Chiral organometallic reagents. Part XXIV.1 Iodine ate-complexes as intermediates in the iodine-lithium exchange reaction on 1,1-diiodoalkanes

Article abstract of DOI:10.1039/a900121b

The iodine-lithium exchange reaction on the 1,1-diiodoalkanes 17 at -110 °C is initiated by the irreversible formation of yellow iodine ate-complexes, which are slowly transformed into the α-iodoalkyllithium compounds 21.

Full text of DOI:10.1039/a900121b

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Chiral organometallic reagents. Part XXIV.1 Iodine ate-complexes
as intermediates in the iodine–lithium exchange reaction on
1,1-diiodoalkanes
Michael Müller, Hans-Christian Stiasny, Mark Brönstrup, Andrew Burton and
Reinhard W. Hoffmann*
Fachbereich Chemie der Philipps-Universität Marburg, Hans-Meerwein-Strasse D-35032
Marburg, Germany
Received (in Cambridge) 5th January 1999, Accepted 28th January 1999
The iodine–lithium exchange reaction on the 1,1-diiodoalkanes 17 at Ϫ110 ЊC is initiated by the irreversible
formation of yellow iodine ate-complexes, which are slowly transformed into the α-iodoalkyllithium compounds 21.
PGO
R
X
Introduction
We have previously reported on the differentiation of diastereo-
topic bromine atoms in a bromine–lithium exchange reaction
on various β- and γ-substituted 1,1-dibromoalkanes 1.2,3 We
X
5
PG = protecting group
X = Br, I
nBuLi
PGO
R
Br
PGO
R
Br
PGO
R
Br
nBuLi
+
k 1
k '1
-110 o
C
Li
Li
Br
?
k '–1
1
k
+
+
PGO
R
X
PGO
X
Li
Li
have put forward some ideas about how a conformational
preorganization of the substrate dibromoalkanes affects the
sense of the asymmetric induction.4
-
-
X
X
R
Bu
Bu
6b
6a
Any discussion of the nature of the stereodifferentiating step
has to address the mechanism of the bromine–lithium exchange
reaction, which had been postulated by Wittig5 to proceed
via halogen ate-complexes. The indirect kinetic evidence,6
followed by spectroscopic observations7 and finally a crystal
structure determination8 lend credence to the notion that such
ate-complexes are true intermediates and not merely high
energy constellations or transition states in the halogen–metal
exchange reaction. Recently the stoichiometric formation of
long-lived iodine ate-complexes 3 was demonstrated in the
iodine–magnesium exchange reaction on 1,1-diiodoalkanes 2.9
k '2
k 2
PGO
R
X
PGO
R
X
+ IBu
+ IBu
Li
Li
7b
7a
significant amounts of protonation products 9 are formed on
reaction of the 1,1-diiodoalkane 8 with butyllithium in the
presence of acetone.10 We surmised (but could not in the end
substantiate, see below) that 9 could arise by protonation of
long-lived ate-complex intermediates 12. In fact, a reaction of 8
in the presence of deuteroacetone proved that acetone is the
proton source, since monodeuterated 9 was formed.
+
I
I
BrMg
fast
BrMg
Ph
Ph
-
I
I
2
3
nBuLi
TBDMSO
I
TBDMSO
H(D)
slow
– 110 o
C
I
I
I
8
9
Trapp solvent mixture
Acetone
I
Ph
+
MgBr
4
TBDMSO
O
CH(D)3
We therefore readdressed the question of the stereodefining
step in the halogen–lithium exchange reactions on compounds
of the type 1. When ate-complexes 6 are intermediates in
the halogen–metal exchange reaction, the stereoselectivity on
reaction of the diiodoalkane 5 to give the lithium compound 7
may be defined either in the formation or in the subsequent
transformation of the ate-complexes 6 to give 7. This depends
on whether the formation of 6 is irreversible or reversible. The
latter would constitute a Curtin–Hammett situation.
10
CH(D)3
CH3COCH3
CD3COCD3
9:10
9-d1:10-d6
9 + 10
9-d1 + 10-d6
=
=
90%
86%
73 : 23
63 : 37
=
=
The product ratios obtained on quenching with acetone or
deuteroacetone respectively revealed a partitioning isotope
effect, but it remained unknown whether partitioning occurred
at the stage of the ate-complexes 6 or the lithium compounds 7.
This investigation was stimulated by the observation that
J. Chem. Soc., Perkin Trans. 2, 1999, 731–736
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Experience with the ate-complexes 3 with magnesium as
counter ion indicated9 that α-iodoalkyl iodine ate-complexes
should be the most stable ones and also the longest lived of
all α-halogenoalkyl halogen ate-complexes.11 This led us to
scrutinize more closely the iodine–lithium exchange reaction
of 1,1-diiodoalkanes hoping to define the role of α-iodoalkyl
iodine ate-complexes in these processes.
diastereomer resolution of the equilibrating ate-complexes 6a
and 6b. In this case the product ratio derived from 7 could be
different from the ratio of the ate-complexes 6.
