New chiral hypervalent iodine compounds in asymmetric synthesis

Article abstract of DOI:10.1021/jo980475x

The synthesis of new chiral hypervalent iodine compounds 3 and their use in asymmetric oxidative functionalizations are described. The substituents in the chiral moiety and the stereoelectronic properties of the reagents 3, as well as the reaction conditions, have been optimized. Chiral hypervalent iodine compounds 3 have been investigated in the asymmetric dioxytosylation of styrène and in the a-oxytosylation of propiophenone as test reactions. X-ray structural analysis of some reagents shows an interaction between the chiral moiety and the iodine resulting in stereoselectivities up to 53% ee in the products.

Full text of DOI:10.1021/jo980475x

7674
J . Org. Chem. 1998, 63, 7674-7679
New Ch ir a l Hyp er va len t Iod in e Com p ou n d s in Asym m etr ic
Syn th esis
Urs H. Hirt,† Bernhard Spingler,‡ and Thomas Wirth*,†
Institut fu¨r Organische Chemie der Universita¨t Basel, St. J ohanns-Ring 19, CH-4056 Basel, Switzerland,
and Institut fu¨r Anorganische Chemie der Universita¨t Basel, Labor fu¨r Kristallographie, Spitalstrasse 51,
CH-4056 Basel, Switzerland
Received March 12, 1998
The synthesis of new chiral hypervalent iodine compounds 3 and their use in asymmetric oxidative
functionalizations are described. The substituents in the chiral moiety and the stereoelectronic
properties of the reagents 3, as well as the reaction conditions, have been optimized. Chiral
hypervalent iodine compounds 3 have been investigated in the asymmetric dioxytosylation of styrene
and in the R-oxytosylation of propiophenone as test reactions. X-ray structural analysis of some
reagents shows an interaction between the chiral moiety and the iodine resulting in stereoselec-
tivities up to 53% ee in the products.
Sch em e 1
In tr od u ction
Hypervalent iodine compounds have been known for
more than a century, but only recently they were found
to be versatile and mild reagents for various oxidation
and oxygenation reactions. They can substitute for
various toxic and heavy metal containing reagents, which
have been used frequently for oxidative transformations
in former times. The class of hypervalent iodine com-
pounds has found broad application in various natural
product synthesis and for the preparation of complex
target molecules, because of the mild reaction conditions
and the high selectivities obtained with these reagents.1
Beside the oxidation of alcohols with the Dess-Martin
periodinane to the corresponding carbonyl compounds
also other hypervalent iodine compounds such as diac-
etoxyiodobenzene,2 iodosobenzene, or hydroxy(tosyloxy)-
iodobenzene [PhI(OH)OTs, Koser’s reagent] and its ana-
logues have found many applications in organic synthesis.
Hypervalent iodine compounds can be used not only as
oxidants but also as electrophilic reagents to functionalize
CdC bonds. Subsequent reactions such as iodolacton-
izations,3 dioxytosylations,4 or R-oxytosylations of ke-
tones5 are yielding versatile building blocks for further
synthesis. Recently it was shown that iodonium salts can
be used for C-C bond formations as well.1b,6 In some of
these reactions new stereogenic centers are created. The
reactions of electrophilic iodine species with double bonds
have been shown to proceed via a SN2 type mechanism
(Scheme 1).7
Chiral hypervalent iodine compounds should therefore
be promising reagents for asymmetric variants of these
reactions. Until now only few chiral hypervalent iodine
compounds have been synthesized.8 Most of them are
compounds of type 1 bearing a chiral substituent on the
iodine. They have only been used in asymmetric oxida-
tions to convert sulfides into sulfoxides.9 Chiral hyper-
valent iodine compounds of type 2 and 3, in which the
chiral moiety is fixed in the ortho-position to the iodine,
were recently described by us10 and others11 (Chart 1).
Compounds of type 3 with a protected alcohol as chiral
moiety beside the iodine atom are readily accessible. The
oxygen has a strong interaction with the iodine which
was shown by X-ray structural analysis. We described
for the first time that hypervalent iodine compounds 3
can be employed in asymmetric functionalizations of
alkenes and ketones.10
† Institut fu¨r Organische Chemie.
‡ Institut fu¨r Anorganische Chemie, Labor fu¨r Kristallographie.
(1) Reviews: (a) Stang, P. J . Chem. Rev. 1996, 96, 1123-1178. (b)
Varvoglis, A. Hypervalent Iodine In Organic Synthesis; Academic
Press: London, 1997. (c) Varvoglis, A. Tetrahedron 1997, 53, 1179-
1255.
(8) (a) Merkushev, E. B.; Novikov, A. N.; Makarchenko, S. S.;
Moskal’chuk, A. S.; Glushkova, V. V.; Kogai, T. I.; Polyakova, L. G. J .
Org. Chem. USSR (Engl. Transl.) 1975, 11, 1246-1249. (b) Imamoto,
T.; Koto, H. Chem. Lett. 1986, 967-968. (c) Hatzigrigoriou, E.;
Varvoglis, A.; Bakola-Christianopoulou, M. J . Org. Chem. 1990, 55,
315-318. (d) Ray, D. G.; Koser, G. F. J . Am. Chem. Soc. 1990, 112,
5672-5673. (e) Ochiai, M.; Takaoka, Y.; Masaki, Y.; Nagao, Y.; Shiro,
M. J . Am. Chem. Soc. 1990, 112, 5677-5678. (f) Ray, D. G.; Koser, G.
F. J . Org. Chem. 1992, 57, 1607-1610.
(2) Kirschning, A. J . Prakt. Chem. 1998, 340, 184-186.
(3) Moriarty, R. M.; Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.; Prakash,
O. Tetrahedron Lett. 1990, 31, 201-204.
(4) Rebrovic, L.; Koser, G. F. J . Org. Chem. 1984, 49, 2462-2472.
(5) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach,
R. H. J . Org. Chem. 1982, 47, 2487-2489.
(9) Koser, G. F.; Kokil, P. B.; Shah, M. Tetrahedron Lett. 1987, 28,
5431-5434.
(6) Moriarty, R. M.; May, E. J .; Guo, L.; Prakash, O. Tetrahedron
Lett. 1998, 39, 765-766.
(10) Wirth, T.; Hirt, U. H. Tetrahedron: Asymmetry 1997, 8, 23-
26.
(11) Rabah, G. A.; Koser, G. F. Tetrahedron Lett. 1996, 37, 6453-
6456.
(7) Hembre, R. T.; Scott, C. P.; Norton, J . R. J . Org. Chem. 1987,
52, 3650-3654.
