New chiral propargylic silanes and the first examples of asymmetric intramolecular Sakurai reactions

Article abstract of DOI:10.1055/s-2001-18712

The syntheses of four new chiral propargylic silanes are reported. The syntheses of these cyclization precursors offer the possibility of studying the asymmetry of the first examples of the intramolecular version of the Sakurai reaction.

Full text of DOI:10.1055/s-2001-18712

2470
PAPER
New Chiral Propargylic Silanes and the First Examples of Asymmetric
Intramolecular Sakurai Reactions
A
symmetric Intramole
a
cular Sukur
r
ai Reac
t
t
ions in Cordes*
Chemisches Institut der Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany
Fax +49(391)6712223; E-mail: Martin.Cordes@vst.uni-magdeburg.de
Received 26 June 2001; revised 29 August 2001
Abstract: The syntheses of four new chiral propargylic silanes are
reported. The syntheses of these cyclization precursors offer the
possibility of studying the asymmetry of the first examples of the in-
tramolecular version of the Sakurai reaction.
Key words: chiral auxiliaries, cyclizations, Lewis acids, Sakurai
reaction, spiro compounds
Scheme 1 Asymmetric intramolecular Sakurai reactions
The last three decades witnessed an enormous develop-
ment of methods in the use of organosilicon compounds
for organic synthesis.1,2 Nowadays, in nearly every major
synthesis, an organosilicon reagent is used for C–C bond
formation, functional group transformation, or protection.
With the current challenge in synthesis being focussed on
enantio- and diastereoselectivity, it is not surprising that
increasing attention has been directed towards the use of
organosilicon compounds for asymmetric synthesis.3
yl)dimethylsilane (4)8 afforded the iodide 5 in 94% yield.
The chiral precursor 7 for asymmetric Sakurai cyclization
was then prepared by the action of iodide 5 with the
known SAMP precursor (2S)-(+)-2-(methoxymethyl)pyr-
rolidine (6) developed by Seebach and Enders.9 Finally,
treatment of 7 with diethylaluminum chloride in dichlo-
romethane at –95 °C resulted in the formation of the
spiroannulated ketal 2 in 73% yield and 25% ee. The use
of titanium tetrachloride as Lewis acid afforded the com-
pound 2 in 71% yield and 42% ee (Scheme 2).10
Optically active Si-centered chiral organosilicon com-
pounds became available in the early 1960s by the pio-
neering work of Sommer and his co-workers.4 Most of
these compounds were derivatives of the methyl- -naph-
thylphenylsilyl system. One of the limitations in using Si-
centered chiral organosilicon compounds is the need to
prepare these compounds by optical resolution. Further-
more, since organosilicon compounds can easily undergo
racemization, recovery and recycling of the valuable opti-
cally active silicon compounds with its optical purity in-
tact cannot be guaranteed. Therefore, considerable
interest has been focused on the preparation of C-centered
chiral organosilicon compounds where the chiral moiety,
while attached to a silicon, is located at a carbon center.5
For potential application in organic synthesis such com-
pounds have to be prepared in synthetically useful quanti-
ties from readily available optically active natural
products, the so-called “chiral pool”. Seeking an exten-
sion of such enantioselective chemistry, we became inter-
ested in the synthesis of optically active propargylic
silanes and studied their ability to induce asymmetry in
the intramolecular version of the Sakurai reaction
(Scheme 1).6
Starting from the hitherto unknown acetylene 3, which is
readily available from the corresponding enone described
by Gleiter et al.,7 the coupling with the bis(iodometh-
Synthesis 2001, No. 16, 30 11 2001. Article Identifier:
1437-210X,E;2001,0,16,2470,2476,ftx,en;T06301SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
Scheme 2 The proline model

PAPER
Asymmetric Intramolecular Sukurai Reactions
2471
The versatile oxazolidin-2-one based methodology devel-
oped by Evans has been widely used in asymmetric syn-
thesis for the preparation of highly functionalized
homochiral molecules.11 Encouraged by these results, we
focused on the synthesis of propargylic silanes bearing the
chiral information derived from an oxazolidin-2-one. Ac-
cording to Davies the oxazolidin-2-one auxiliary 8 was
easily prepared in 4 steps from L-phenylalanine in 40%
overall yield.12 Ensuing alkylation with the iodide 5 in
THF in the presence of BuLi generated the chiral orga-
nosilane 9 in excellent yield. Subsequent cyclization with
diethylaluminum chloride in dichloromethane at –95 °C
led to the spiroketal 2 in 79% yield. In this case no enan-
tioselectivity was observed. Compound 2 was obtained as
a racemate (Scheme 3).10 Attempts to use titanium tetra-
chloride as Lewis acid also led to the racemic compound
2.
O
1] n-BuLi
O
NH
2]
O
O
Si
Bn
Scheme 4 The Seebach “HyperQuat” auxiliary
I
8
5
steps from (1R)-(–)-myrtenal,15 was converted to the pro-
pargylic silane 19 in 2 steps in 86% overall yield. Final io-
dination gave the compound 20 in excellent yield
(Scheme 5).
O
Si
N
O
O
O
O
O
•
Et2AlCl
–95 °C
O
O
O
79%
racemic
I
I
PPTS
80%
38%
2
9
O
O
15
OMe
16
14
Scheme 3 The SuperQuat model
In order to increase the stability of the transition state of
the latter cyclization, the more steric hindered oxazolidin-
2-one 10 was used to generate a chiral precursor for asym-
metric intramolecular Sakurai reactions. Thus, treatment
of the chiral Seebach auxiliary 10,13 available in 4 steps
from L-valine in 45% overall yield, with bis(iodometh-
yl)dimethylsilane (4)8 gave the iodide 11 in 21% yield.