On the other hand, if the formation of the ate-complexes 6
was irreversible, the ratio of the lithium compounds 7 and the
product ratio derived thereof should reflect the ratio of the ate-
complexes 6. The ate-complexes 6 appear to be instantaneously
quenched by addition of methanol. This allows for the
determination of the ratio of the ate-complexes 6 by quenching
with CH3OD either in situ or within the first minutes after the
formation of the ate-complexes, when the solution is still
intensely yellow colored. The ratio of the α-iodoalkyllithium
compounds 7 in turn can be derived from quenching of the
decolorized solutions after the appropriate period of time.
These aspects have been studied in a series of experiments
using the diiodoalkane 17, which has been prepared from the
alkene 1414 by ozonolysis and iodination of the hydrazone.15
The latter reaction gave rise to several side products. Separation
of the desired product became possible after conversion of the
TMS ether 15 into the alcohol 16. The latter was ultimately
reprotected with TBDMS-triflate to give racemic 17.
Qualitative evidence for á-iodoalkyl iodine
ate-complexes
The α-iodoalkyl iodine ate-complex 3 with a magnesium
counter ion has a strong absorption in the visible (λmax = 409
nm, ε ≈ 500 L molϪ1 cmϪ1) forming intensely pumpkin-yellow
solutions.9 The formation and decay of such ate-complexes are
easily monitored by following the color change. Indeed, when
the 1,1-diiodoalkane 2 was treated at Ϫ100 ЊC in a Trapp
solvent mixture12 with n-butyllithium the solution acquired a
deep yellow color, indicative of the formation of 11, which
faded after 20 min.13 Likewise, reaction of 8 with n-butyllithium
in a Trapp solvent mixture led to an intensive yellow coloration
which persisted for up to 60 min. Some further observations are
given below.
TMSO
TMSO
I
1) O3
H2NNH2•H2O
I
Persistence of the Yellow Color
(Trapp = Trapp solvent mixture)
2) PPh3
I2 , Et3N
52%
TBDMSO
14
15
+
+
I
TMSO
I
Li
Li
HO
I
I
Ph
11
TBDMSOTf
HF
-
-
I
I
I
I
Bu
Bu
– 100 oC : 20 min (THF)
CH3CN
Lutidine
93%
96%
– 100 oC : 20 min (THF)
16
17
– 110 oC : 60 - 90 min (Trapp)
Treatment of the diiodoalkane 17 with n-butyllithium in a
Trapp solvent mixture12 at Ϫ110 ЊC generated the intense
yellow color of the ate-complexes 18, which persisted for ca.
30 min under these conditions. When a precooled solution of
CH3OH was added in a two-compartment reaction vessel10 to
such yellow solutions, the color was immediately discharged,
resulting in the quantitative formation of the monoiodoalkane
19.
+
+
TBDMSO
I
Li
TBDMSO
Br
Li
-
-
I
I
Bu
Bu
12
– 110 oC : 60 min (Trapp)
13
– 110 oC : 5 min (Trapp)
Even with an α-bromoiodo-compound the color charac-
teristic for the ate-complexes 13 could be seen, although it
faded much more rapidly. Thus, by prima facie evidence the
color of the solution suggests the formation of long-lived
ate-complexes also in the iodine–lithium exchange reaction on
1,1-diiodoalkanes at low temperatures.
+
TBDMSO
I
TBDMSO
I
Li
nBuLi
-
I
I
Trapp
solvent
-110 o
Bu
18
17
C
The ate-complexes 3 and the Grignard reagent 4 have been
differentiated by an isotope effect on quenching into a 1:1
mixture of CH3OD and CH3OH.9 Thus, quenching of the
yellow solution into CH3OD–CH3OH, 5 to 30 min after
interaction of the diiodo-compound 2 with butyllithium at
Ϫ110 ЊC, occured with an apparent isotope effect of kH/kD of
0.6. Quenching of the solution after 2.5 hours, when the yellow
color of the solution had faded, proceeded with an apparent
isotope effect of kH/kD of 1.1. This shows that at least two
different species, which can be protonated, are present in the
solution in substantial amounts, when the solution is colored
and when it has become colorless. We therefore reason that the
yellow ate-complexes 11 are initially formed in a stoichiometric
manner on reaction of the diiodoalkane 2 with butyllithium in
a Trapp solvent mixture at Ϫ110 ЊC.