10.1021/jo980475x CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/01/1998

Chiral Hypervalent Iodine Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7675
Ch a r t 1
Sch em e 3a
Sch em e 2
a
Key: (a) N,N,N′,N′-TMEDA, n-BuLi, I2, 22%; (b) NaH, MeI,
72%; (c) (-)-Ipc2BCl, 92%; (d) NaH, MeI, 92%; (e) t-BuLi, I2, 74%;
(f) (i) NaBO3‚4H2O, AcOH, 73%, (ii) p-TsOH‚H2O, 95%.
Resu lts a n d Discu ssion
Hypervalent iodine compounds are electrophilic species
and can attack double bonds as shown in Scheme 1. We
confirmed this mechanism by converting either (E)- or
(Z)-2-pentene with the hypervalent iodine compounds 3
into syn- or anti-2,3-bis(tosyloxy)pentane selectively. A
clean SN2 type mechanism is the prerequisite for the
development of asymmetric reactions with chiral hyper-
valent iodine compounds. For these investigations we
chose the dioxytosylation of styrene and the R-oxytosy-
lation of propiophenone as test reactions (Scheme 2). In
these reactions new stereocenters are created and the
products of these reactions, 1,2-bis(tosyloxy)phenylethane
(4) and R-(tosyloxy)propiophenone (5), are compounds
containing asymmetric carbon atoms.
Employing chiral hypervalent iodine compounds of
type 3 as electrophilic reagents, we observe a facial
selectivity upon reaction with alkenes and ketones and
enantiomerically enriched products 4 and 5 are gener-
ated. With compound 3a (R ) Et, R′ ) Me, R′′ ) H) we
reported asymmetric reactions yielding 4 and 5 with 21%
ee and 15% ee, respectively.10 Because of the low
stereoselectivities we tried to optimize the chiral hyper-
valent iodine compounds of type 3. First we focused our
interest on the substituents R and R′ in the chiral moiety
of 3. In a second step we then varied the substituent R′′
to understand its influence on the electronic properties
of the reagent. A further target was the optimization of
the reaction conditions to obtain better yields and ste-
reoselectivities.
We chose to synthesize the most simple compound 3b
with R ) R′ ) Me and R′′ ) H. The synthesis of this
compound starts with an ortho-deprotonation of (S)-1-
phenylethanol (6) with n-BuLi followed by introduction
of iodine yielding compound 7a . The hydroxy group was
methylated, and the precursor 7b was oxidized with
sodium perborate in glacial acetic acid.12 Subsequent
treatment with p-toluenesulfonic acid monohydrate leads
to the hypervalent iodine compound 3b. An alternative
way to obtain 3b is chiral reduction13 of 2-bromoac-
etophenone (8) followed by methylation. After the bro-
mine-iodine exchange compound 7b can be oxidized as
described above. Because of the inefficent ortho-depro-
F igu r e 1. X-ray structure of 3b.
tonation of 6, the second route leads to a higher overall
yield of 3b (43%) (Scheme 3).
The hypervalent iodine compound 3b can be purified
only by recrystallization. The X-ray structural analysis
shows a strong interaction between the oxygen of the
methoxy group and the iodine (Figure 1). The distance
between these two atoms (2.47 Å) is much less than the
distance from the iodine to the oxygen of the tosyloxy
group (2.82 Å). Because the hydroxy group is tightly
bound to the iodine (1.94 Å), we prefer writing the
structures of these hypervalent iodine compounds as salts
of p-toluenesulfonic acid.
Compound 3b shows a similar T-shaped structure like
the Koser reagent.14 Interestingly, the oxygen of the
methoxy group is now replacing the tosylate leading to
an oxygen-iodine-oxygen angle of 166° (Koser reagent:
179°).14 Compared with the X-ray structural analysis of
3a , the hypervalent iodine compound 3b shows a very
similar geometry at the iodine atom. With 3b the
products 4 and 5 were obtained with 33% ee and 15%
ee, respectively.
Compared to 3a , the smaller substituent R ) Me in
3b shows a higher enantiomeric excess in the product 4.
If R′ is changed into a larger substituent in 3c (R ) Me,
R′ ) Et), the product 4 is obtained with only 21% ee.
With the optimized chiral moiety in 3b (R ) R′ ) Me),
we started to synthesize derivatives with methoxy groups
(R′′ ) OMe) in the ortho-, meta-, and para-positions with
respect to iodine.
Two synthetic routes to the chiral hypervalent iodine
compound 3d with an ortho-methoxy substituent have
(12) McKillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299-3306.
(13) Resnick, S. M.; Torok, D. S.; Gibson, D. T. J . Org. Chem. 1995,
60, 3546-3549.
(14) Koser, G. F.; Wettach, R. H.; Troup, J . M.; Frenz, B. A. J . Org.
Chem. 1976, 41, 3609-3611.

7676 J . Org. Chem., Vol. 63, No. 22, 1998
Hirt et al.
Sch em e 4a
Sch em e 5a
a
Key: (a) (-)-Ipc2BCl, 13a , 92%, and 13b, 89%; (b) NaH, MeI,
14a , 90%, and 14b, 93%; (c) (i) NaBO3‚4H2O, (ii) p-TsOH‚H2O,
3e, 83%, and 3f, 37%.
Ta ble 1. Dioxytosyla tion of Styr en e w ith Ch ir a l
Hyp er va len t Iod in e Com p ou n d s 3
entry reagent
R
R′
R′′
temp (°C) ee of 4 (%)24
1
2
3
4
5
6
7
3a
3b
3b
3c
3d
3e
3f
Et
Me
H
H
H
H
25
25
-30
25
-30
-30
-30
21
26
33
21
53
37
42
a
Key: (a) (-)-Ipc2BCl, 80%; (b) N,N,N′,N′-TMEDA, n-BuLi, I2,
Me Me
Me Me
Me Et
Me Me 6-OMe
Me Me 5-OMe
Me Me 4-OMe
22%; (c) NaH, MeI, 80%; (d) NaBO3‚4H2O, AcOH, 87%; (e) (-)-
Ipc2BCl, 91%; (f) p-TsOH‚H2O, 95%.