Subsequent coupling of the iodide 11 with the acetylene 3
according to Scheme 4 gave the chiral cyclization precur-
sor 12 in 83% yield. Terminal ring closure with diethyla-
luminum chloride in dichloromethane afforded the
spiroketone 13 in 80% yield. The stereoselectivity howev-
er was very poor (4% ee).10 The use of titanium tetrachlo-
ride as Lewis acid resulted in the decomposition of the
starting material.
MeO
MeO
MgBr
•
Si
Si
Br2
Ph
Br
17
MeO
18
MeO
I
Si
n-BuLi
Si
I2
95%
86%
20
19
Scheme 5 Synthesis of the iodide 16 and the new chiral propargylic
silane 20
In compliance with Scheme 5, 3-(3-iodopropyl)cyclohex-
2-en-1-one (14)14 was first converted to its ketal 16 in
38% yield without isomerization of the double bond, us-
ing 2-methoxy-1,3-dioxolane (15) in the presence of pyri-
dinium p-toluenesulfonate as catalyst. In addition, the
starting material was recovered in 60% yield. The chiral
phenylsilane 17, available by a procedure of Taddei in 3
We would like to point out that the absolute configuration
of 17 is the same as that of myrtenal and the relative con-
figuration of the two new stereocenters is “trans” and not
“cis” as previously mentioned in the literature.15,16 This
fact was proven by the first X-ray crystal analysis of 17
(Figure).17
Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York

2472
M. Cordes
PAPER
Figure Molecular structure of the chiral phenylsilane 17 in the cry-
stal
The coupling of the chiral propargylic silane 20 with io-
dide 16, using the Knochel protocol gave a new chiral cy-
clization precursor 22 in fair yield (Scheme 6).18,19
Scheme 7 The myrtenal model
Solvents were dried by standard procedures and redistilled under N2
prior to use. All organometallic reactions were run under N2 or ar-
gon, and pure products were obtained after flash chromatography
using Merck silica gel 60 (40–63 mm). Mass spectra were recorded
on Finnigan MAT 95, 8430 and SSQ 7000 spectrometers and high
resolution mass spectra were obtained on the first two spectrometers
(reference PFK, peak matching method, accuracy 2 ppm). IR spec-
tra were recorded on Perkin-Elmer 2000, 580, FT 1710 and Nicolet
320 FT-IR spectrometers. NMR spectra were recorded on Bruker
AC 200, AM 400, and DPX 400 spectrometers. Optical rotations
were recorded with a Perkin Elmer 241 polarimeter. GC analyses
were accomplished with a Hewlett Packard 5890A gas chromato-
graph using a 12 m 0.25 mm (i.d.) fused silica capillary column,
containing immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -
cyclodextrin, 120 °C, 1 bar hydrogen.
3-[5-(Trimethylsilyl)pent-4-ynyl]cyclohex-2-en-1-one,7
bis(io-
Scheme 6 Synthesis of cyclization precursor 22
domethyl)dimethylsilane (4),8 (2S)-(+)-2-(methoxymethyl)pyrroli-
dine (6),9 (4S)-4-benzyl-5,5-dimethyloxazolidin-2-one (8),12 (4S)-
4-isopropyl-5,5-diphenyloxazolidin-2-one (10),13 3-(3-iodopro-
pyl)cyclohex-2-en-1-one (14)14 and (1S,2R,3S,5R)-(2-methoxyme-
thyl-6,6-dimethylbicyclo[3.1.1]hept-3-yl)dimethylphenylsilane
Cyclization of 22 with diethylaluminum chloride in
dichloromethane at –95 °C yielded the optically active
spiroketal 2 in good yield, but with a low enantioselectiv-
ity of 8% ee. However, the use of titanium tetrachloride as (17)15 were prepared according to the literature.
Lewis acid afforded compound 2 in 76% yield and a re-
markable 51% ee (Scheme 7).10
7-Pent-4-ynyl-1,4-dioxaspiro[4.5]dec-6-ene (3)
Ethane-1,2-diol (11 g, 177.2 mmol) and pyridinium p-toluene-
Our results demonstrate the possibility of building C-cen-
tered optically active organosilanes for asymmetric syn-
thesis. Considering the fact that the generation of chiral
quaternary centers is nontrivial, we presented four cy-
clization precursors which led to optically active products
in the range of a low 4% ee up to a remarkable 51% ee.
Even though the enantioselectivity is too weak for appli-
cation in natural product synthesis, this approach nonethe-
sulfonate (251 mg, 1.0 mmol) were added to a solution of 3-[5-(tri-
methylsilyl)pent-4-ynyl]cyclohex-2-en-1-one7 (5.94 g, 25.3 mmol)
in anhyd benzene (50 mL). The mixture was refluxed for 22 h with
water separation by a Dean–Stark trap. After removal of the sol-
vents in vacuo, Et2O (50 mL) was added to the residue. The solution
was washed with sat. aq NaHCO3 solution (20 mL) and brine (20
mL), dried (MgSO4) and evaporated in vacuo. To the crude product
was added THF (10 mL) and a solution of 1.0 M TBAF (tetrabuty-
lammonium fluoride) in THF (38 mL, 38 mmol). The mixture was
less demonstrated the synthetic potential of such stirred at r.t. for 1 h. Finally aq NaHCO3 solution (50 mL) was add-
ed and the aqueous layer was extracted with Et2O (3 50 mL). The
asymmetric cyclizations, and it underscores the impor-
combined organic extracts were dried (MgSO4) and evaporated in
tance of improving the enantioselectivity of these kinds of
vacuo. The residue was purified by flash chromatography on silica
gel (pentane–Et2O, 10:1) to afford the pure ketal 3 (4.5 g, 86%) as a
colorless oil which solidified during storage at low temperature
reactions. Further investigations along these lines are cur-
rently underway in our laboratory.