CH3OH
TBDMSO
I
19
Quenching of the ate-complexes 18 with CH3OD, C6H5SD or
CD3COCD3 generated the mono-deuterated compounds 20,
the diastereoisomer ratio of which was determined by 2D-
NMR spectroscopy. The results are compiled in Table 1.
+
+
TBDMSO
I
TBDMSO
I
Li
Li
+
-
-
I
I
Bu
Bu
Is the formation of the ate-complexes reversible?
18a
18b
The rapid appearance and slow bleaching of the yellow color
on reaction of 5 with butyllithium suggests that the ate-
complexes 6 are rapidly formed and slowly transformed into
the α-iodoalkyllithium compounds 7. If the formation of the
ate-complexes were reversible, i.e. kϪ1 > k2, a Curtin–Hammett
situation would prevail, in which the diastereomer ratio of the
lithium compounds 7a and 7b is determined by the kinetic
CH3OD or C6H5SD
TBDMSO
I
TBDMSO
I
D
D
20b
20a
732
J. Chem. Soc., Perkin Trans. 2, 1999, 731–736

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Table 1
For all experiments in which deuteroacetone was added after
the generation of the ate-complexes, the product ratio 20/22
is about 30:70, irrespective of the time of quenching. This
constant partitioning ratio suggests that it is one and the same
species that leads to those products. Since after 30 min the
solution is colorless, i.e. there are no longer ate-complexes 18
present, it must be the α-iodoalkyllithium compounds 21 that
are being quenched with acetone. It follows that the ate-
complexes 18 do not react with acetone to give either 20 or 22
or both, a reaction that would be likely to give rise to a different
ratio of 20 and 22. Since the addition of acetone after 1 or 5
min led to a moderately rapid (ca. 10 min) decolorization, all
that acetone possibly does is to speed up the transformation of
the ate-complexes 18 into the α-iodoalkyllithium compounds
21, which then are eventually trapped with acetone.
TBDMSO
I
TBDMSO
I
1) nBuLi, –110 oC, Trapp
2) CH3OD, or C6H5SD
I
D
17
20a
+
TBDMSO
I
D
20b
Addition after
Yield
Ratio 20a/20b
Quenching with CH3OD
in situ
1 min
80%
77%
80%
65%
74%
78%
68:32
70:30
72:28
73:27
68:32
70:30
A look at the diastereomer ratios of 20 and of 22 shows them
to be different from one another. These differences arise
probably from a kinetic resolution in the reaction of the
diastereomeric α-iodoalkyllithium compounds 21 with acetone
along the two reaction pathways.
5 min
5 mina
5 minb
30 min
Quenching with C6H5SD
+
+
TBDMSO
I
TBDMSO
I
Li
in situ
1 min
5 min
30 min
20%
48%
45%
43%
70:30
74:26
74:26
68:32
Li
+
-
-
I
I
Bu
Bu
18a
18b
a In the presence of 2 equiv. of DMPU. b In the presence of 2 equiv. of
HMPT.
70 : 30
TBDMSO
I
TBDMSO
I
A detailed analysis of the coupling constants in the 1H-NMR
spectrum of 19 allowed an assignment of the diastereotopic
hydrogen atoms Ha and Hb in 19 resonating at 3.34 and 3.14
ppm. MM3* calculations16 indicate that 19 populates mainly
two conformations 19a and 19b. This allowed us to calculate
population averaged 3JH,H coupling constants for 19.
+
Li
Li
21b
70 : 30
21a
CD3COCD3
TBDMSO
TBDMSO
I
I
O
TBDMSO
TBDMSO
CD3
Hb
Ha
D
D
20a
22a
TBDMSO
Hc
Hc
Hb
I
CD3
Ha
+
+
I
19a
19b
Hd
Hd
TBDMSO
O
CD3
Coupling constants (Hz)
Calculated for
Population
averaged
19a
19b
Experimental
20b
22b
CD3
70%, dr ca. 73 : 27
Ha Hc
Ha Hd
Hb Hc
Hb Hd
4.5
9.1
9.0
5.8
4.8
8.7
8.2
8.3
3.6
13.1
13.3
2.2
4.9
2.4
30%, dr ca. 53 : 47
Since the individual stereostructures of the diastereomers of
20 and 22 are known, the diastereomer ratio observed for 20
and 22 can be traced back to a calculated diastereomer ratio of
the organolithium compounds 21 as indicated in the last
column of Table 2. The calculated values are in line with the
assumption that the organolithium compounds 21a and 21b are
generated in a ca. 70:30 ratio.