Ta ble 2. r-Oxytosyla tion of P r op iop h en on e w ith Ch ir a l
Hyp er va len t Iod in e Com p ou n d s 3 a t 0 °C
entry
reagent
R
R′
R′′
ee of 5 (%)25
1
2
3
4
5
3a
3b
3d
3e
3f
Et
Me
Me
Me
Me
Me
H
H
10
15
28
26
15
Me
Me
Me
Me
6-OMe
5-OMe
4-OMe
F igu r e 2. X-ray structure of 10d .
substituted 2-iodoacetophenones 12a (5-OMe)19 and 12b
(4-OMe)20 were used to prepare the chiral alcohols 13a
(92% ee) and 13b (91% ee) by reduction with (-)-B-
chlorodiisopinocampheylborane.21 After methylation the
compounds 14a ,b were oxidized to 3e,f, respectively
(Scheme 5).
been worked out. Reduction of 3-methoxyacetophenone
(9) with (-)-B-chlorodiisopinocampheylborane leads to
the chiral alcohol 10a (96% ee).15 Iodine is introduced
by ortho-lithiation,16 and after methylation 10c is ob-
tained. Oxidation of the iodine generates the diacetoxy-
iodo derivative 10d , which is then transformed into the
hypervalent iodine compound 3d . A better synthetic
access can be achieved by the use of 11 as easily
accessible precursor.17 After chiral reduction (96% ee)
and methylation the iodine is oxidized and 3d is obtained
in 60% overall yield (Scheme 4).
The methoxy-substituted chiral hypervalent iodine
compounds 3d -f have subsequently been employed in
the reactions mentioned above. The stereoselectivities
obtained with these reagents are in all cases higher than
with compounds 3b having no further substituents. The
electronic properties in the reagents 3d -f are not neg-
ligible and do indeed have an influence on the stereose-
lectivity. As it can be seen from Tables 1 and 2, the
dioxytosylation of styrene as well as the R-oxytosylation
of propiophenone proceeds with the highest stereoselec-
tivities using the chiral hypervalent iodine compound 3d .
The compounds 4 and 5 were obtained with 53% ee and
28% ee, respectively. The results indicate that the
methoxy group has additional steric effects on the reac-
tion course, which seems to play an important role. The
influence of the methoxy group in the ortho- and para-
positions to the iodine is larger than in the meta-position.
The diacetoxyiodo derivative 10d was purified by
recrystallization from hexane. The X-ray structural
analysis shows the same shape around the iodine as it
is found in diacetoxyiodobenzene (Figure 2).18 It is
interesting that the oxygen of the chiral side chain does
not interact with the iodine. The coordination sphere
around the iodine is pentagonal planar like in diacetoxy-
iodobenzene. The reagent 3d prepared from 10d is an
amorphous solid, and no crystals suitable for an X-ray
structural analysis could be obtained.
The synthetic strategy of the chiral hypervalent iodine
compounds with methoxy substituents in the meta- and
para-positions to the iodine is different from the synthesis
of 3d . The ortho-deprotonation of the corresponding
alcohols could not be achieved. Therefore the methoxy-
1
The H NMR of 3d shows broad and shifted signals for
the methoxy group in position 3 which might indicate
an interaction between the oxygen of the methoxy group
and the iodine.
(19) Hellwinkel, D.; Bohnet, S. Chem. Ber. 1987, 120, 1151-1174.
(20) Compound 12b was synthesized from 2-amino-5-methoxyac-
etophenone: (a) Fu¨rstner, A.; J umbam, D. N.; Seidel, G. Chem. Ber.
1994, 127, 1125-1130. For spectroscopic data see: (b) Buchwald, S.
L.; Watson, B. T.; Lum, R. T.; Nugent, W. A. J . Am. Chem. Soc. 1987,
109, 7137-7141.
(21) Srebnik, M.; Ramachandran, P. V.; Brown, H. C. J . Org. Chem.
1988, 53, 2916-2920. Brown, H. C.; Chandrasekharan, J .; Ramachan-
dran, P. V. J . Am. Chem. Soc. 1988, 110, 1539-1546.
(15) Zhao, M.; King, A. O.; Larsen, R. D.; Verhoeven, T. R.; Reider,
P. J . Tetrahedron Lett. 1997, 38, 2641-2644. Handa, S.; J ones, K.;
Newton, C. G. J . Chem. Soc., Perkin Trans. 1 1995, 1623-1633.
(16) Meyer, N.; Seebach, D. Chem. Ber. 1980, 113, 1304-1319.
(17) Barr, K. J .; Watson, B. T.; Buchwald, S. L. Tetrahedron Lett.
1991, 32, 5465-5468.
(18) Alock, N. W.; Countryman, R. M.; Esperas, S.; Sawyer, J . F. J .
Chem. Soc., Dalton Trans. 1979, 854-860.

Chiral Hypervalent Iodine Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7677
Ta ble 3. Solven t Va r ia tion in th e Dioxytosyla tion of
Ch a r t 2
Styr en e a t 25 °C
ee of 4
ee of 4
solvent
(%)
solvent
(%)
dichloromethane
1,2-dichloroethane
1,2-dimethoxyethane
26
16
7
trichloroethene
a,a,a-trifluorotoluene
ethyl acetate
20
23
16
a
No reaction took place with the solvents chloroform, carbon
tetrachloride, acetonitrile, ethylene glycol, dimethyl sulfoxide, and
dimethyl formamide.
The reaction of (S)-configured compounds 3 with
styrene yields the dioxytosylate 4 with (R)-configura-
tion.22 This corresponds to a re attack of styrene as
shown in the intermediate 15a + (Chart 2). The diaster-
eomeric intermediate 15b+ can also gain from π-stacking
but is assumed to be higher in energy as we calculated
it for the corresponding seleniranium ions.23
The dioxytosylation of styrene with hypervalent iodine
compounds of type 3 is very efficient. Full conversion of
the hypervalent iodine compound is usually observed,
and 1,1-ditosyloxy-2-phenylethane is the only (known)
byproduct isolated in small amounts.4 Following puri-
fication of the crude reaction mixture on silica gel we
isolated 4 in 75% yield.
tigation of other asymmetric reactions as well as modified
chiral hypervalent iodine compounds are in progress.
Exp er im en ta l Section
Gen er a l Met h od s. All reactions were performed under
1
argon with anhydrous solvents. The H and 13C NMR spectra
were measured in CDCl3 using TMS as an internal standard
at 300 and 75 MHz, respectively. Melting points are uncor-
rected.
All starting materials are commercially available and used
without further purification. Compounds 1117 and 1319 were
synthesized according to literature procedures.
Gen er a l P r oced u r es. GP 1. Chiral reductions of ac-
etophenone derivatives with (-)-B-chlorodiisopinocampheyl-
borane were carried out as described.21 To a solution of 1.1
equiv of (-)-B-chlorodiisopinocampheylborane in THF (1.0 M)
at -25 °C the acetophenone derivative dissolved in THF was
added. After the reaction (15-25 h) the solution was allowed
to warm to room temperature and the solvent was removed.
The residue was dissolved in diethyl ether, and 2.2 equiv of
diethanolamine was added. After 2 h of stirring at room
temperature, the mixture was filtered through Celite and
concentrated in vacuo. The products were purified by flash-
chromatography on silica gel.