(–40 °C).
Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Intramolecular Sukurai Reactions
2473
1H NMR (400 MHz, CDCl3): = 1.62–1.70 (m, 2 H), 1.71–1.81 (m,
4 H), 1.95 (t, J = 2.7 Hz, 1 H), 1.96 (t, J = 1.5 Hz, 2 H), 2.11 (br t,
J = 7.6 Hz, 2 H), 2.18 (dt, J = 2.7 Hz, J = 7.1 Hz, 2 H), 3.91–4.01
(m, 4 H), 5.36 (br t, J = 1.1 Hz, 1 H).
IR (neat): 3501 (w), 2944 (s), 2875 (s), 2830 (s), 2810 (s), 2219 (w),
1668 (m), 1456 (m), 1248 (s), 1186 (s), 1100 (s), 934 (s), 844 (s)
cm–1.
(4S)-4-Benzyl-3-({[6-(1,4-dioxaspiro[4.5]dec-6-en-7-yl)hex-2-
ynyl]dimethylsilyl}methyl)-5,5-dimethyloxazolidin-2-one (9)
To a solution of 812 (90 mg, 0.44 mmol) in anhyd THF (2 mL) at –
78 °C was added a solution of 2.5 M BuLi in hexane (176 L, 0.44
mmol). The resulting red-orange solution was warmed to r.t. within
1 h. Finally, a solution of 5 (183 mg, 0.44 mmol) in THF (1 mL) was
added and the mixture was stirred for 15 h at 60 °C. Subsequent
flash chromatography on silica gel (pentane–Et2O, 1:2) of the crude
reaction mixture yielded pure 9 (173 mg, 80%) as a colorless oil;
[ ]D20 –5.6 (c = 1.98, CHCl3).
13C NMR (100 MHz, CDCl3): = 17.99 (t), 20.88 (t), 26.00 (t),
28.38 (t), 33.26 (t), 36.06 (t), 64.30 (t), 68.46 (s), 84.04 (s), 106.45
(s), 122.15 (d), 144.13 (s).
MS (EI): m/z (%) = 206 ([M+], 10), 178 (20), 167 (95), 126 (100),
106 (45), 99 (27), 91 (35), 79 (16), 77 (18), 53 (10).
HRMS (EI): m/z calcd for C13H18O2: 206.1307, found: 206.1306.
IR (neat): 3291 (s), 2944 (s), 2875 (s), 2361 (s), 2341 (s), 1667 (m),
1439 (m), 1355 (m), 1099 (s), 1078 (s), 933 (s), 642 (m) cm–1.
1H NMR (400 MHz, CDCl3): = 0.21 (s, 3 H), 0.22 (s, 3 H), 1.19
(s, 3 H), 1.31 (s, 3 H), 1.54 (t, J = 2.7 Hz, 2 H), 1.57 (qui, J = 7.5
Hz, 2 H), 1.73–1.78 (m, 4 H), 1.91–1.96 (m, 2 H), 2.05 (t, J = 7.5
Hz, 2 H), 2.11 (tt, J = 2.7 Hz, J = 7.1 Hz, 2 H), 2.51 (d, J = 15.4 Hz,
1 H), 2.72 (dd, J = 9.5 Hz, J = 14.4 Hz, 1 H), 2.83 (d, J = 15.4 Hz,
1 H), 3.13 (dd, J = 5.1 Hz, J = 14.4 Hz, 1 H), 3.74 (dd, J = 5.1 Hz,
J = 9.5 Hz, 1 H), 3.91–4.00 (m, 4 H), 5.33 (br s, 1 H), 7.21–7.35 (m,
5 H).
13C NMR (100 MHz, CDCl3): = –3.37 (q), –3.13 (q), 5.99 (t),
18.75 (t), 20.97 (t), 22.21 (q), 27.02 (t), 28.06 (q), 28.47 (t), 32.04
(t), 33.33 (t), 34.73 (t), 36.47 (t), 64.38 (t), 67.79 (d), 77.06 (s),
79.11 (s), 80.85 (s), 106.59 (s), 121.98 (d), 126.86 (d), 128.79 (d),
128.88 (d), 136.89 (s), 144.64 (s), 157.56 (s).
[6-(1,4-Dioxaspiro[4.5]dec-6-en-7-yl)hex-2-ynyl]iodomethyl-
dimethylsilane (5)
To a stirred solution of 3 (69 mg, 0.33 mmol) in anhyd THF (3 mL)
at –78 °C was added a solution of 2.5 M BuLi in hexane (150 L,
0.37 mmol). Stirring was continued for 1 h at this temperature and
the mixture was treated with DMPU [1,3-dimethyl-3,4,5,6-tetrahy-
dropyrimidin-2(1H)-one, 80 L, 0.67 mmol]. After 10 min at
–78 °C, a solution of 48 (125 mg, 0.37 mmol) in THF (1 mL) was
added and the mixture was allowed to warm up to r.t. over a period
of 15 h. The mixture was quenched with sat. aq NaHCO3 solution
(5 mL) and the aqueous layer was extracted with Et2O (3 10 mL).
The combined organic extracts were dried (MgSO4) and evaporated
in vacuo. The residue was purified by flash chromatography on sil-
ica gel (pentane–Et2O, 15:1) to afford the iodide 5 (130 mg, 94%)
as a colorless oil.
MS (EI): m/z (%) = 495 ([M+], 2), 278 (8), 277 (25), 276 (100), 232
(21), 145 (8), 99 (6), 91 (14), 86 (4), 75 (4).