All the data so far are consistent with the picture that the
ate-complexes 18a and 18b are formed in a ca. 70:30 ratio and
that this ratio is transformed into the ratio of the lithium-
compounds 21a, 21b with high fidelity, suggesting an irrevers-
ible formation of the ate-complexes 18a and 18b. There is,
however, one aberrant result, which we are unable to explain at
present. This is the result obtained on in situ trapping with
deuteroacetone, cf. the last entry of Table 2. The yellow color of
the ate complexes is observed when the diiodo-compound 17
is treated with butyllithium in the presence of two equivalents
of acetone. The ratio of the deuterated products 20 to the
epoxides 22 is, however, reversed compared to the results of the
sequential trapping experiments. This clearly indicates that a
different species other than the lithium compounds 21 is being
trapped. The diastereomer ratio of the deuterated products 20a
and 20b (67:33) and of the epoxides 22a and 22b (91:9) can be
1.5
13.2
It is evident that the signal at 3.34 ppm with the small
coupling constant (4.7 Hz) corresponds to Ha, whereas the
signal at 3.14 ppm with the large coupling constants stems from
Hb. This allowed the structure of the predominant diastereomer
of the deuterated compound 20 to be assigned as 20a.
The results obtained on quenching of the reaction mixtures
with CH3OD or C6H5SD show that the diastereomeric ate-
complexes 18a and 18b are generated in a (70 5):(30 5)
ratio. Since the same stereoisomer ratio resulted from in situ
quenching with two equivalents of CH3OD, it may be assumed
that the ratio of the ate-complexes 18a and 18b is kinetically
controlled. The product ratio 20a/20b did not change upon
conversion of the ate-complexes 18 into the α-iodoalkyllithium
compounds 21 as seen from quenching after 5 and eventually
after 30 min.
The results obtained on quenching with deuteroacetone are
more complex, since in addition to the deuterated compound
20, the epoxides 22 were formed, cf. Table 2. The stereo-
structure of the epoxides 22 has been assigned before.2
J. Chem. Soc., Perkin Trans. 2, 1999, 731–736
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Table 2
TBDMSO
I
TBDMSO
D
TBDMSO
1) nBuLi, –110 oC, Trapp
2) CD3COCD3
O
CD3
+
I
I
17
20
22
CD3
Addition of
CD3COCD3 after
Yield (%)
of 20
Yield (%)
of 22
Calculated Ratio
of 21a/21b
Ratio 20a/20b
Ratio 20/22
29:71
31:69
27:73
27:73
30:70
63:37
Ratio 22a/22b
1 min
5 min
30 min
60 min
150 min
in situ
20
19
20
23
21
48
53:47
54:46
56:44
52:48
54:46
67:33
50
34
45
58
56
27
74:26
74:26
73:27
73:27
72:28
91:9
74:26
74:26
73:27
73:27
72:28
76:24
calculated back to a diastereomer ratio of the ate-complexes
18 of 76:24, which is by and large the same as seen before
(70 5):(30 5).
Apparently, the presence of acetone does not change the
ratio in which the diastereomeric ate-complexes 18 are being
formed. This is in line with the notion that polar cosolvents do
not alter the ratio in which the ate-complexes 18 are being
formed (cf. relevant entries in Table 1).
We do not have any clue as to the nature of a further inter-
mediate between the ate-complexes 18 and the organolithium
compounds 21, an intermediate which is being trapped in these
in situ experiments. It is puzzling that there is no gradual change
between the values for the in situ trapping to those resulting
from trapping after 1 or 5 min, at which time the ate-complexes
are still present.
chromatographed on silica gel (20 g) with pentane to pentane/
tert-butyl methyl ether 20:1 to give 92 mg (0.25 mmol, 52%) of
9-d1 and 49 mg (0.16 mmol, 34%) of 10-d6 as colorless oils. 9-d1:
1H NMR (300 MHz, CDCl3): δ = 0.08 (s, 3H), 0.10 (s, 3H), 0.90
(s, 9H), 0.97 (s, 6H), 1.88 (ddd, J = 14.6, 8.2, 7.3 Hz, 1H), 2.06
(ddd, J = 14.5, 8.2, 2.9 Hz, 1H), 3.09 (dd, J = 8.2, 8.2 Hz), 3.28
(dd, 8.8, 5.1 Hz), together 1H, 3.38 (dd, J = 7.2, 3.1 Hz, 1H),
4.97 (dd, J = 17.8, 1.4 Hz, 1H), 4.97 (dd, J = 10.5, 1.4 Hz, 1H),
5.86 (dd, J = 17.9, 10.5 Hz, 1H). 13C NMR (75 MHz, CDCl3):
δ = Ϫ3.9, Ϫ3.4, 4.7 (t, J = 23 Hz), 18.4, 22.8, 24.7, 26.1, 38.2,
42.1, 79.7, 112.0, 145.6. C14H28DOSiI (369.4): calcd. C 45.52,
H ϩ D 7.91; found C 45.43, H ϩ D 7.83%. 10-d6-syn: 1H NMR
(300 MHz, CDCl3): δ = 0.05 (s, 3H), 0.06 (s, 3H), 0.90 (s, 9H),
0.99 (s, 6H), 1.64–1.72 (m, 2H), 2.85 (dd, J = 6.0, 6.0 Hz, 1H),
3.51 (dd, J = 5.3, 5.3 Hz, 1H), 4.97 (dd, J = 10.5, 1.5 Hz, 1H),
4.97 (dd, J = 17.8, 1.5 Hz, 1H), 5.85 (dd, J = 17.9, 10.5 Hz, 1H).