The R-oxytosylation of propiophenone is less efficient
than the dioxytosylation of styrene. Up to 28% ee is
obtained, and the product 5 is isolated in about 35% yield.
It was already shown that compound 5 has the (R)-
configuration.10 It is known that some ketones show low
conversions in the reaction with the Koser reagent.5 The
enantiomeric excess depends on the hypervalent iodine
compound 3. Probably steric effects do not play an
important role because of the almost same results using
the hypervalent iodine compounds 3d ,e (Table 2, entries
3 and 4).
During our work using the Koser reagent and its
analogues in oxidative functionalizations we observed a
dramatic increase of the reaction rate after the addition
of a little amount of p-toluenesulfonic acid monohydrate
to the reaction mixture of the hypervalent iodine com-
pound and the alkene. The reactions at room tempera-
ture are finished after approximately 4 h and can now
be performed even at -30 °C. Only a small amount of
the additional p-toluenesulfonic acid is dissolved. We
suspect that also the Koser reagent and its analogues
are dissociated only partially in the dichloromethane
solution and that the additional p-toluenesulfonic acid
is used to attack the activated double bonds.
GP 2. Sodium hydride (4 equiv) (55-65% in oil) was washed
with pentane (4×). N,N-Dimethylformamide was added to
obtain a 0.8 M solution. To this mixture 1 equiv of the alcohol
was added at 0 °C. After 1 h of stirring at room temperature,
the mixture was cooled to 0 °C and methyl iodide (4.2 equiv)
was added. After an additional 3-5 h at room temperature,
water was added carefully. The solution was extracted with
tert-butyl methyl ether (3×), the combined organic phases were
washed with brine (3×) and dried with MgSO4.
GP 3.12 A 0.1 M solution of an aryliodine in glacial acetic
acid was heated to 50-65 °C. To this solution 10 equiv of
sodium perborate tetrahydrate was added slowly. The reaction
mixture was stirred for 3-4 h. The conversion was monitored
by TLC. After completion of the reaction, the reaction mixture
was extracted quickly with a small amount of methylene
chloride (2×) and dried with MgSO4. The solvent was removed
in vacuo. The diacetoxyiodo derivatives can be either purified
by washing with pentane or by dissolving the crude product
in acetonitrile and washing with pentane.
The nature of the solvent seems to play also an
important role. We screened a variety of solvents as
shown in Table 3 using the chiral hypervalent iodine
compound 3b. The solvent of choice is dichloromethane
which was employed in all the reactions mentioned above.
GP 4. The diacetoxyiodobenzene derivative was dissolved
in acetonitrile (∼0.9 M). To this solution exactly 1 equiv of
p-toluenesulfonic acid monohydrate in acetonitrile (0.4 M) was
added. After the solution was stirred for 1 h the solvent was
removed in vacuo. Some of the products were found to be
instable and therefore characterized only by NMR spectros-
copy.
GP 5. The alcohol was dissolved in pentane (0.55 M), and
2 equiv of N,N,N′,N′-tetramethylethylenediamine was added.
At 0 °C 2 equiv of n-butyllithium (1.6 M in hexane) was added.
The first 1 equiv was added slowly while the second was added
quickly. The mixture was refluxed for 12 h, and then THF
was added to dissolve the precipitate. After the solution was
cooled to 0 °C, 1.2 equiv of iodine in THF (1 M) was added.
After additional stirring for 3 h the reaction mixture was
diluted with aqueous sodium thiosulfate and extracted with
tert-butyl methyl ether (3×). The product was purified by flash
chromatography on silica gel.
Con clu sion
New chiral hypervalent iodine compounds have been
developed, and their use in asymmetric oxygenation
reactions has been described. With sterically and elec-
tronically modified reagents of type 3, the reaction
products were obtained with up to 53% ee. The inves-
(22) The absolute configuration was determined by comparison with
(S)-4, which was synthesized from (S)-mandelic acid by reduction and
tosylation: Dale, J . A.; Mosher, H. S. J . Org. Chem. 1970, 35, 4002-
4003.
(23) Wirth, T.; Fragale, G.; Spichty, M. J . Am. Chem. Soc. 1998,
120, 3376-3381.

7678 J . Org. Chem., Vol. 63, No. 22, 1998
Hirt et al.
Dioxytosyla tion a n d r-Oxytosyla tion . The chiral hy-
pervalent iodine compound 3 (0.5 mmol) and p-toluenesulfonic
acid monohydrate (0.6 mmol, 115 mg) were dissolved in
CH2Cl2 (3 mL). For the dioxytosylation styrene (0.6 mmol, 62
mg) and for the R-oxytosylation propiophenone (1.2 mmol, 160
mg) was added at the temperature indicated in Tables 1 and
2. The solution was stirred at this temperature for 4-24 h.
After filtration over silica gel the solvent was removed in vacuo
and the residue purified by flash chromatography on silica gel.
(S)-Hydr oxy(4-m eth ylben zen esu lfon ato-KO)[2-(1-m eth -
oxyeth yl)p h en yl]iod in e (3b). GP4: yield 95% (1.12 g);
recrystallized from acetonitrile; colorless crystals; mp 124-
126 °C; [R]2D5 ) 16.3 (c ) 1.045, CHCl3); 1H NMR δ 1.49 (d,
3H, J ) 6.6 Hz), 2.36 (s, 3H), 3.68 (s, 3H), 4.75 (q, 1H, J ) 6.4
Hz), 7.1 (d, 2H, J ) 7.8 Hz), 7.29 (d, 1H, J ) 1.5 Hz, J ) 7.5
Hz), 7.4-7.6 (m, 2H), 7.74 (d, 2H, J ) 8.1 Hz), 7.83 (d, 1H, J
) 7.8 Hz); 13C NMR δ 20.6, 21.3, 59.3, 82.1, 113.3, 126.1, 127.5,
127.9, 128.8, 130.9, 131.1, 140.1, 140.2, 141.6; IR (CHCl3) ν
ether/pentane): yield 74% (4.31 g). GP2: deprotonation, 1 h;
methylation, 4 h; 72% (189 mg) yield; purification by flash
chromatography on silica gel (1:10 tert-butyl methyl ether/
pentane); [R]2D5 ) -42.0 (c ) 1.04, CHCl3); H NMR δ 1.37 (d,
1
3H, J ) 6.4 Hz), 3.24 (s, 3H), 4.53 (q, 1H, J ) 6.3 Hz), 6.95
(m, 1H), 7.36 (dt, 1H, J ) 1.0 Hz, J ) 7.4 Hz), 7.42 (dd, 1H, J
) 2.0 Hz, J ) 7.8 Hz), 7.79 (dd, 1H, J ) 1.1 Hz, J ) 7.9 Hz);
13C NMR δ 22.6, 56.7, 82.8, 98.1, 126.5, 128.7, 129.0, 139.3,
145.4; MS (EI) m/z (relative intensity) 262 (19), 247 (100), 231
(9), 105 (6), 104 (12), 91 (6), 77 (11); HRMS M+ m/e 261.9859,
calcd for C9H11IO m/e 261.9855; IR (CHCl3) ν 2981, 2931, 1564,
1464, 1454, 1435, 1372, 1110 cm-1
.