1H NMR (400 MHz, CDCl3): = 0.24 (s, 6 H), 1.56–1.65 (m, 4 H),
1.73–1.80 (m, 4 H), 1.94–1.97 (m, 2 H), 2.05–2.15 (m, 6 H), 3.92–
4.02 (m, 4 H), 5.35 (br s, 1 H).
HRMS (EI): m/z calcd for C29H41NO4Si: 495.2805, found:
495.2809.
IR (neat): 3474 (w), 2942 (s), 1748 (s), 1456 (s), 1398 (s), 1098 (s),
1077 (s), 933 (s), 843 (s), 701 (m), 531 (w) cm–1.
13C NMR (100 MHz, CDCl3): = –14.90 (t), –3.56 (q), 5.49 (t),
18.69 (t), 21.02 (t), 26.99 (t), 28.53 (t), 33.38 (t), 36.46 (t), 64.42 (t),
76.36 (s), 79.18 (s), 106.63 (s), 121.99 (d), 144.71 (s).
MS (EI): m/z (%) = 418 ([M+], 5), 199 (100), 170 (46), 167 (23),
128 (51), 99 (32), 73 (17), 55 (5).
(4S)-3-[(Iodomethyldimethylsilyl)methyl]-4-isopropyl-5,5-
diphenyloxazolidin-2-one (11)
To a slurry of 1013 (3 g, 10.66 mmol) in anhyd THF (20 mL) at
–10 °C was added a solution of 2.5 M BuLi in hexane (5 mL, 12.5
mmol). The resulting violet solution was warmed to r.t. within 1 h.
Finally a solution of 48 (5.7 g, 16.76 mmol) in anhyd THF (10 mL)
was added and the mixture was stirred for 6 h at 50 °C. The mixture
was quenched with sat. aq NaHCO3 solution (50 mL) and the aque-
ous layer was extracted with Et2O (3 100 mL). The combined or-
ganic extracts were dried (MgSO4) and evaporated in vacuo. The
residue was purified by flash chromatography on silica gel (pen-
tane–Et2O, 1:1) to give the pure iodide 11 (1.1 g, 21%) as a white
solid; [ ]D20 –160.1 (c = 1.10, CHCl3).
HRMS (EI): m/z calcd for C17H27IO2Si: 418.0825, found: 418.0829.
IR (neat): 3292 (w), 2941 (s), 2877 (s), 1669 (m), 1250 (s), 1099 (s),
933 (s), 842(s) cm–1.
(2S)-1-({[6-(1,4-Dioxaspiro[4.5]dec-6-en-7-yl)hex-2-ynyl]di-
methylsilyl}methyl)-2-methoxymethylpyrrolidine (7)
A neat mixture of 69 (522 mg, 4.53 mmol) and the iodide 5 (84 mg,
0.20 mmol) was heated at 80 °C with magnetic stirring for about 24
h. The crude mixture was purified by flash chromatography on sili-
ca gel (Et2O, 1% Et3N) to furnish the pure ketal 7 (81 mg, >99%) as
a colorless oil; [ ]D20 –49.6 (c = 1.88, CHCl3).
1H NMR (400 MHz, CDCl3): = 0.00 (s, 3 H), 0.04 (s, 3 H), 0.76
(d, J = 7.0 Hz, 3 H), 1.17 (d, J = 7.0 Hz, 3 H), 1.73 (d, J = 12.5 Hz,
1 H), 1.91 (d, J = 12.5 Hz, 1 H), 1.97–2.05 (m, 1 H), 2.71 (d,
J = 15.4 Hz, 1 H), 3.22 (d, J = 15.4 Hz, 1 H), 4.31 (d, J = 1.4 Hz, 1
H), 7.24–7.68 (m, 10 H).
13C NMR (100 MHz, CDCl3): = –14.10 (t), –3.27 (q), –3.20 (q),
15.48 (q), 22.81 (q), 30.03 (d), 35.04 (t), 71.42 (d), 87.49 (s), 124.99
(d), 125.94 (d), 127.51 (d), 128.18 (d), 128.59 (d), 138.79 (s),
144.81 (s), 157.03 (s).
1H NMR (400 MHz, CDCl3): = 0.16 (s, 6 H), 1.21 (t, J = 6.9 Hz,
1 H), 1.50 (t, J = 2.6 Hz, 2 H), 1.56–1.66 (m, 2 H), 1.68–1.83 (m, 5
H), 1.86–1.98 (m, 4 H), 2.09 (t, J = 7.4 Hz, 2 H), 2.12–2.16 (m, 2
H), 2.18–2.24 (m, 1 H), 2.44–2.53 (m, 1 H), 2.57 (d, J = 14.5 Hz, 1
H), 3.09–3.19 (m, 1 H), 3.27 (dd, J = 6.3 Hz, J = 9.4 Hz, 2 H), 3.35
(s, 3 H), 3.45–3.50 (m, 1 H), 3.92–4.00 (m, 4 H), 5.35 (br s, 1 H).
13C NMR (100 MHz, CDCl3): = –3.38 (q), –3.26 (q), 5.53 (t),
18.72 (t), 20.99 (t), 23.14 (t), 27.08 (t), 28.20 (t), 28.52 (t), 33.35 (t),
36.46 (t), 44.54 (t), 57.53 (t), 59.09 (q), 64.37 (t), 65.81 (d), 67.90
(t), 75.67 (s), 78.75 (s), 106.61 (s), 121.93 (d), 144.73 (s).
MS (EI): m/z (%) = 493 ([M+], 1), 478 (14), 450 (14), 406 (22), 353
(29), 352 (98), 222 (66), 207 (100), 199 (32), 165 (22), 129 (16), 91
(16), 73 (14), 61 (16).