13C NMR (75 MHz, CDCl3): δ = Ϫ4.1, Ϫ3.9, 18.2, 22.1, 24.6,
We have addressed in this study the role of α-iodoalkyliodine
ate-complexes
6 in the diastereoselective iodine–lithium
1
exchange on 1,1-diiodoalkanes 5. The results obtained are in
line with the assumption that the stereodefining step is the
irreversible formation of the ate-complexes 6. As in any
mechanistic study, our experiments can only be in line with, but
cannot prove such a conjecture.
26.0, 33.7, 42.4, 58.3, 62.2, 77.6, 122.0, 145.7. 10-d6-anti: H
NMR (300 MHz, CDCl3): δ = 0.07 (s, 3H), 0.08 (s, 3H), 0.91
(s, 9H), 3.59 (dd, J = 6.9, 4.1 Hz, 1H), remaining signals hidden.
13C NMR (75 MHz, CDCl3): δ = 22.7, 26.1, 32.7, 61.9, 111.7,
remaining signals hidden. C17H28D6O2Si (304.6): calcd. C 67.04,
H ϩ D 11.25; found C 66.95, H ϩ D 11.41%.
Experimental
2. 1,1-Diiodo-4,4-dimethyl-3-(trimethylsilyloxy)pentane (15)
All temperatures quoted are not corrected. 1H, 13C NMR:
Bruker AC-300, AM-400 and AMX-500. Flash chrom-
atography: Kieselgel 60 (0.040–0.063 mm, Merck, Darmstadt).
Analytical gas chromatography: Siemens Sichromat 3 with a
30 m × 0.35 mm column with Durabond 5, 1.0 bar He. pH 7
Buffer-solution: NaH2PO4ؒ2H2O (56.2 g) and Na2HPO4ؒ2H2O
(213 g) in H2O (1 L).
A stream of ozone was introduced at Ϫ78 ЊC into a solution
of 5,5-dimethyl-4-(trimethlysilyloxy)hex-1-ene 14 (12.0 g, 60
mmol) in dry CH2Cl2 (120 mL) until the blue color persisted.
The excess of ozone was removed by a stream of oxygen.
Triphenylphosphine (17.3 g, 66 mmol) was then added. After
the mixture had reached room temperature the solution was
adsorbed onto silica gel (30 g) and chromatographed on silica
gel (100 g) with pentane to give a clear liquid. This liquid was
immediately dissolved in methanol (30 mL) and hydrazine
hydrate (30 mL, 85%) was added, whilst maintaining the reac-
tion at room temperature. After stirring for 1 h the reaction
mixture was extracted with CH2Cl2 (3 × 20 mL) and the
combined organic phases were dried with Na2SO4 and con-
centrated. The residual oil was immediately dissolved in diethyl
ether (100 mL) and triethylamine (50 mL) was added. Iodine
was added with stirring until a brown color persisted (care:
evolution of nitrogen). After 1 h aqueous sodium thiosulfate (50
mL, 20%) was added and the aqueous phase was extracted with
ether (3 × 20 mL). The combined organic phases were washed
with brine (30 mL), dried with Na2SO4 and concentrated. The
residual liquid was chromatographed on silica gel (100 g) with
1. 3-(tert-Butyldimethylsilyloxy)-1-deutero-4,4-dimethyl-1-
iodohex-5-ene (9-d1) and 5-(tert-butyldimethylsilyloxy)-2,3-
epoxy-6,6-dimethyl-2-trideuteromethyl-1,1,1-trideuterooct-7-ene
(10-d6)
Following the procedure given10 for the preparation of 9 and
10, a pre-cooled (Ϫ110 ЊC) solution of n-butyllithium in hexane
(0.43 mL, 1.67 M, 0.72 mmol) and pentane (1 mL) was added
at Ϫ110 ЊC to a solution of 3-(tert-butyldimethylsilyloxy)-1,1-
diiodo-4,4-dimethylhex-5-ene (8) (235 mg, 0.48 mmol) and
deuteroacetone (70 µL, 1.0 mmol) in Trapp solvent mixture
(5 mL). The reaction mixture was stirred at Ϫ110 ЊC for 30 min
and then allowed to warm to room temperature and stirred for
1 h. Then aqueous pH 7 buffer solution (5 mL) was added and
the reaction mixture was extracted with pentane (3 × 10 mL).
