H, H
arom.), 7.51Ϫ7.53 (m, 2 H, H arom.). Ϫ 13C NMR (CDCl3): δ ϭ
22.5 [q, CH(OMe)CH3], 56.7 (q, OCH3), 71.0 (t, CH2), 83.0 [d,
CH(OH)Me], 91.4 (s, arom. C-2), 111.2 (d, arom. C-4), 119.1 (d,
arom. C-6), 127.0 (d, 2 C), 127.8 (d), 128.5 (d, 2 C), 129.4 (d, arom.
C-5), 136.5 (s), 147.7 (s, arom. C-1), 156.7 (s, arom. C-3). Ϫ IR
(KBr): ν˜ ϭ 3064, 3024, 2990, 2980, 2910, 2879, 2823, 1942, 1873,
1859, 1815, 1774, 1752, 1686, 1654, 1584, 1564, 1498, 1380, 1365,
1267, 1116, 904, 789 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 369 [Mϩ
ϩ H] (8), 368 (35), 353 (3), 246 (14), 241 (1), 209 (7), 91 (100), 77
(3), 65 (12), 59 (3), 37 (3). Ϫ C16H17IO2 (368.21): calcd. C 52.19,
H 4.65, O 8.69; found C 52.00, H 4.73, O 8.70.
(S)-2-Iodo-1-(1-methoxyethyl)-3-(methoxymethoxy)benzene
(5j):
GP3; 90% (1.54 g) yield; no purification necessary; yellow oil. Ϫ
1H NMR (CDCl3): δ ϭ 1.38 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3],
3.25 (s, 3 H, OCH3), 3.53 (s, 3 H, arom. OCH3), 4.67 [q, 1 H, J ϭ
6.4 Hz, CH(OMe)Me], 5.25 (s, 2 H, CH2), 6.98 (dd, 1 H, J ϭ
8.0 Hz, J ϭ 1.4 Hz, 3- or 5-H arom.), 7.11 (dd, 1 H, J ϭ 7.8 Hz,
J ϭ 1.4 Hz, 3- or 5-H arom.), 7.29 (t, 1 H, J ϭ 7.9 Hz, 4-H arom.).
Ϫ
13C NMR (CDCl3): δ ϭ 22.5 [q, CH(OMe)CH3], 56.4 (q,
OCH3), 56.7 (q, OCH3), 83.0 [d, CH(OMe)Me], 91.8 (s, arom. C-
2), 95.0 (t, CH2), 113.4 (d, arom. C-6), 119.9 (d, arom. C-4), 129.4
(d, arom. C-5), 147.5 (s, arom. C-3), 155.6 (s, arom. C-1). Ϫ IR
(KBr): ν˜ ϭ 3005, 2983, 2932, 2827, 1587, 1567, 1460, 1442, 1254,
1154, 1108, 1084, 1018, 990 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ
323 [Mϩ ϩ H] (10), 322 (46), 307 (19), 291 (10), 277 (17), 246 (54),
134 (5), 120 (11), 104 (8), 91 (12), 77 (9), 65 (8), 63 (8), 59 (14), 45
(100), 43 (8), 39 (6).
(S)-1-Ethoxy-2-iodo-3-(1-methoxyethyl)benzene (5g): Starting mat-
erial: 8. GP3 (using ethyl iodide instead of methyl iodide); 99%
1
(83 mg) yield; no purification necessary; colorless oil. Ϫ H NMR
(CDCl3): δ ϭ 1.37 [d, 3 H, J ϭ 6.4 Hz, CH(OCH3)CH3], 1.50 (t, 3
H, J ϭ 7.0 Hz, OCH2CH3), 3.24 (s, 3 H, OCH3), 4.06Ϫ4.13 (m, 2
H, OCH2CH3), 4.68 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 6.71 [dd,
1 H, J ϭ 8.0 Hz, J ϭ 1.3 Hz, 3- or 5-H arom.), 7.05 (dd, 1 H, J ϭ
7.8 Hz, J ϭ 1.3 Hz, 3- or 5-H arom.), 7.28 (t, 1 H, J ϭ 7.9 Hz, 4-
H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 14.8 (q, OCH2CH3), 22.5
[q, CH(OMe)CH3], 56.7 (q, OCH3), 65.0 (t, OCH2CH3), 83.1 [d,
CH(OMe)Me], 91.4 (s, arom. C-2), 110.8 (d, arom. C-4), 118.7 (d,
arom. C-6), 129.4 (d, arom. C-5), 147.5 (s, arom. C-1), 157.1 (s,
arom. C-3). Ϫ IR (KBr): ν˜ ϭ 2984, 2932, 2825, 1586, 1566, 1456,
1392, 1372, 1345, 1315, 1283, 1263, 1155, 1113, 1054, 1011, 959,
871, 833, 693 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 307 [Mϩ ϩ H]
(9), 306 (58), 291 (100), 276 (6), 263 (24), 248 (7), 247 (7), 149 (8),
120 (19), 91 (13), 77 (9), 65 (8), 59 (18), 43 (9), 39 (2).