MS (EI): m/z (%) = 405 ([M+], 2), 363 (4), 362 (20), 361 (74), 360
(100), 316 (4), 206 (5), 186 (6), 128 (18), 91 (4), 59 (4).
HRMS (EI): m/z calcd for C22H28INO2Si: 493.0934, found:
493.0930.
HRMS (EI): m/z calcd for C23H39NO3Si: 405.2699, found:
405.2699.
IR (KBr): 3448 (m), 2961 (m), 2928 (m), 2362 (w), 1740 (s), 1450
(s), 1255 (s), 1034 (s), 843 (s), 706 (s) cm–1.
Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York

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M. Cordes
PAPER
(4S)-3-({[6-(1,4-Dioxaspiro[4.5]dec-6-en-7-yl)hex-2-ynyl]dime-
thylsilyl}methyl)-4-isopropyl-5,5-diphenyloxazolidin-2-one (12)
To a solution of 3 (122 mg, 0.59 mmol) and anhyd THF (10 mL) at
–30 °C was added a solution of 2.5 M BuLi in hexane (300 L, 0.75
mmol). The mixture was allowed to reach 0 °C within 1 h. Finally a
solution of 11 (255 mg, 0.52 mmol) in anhyd THF (5 mL) was add-
ed and the mixture was heated at 45 °C for 16 h. The mixture was
quenched with sat. aq NaHCO3 solution (20 mL) and the aqueous
layer was extracted with Et2O (3 50 mL). The combined organic
extracts were dried (MgSO4) and evaporated in vacuo. The residue
was purified by flash chromatography on silica gel (pentane–Et2O,
1:1) to afford pure 12 (246 mg, 83%) as a colorless oil;
[ ]D20 –150.0 (c = 1.04, CHCl3).
1H NMR (400 MHz, CDCl3): = –0.12 (s, 3 H), 0.00 (s, 3 H), 0.77
(d, J = 7.0 Hz, 3 H), 1.17 (d, J = 7.0 Hz, 3 H), 1.27 (t, J = 2.6 Hz, 1
H), 1.35 (t, J = 2.6 Hz, 1 H), 1.64 (qui, J = 7.4 Hz, 2 H), 1.78–1.82
(m, 4 H), 1.99–2.03 (m, 3 H), 2.11 (t, J = 7.8 Hz, 2 H), 2.16 (tt,
J = 2.6 Hz, J = 7.1 Hz, 2 H), 2.70 (d, J = 15.4 Hz, 1 H), 3.21 (d,
J = 15.4 Hz, 1 H), 3.94–4.03 (m, 4 H), 4.32 (d, J = 1.6 Hz, 1 H),
5.39 (br s, 1 H), 7.23–7.69 (m, 10 H).
quenched with crushed ice and sat. aq NH4Cl solution (10 mL). The
aqueous layer was extracted with pentane (3 30 mL) and the com-
bined organic extracts were dried (MgSO4) and evaporated in vac-
uo. The residue was purified by flash chromatography on silica gel
(pentane–Et2O, 100:1) to yield the pure propargylic silane 19 (180
mg, 86%) as a colorless liquid; [ ]D20 +34.0 (c = 1.60, CHCl3).
1H NMR (400 MHz, CDCl3): = 0.14 (s, 3 H), 0.15 (s, 3 H), 0.75
(d, J = 9.7 Hz, 1 H), 0.93 (ddd, J = 7.0 Hz, J = 8.4 Hz, J = 11.2 Hz,
1 H), 1.05 (s, 3 H), 1.19 (s, 3 H), 1.54 (d, J = 2.9 Hz, 2 H), 1.76 (ddd,
J = 2.8 Hz, J = 7.0 Hz, J = 13.4 Hz, 1 H), 1.84 (t, J = 2.9 Hz, 1 H),
1.91 (sept, J = 3.0 Hz, 1 H), 2.01–2.08 (m, 1 H), 2.15 (dt, J = 2.0
Hz, J = 6.9 Hz, 1 H), 2.18–2.24 (m, 1 H), 2.27–2.33 (m, 1 H), 3.15
(dd, J = 4.1 Hz, J = 9.4 Hz, 1 H), 3.31 (s, 3 H), 3.43 (t, J = 9.6 Hz,
1 H).
13C NMR (100 MHz, CDCl3): = –5.41 (q), –5.12 (q), 4.24 (t),
15.52 (d), 22.84 (q), 27.84 (q), 27.92 (t), 31.82 (t), 38.85 (s), 41.17
(d), 42.46 (d), 42.68 (d), 58.73 (q), 67.04 (d), 77.20 (t), 82.65 (s).
MS (EI): m/z (%) = 264 ([M+], 1), 225 (38), 219 (8), 163 (8), 97
(40), 89 (100), 79 (6), 69 (8), 59 (10).
13C NMR (100 MHz, CDCl3): = –4.18 (q), –4.16 (q), 5.29 (t),
15.35 (q), 18.60 (t), 20.86 (t), 22.64 (q), 26.94 (t), 28.40 (t), 29.90
(d), 33.22 (t), 34.33 (t), 36.33 (t), 64.24 (t), 71.13 (d), 76.91 (s),
78.80 (s), 87.22 (s), 106.44 (s), 121.98 (d), 124.91 (d), 125.31 (d),
125.88 (d), 127.33 (d), 127.96 (d), 128.02 (d), 128.41 (d), 138.87
(s), 144.41 (s), 144.79 (s), 156.86 (s).
HRMS (EI): m/z calcd for C16H28OSi: 264.1909, found: 264.1907.
IR (neat): 3315 (m), 2900 (s), 2116 (w), 1457 (m), 1250 (s), 1116
(s), 837 (s), 629 (m) cm–1.