(S)-1-(2-Br om op h en yl)eth a n ol (7c). GP1: reaction time,
15 h at -25 °C; 92% (9.25 g) yield; 95% ee.26 Purification by
flash-chromatography (silica gel, 1:5 tert-butyl methyl ether/
pentane). Spectroscopic data: lit.13
(S)-2-Br om o-1-(1-m eth oxyethyl)benzene (7d). GP2: depro-
tonation, 1 h; methylation 4 h; 92% (4.94 g) yield without
further purification; colorless oil; [R]2D5 ) -71.2 (c ) 0.75,
3374, 2934, 1178, 1135, 1008 cm-1. Anal. Calcd for C13H17
-
1
IO5: C, 42.68; H, 4.25; O, 17.77. Found: C, 42.74; H, 4.25; O,
17.72.
CHCl3); H NMR δ 1.39 (d, 3H, J ) 6.4 Hz), 3.24 (s, 3H), 4.7
(q, 1H, J ) 6.4 Hz), 7.1 (dt, 1H, J ) 1.8 Hz, J ) 7.6 Hz), 7.32
(dt, 1H, J ) 0.9 Hz, J ) 7.5 Hz), 7.46 (dd, 1H, J ) 1.8 Hz, J
) 7.9 Hz), 7.50 (dd, 1H, J ) 1.2 Hz, J ) 8.0 Hz); 13C NMR δ
22.4, 56.6, 78.2, 122.6, 126.9, 127.8, 128.6, 132.6, 142.6; MS
(EI) m/z (relative intensity) 216 (8), 214 (8), 201 (98), 199 (100),
185 (16), 183 (16), 104 (24), 91 (16), 77 (29), 59 (13), 51 (13),
45 (16); HRMS M+ m/e 214.0000, calcd for C9H11BrO m/e
213.9993; IR (CHCl3) ν 2983, 2932, 1470, 1442, 1372, 1111
(S)-Hydr oxy(4-m eth ylben zen esu lfon ato-KO)[2-(1-eth oxy-
eth yl)p h en yl]iod in e (3c). GP4: yield 92% (162 mg); yellow
1
oil; H NMR δ 1.37 (t, 3H, J ) 6.9 Hz) 1.49 (d, 3H, J ) 6.5
Hz), 2.34 (s, 3H), 3.85 (m, 2H), 4.86 (q, 1H, J ) 6.5 Hz), 7.14
(d, 2H, J ) 7.7 Hz), 7.29 (d, 1H, J ) 1.0 Hz, J ) 7.7 Hz), 7.47
(t, 1H, J ) 7.0 Hz), 7.55 (t, 1H, J ) 7.7 Hz), 7.76 (d, 2H, J )
8.2 Hz), 7.87 (d, 1H, J ) 8.0 Hz); 13C NMR δ 15.1, 21.3, 21.4,
64.2, 68.9, 80.1, 112.4, 126.2, 127.2, 127.9, 128.8, 131.0, 131.2,
140.6, 140.7; IR (CHCl3) ν 3306, 2981, 1717, 1435, 1115, 1009
cm-1
.
(S)-1-(1-Eth oxyeth yl)-2-iod oben zen e (7e). GP2: ethyl
cm-1
.
iodide is used instead of methyl iodide; deprotonation, 45 min;
ethylation, 3 h; yield 91% (203 mg) as colorless oil; [R]D25
)
(S)-Hydr oxy(4-m eth ylben zen esu lfon ato-KO)[2-(1-m eth -
oxyeth yl)-6-m eth oxyp h en yl]iod in e (3d ). GP4: yield 95%
(150 mg); amorphous yellow solid; 1H NMR δ 1.4 (b, 3H), 2.35
(s, 3H), 3.08 (b, 3H), 4.15 (b, 3H), 4.65 (b, 1H), 6.2 (b, 1H), 7.1
(m, 1H), 7.15 (d, 2H, J ) 8.0 Hz), 7.23 (m, 1H), 7.57 (d, 2H, J
) 8.2 Hz), 7.64 (m, 1H).
1
22.1 (c ) 0.480, CHCl3); H NMR δ 1.19 (t, 3H, J ) 7.0 Hz),
1.37 (d, 3H, J ) 6.4 Hz), 3.35 (m, 2H), 4.62 (q, 1H, J ) 6.4
Hz), 6.94 (dt, 1H, J ) 1.8 Hz, J ) 7.5 Hz), 7.36 (dt, 1H, J )
1.1 Hz, J ) 7.5 Hz), 7.46 (dd, 1H, J ) 1.8 Hz, J ) 7.8 Hz),
7.78 (dd, 1H, J ) 1.2 Hz, J ) 7.9 Hz); 13C NMR δ 15.4, 22.9,
64.1, 80.8, 98.0, 126.6, 128.6, 128.9, 139.2, 146.1; MS (EI) m/z
(relative intensity) 276 (23), 262 (18), 261 (100), 233 (59), 231
(26), 104 (34), 78 (44), 77 (34); HRMS M+ m/e 276.0015, calcd
for C10H13IO m/e 276.0011; IR (CHCl3) ν 2978, 1464, 1435,
(S)-Hydr oxy(4-m eth ylben zen esu lfon ato-KO)[2-(1-m eth -
oxyeth yl)-5-m eth oxyp h en yl]iod in e (3e). GP4: yield 93%
(100 mg); amorphous yellow solid; 1H NMR δ 1.46 (d, 3H, J )
6.4 Hz), 2.34 (s, 3H), 3.70 (s, 3H), 3.80 (s, 3H), 4.74 (q, 1H, J
) 6.3 Hz), 6.95 (m, 1H), 7.13 (m, 2H), 7.3 (m, 2H), 7.72 (d, 2H,
J ) 8.2 Hz); IR (CHCl3) ν 3300, 3034, 1597, 1488, 1136, 1035
1372, 1114, 1010 cm-1
.
(S)-1-(3-Meth oxyp h en yl)eth a n ol (10a ). GP1: reaction
time, 21 h at -25 °C; 80% (2.02 g) yield, 96% ee;27 purification
by flash-chromatography (silica gel, 1:5 tert-butyl methyl ether/
cm-1
.