(S)-Bis(acetato-O)[2-(1-methoxyethyl)-6-methylphenyl]iodine (6a):
1
GP4; 88% (132 mg) yield; yellow solid. Ϫ H NMR (CDCl3): δ ϭ
1.47 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3], 1.95 (s, 3 H, OCOCH3),
1.96 (s, 3 H, OCOCH3), 2.76 (s, 3 H, CH3), 3.23 (s, 3 H, OCH3),
4.73 [q, 1 H, J ϭ 6.3 Hz, CH(OMe)Me], 7.43 (dd, 1 H, J ϭ 1.9 Hz,
J ϭ 6.9 Hz, 3- or 5-H arom.), 7.49 (dd, 1 H, J ϭ 2.2 Hz, J ϭ
7.9 Hz, 3- or 5-H arom.), 7.54 (t, 1 H, J ϭ 7.3 Hz, 4-H arom.). Ϫ
13C NMR (CDCl3): δ ϭ 20.2 (q, 2 C, OCOCH3), 24.0 [q, CH(O-
Me)CH3], 27.0 (q, CH3), 56.8 (q, OCH3), 83.1 [d, CH(OMe)Me],
125.0 (d, arom. C), 130.1 (d, arom. C), 130.8 (s, arom. C-1), 133.1
(d, arom. C), 141.0 (s, arom. C-6), 145.6 (s, arom. C-2), 176.2 (s,
OCOMe), 176.6 (s, OCOMe).
(S)-2-Iodo-1-(1-methoxyethyl)-3-(1-methylethoxy)benzene
(5h):
Starting material: 8. GP3 (using isopropyl iodide instead of methyl
iodide); 93% (108 mg) yield; no purification necessary; colorless oil.
Ϫ
(S)-Bis(acetato-O)[2-ethyl-6-(1-methoxyethyl)phenyl]iodine
(6b):
1H NMR (CDCl3):
δ ϭ 1.37 [d, 3 H, J ϭ 6.3 Hz,
GP4; 81% (112 mg) yield; colorless solid, m.p. 97Ϫ100 °C. Ϫ 1H
CH(OCH3)CH3], 1.40Ϫ1.42 [m, 6 H, OCH(CH3)2], 3.24 (s, 3 H, NMR (CDCl3): δ ϭ 1.34 (t, 3 H, J ϭ 7.5 Hz, CH2CH3), 1.48 [d, 3
OCH3), 4.57 (sept, 1 H, J ϭ 6.1 Hz, OCHMe2), 4.68 [q, 1 H, J ϭ H, J ϭ 6.3 Hz, CH(OMe)CH3], 1.95 (s, 3 H, OCOCH3), 1.96 (s, 3
6.3 Hz, CH(OMe)Me], 6.72 (dd, 1 H, J ϭ 8.1 Hz, J ϭ 1.3 Hz, 3-
H, OCOCH3), 3.05 (q, 2 H, J ϭ 7.5 Hz, CH2CH3), 3.23 (s, 3 H,
or 5-H arom.), 7.03 (dd, 1 H, J ϭ 7.7 Hz, J ϭ 1.4 Hz, 3- or 5-H OCH3), 4.74 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 7.44 (dd, 1 H,
arom.), 7.27 (t, 1 H, J ϭ 7.9 Hz, 4-H arom.). Ϫ 13C NMR (CDCl3):
δ ϭ 22.08 [q, OCH(CH3)2], 22.12 [q, OCH(CH3)2], 22.5 [q, CH(O-
J ϭ 2.0 Hz, J ϭ 7.3 Hz, 3- or 5-H arom.), 7.52 (dd, 1 H, J ϭ
2.0 Hz, J ϭ 7.7 Hz, 3- or 5-H arom.), 7.60 (t, 1 H, J ϭ 7.4 Hz, 4-
Me)CH3], 56.7 (q, OCH3), 72.1 (d, OCHMe2), 83.2 [d, CH(O- H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 15.2 (q, CH2CH3), 20.2 (q,
Me)Me], 93.1 (s, arom. C-2), 112.6 (d, arom. C-6), 118.7 (d, arom. OCOCH3), 20.3 (q, OCOCH3), 24.0 [q, CH(OMe)CH3], 33.6 (t,
1576
Eur. J. Org. Chem. 2001, 1569Ϫ1579

Chiral Hypervalent Organo-Iodine(III) Compounds
FULL PAPER
1
CH2CH3), 56.7 (q, OCH3), 83.3 [d, CH(OMe)Me], 125.2 (d, arom.