(1S,2R,3S,5R)-(3-Iodoprop-2-ynyl)-(2-methoxymethyl-6,6-
dimethylbicyclo[3.1.1]hept-3-yl)dimethylsilane (20)
MS (EI): m/z (%) = 571 ([M+], 1), 354 (8), 353 (24), 352 (100), 308
(18), 252 (8), 233 (8), 208 (12), 167 (12), 91 (8).
To a solution of 19 (58 mg, 0.22 mmol) in anhyd THF (3 mL) at
–78 °C was added a solution of 1.6 M BuLi in hexane (200 L, 0.33
mmol). After stirring for 1 h at this temperature, solid I2 (95 mg,
0.37 mmol) was added at –20 °C. The violet solution was allowed
to reach r.t. within 1 h whereupon solid Na2S2O3 was added. The re-
sulting colorless slurry was filtered through a short path column of
Celite (pentane–Et2O, 1:1). Removal of the solvent in vacuo and pu-
rification of the residue by flash chromatography on silica gel (pen-
tane–Et2O, 30:1) yielded the pure iodide 20 (82 mg, 95%) as a
colorless oil; [ ]D20 +30.5 (c = 3.09, CHCl3).
1H NMR (400 MHz, CDCl3): = 0.13 (s, 3 H), 0.14 (s, 3 H), 0.74
(d, J = 9.7 Hz, 1 H), 0.91 (ddd, J = 7.0 Hz, J = 8.4 Hz, J = 11.2 Hz,
1 H), 1.05 (s, 3 H), 1.19 (s, 3 H), 1.74 (s, 2 H), 1.75 (ddd, J = 2.8
Hz, J = 7.0 Hz, J = 13.4 Hz, 1 H), 1.91 (sept, J = 3.0 Hz, 1 H), 2.00–
2.07 (m, 1 H), 2.12–2.16 (m, 1 H), 2.17–2.22 (m, 1 H), 2.26–2.33
(m, 1 H), 3.13 (dd, J = 4.1 Hz, J = 9.4 Hz, 1 H), 3.30 (s, 3 H), 3.42
(t, J = 9.6 Hz, 1 H).
HRMS (EI): m/z calcd for C35H45NO4Si: 571.3118, found:
571.3125.
IR (neat): = 3474 (w), 2940 (s), 1736 (s), 1451 (s), 1252 (s), 1099
(s), 843 (s), 756 (s), 708 (s) cm–1.
7-(3-Iodopropyl)-1,4-dioxaspiro[4.5]dec-6-ene (16)
To a mixture of 1414 (4.07 g, 15.4 mmol) and 15 (6 mL, 61.6 mmol)
in anhyd benzene (15 mL) was added pyridinium p-toluene-
sulfonate (193 mg, 5 mol%). The resulting solution was stirred at r.t.
for 24 h. The mixture was quenched with sat. aq NaHCO3 solution
(20 mL) and the aqueous layer was extracted with Et2O (3 50 mL).
The combined organic extracts were dried (MgSO4) and evaporated
in vacuo. The residue was purified by flash chromatography on sil-
ica gel (pentane–Et2O, 8:1) to afford the pure ketal 16 (1.79 g, 38%)
as a colorless oil. In addition, unreacted starting material 14 (2.44 g,
60%) was recovered.
13C NMR (100 MHz, CDCl3): = –5.47 (q), –5.22 (q), 6.89 (t),
15.60 (d), 22.55 (q), 27.55 (q), 27.68 (t), 31.56 (t), 38.54 (s), 40.93
(d), 42.32 (d), 42.42 (d), 58.42 (q), 77.00 (t), 91.92 (s) (one acety-
lenic carbon atom not detected).
MS (EI): m/z (%) = 390 ([M+], 1), 225 (16), 167 (24), 135 (26), 105
(12), 97 (34), 93 (22), 91 (32), 89 (100), 77 (18), 59 (12).
1H NMR (400 MHz, CDCl3): = 1.69–1.81 (m, 4 H), 1.92–2.00 (m,
4 H), 2.11 (dd, J = 7.5 Hz, J = 14.9 Hz, 2 H), 3.17 (t, J = 6.9 Hz, 2
H), 3.92–4.02 (m, 4 H), 5.37 (br s, 1 H).
13C NMR (100 MHz, CDCl3): = 6.55 (t), 21.18 (t), 28.72 (t), 31.24
(t), 33.53 (t), 38.05 (t), 64.68 (t), 106.67 (s), 122.94 (d), 143.49 (s)
MS (EI): m/z (%) = 308 ([M+], 12), 280 (44), 265 (4), 252 (17), 181
(72), 153 (12), 139 (14), 126 (100), 99 (12), 79 (10); 53 (6).
HRMS (EI): m/z calcd for C16H27IOSi: 390.0876, found: 390.0883.
IR (neat): 3314 (w), 2900 (s), 2362 (s), 2342 (s), 1457 (m), 1250 (s),
1115 (s), 836 (s) cm–1.
HRMS (EI): m/z calcd for C11H17IO2: 308.0273, found: 308.0266.
IR (neat): 2940 (s), 2878 (s), 2360 (s), 2342 (s), 1669 (m), 1438 (m),
1355 (m), 1219 (s), 1186 (s), 1095 (s), 933 (s) cm–1.
(1S,2R,3S,5R)-[6-(1,4-Dioxaspiro[4.5]dec-6-en-7-yl)hex-2-
ynyl]-(2-methoxymethyl-6,6-dimethylbicyclo[3.1.1]hept-3-
yl)dimethylsilane (22)
(1S,2R,3S,5R)-(2-Methoxymethyl-6,6-
An argon flushed Schlenk tube was charged with freshly prepared
Rieke zinc19 (203 mg, 3.1 mmol) and anhyd THF (3 mL). A solution
of 16 (96 mg, 0.31 mmol) in anhyd THF (1 mL) was added to the
resulting fine black zinc dispersion and the mixture was heated 2 h
at 50 °C. Complete insertion of zinc had occurred as indicated by
TLC analysis of reaction aliquots. The excess of zinc was allowed
to settle and a clear solution of the zinc reagent was ready for use.