(S)-Hydr oxy(4-m eth ylben zen esu lfon ato-KO)[2-(1-m eth -
oxyeth yl)-4-m eth oxyp h en yl]iod in e (3f). GP4: yield 93%
pentane); [R]2D5 ) -32.0 (c ) 1.135, MeOH); H NMR δ 1.45
1
1
(30 mg); amorphous yellow solid; H NMR δ 1.48 (d, 3H, J )
(d, 3H, J ) 6.5 Hz), 2.4 (d, 1H, J ) 2.4 Hz), 3.78 (s, 3H), 4.8
(dq, 1H, J ) 1.6 Hz, J ) 6.4 Hz), 6.78 (ddd, 1H, J ) 1.0 Hz, J
) 2.5 Hz, J ) 8.2 Hz), 6.9 (m, 2H), 7.23 (t, 1H, J ) 8.1 Hz);
13C NMR δ 25.1, 55.1, 70.1, 110.8, 112.7, 117.6, 129.4, 147.6,
159.6; MS (EI) m/z (relative intensity) 278 (100), 263 (92), 247
(6), 220 (7), 136 (62), 108 (70), 92 (18), 91 (17), 77 (27), 65 (19),
63 (20); IR (CHCl3) ν 3431, 2975, 1602, 1487, 1456, 1157, 1045
6.5 Hz), 2.32 (s, 3H), 3.62 (s, 3H), 3.85, (s, 3H), 4.70 (q, 1H, J
) 6.3 Hz), 6.85 (s, 1H), 7.01 (d, 1H, J ) 8.1 Hz), 7.12 (d, 2H,
J ) 8.5 Hz) 8.7 (d, 3H, J ) 8.5 Hz); 8.9 (s, 1H).
(S)-1-(2-Iod op h en yl)eth a n ol (7a ). GP5: purification by
flash chromatography on silica gel (1:5 tert-butyl methyl ether/
pentane); yield 22% (935 mg); colorless crystals; [R]2D5 ) 46.1
cm-1
.
1
(c ) 1.26, CHCl3), mp 63-65 °C; H NMR δ 1.39 (d, 3H, J )
(S)-1-(2-Iod o-3-m eth oxyp h en yl)eth a n ol (10b). GP1: re-
action time, 18 h at -25 °C; purification by flash chromatog-
raphy (1:10 ethyl acetate/pentane); yield 91% (580 mg);
colorless crystals. GP5: purification by flash chromatography
(1:2 tert-butyl methyl ether/pentane); yield 13% (214 mg); mp
68-70 °C; [R]2D5 ) -41.5 (c ) 0.71, CHCl3); 96% ee; 1H NMR δ
1.46 (d, 3H, J ) 6.4 Hz), 2.0 (d, 1H, J ) 2.4 Hz), 3.89 (s, 3H),
5.19 (dq, 1H, J ) 2.2 Hz, J ) 6.2 Hz), 6.74 (dd, 1H, J ) 1.4
Hz, J ) 8.0 Hz), 7.19 (dd, 1H, J ) 1.4 Hz, J ) 7.8 Hz), 7.32 (t,
1H, J ) 7.9 Hz); 13C NMR δ 23.5, 56.5, 73.7, 89.6, 109.7, 118.6,
129.4, 149.6, 157.8; MS (EI) m/z (relative intensity) 279 (15),
278 (100), 264 (12), 263 (93), 220 (6), 218 (5), 136 (63), 135
6.3 Hz), 2.7 (b, 1H), 4.99 (q, 1H, J ) 6.1 Hz), 6.92 (dt, 1H, J )
1.7 Hz, J ) 7.6 Hz), 7.33 (dt, 1H, J ) 1.1 Hz, J ) 7.5 Hz), 7.49
(dd, 1H, J ) 1.5 Hz, J ) 7.9 Hz), 7.74 (dd, 1H, J ) 1.0 Hz, J
) 7.8 Hz); 13C NMR δ 23.7, 73.5, 97.1, 126.3, 128.6, 129.0,
139.1, 147.4; MS (EI) m/z (relative intensity) 248 (54), 234 (15),
233 (100), 231 (15), 127 (9), 105 (31), 103 (10), 91 (13), 78 (75),
77 (49), 76 (20); HRMS M+ m/e 247.9702, calcd for C8H9IO m/e
247.9698; IR (CHCl3) ν 3604, 2966, 1464, 1437, 1087 cm-1
.
(S)-1-Iod o-2-(1-m eth oxyeth yl)ben zen e (7b). A 4.77 g
(22.2 mmol) amount of 7a was dissolved in 100 mL of THF
under argon at -78 °C. A solution of 25 mL (40 mmol) tert-
butyllithium (1.6 M in pentane) was added slowly. The
solution was stirred for 10 min at this temperature and
allowed to warm at 0 °C. After additional 30 min at -78 °C,
10.2 g (40 mmol) of iodine in 60 mL of THF was added. The
reaction mixture was allowed to warm slowly to room tem-
perature. After 12 h the mixture was diluted with aqueous
sodium thiosulfate and extracted with tert-butyl methyl ether
(3×). After drying with MgSO4 the crude product was purified
by flash chromatography on silica gel (1:50 tert-butyl methyl
(24) The enantiomeric excess was determined by HPLC: Chiralcel
OD; 9:1 hexane/2-propanol; 0.5 mL/min; 254 nm.
(25) The enantiomeric excess was determined by HPLC: Chiralcel
OB; 4:1 hexane/2-propanol, 0.5 mL/min; 240 nm.
(26) The enantiomeric excess was determined by GC: Chrompack,
â-CD-permethylated; 25 m, 80 f 140 °C; 5 °C/min.
(27) The enantiomeric excess was determined by HPLC: Chiralcel
OD; 9:1 hexane/2-propanol, 0.5 mL/min; 220 nm.

Chiral Hypervalent Iodine Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7679
(37), 134 (9), 109 (12), 108 (75), 107 (12), 103 (10), 92 (19), 91
1.075, CHCl3); 1H NMR δ 1.35 (d, 3H, J ) 6.3 Hz), 3.22 (s,
3H), 3.78 (s, 3H), 4.49 (q, 1H, J ) 6.3 Hz), 6.95 (dd, 1H, J )
2.6 Hz, J ) 8.6 Hz), 7.30 (d, 1H, J ) 8.6 Hz), 7.33 (d, 1H, J )
2.6 Hz); 13C NMR δ 22.7, 55.4, 56.4, 82.1, 98.1, 115.0, 124.0,
126.8, 137.4, 159.0; MS (EI) m/z (relative intensity) 292 (28),
278 (19), 277 (100), 261 (21), 149 (7), 134 (17), 121 (7), 119 (6),
(19), 79 (9), 77 (33); HRMS M+ m/e 277.9814, calcd for C9H11
-
IO2 m/e 277.9804; IR (CHCl3) ν 3604, 2967, 1567, 1466, 1427,
1059 cm-1
.