C-5), 128.8 (d, arom. C-4), 130.6 (s, arom. C-1), 133.2 (d, arom. C-
able from 5g; yellow oil. Ϫ H NMR (CDCl3): δ ϭ 1.42 [t, 6 H,
J ϭ 6.3 Hz, OCH(CH3)2], 1.47 [d, 3 H, J ϭ 6.5 Hz, CH(OMe)CH3],
3), 145.5 (s, arom. C-2 or C-6), 146.0 (s, arom. C-2 or C-6), 176.2 1.94 (s, 3 H, OCOCH3), 1.95 (s, 3 H, OCOCH3), 3.24 (s, 3 H,
(s, OCOMe), 176.5 (s, OCOMe). Ϫ [α]2D5 ϭ Ϫ87.8 (c ϭ 0.95,
CHCl3).
OCH3), 4.66Ϫ4.79 [m, 2 H, CH(OMe)Me and OCHMe2], 7.03 (dd,
1 H, J ϭ 8.5 Hz, J ϭ 1.2 Hz, 3- or 5-H arom.), 7.23 (dd, 1 H, J ϭ
7.8 Hz, J ϭ 1.2 Hz, 3- or 5-H arom.), 7.56 (t, 1 H, J ϭ 8.0 Hz, 4-
H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 20.3 (q, 2 C, OCOCH3), 21.8
[q, OCH(CH3)2], 21.9 [q, OCH(CH3)2], 23.8 [q, CH(OMe)CH3],
56.8 (q, OCH3), 72.8 (d, OCHMe2), 82.5 [d, CH(OMe)Me], 112.7
(d, arom. C-3), 119.0 (d, arom. C-5), 129.2 (s, arom. C-1), 134.4 (d,
arom. C-4), 147.1 (s, arom. C-6), 154.4 (s, arom. C-2), 176.5 (s,
OCOMe), 176.6 (s, OCOMe).
(S)-Bis(acetato-O)[2-(1-methoxyethyl)-6-(1-methylethyl)-
phenyl]iodine (6c): GP4; inseparable from 5c; colorless oil. Ϫ 1H
NMR (CDCl3): δ ϭ 1.35 [dd, 6 H, J ϭ 1.9 Hz, J ϭ 6.8 Hz,
CH(CH3)2], 1.48 [d, 3 H, J ϭ 6.5 Hz, CH(OMe)CH3], 1.95 (s, 3 H,
OCOCH3), 1.96 (s, 3 H, OCOCH3), 3.24 [s, 3 H, CH(OCH3)Me],
3.40 (sept, 1 H, J ϭ 6.7 Hz, CHMe2), 4.76 [q, 1 H, J ϭ 6.3 Hz,
CH(OMe)Me], 7.46 (dd, 1 H, J ϭ 1.8 Hz, J ϭ 7.4 Hz, 3- or 5-H
arom.), 7.54 (dd, 1 H, J ϭ 1.8 Hz, J ϭ 7.6 Hz, 3- or 5-H arom.),
7.62 (t, 1 H, J ϭ 7.5 Hz, 4-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ
20.2 (q), 24.0 (q), 24.1 (q), 24.4 (q), 39.0 (d, CHMe2), 56.8 (q,
OCH3), 83.6 [d, CH(OMe)Me], 125.7 (d, arom. C), 126.8 (d, arom.
C), 131.4 (s, arom. C-1), 133.2 (s, arom. C), 145.4 (s, arom. C-2),
150.3 (s, arom. C-6), 176.3 (s, OCOMe), 176.5 (s, OCOMe).
(S)-Bis(acetato-O)[2-(1,1-dimethylethoxy)-6-(1-methoxyethyl)-
phenyl]iodine (6i): GP4; 47% yield; yellow oil. Ϫ 1H NMR (CDCl3):
δ ϭ 1.47 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3], 1.55 [s, 9 H,
C(CH3)3], 1.95 (s, 3 H, OCOCH3), 1.96 (s, 3 H, OCOCH3), 3.24 (s,
3 H, OCH3), 4.69 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 7.28 (d, 2
H, J ϭ 8.1 Hz, 3- and 5-H arom.), 7.52 (t, 1 H, J ϭ 7.9 Hz, 4-H
arom.). Ϫ 13C NMR (CDCl3): δ ϭ 20.3 (q, 2 C, OCOCH3), 23.7
[q, CH(OMe)CH3], 29.0 [q, 3 C, C(CH3)3], 56.8 (q, OCH3), 82.5 (s,
CMe3), 82.7 [d, CH(OMe)Me], 117.9 (d, arom. C-5), 120.0 (d,
arom. C-3), 123.4 (s, arom. C-1), 133.7 (d, arom. C-4), 147.1 (s,
arom. C-2), 153.7 (s, arom. C-6), 176.4 (s, OCOMe), 176.6 (s,
OCOMe).