The zinc reagent was transferred via cannula to a solution of CuCN
dimethylbicyclo[3.1.1]hept-3-yl)dimethylprop-2-ynylsilane (19)
An argon flushed Schlenk tube was charged with 1715 (240 mg, 0.79
mmol) and cooled to 0 °C. Neat Br2 (82 L, 1.59 mmol) was added
in one portion and the mixture was stirred for 1 h. After cooling the
mixture to –10 °C, a freshly prepared solution of 0.5 M allenylmag-
nesium bromide20 in Et2O (16 mL, 7.9 mmol) was slowly added.
The mixture was allowed to come to r.t. within 1 h and was
Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Intramolecular Sukurai Reactions
2475
(28 mg, 0.31 mmol) and LiCl (26 mg, 0.62 mmol) in anhyd THF (2
mL) at –20 °C and stirred for 20 min. The slightly green solution of
21 obtained, was cooled to –78 °C and the iodoalkyne 20 (60 mg,
0.15 mmol) in anhyd THF (1 ml) was slowly added. The reaction
was allowed to warm to r.t. within 12 h. Finally the mixture was di-
luted with pentane (20 mL) and filtered through a short path of silica
gel. Removal of the solvent in vacuo and purification of the residue
by flash chromatography on silica gel (pentane–Et2O, 5:1) yielded
the pure silane 22 (41 mg, 60%) as a colorless oil; [ ]D20 +24.0
(c = 2.48, CHCl3).
1H NMR (400 MHz, CDCl3): = 0.11 (s, 3 H), 0.12 (s, 3 H), 0.76
(d, J = 9.7 Hz, 1 H), 0.86–0.94 (m, 2 H), 1.05 (s, 3 H), 1.19 (s, 3 H),
1.48 (t, J = 2.6 Hz, 2 H), 1.60 (qui, J = 7.4 Hz, 2 H), 1.74–1.79 (m,
4 H), 1.90 (sept, J = 2.8 Hz, 1 H), 1.96–2.04 (m, 4 H), 2.07–2.11 (m,
2 H), 2.12–2.18 (m, 2 H), 2.19–2.24 (m, 1 H), 2.26–2.32 (m, 1 H),
3.13–3.15 (m, 1 H), 3.30 (s, 3 H), 3.42 (t, J = 9.7 Hz, 1 H), 3.92–
4.01 (m, 4 H), 5.34 (br s, 1 H).
Et2O, 1:1). Removal of the solvent in vacuo and purification of the
residue by flash chromatography on silica gel (pentane–Et2O, 10:1)
afforded the spiroketal 2 (27 mg, 0.12 mmol, 71%, 42% ee) as a col-
orless oil. The determination of the enantiomeric excess of 2 was
performed on a 12 m 0.25 mm (i.d.) fused silica capillary column,
containing immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -
cyclodextrin, 120 °C, 1 bar hydrogen.10 The analytical data were
identical with those reported above.
Cyclization of 12 to 1-Vinylidenespiro[4.5]decan-7-one (13)
with Diethylaluminum Chloride
Et2AlCl (1.0 M solution in hexanes, 300 L, 0.3 mmol) was added
dropwise to a stirred and cooled solution (–95 °C) of 12 (170 mg,
0.297 mmol) in anhyd CH2Cl2 (10 mL). The solution was allowed
to warm up to r.t. over a period of 10 h. The mixture was quenched
with sat. aq NaHCO3 solution and the aqueous layer was extracted
with Et2O (3 10 mL). The combined organic extracts were dried
(MgSO4) and evaporated in vacuo. The residue was purified by
flash chromatography on silica gel (pentane–Et2O, 30:1) to afford
the spiroketone 13 (42 mg, 0.238 mmol, 80%, 4% ee) as a colorless
oil. The determination of the enantiomeric excess of 13 was per-
formed on a 12 m 0.25 mm (i.d.) fused silica capillary column,
containing immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -
cyclodextrin, 120 °C, 1 bar hydrogen.10
13C NMR (100 MHz, CDCl3): = –5.23 (q), –4.97 (q), 4.37 (t),
15.70 (d), 18.73 (t), 20.98 (t), 22.82 (q), 27.07 (t), 27.86 (q), 27.98
(t), 28.52 (t), 31.83 (t), 33.36 (t), 36.44 (t), 38.86 (s), 41.27 (d),
42.50 (d), 42.73 (d), 58.67 (q), 64.36 (t), 77.21 (t), 77.75 (s), 78.58
(s), 106.60 (s), 121.88 (d), 144.72 (s).
MS (EI): m/z (%) = 444 ([M+], 1), 226 (8), 225 (42), 167 (26), 135
1H NMR (400 MHz, CDCl3): = 1.42–1.54 (m, 2 H), 1.59–1.76 (m,
6 H), 1.93–2.00 (m, 1 H), 2.19–2.23 (m, 2 H), 2.29 (t, J = 13.8 Hz,
1 H), 2.37–2.43 (m, 2 H), 4.73 (dt, J = 0.6 Hz, J = 4.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): = 22.95 (t), 23.68 (t), 30.33 (t),
35.82 (t), 37.63 (t), 41.03 (t), 49.27 (s), 52.32 (t), 78.64 (t), 110.82
(s), 202.31 (s), 211.39 (s).
(8), 91 (12), 89 (100), 75 (8).
HRMS (EI): m/z calcd for C27H44O3Si: 444.3060, found: 444.3065.