(S)-2-Iod o-3-m eth oxy-(1-m eth oxyeth yl)ben zen e (10c).
GP2: deprotonation, 30 min; methylation 4 h; purification by
flash-chromatography (silica gel, 1:10 tert-butyl methyl ether/
91 (10), 77 (8), 63 (8); HRMS M+ m/e 291.9954, calcd for C10H13
IO2 m/e 291.9960; IR (CHCl3) ν 2978, 1597, 1562, 1488, 1284,
1110, 1037 cm-1
-
pentane); 80% (145 mg) yield; colorless oil; [R]2D5 ) -79.8 (c )
1.615, CHCl3); 1H NMR δ 1.37 (d, 3H, J ) 6.4 Hz), 3.24 (s,
3H), 3.88 (s, 3H), 4.68 (q, 1H, J ) 6.4 Hz), 6.73 (dd, 1H, J )
1.4 Hz, J ) 8.0 Hz), 7.07 (dd, 1H, J ) 1.4 Hz, J ) 7.7 Hz),
7.30 (t, 1H, J ) 8.0 Hz); 13C NMR δ 22.5, 56.5, 56.7, 83.0, 90.7,
109.7, 118.8, 129.5, 147.5, 157.6; MS (EI) m/z (relative
intensity) 292 (50), 277 (100), 262 (20), 134 (19), 91 (14), 77
(13); HRMS M+ m/e 291.9957, calcd for C10H13IO2 m/e 291.9960;
.
(S)-2-Iod o-5-m eth oxy-(1-m eth oxyeth yl)ben zen e (14b).
GP2: deprotonation, 30 min; methylation, 4 h; purification by
flash-chromatography (silica gel, 1:50 tert-butyl methyl ether/
pentane); 93% (146 mg) yield; colorless oil; [R]2D5 ) -75.9 (c )
0.70, CHCl3); 1H NMR δ 1.36 (d, 3H, J ) 6.5 Hz), 3.25 (s, 3H),
3.80 (s, 3H), 4.47 (q, 1H, J ) 6.4 Hz), 6.58 (dd, 1H, J ) 3.1
Hz, J ) 8.7 Hz), 7.01 (d, 1H, J ) 3.2 Hz), 7.65 (d, 1H, J ) 8.7
Hz); 13C NMR δ 22.6, 55.3, 56.7, 82.7, 86.3, 111.856, 115.6,
139.7, 146.6, 160.5; MS (EI) m/z (relative intensity) 293 (10),
292 (61), 278 (18), 277 (100), 262 (29), 261 (13), 135 (21), 134
IR (CHCl3) ν 2981, 1567, 1465, 1136, 1109 cm-1
.
(S)-Bis(a ceta to-O)[2-(1-m eth oxyeth yl)-6-m eth oxyp h e-
n yl]iod in e (10d ). GP3: reaction conditions, 65 °C, 4 h;
recrystallization from hexane, 87% (100 mg) as colorless
(26), 91 (17), 77 (13); HRMS M+ m/e 291.9956 calcd for C10H13
IO2 m/e 291.9960; IR (CHCl3) ν 2932, 1590, 1467, 1285, 1111,
1006 cm-1
-
crystals; mp 94-97 °C; [R]2D5 ) -75.2 (c ) 0.94 CHCl3); 1H
NMR δ 1.47 (d, 3H, J ) 6.4 Hz), 1.95 (s, 3H), 1.96 (s, 3H),
3.23 (s, 3H), 3.99 (s, 3H), 4.71 (q, 1H, J ) 6.5 Hz), 7.07 (dd,
1H, J ) 1.2 Hz, J ) 8.2 Hz), 7.27 (dd, 1H, J ) 1.3 Hz, J ) 7.9
Hz), 7.60 (t, 1H, J ) 8.0 Hz); 13C NMR δ 20.2, 23.7, 56.8, 57.1,
82.4, 110.9, 117.4, 119.4, 134.6, 146.9, 155.9, 176.7, 176.9; IR
.
(S)-Bis(a cet a t o-O)[2-(1-m et h oxyet h yl)p h en yl]iod in e.
GP3: reaction conditions, 50 °C, 3 h; yield 73% (1.58 g); white
powder, mp 104-106 °C; [R]2D5 ) -61.1 (c ) 0.94, CHCl3); H
1
(CHCl3) ν 2934, 1646, 1586, 1469, 1366, 1274, 1053 cm-1
.
NMR δ 1.5 (d, 3H, J ) 6.3 Hz), 1.97 (s, 6H), 3.24 (s, 3H), 4.67
(q, 1H, J ) 6.3 Hz), 7.37 (m, 1H), 7.71 (m, 2H), 8.20 (dd, 1H,
J ) 1.2 Hz, J ) 8.0 Hz); 13C NMR δ 20.2, 23.8, 56.8, 82.0,
124.9, 127.4, 130.3, 133.1, 137.4, 144.6, 176.3; IR (CHCl3) ν
Anal. Calcd for C14H19IO6 (410.21): C, 40.99; H, 4.67.
Found: C, 41.00; H, 4.68.
2-Iodo-5-m eth oxyacetoph en on e (12b). A 484 mg amount
of sodium nitrite was dissolved in 2.5 mL of water and stirred
at 0 °C for 15 min. To this solution 1.055 g of 15a was added
slowly followed by 4 mL of concentrated HCl in 4 g of ice. After
20 min at 0 °C 10.6 g of potassium iodide in 12 mL of water
was added and the solution was stirred for additional 5 h at
room temperature. After extraction with tert-butyl methyl
ether (3×) the product was isolated. Yield: 75% (1.32 g).
Spectroscopic data: lit.20b
2933, 1714, 1648, 1365, 1110 cm-1
.
(S)-Bis(a ceta to-O)[2-(1-m eth oxyeth yl)-5-m eth oxyp h e-
n yl]iod in e. GP3: reaction conditions, 60 °C, 3 h; yield 89%
(73 mg); white solid, mp 93-96 °C; [R]2D5 ) -45.2 (c ) 0.98,
CHCl3); 1H NMR δ 1.47 (d, 3H, J ) 6.4 Hz), 1.98 (s, 6H), 3.21
(s, 3H), 3.87 (s, 3H), 4.6 (q, 1H, J ) 6.4 Hz), 7.21 (dd, 1H, J )
2.5 Hz, J ) 8.7 Hz), 7.62 (dd, 1H, J ) 0.9 Hz, J ) 8.7 Hz),
7.72 (d, 1H, J ) 2.6 Hz); 13C NMR δ 20.3, 23.9, 55.8, 56.6,
81.1, 119.6, 121.9, 124.7, 128.1, 136.0, 159.8, 176.3; IR (CHCl3)
(S)-1-(2-Iod o-4-m eth oxyp h en yl)eth a n ol (13a ). GP1: re-
action time, 18 h at -25 °C; 92% (920 mg) yield; 92% ee;28
purification by flash-chromatography (silica gel, 1:5 tert-butyl
ν 2980, 1730, 1597, 1488, 1284, 1110, 1020 cm-1
.