(S)-Bis(acetato-O)[3-(1-methoxyethyl)-1,1Ј-biphenyl-2-yl]iodine (6d):
GP4; 92% (248 mg) yield, inseparable from 5d; colorless solid. Ϫ
1H NMR (CDCl3): δ ϭ 1.52 [d, 3 H, J ϭ 6.3 Hz, CH(OMe)CH3],
1.90 (s, 3 H, COCH3), 1.93 (s, 3 H, COCH3), 3.28 [s, 3 H,
CH(OCH3)Me], 4.76 [q,
1 H, J ϭ 6.3 Hz, CH(OMe)Me],
7.37Ϫ7.50 (m, 6 H, H arom.), 7.69 (m, 2 H, H arom.). Ϫ 13C NMR
(CDCl3): δ ϭ 20.18 (q), 20.23 (q), 24.0 [q, CH(OMe)CH3], 56.9 (q,
OCH3), 83.3 [d, CH(OMe)Me], 126.1 (d, arom. C), 128.1 (d, arom.
C), 128.6 (d, arom. C), 129.0 (d, arom. C), 129.6 (s, arom. C-1),
130.0 (d, arom. C), 132.6 (d, arom. C), 142.7 (s), 145.4 (s, arom.
C-2 or C-6), 146.7 (s, arom. C-2 or C-6), 176.0 (s, OCOMe), 176.7
(s, OCOMe). Ϫ [α]2D5 ϭ Ϫ69.1 (c ϭ 0.63, CHCl3).
(S)-Bis(acetato-O)[2-(methoxymethoxy)-6-(1-methoxyethyl)-
1
phenyl]iodine (6j): GP4; 83% yield, colorless crystals. Ϫ H NMR
(CDCl3): δ ϭ 1.48 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3], 1.947 (s, 3
H, OCOCH3), 1.953 (s, 3 H, OCOCH3), 3.24 (s, 3 H, OCH3), 3.53
(s, 3 H, CH2OCH3), 4.72 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 5.32
(d, 1 H, J ϭ 6.9 Hz, CH2), 5.35 (d, 1 H, J ϭ 7.1 Hz, CH2),
7.29Ϫ7.34 (m, 2 H, 3- and 5-H arom.), 7.58 (t, 1 H, J ϭ 8.0 Hz,
4-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 20.2 (q, 2 C, OCOCH3),
23.7 [q, CH(OMe)CH3], 56.5 (q, OCH3), 56.8 (q, OCH3), 82.4 [d,
CH(OMe)Me], 95.1 (t, CH2), 114.0 (d, arom. C-5), 118.2 (s, arom.
C-1), 120.4 (d, arom. C-3), 134.5 (d, arom. C-4), 146.8 (s, arom. C-
2), 153.7 (s, arom. C-6), 176.8 (s, OCOMe), 177.0 (s, OCOMe).
(S)-Bis(acetato-O)[2-(benzyloxy)-6-(1-methoxyethyl)phenyl]iodine
(6f): GP4; 87% yield (determined by NMR), inseparable from 5f;
colorless solid. Ϫ 1H NMR (CDCl3): δ ϭ 1.48 [d, 3 H, J ϭ 6.4 Hz,
CH(OMe)CH3], 1.939 (s, 3 H, COCH3), 1.942 (s, 3 H, COCH3),
3.24 [s, 3 H, CH(OCH3)Me], 4.73 [q, 1 H, J ϭ 6.3 Hz, CH(O-
Me)Me], 5.28 (s, 2 H, CH2), 7.07 (dd, 1 H, J ϭ 8.2 Hz, J ϭ 1.1 Hz,
H arom.), 7.28 (dd, 1 H, J ϭ 7.9 Hz, J ϭ 1.1 Hz, H arom.),
7.45Ϫ7.33 (m, 5 H, H arom.), 7.55 (t, 1 H, J ϭ 7.9 Hz, 4-H arom.).