IR (neat): 2942 (s), 2363 (w), 2342 (w), 1671 (m), 1456 (s), 1248
(s), 1099 (s), 1077 (s), 943 (s), 835 (s) cm–1.
Cyclization of 7 to 8-Vinylidene-1,4-dioxadispiro[4.1.4.3]tetra-
decane (2) with Et2AlCl
MS (EI): m/z (%) = 176 ([M+], 29), 134 (58), 119 (43), 105 (56), 91
Et2AlCl (1.0 M solution in hexanes, 400 L, 0.4 mmol) was added
dropwise to a stirred and cooled solution (–95 °C) of propargylic si-
lane 7 (41 mg, 0.1 mmol) in anhyd CH2Cl2 (10 mL). The solution
was allowed to warm up to r.t. over a period of 10 h. The mixture
was quenched with sat. aq NaHCO3 solution (2 mL) and the result-
ing slurry was filtered through a short path of silica gel (pentane–
Et2O, 1:1). Removal of the solvent in vacuo and purification of the
residue by flash chromatography on silica gel (pentane–Et2O, 10:1)
afforded the spiroketal 2 (16 mg, 0.073 mmol, 73%, 25% ee) as a
colorless oil. The determination of the enantiomeric excess of 2 was
performed on a 12 m 0.25 mm (i.d.) fused silica capillary column,
containing immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -
cyclodextrin, 120 °C, 1 bar hydrogen.10
1H NMR (400 MHz, CDCl3): = 1.18–1.27 (m, 2 H), 1.42–1.50 (m,
1 H), 1.54–1.83 (m, 9 H), 2.37–2.44 (m, 2 H), 3.87–3.95 (m, 4 H),
4.74 (dt, J = 1.0 Hz, J = 4.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): = 21.10 (t), 24.37 (t), 30.11 (t),
34.91 (t), 36.07 (t), 36.53 (t), 44.13 (t), 46.67 (s), 63.71 (t), 64.47 (t),
77.92 (t), 109.54 (s), 113.31 (s), 201.92 (s).
(100), 84 (57), 79 (59), 50 (60), 41 (57), 39 (63).
HRMS (EI): m/z calcd for C12H16O: 176.1201, found: 176.1206.
IR (neat): 2953 (s), 2872 (s), 1956 (s), 1713 (s), 1446 (m) cm–1.
Cyclization of 22 to the Spiroketal 2 with Et2AlCl
Using the same reaction and workup conditions as reported for the
cyclization of compound 7, treatment of 22 (52 mg, 0.117 mmol)
with Et2AlCl (1.0 M solution in hexanes, 234 L, 0.234 mmol) af-
forded the spiroketal 2 (20 mg, 0.09 mmol, 77%, 8% ee) as a color-
less oil. The determination of the enantiomeric excess of 2 was
performed on a 12 m 0.25 mm (i.d.) fused silica capillary column,
containing immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -
cyclodextrin, 120 °C, 1 bar hydrogen.10 The analytical data were
identical with those reported above.
Cyclization of 22 to the Spiroketal 2 with TiCl4
Using the same reaction and workup conditions as reported for the
cyclization of compound 7, treatment of 22 (45 mg, 0.1 mmol) with
TiCl4 (1.0 M solution in CH2Cl2, 200 L, 0.2 mmol) afforded
spiroketal 2 (17 mg, 0.077 mmol, 76%, 51% ee) as a colorless oil.
The determination of the enantiomeric excess of 2 was performed
on a 12 m 0.25 mm (i.d.) fused silica capillary column, containing
immobilized octakis(2,6-di-O-methyl-3-O-pentyl)- -cyclodextrin,
120 °C, 1 bar hydrogen.10 The analytical data were identical with
those reported above.
MS (EI): m/z (%) = 220 ([M+], 8), 205 (15), 192 (100), 177 (37),
136 (26), 119 (22), 99 (58), 91 (38).
HRMS (EI): m/z calcd for C14H20O2: 220.1463, found: 220.1463.
IR (neat): 2938 (s), 2871 (s), 1955 (m), 1729 (m), 1448 (m), 1172
(s), 1090 (s), 948 (s), 845 (s) cm–1.
Cyclization of 7 with Titanium Tetrachloride
Acknowledgements
TiCl4 (1.0 M solution in CH2Cl2, 690 L, 0.69 mmol) was added
dropwise to a stirred and cooled solution (–95 °C) of propargylic si-
lane 7 (70 mg, 0.17 mmol) in anhyd CH2Cl2 (10 mL). The solution
was allowed to warm up to r.t. over a period of 10 h. The mixture
was quenched with sat. aq NaHCO3 solution (2 mL) and the result-
ing slurry was filtered through a short path of silica gel (pentane–
The author is indebted to Prof. Dr. W. A. König for allowing the use
of a chiral GC column. Thanks are also due to Dr. Jürgen Müller (†)
and Dr. Editha Müller for the GC analyses and to Dr. Axel Fischer
for the X-ray crystal structure.
Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York

2476
M. Cordes
PAPER
(14) Miller, R. D.; McKean, D. R. J. Org. Chem. 1981, 46, 2412.
(15) Coppi, L.; Ricci, A.; Taddei, M. Tetrahedron Lett. 1987, 28,
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(16) Lipshutz, B. H.; Sclafani, J. A.; Takanami, T. J. Am. Chem.
Soc. 1998, 120, 4021.
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b = 13.3330(10) Å, c = 14.0385(3) Å, U = 1839.35(19) Å3,
Z = 4, D = 1.061 Mgm–3, F(000) = 664, (MoK ) = 0.122
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Synthesis 2001, No. 16, 2470–2476 ISSN 0039-7881 © Thieme Stuttgart · New York