(S)-Bis(a ceta to-O)[2-[1-m eth oxyeth yl]-4-m eth oxyp h e-
methyl ether/pentane); [R]2D5 ) -37.4 (c ) 0.760, CHCl3); H
n yl]iod in e. GP3: reaction conditions, 60 °C, 3 h; yield 40%
1
(55 mg); white powder, mp 91-94 °C; [R]2D5 ) -68.6 (c ) 0.55,
CHCl3); 1H NMR δ 1.49 (d, 3H, J ) 6.4 Hz), 1.95 (s, 6H), 3.26
(s, 3H), 3.89 (s, 3H), 4.62 (q, 1H, J ) 6.4 Hz), 6.87 (dd, 1H, J
) 3.1 Hz, J ) 8.8 Hz), 7.17 (d, 1H, J ) 3.1 Hz), 8.11 (d, 1H, J
) 8.8 Hz); 13C NMR δ 20.3, 23.9, 55.7, 57.0, 82.0, 112.7, 114.9,
139.3, 147.2, 163.4, 176.4; IR (CHCl3) ν 2936, 1645, 1588, 1470,
NMR δ 1.4 (d, 3H, J ) 6.4 Hz), 2.3 (s, 1H), 3.77 (s, 3H), 5.0 (q,
1H, J ) 6.3 Hz), 6.9 (dd, 1H, J ) 2.6 Hz, J ) 8.6 Hz), 7.3 (d,
1H, J ) 2.3 Hz), 7.4 (d, 1H, J ) 8.5 Hz); 13C NMR δ 23.8,
55.5, 73.1, 97.2, 114.7, 124.2, 126.6, 139.6, 159.0; MS (EI) m/z
(relative intensity) 278 (44), 264 (16), 263 (100), 136 (5), 135
(20), 134 (7), 108 (38), 92 (6), 77 (12), 63 (11); HRMS M+ m/e
277.9794, calcd for C9H11IO2 m/e 277.9804; IR (CHCl3) ν 3424,
2974, 1598, 1488, 1283, 1037 cm-1. Anal. Calcd for C9H11IO2
(278.09): C, 38.87; H, 3.99; O, 11.51. Found: C, 38.88; H, 4.07;
O, 11.61.
1365, 1295, 1111 cm-1
.
(S )-Bis(a ce t a t o-O)[2-(1-e t h oxye t h yl)p h e n yl]iod in e .
1
GP3: reaction conditions, 50 °C, 4 h; yield 61% (165 mg); H
NMR δ 1.19 (t, 3H, J ) 7.0 Hz), 1.50 (d, 3H, J ) 6.5 Hz), 1.96
(s, 6H), 3.38 (m, 2H), 4.77 (q, 1H, J ) 6.4 Hz), 7.36 (tm, 1H, J
) 7.6 Hz), 7.67 (t, 1H, J ) 7.5 Hz), 7.75 (d, 1H, J ) 7.7 Hz),
8.20 (d, 1H, J ) 7.9 Hz); 13C NMR δ 15.2, 20.15, 24.0, 64.3,
80.0, 124.7, 127.8, 130.1, 133.0, 137.3, 145.2, 176.2; IR (CHCl3)
(S)-1-(2-Iod o-5-m eth oxyp h en yl)eth a n ol (13b). GP1: re-
action time, 19 h at -25 °C; 89% (895 mg) yield; 96% ee;29
purification by flash-chromatography (silica gel, 1:20 ethyl
acetate/pentane). [R]D25 ) -41.9 (c ) 0.675, CHCl3); H NMR
1
ν 2979, 1650, 1435, 1371, 1275, 1098, 1009 cm-1
.
δ 1.42 (d, 3H, J ) 6.4 Hz), 2.3 (br, 1H), 3.79 (s, 3H), 4.99 (q,
1H, J ) 6.3 Hz), 6.56 (dd, 1H, J ) 3.0 Hz, J ) 8.7 Hz), 7.14 (d,
1H, J ) 3.0 Hz), 7.63 (d, 1H, J ) 8.7 Hz); 13C NMR δ 23.7,
55.4, 73.5, 85.3, 111.9, 115.4, 139.7, 148.6, 160.3; MS (EI) m/z
(relative intensity) 278 (100), 263 (68), 136 (53), 135 (31), 109
(10), 108 (74), 107 (11), 92 (14), 91 (12), 77 (24); HRMS M+
m/e 277.9806, calcd for C9H11IO2 m/e 277.9804; IR (CHCl3) ν
Ack n ow led gm en t . This investigation was sup-
ported by the Stipendienfonds der Basler Chemischen
Industrie (scholarships for U.H.H. and B.S.), the Sch-
weizer Nationalfonds, the Deutsche Forschungsgemein-
schaft, and the Treubel-Fonds (scholarship for T.W.).
We thank Prof. S. L. Buchwald for valuable suggestions
and Prof. B. Giese for his continuous interest and
generous support.
3424, 2976, 1591, 1567, 1467, 1288, 1006 cm-1
.
(S)-2-Iod o-4-m eth oxy-(1-m eth oxyeth yl)ben zen e (14a ).
GP2: deprotonation, 30 min; methylation 3 h; purification by
flash-chromatography (silica gel, 1:20 tert-butyl methyl ether/
pentane); 90% (135 mg) yield; colorless oil; [R]2D5 ) -70.6 (c )
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 3d , 7a ,b,d ,e, 10b-d , 13a ,b, and 14a ,b and X-ray
diagrams and crystallographic data tables for compounds 3b
and 10d (27 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(28) The configuration is determined by reduction of 13a with
LiAlH4 to (S)-1-(4-methoxyphenyl)ethanol and comparison of the optical
rotation with the literature: Brown, S. M.; Davies, S. G.; Sousa, J . A.
A. Tetrahedron: Asymmetry 1993, 4, 813-822.
(29) The configuration is determined by reduction of 13b with
LiAlH4 to (S)-1-(3-methoxyphenyl)ethanol and comparison of the optical
rotation with the literature: Chen, C. P.; Prasad, K.; Repic, O.
Tetrahedron Lett. 1991, 32, 7175-7178.
J O980475X