3-Hydroxy-2-iodoacetophenone:[47]
Compound
3f
(4.13 g,
11.7 mmol) was dissolved in CH2Cl2 (150 mL) and a solution of
BBr3 (1.55 mL, 16.1 mmol) in CH2Cl2 (20 mL) was slowly added
(over 20 min) at Ϫ70 °C. After 30 min, water (50 mL) was added
and after stirring for a further 60 min, the organic solvent was re-
moved in vacuo. The aqueous phase was extracted with tert-butyl
methyl ether (4 ϫ 30 mL) and then the combined organic phases
were extracted with 1  aq. NaOH (3 ϫ 20 mL). After acidification
of the combined aqueous extracts with 2  HCl, extraction with
tert-butyl methyl ether and subsequent evaporation the solvent gave
Ϫ
13C NMR (CDCl3): δ ϭ 20.3 (q, 2 C), 23.7 [q, CH(OMe)CH3],
56.8 (q, OCH3), 71.6 (t, CH2), 82.4 [d, CH(OMe)Me], 112.2 (d,
arom. C), 117.7 (s, arom. C), 119.7 (d, arom. C), 126.9 (d, 2 C,
arom. C), 128.2 (d, arom. C), 128.7 (d, 2 C, arom. C), 134.5 (d,
arom. C), 135.6 (s, arom. C-2), 147.1 (s, arom. C-6), 154.9 (s, arom.
C), 176.6 (s, OCOMe), 176.7 (s, OCOMe).
(S)-Bis(acetato-O)[2-ethoxy-6-(1-methoxyethyl)phenyl]iodine (6g):
GP4; 69% yield (determined by NMR), inseparable from 5g; yellow
1
1
the product; 93% (2.87 g), colorless crystals, m.p. 93Ϫ97 °C. Ϫ H
oil. Ϫ H NMR (CDCl3): δ ϭ 1.46Ϫ1.50 [m, 6 H, OCH2CH3 and
NMR (CDCl3): δ ϭ 2.82 (s, 3 H, CH3), 5.95 (s, 1 H, OH),
7.10Ϫ7.15 (m, 2 H), 7.29 (t, 1 H, J ϭ 8.1 Hz, 4-H arom.). Ϫ 13C
NMR (CDCl3): δ ϭ 29.2 (q, CH3), 83.7 (s, arom. C-2), 117.4 (d,
arom. C-4 or C-6), 121.0 (d, arom. C-4 or C-6), 129.7 (d, arom. C-
5), 143.7 (s, arom. C-3), 155.7 (s, arom. C-1), 201.1 (s, CO). Ϫ IR
(KBr): ν˜ ϭ 3192, 3080, 3050, 3000, 2911, 1673, 1589, 1567, 1453,
1418, 1358, 1324, 1294, 1233, 1175, 1015, 892, 782 cmϪ1. Ϫ MS
(EI, 70 eV): m/z (%) ϭ 263 [Mϩ ϩ H] (8), 262 (81), 247 (100), 219
(14), 191 (3), 92 (23), 63 (5), 43 (6), 39 (1).
CH(OMe)CH3], 1.94 (s, 3 H, OCOCH3), 1.95 (s, 3 H, OCOCH3),
3.23 (s, 3 H, OCH3), 4.19Ϫ4.26 (m, 2 H, OCH2CH3), 4.70 [q, 1 H,
J ϭ 6.4 Hz, CH(OMe)Me], 7.03 (dd, 1 H, J ϭ 8.2 Hz, J ϭ 1.3 Hz,
3- or 5-H arom.), 7.26 (dd, 1 H, J ϭ 7.8 Hz, J ϭ 1.3 Hz, 3- or 5-
H arom.), 7.57 (t, 1 H, J ϭ 7.9 Hz, 4-H arom.). Ϫ 13C NMR
(CDCl3): δ ϭ 14.5 (q, OCH2CH3), 20.3 (q, 2 C, OCOCH3), 23.8
[q, CH(OMe)CH3], 56.8 (q, OCH3), 65.9 (t, OCH2CH3), 82.4 [d,
CH(OMe)Me], 111.9 (d, arom. C-5), 119.3 (d, arom. C-3), 129.4 (s,
arom. C-1), 134.5 (d, arom. C-4), 147.0 (s, arom. C-2 or C-6), 155.3
(s, arom. C-2 or C-6), 176.5 (s, OCOMe), 176.7 (s, OCOMe). Ϫ IR
(CHCl3): ν˜ ϭ 2988, 2934, 2827, 1715, 1646, 1588, 1567, 1461, 1366,
2-Iodo-3-(methoxymethoxy)acetophenone:[48]
Powdered
KOH
(1.27 g, 19.3 mmol) was suspended in CH3CN (25 mL) and a solu-
tion of 3-hydroxy-2-iodoacetophenone (2.68 g, 10.2 mmol) in
CH3CN (15 mL) was added. After 1 h, methoxymethyl chloride
(1.0 mL, 13.2 mmol) was slowly added. After stirring for a further
1275, 1111, 1051, 1007, 909, 871 cmϪ1
.