The combined organic phases were washed with brine (10 mL),
dried with Na2SO4 and concentrated. The ratio of the yields of
the mono-deuterated compounds 9-d1 and the epoxides 10-d6
and the diastereomeric ratio of these two products was deter-
1
pentane to give 13.7 g (52%) of 15 as a clear liquid. H NMR
(300 MHz, CDCl3): δ = 0.17 (s, 9H), 0.86 (s, 9H), 2.46 (ddd,
J = 14.5, 8.9, 3.6 Hz, 1H), 2.50 (ddd, J = 14.5, 10.9, 2.4 Hz, 1H),
3.21 (dd, J = 8.9, 2.4 Hz, 1H), 4.96 (dd, J = 10.9, 3.6 Hz, 1H).
13C NMR (75 MHz, CDCl3): δ = Ϫ27.0, 1.1, 26.4, 34.9, 52.0,
81.9. C10H22OSiI2 (440.2): calcd. C 27.28, H 5.04; found C
27.32, H 5.01%.
mined to be 9-d1(a/b)/10-d6(syn/anti) = 63(68/32)/37(89/11), by H NMR
spectroscopy of the crude product. The crude product was then
1
734
J. Chem. Soc., Perkin Trans. 2, 1999, 731–736

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3. 1,1-Diiodo-4,4-dimethylpentan-3-ol (16)
residual liquid was chromatographed on silica gel (10 g) with
pentane to give 20 as a colorless oil. The ratio of isotopomers
was determined by 2H NMR spectroscopy. 1H NMR (300
MHz, CDCl3): δ = 0.06 (s, 3H), 0.08 (s, 3H), 0.85 (s, 9H), 0.89
(s, 9H), 1.88 (ddd, J = 14.8, 7.8, 7.5 Hz, 1H), 2.08 (ddd, J = 14.4,
8.4, 2.3 Hz, 1H), 3.10 (dd, J = 8.3, 8.3 Hz), 3.31 (dd, J = 8.8, 4.9
To a solution of 15 (13.7 g, 31 mmol) in acetonitrile (10 mL)
was added HF in acetonitrile (20 mL, 5%). After stirring for 1 h
the reaction mixture was neutralized with saturated aqueous
NaHCO3 and the aqueous phase was extracted with diethyl
ether (3 × 20 mL). The combined organic phases were washed
with brine (20 mL), dried with Na2SO4 and concentrated. The
residual liquid was chromatographed on silica gel (100 g)
with pentane–diethyl ether 5:1 to give 11.1 g (97%) of 16 as
a colorless solid (mp 55 ЊC). 1H NMR (300 MHz, CDCl3):
δ = 0.89 (s, 9H), 1.79 (br s, 1H), 2.32 (ddd, J = 14.7, 9.8, 3.1 Hz,
1H), 2.47 (ddd, J = 14.7, 11.5, 2.1 Hz, 1H), 3.19 (dd, J = 9.8, 2.1
Hz, 1H), 5.19 (dd, J = 11.5, 3.1 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ = Ϫ27.3, 25.7, 34.4, 50.4, 80.3. C7H14OI2 (368.0):
calcd. C 22.85, H 3.83; found C 22.96, H 4.00%.
2
Hz), together = 1H, 3.27 (dd, J = 7.6, 2.7 Hz, 1H). H NMR
(400 MHz, CHCl3): δ = 3.10 (br s), 3.31 (br s), together = 1D.
13C NMR (75 MHz, CDCl3): δ = Ϫ3.9, Ϫ3.3, 18.5, 26.2, 26.5,
35.7, 37.8, 80.6. C13H28DOSiI (357.4): calcd. C 43.69, H ϩ D
8.18; found C 43.79, H ϩ D 8.27%.
Quench with deuterated acetone. 3-(tert-Butyldimethylsil-
yloxy)-1-deutero-4,4-dimethyl-1-iodopentane (20) and 5-(tert-
butyldimethylsilyloxy)-2,3-epoxy-6,6-dimethyl-2-trideutero-
methyl-1,1,1,-trideuteroheptane (22): A pre-cooled (Ϫ110 ЊC)
solution of n-butyllithium in hexane (0.50 mL, 1.43 M, 0.72
mmol) and pentane (1 mL) was added at Ϫ110 ЊC to a solution
of 17 (230 mg, 0.48 mmol) in Trapp solvent mixture (5 mL).
After the indicated reaction time deuterated acetone (70 µL, 1.0
mmol) was added. The reaction mixture was stirred at Ϫ110 ЊC
for 30 min and then allowed to warm to room temperature and
stirred for 1 h. Then aqueous pH 7 buffer solution (5 mL) was
added and the reaction mixture was extracted with pentane
(10 mL). The combined organic phases were washed with brine
(10 mL), dried with Na2SO4 and concentrated. The ratio of the
yields of 20 and 22 as well as the diastereomeric ratio of 22 was
4. 3-(tert-Butyldimethylsilyloxy)-1,1-diiodo-4,4-dimethylpentane
(17)
To a solution of 16 (626 mg, 1.7 mmol) in CH2Cl2 (3 mL) was
added 2,6-lutidine (0.50 mL, 4.3 mmol) and tert-butyl-
dimethylsilyltriflate (0.55 mL, 2.4 mmol). After stirring for 2 h
methanol (2 mL) was added and the reaction mixture stirred
for a further 1 h. Then aqueous pH 7 buffer solution (5 mL) was
added and the reaction mixture was extracted with pentane
(5 mL). The combined organic phases were washed with brine
(5 mL), dried with Na2SO4 and concentrated. The residual
liquid was chromatographed on silica gel (30 g) with pentane to
give 762 mg (93%) of 17 as a white solid (mp 29 ЊC). 1H NMR
(300 MHz, CDCl3): δ = 0.10 (s, 3H), 0.16 (s, 3H), 0.88 (s, 9H),
0.90 (s, 9H), 2.52 (ddd, J = 14.9, 8.0, 3.4 Hz, 1H), 2.64 (ddd,
J = 14.9, 11.3, 1.8 Hz, 1H), 3.13 (dd, J = 8.0, 1.8 Hz, 1H), 5.02
(dd, J = 11.3, 3.4 Hz, 1H). 13C NMR (75 MHz, CDCl3):
δ = Ϫ26.9, Ϫ3.8, Ϫ3.2, 18.6, 26.2, 26.4, 35.2, 53.4, 81.4.
C13H28OSiI2 (482.3): calcd. C 32.37, H 5.85; found C 32.35,
H 6.02%.
1
determined by H NMR spectroscopy of the crude product.
The crude product was then chromatographed on silica gel (20
g) with pentane to pentane–tert-butyl methyl ether 10:1 to give
20 and 22 as colorless oils. The ratio of isotopomers of 20 was
2
1
determined by H NMR spectroscopy. 22-syn: H NMR (300
MHz, CDCl3): δ = 0.04 (s, 6H), 0.87 (s, 9H), 0.89 (s, 9H), 1.59–
1.73 (m, 2H), 2.91 (dd, J = 5.9, 5.9 Hz, 1H), 3.44 (dd, J = 5.2,
5.2 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ = Ϫ4.1, Ϫ3.8, 18.3,
1
26.2, 26.4, 33.4, 35.9, 55.8, 62.1, 78.4. 22-anti: H NMR (300
MHz, CDCl3): δ = 0.04 (s, 3H), 0.07 (s, 3H), 0.85 (s, 9H), 0.90 (s,
9H), 1.55–1.64 (m, 2H), 2.90 (dd, J = 5.8, 5.8 Hz, 1H), 3.51 (dd,
J = 7.1, 3.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ = Ϫ4.0,
Ϫ3.7, 18.4, 26.1, 26.6, 32.3, 35.8, 55.8, 62.1, 78.1.
5. 3-(tert-Butyldimethylsilyloxy)-4,4-dimethyl-1-iodopentane
(19)
A pre-cooled (–110 ЊC) solution of n-butyllithium in hexane
(0.50 mL, 1.42 M, 0.71 mmol) and pentane (1 mL) was added at
Ϫ110 ЊC to a solution of 17 (200 mg, 0.42 mmol) in Trapp
solvent mixture (4 mL). After 5 min the reaction was quenched
with methanol (0.25 mL). Then brine (5 mL) was added and the
reaction mixture was extracted with pentane (3 × 5 mL). The
combined organic phases were dried with Na2SO4 and con-
centrated. The residual liquid was chromatographed on silica
gel (10 g) with pentane to give 142 mg (96%) of 19 as a colorless
oil. 1H NMR (500 MHz, CDCl3): δ = 0.08 (s, 3H), 0.11 (s, 3H),
0.87 (s, 9H), 0.91 (s, 9H), 1.91 (dddd, J = 14.5, 8.2, 7.6, 4.8 Hz,
1H), 2.12 (dddd, J = 14.8, 8.3, 8.3, 2.7 Hz, 1H), 3.14 (ddd,
J = 9.3, 8.3, 8.2 Hz, 1H), 3.29 (dd, J = 7.5, 2.7 Hz, 1H), 3.34
(ddd, J = 9.1, 9.1, 4.8 Hz, 1H). 13C NMR (75 MHz, CDCl3):
δ = Ϫ3.9, Ϫ3.3, 18.4, 26.1, 26.4, 35.7, 37.9, 80.6. C13H29OSiI
(356.4): calcd. C 43.81, H 8.20; found C 43.98, H 8.44%.