(S)-Bis(acetato-O)[2-(1-methoxyethyl)-6-(1-methylethoxy)-
phenyl]iodine (6h): GP4; 69% yield (determined by NMR), insepar-
Eur. J. Org. Chem. 2001, 1569Ϫ1579
1577

U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest, T. Wirth
FULL PAPER
2.5 h, water (25 mL) was added. The aqueous phase was extracted
with tert-butyl methyl ether (3 ϫ 25 mL), and the combined or-
ganic phases were dried with MgSO4 and concentrated in vacuo.
Ϫ MS (EI, 70 eV): m/z (%) ϭ 298 (99), 283 (100), 155 (16), 141
(12), 128 (90), 115 (7), 86 (12), 77 (9), 43 (38). Ϫ HRMS: calcd.
for C12H11IO 297.9855; found 297.9860 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ56.0 (c ϭ
0.30, CHCl3).
1
Quantitative yield (3.21 g), light-brown oil. Ϫ H NMR (CDCl3):
δ ϭ 2.60 (s, 3 H, COCH3), 3.52 (s, 3 H, OCH3), 5.27 (s, 2 H, CH2),
6.97 (dd, 1 H, J ϭ 7.5 Hz, J ϭ 1.3 Hz), 7.11 (dd, 1 H, J ϭ 8.3 Hz,
J ϭ 1.3 Hz), 7.32 (t, 1 H, J ϭ 7.9 Hz, 4-H arom.). Ϫ 13C NMR
(CDCl3): δ ϭ 30.0 (q, CH3), 56.5 (q, OCH3), 84.1 (s, arom. C-2),
95.0 (t, CH2), 115.8 (d, arom. C-4 or C-6), 120.5 (d, arom. C-4 or
C-6), 129.5 (d, arom. C-5), 147.8 (s, arom. C-3), 156.2 (s, arom. C-
1), 203.6 (s, CO). Ϫ IR (KBr): ν˜ ϭ 3006, 2960, 2935, 2852, 2830,
1701, 1564, 1458, 1443, 1420, 1355, 1284, 1263, 1156, 1082, 1019,
968, 922 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 307 [Mϩ ϩ H] (7),
306 (44), 276 (5), 275 (7), 261 (7), 179 (2), 119 (5), 75 (6), 63 (10),
45 (100), 43 (27), 39 (2).
(S)-1-Iodo-2-(1-methoxyethyl)naphthalene: GP3; 87% (1.28 g) yield;
purification by flash chromatography on silica gel (tert-butyl
methyl ether/pentane, 1:5); colorless oil. Ϫ 1H NMR (CDCl3): δ ϭ
1.47 [d, 3 H, J ϭ 7.0 Hz, CH(OMe)CH3], 3.27 (s, 3 H, OCH3), 4.98
[q, 1 H, J ϭ 6.3 Hz, CH(OMe)Me], 7.48Ϫ7.62 (m, 3 H), 7.78 (d,
1 H, J ϭ 8.0 Hz), 7.84 (d, 1 H, J ϭ 8.0 Hz), 8.27 (d, 1 H, J ϭ
9.0 Hz). Ϫ 13C NMR (CDCl3): δ ϭ 22.5 (q, CH3), 56.8 (q, OCH3),
84.3 [d, CH(OMe)Me], 103.6 (s), 123.9 (d), 126.5 (d), 127.7 (d),
128.3 (d), 129.5 (d), 132.7 (d), 134.0 (s), 134.6 (s), 144.6 (s). Ϫ IR
(CHCl3): ν˜ ϭ 2960, 2930, 2855, 2330, 2250, 1460, 1366 cmϪ1. Ϫ
MS (EI, 70 eV): m/z (%) ϭ 312 (38), 297 (100), 282 (10), 154 (19),
141 (7), 126 (12), 76 (5), 59 (5), 43 (6). Ϫ HRMS: calcd. for
C13H13IO 312.0011; found 312.0008 [Mϩ]. Ϫ [α]2D5 ϭ Ϫ77.1 (c ϭ
0.69, CHCl3).
(S)-2-Iodo-3-(1-methoxyethyl)phenol (8): Compound 5j (1.36 g,
4.22 mmol) was dissolved in MeOH (25 mL) and treated with conc.
HCl (0.5 mL). After stirring for 75 min at 55 °C, the solvent was
removed in vacuo and the residue was redissolved in tert-butyl
methyl ether (40 mL). After washing with water (2 ϫ 15 mL), the
organic phase was extracted with 1  aq. NaOH (3 ϫ 15 mL).
After acidification of the combined aqueous extracts with 2  HCl,
extraction with tert-butyl methyl ether (3 ϫ 20 mL), drying of the
extracts with MgSO4, and evaporation the solvent gave the prod-
uct. Recrystallization from tert-butyl methyl ether/pentane gave
89% (1.05 g) yield; colorless crystals, m.p. 119Ϫ121 °C. Ϫ 1H NMR
(CDCl3): δ ϭ 1.38 [d, 3 H, J ϭ 6.4 Hz, CH(OMe)CH3], 3.25 (s, 3
H, OCH3), 4.51 [q, 1 H, J ϭ 6.4 Hz, CH(OMe)Me], 5.50 (s, 1 H,
OH), 6.94 (dd, 1 H, J ϭ 7.9 Hz, J ϭ 1.5 Hz, 3- or 5-H arom.), 6.99
(dd, 1 H, J ϭ 7.7 Hz, J ϭ 1.4 Hz, 3- or 5-H arom.), 7.25 (t, 1
H, J ϭ 7.8 Hz, 4-H arom.). Ϫ 13C NMR (CDCl3): δ ϭ 22.4 [q,
CH(OMe)CH3], 56.7 (q, OCH3), 83.2 [d, CH(OMe)Me], 90.4 (s,
arom. C-2), 113.9 (d, arom. C-4), 118.6 (d, arom. C-6), 129.9 (d,
arom. C-5), 146.4 (s, arom. C-1), 154.5 (s, arom. C-3). Ϫ IR (KBr):
ν˜ ϭ 3164, 2972, 2910, 2832, 1935, 1856, 1778, 1685, 1571, 1458,
1438, 1374, 1362, 1324, 1291, 1219, 1094, 1050, 1010, 988, 936, 841,
796 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 279 [Mϩ ϩ H] (7), 278
(45), 263 (100), 248 (18), 247 (15), 151 (5), 120 (21), 108 (7), 91
(13), 77 (9), 65 (11), 63 (10), 59 (21), 43 (11), 39 (10). Ϫ C9H11IO2
(278.09): calcd. C 38.87, H 3.99, O 11.51; found C 39.24, H 3.98,
O 11.74.
(S)-Bis(acetato-O)[2-(1-methoxyethyl)naphthalen-1-yl]iodine: GP4;
81% (560 mg) yield; inseparable from (S)-1-iodo-2-(1-methoxye-
1
thyl)naphthalene; yellow oil. Ϫ H NMR (CDCl3): δ ϭ 1.57 [d, 3
H, J ϭ 6.4 Hz, CH(OH)CH3)], 1.89 (s, 3 H, COCH3), 1.90 (s, 3 H,
COCH3), 3.26 (s, 3 H, OCH3), 4.98 [q, 1 H, J ϭ 6.3 Hz,
CH(OH)CH3], 7.50Ϫ8.30 (m, 6 H). Ϫ 13C NMR (CDCl3): δ ϭ
20.1 (q, OCOCH3), 20.2 (q, OCOCH3), 23.8 [q, CH(OMe)CH3],
56.9 (q, OCH3), 84.0 [d, CH(OMe)Me], 103.5 (s), 124.0 (d), 127.5
(d), 128.2 (d), 128.9 (d), 129.3 (d), 130.5 (s), 131.6 (s), 134.0 (d),
144.9 (s), 176.5 (s, OCOMe), 176.6 (s, OCOMe).
Acknowledgments
Funding was provided by the Stipendienfonds der Basler Chem-
ischen Industrie (scholarship for U. H. H.), the Research Corpora-
tion (Cottrell College Science Awards CC3894, CC4569, and
DS0261), Albion College (A. N. F.), and the Schweizer Na-
tionalfonds.
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[3]
1-(1-Iodonaphthalen-2-yl)ethanone: 1-Bromonaphthalene was used
in GP1. 61% (1.80 g) yield, pale-brown solid. Ϫ 1H NMR (CDCl3):
δ ϭ 2.66 (s, 3 H, COCH3), 7.26 (d, 1 H, J ϭ 8.3 Hz), 7.47Ϫ7.62
(m, 2 H), 7.73 (dd, 1 H, J ϭ 8.0 Hz, J ϭ 1.4 Hz), 7.80 (d, 1 H, J ϭ
8.3 Hz), 8.23 (d, 1 H, J ϭ 8.4 Hz). Ϫ 13C NMR (CDCl3): δ ϭ 30.3
(q, COCH3), 95.9 (s, arom. C-1), 123.1 (d), 127.5 (d), 128.3 (d),
128.5 (d), 129.3 (d), 132.8 (d), 133.7 (s), 134.1 (s), 145.5 (s, arom.