7. Typical procedure for iodine–lithium exchange on compound 2
1-Iodo-2-phenylethane and 1-deutero-1-iodo-2-phenylethane:
A pre-cooled (Ϫ110 ЊC) solution of n-butyllithium in hexane
(0.48 mL, 1.50 M, 0.72 mmol) and pentane (1 mL) was added
at Ϫ110 ЊC to a solution of 1,1-diiodo-2-phenylethane (2) (172
mg, 0.48 mmol) in Trapp solvent mixture (5 mL). After the
indicated reaction time the reaction was quenched with a 1:1
mixture of methanol and deuterated methanol (0.50 mL, 40
equiv.). Then brine (5 mL) was added and the reaction mixture
was extracted with diethyl ether (3 × 5 mL). The combined
organic phases were dried with Na2SO4 and concentrated. The
residual liquid was chromatographed on silica gel (10 g) with
pentane to give a mixture of 1-iodo-2-phenylethane and 1-
deutero-1-iodo-2-phenylethane as a colorless oil. The ratio of
1
these two products was determined by H NMR spectroscopy.
6. Typical procedures for iodine–lithium exchange reactions with
compound 17
Reaction quenched after 5, 30, 150 min, yield 85, 77, 59%,
kH/kD 0.5, 0.6, 1.1.
Quench with deuterated methanol or deuterated thiophenol.
3-(tert-Butyldimethylsilyloxy)-1-deutero-4,4-dimethyl-1-iodo-
pentane (20): A pre-cooled (Ϫ110 ЊC) solution of n-butyl-
lithium in hexane (0.27 mL, 1.50 M, 0.41 mmol) and pentane
(1 mL) was added at Ϫ110 ЊC to a solution of 17 (130 mg, 0.27
mmol) in Trapp solvent mixture (2 mL). After the indicated
reaction time the reaction was quenched with deuterated
methanol (22 µL, 2 equiv.) or deuterated thiophenol (57 µL,
2 equiv.). Then brine (5 mL) was added and the reaction
mixture was extracted with pentane (5 mL). The combined
organic phases were dried with Na2SO4 and concentrated. The
The undeuterated and the monodeuterated 1-iodo-2-
phenylethane were synthesized independently for analysis
according to the above procedure in 98% yield by quenching
with either methanol or deuterated methanol after 10 min.
1
1-Iodo-2-phenylethane: H NMR (300 MHz, CDCl3): δ = 3.11
(t, J = 7.7 Hz, 2H), 3.28 (t, J = 7.7 Hz, 2H), 7.11–7.27 (m, 5H).
13C NMR (75 MHz, CDCl3): δ = 5.3, 40.3, 126.8, 128.3, 128.6,
140.6. C8H9I (232.1): calcd. C 41.41, H 3.91; found C 41.33, H
3.84%. 1-Deutero-1-iodo-2-phenylethane: 1H NMR (300 MHz,
CDCl3): δ = 3.10 (d, J = 7.7 Hz, 2H), 3.27 (tt, JHH = 7.7 Hz,
JHD = 1.1 Hz, 1H), 7.11–7.27 (m, 5H). 13C NMR (75 MHz,
J. Chem. Soc., Perkin Trans. 2, 1999, 731–736
735

View Article Online
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CDCl3): δ = 5.3 (t, JCD = 22.7 Hz), 40.3, 126.8, 128.3, 128.6,
140.6. C8H8DI (233.1): calcd. C 41.23, H ϩ D 3.89; found C
41.52, H ϩ D 4.19%.
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Acknowledgements
This work has been supported by the Deutsche Forschungsge-
meinschaft (SFB 260 and Graduiertenkolleg “Metallorganische
Chemie”) and the Fonds der Chemischen Industrie. M.M. is
grateful to the latter institution for granting him a Kekulé-
fellowship.
10 H. C. Stiasny and R. W. Hoffmann, Chem. Eur. J., 1995, 1, 619.
11 G. Boche, M. Schimeczek, J. Cioslowski and P. Piskorz, Eur. J. Org.
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Paper 9/00121B
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J. Chem. Soc., Perkin Trans. 2, 1999, 731–736