C-2), 204.5 (s, CO). Ϫ IR (CHCl3): ν˜ ϭ 3125, 2975, 2937, 2850,
2250, 1785, 1485, 1350 cmϪ1. Ϫ MS (EI, 70 eV): m/z (%) ϭ 296
(80), 281 (100), 253 (32), 141 (11), 126 (59), 115 (6), 74 (9), 63 (6),
43 (17). Ϫ HRMS: calcd. for C12H9IO 295.9698; found 295.9700
[Mϩ].
[4]
[5]
[6]
[7]
[8]
[9]
E. B. Merkushev, A. N. Novikov, S. S. Makarchenko, A. S.
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[12]
(S)-1-(1-Iodonaphthalen-2-yl)ethanol: GP2; 84% (1.52 g) yield; or-
1
ange oil; 97% ee.[49] Ϫ H NMR (CDCl3): δ ϭ 1.52 [d, 3 H, J ϭ
[13]
6.4 Hz, CH(OH)CH3], 2.38 (d, 1 H, J ϭ 2.2 Hz, OH), 5.47 [dq, 1
H, J ϭ 6.3 Hz, J ϭ 2.5 Hz, CH(OH)CH3], 7.44Ϫ7.57 (m, 2 H),
7.68 (d, 1 H, J ϭ 8.6 Hz), 7.75 (d, 1 H, J ϭ 8.0 Hz), 7.81 (d, 1 H,
J ϭ 8.5 Hz), 8.25 (d, 1 H, J ϭ 7.8 Hz). Ϫ 13C NMR (CDCl3): δ ϭ
23.7 (q, CH3), 75.1 [d, CH(OH)Me], 102.1 (s), 123.7 (d), 126.2 (d),
127.6 (d), 128.1 (d), 129.2 (d), 132.6 (d), 133.7 (s), 134.3 (s), 146.4
[14]
[15]
[16]
[17]
(s). Ϫ IR (CHCl3): ν˜ ϭ 3602, 3400, 3065, 2977, 2925, 2250 cmϪ1
.
1578
Eur. J. Org. Chem. 2001, 1569Ϫ1579

Chiral Hypervalent Organo-Iodine(III) Compounds
FULL PAPER
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1998.
The enantiomeric excess was determined by HPLC: Chiralcel
OD, 2-propanol/hexane (5:95), 220 nm.
The absolute configuration of 4a was determined by dehalo-
genation and comparison of the optical rotation of the product
with that of the known dehalogenated compound: K. Naka-
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[21]
[22]
[23]
[24]
[25]
[26]
[27]
All attempts to debenzylate the phenol 5f failed, necessitating
the use of a new protecting group that could be easily removed
following the methylation step. The benzyl ether as well as the
MOM ether were also carried through the reaction sequence
to give two additional ortho-alkyloxy iodine(III) compounds 1f
and 1j.
A. Armstrong, J. Brackenridge, R. F. W. Jackson, J. M. Kirk,
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[42]
[43]
[28]
[29]
Reactions of iodine(III) tosylates have typically been found to
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on a large scale. Reactions using compounds 1 were performed
on an analytical scale and were only analyzed by chiral HPLC.
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[44]
[45]
[46]
[47]
[48]
[49]
The enantiomeric excess was determined by HPLC: Chiralcel
OD, 2-propanol/hexane (1:19), 220 nm.
The enantiomeric excess was determined by HPLC: Chiralcel
OD, 2-propanol/hexane (3:97), 254 nm.
The enantiomeric excess was determined by HPLC: Chiralcel
OD, 2-propanol/hexane (10:90), 220 nm.
A. Sogawa, M. Tsukayama, H. Nozaki, M. Nakayama, Hetero-
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[31]
[32]
[33]
1557Ϫ1563.
[34]
The absolute configuration of 1-(1-iodonaphthalen-2-yl)-
ethanol was determined by dehalogenation and comparison of
the optical rotation of the product with that of the commer-
cially available dehalogenated compound. The enantiomeric ex-
cess was determined by HPLC: Chiralcel OD, 2-propanol/hex-
ane (10:90), 220 nm.
[35]
W. Nakanishi, S. Hayashi, H. Kihara, J. Org. Chem. 1999, 64,
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[36]
´
´
M. A. Carroll, S. Martın-Santamarıa, V. W. Pike, H. S. Rzepa,
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Received October 24, 2000
[37]
We also tested the HF/LANL2DZ method, but found that it
[O00533]
Eur. J. Org. Chem. 2001, 1569Ϫ1579
1579