Synthesis of 1-functionalized silylcyclopropanes via cyclization of 3- silylalk-4-enols

Article abstract of DOI:10.1055/s-1998-2072

Tosylation of 3-silylalk-4-en-1-ols 3, as obtained via ring opening of epoxides 2 by silyl-substituted allyl anions 1, yields 4-alkenyl tosylates 4. Anion generation by deprotonation gives vinylcyclopropanes 5. 1- Silylcyclopropane-1-carboxylic acids 7 were prepared in two steps by ozonization of 5.

Full text of DOI:10.1055/s-1998-2072

June 1998
SYNTHESIS
899
Synthesis of 1-Functionalized Silylcyclopropanes Via Cyclization of 3-Silylalk-4-enols
Anette Nowak, Ernst Schaumann*
Institut für Organische Chemie, Technische Universität Clausthal, Leibnizstr. 6, D-38678 Clausthal-Zellerfeld, Germany
Fax +49(5323)722858; E-mail: ernst.schaumann@tu-clausthal.de
Received 17 September 1997; revised 17 November 1997
Abstract: Tosylation of 3-silylalk-4-en-1-ols 3, as obtained via
ring opening of epoxides 2 by silyl-substituted allyl anions 1,
yields 4-alkenyl tosylates 4. Anion generation by deprotonation
gives vinylcyclopropanes 5. 1-Silylcyclopropane-1-carboxylic
acids 7 were prepared in two steps by ozonization of 5.
Key words: 1-silylcyclopropane-1-carboxylic acids, 3-silylalk-4-
en-1-ols, 4-alkenyl tosylates, epoxide ring opening, vinylcyclo-
propanes
Functionalized trimethylsilyl-substituted cyclopropanes
have emerged as useful synthetic building blocks.1 They
are usually obtained by Simmons–Smith cyclopropana-
tion of silyl-substituted olefins2 or sulfur–silicon ex-
change of sulfur-substituted cyclopropanes.3 The latter
approach seems attractive also for the synthesis of the so
far unknown 1-silyl-1-vinylcyclopropanes, promising in-
termediates for the synthesis of, for example, cyclopro-
pane-derived amino acids.4 The required precursors 1-
(phenylthio)-1-vinylcylopropanes 5a,b are accessible by
cyclization of tosylated 3-(phenylthio)alk-4-en-1-ols
4a,b, the ring-opening products of epoxides 2 by phe-
nylthio-stabilized allyl anions.5 In fact, reductive lithia-
tion of 5a,b using the aromatic radical anions lithium 4,4¢-
di-tert-butylbiphenylide (LDBB)6 or lithium 1-(dimethy-
lamino)naphthalenide (LDMAN)7 and treatment of the re-
sulting 1-lithio-1-vinylcyclopropanes with trialkyl-
a: (i) BuLi, THF, –78°C, 4 h; (ii) 2, –78°C to r.t. b: BuLi, THF,
chlorosilanes gave the desired 1-silyl-1-vinylcyclopro-
–78°C, 3 h. c: (i) LDMAN (for 5a) or LDBB (for 5b), THF, –78°C,
panes, but gave 5d in only 13% yield from the reaction of
5b with LDBB/chlorotrimethylsilane and gave 5e in 16%
yield from the reaction of 5a with LDMAN/chlorodime-
thylphenylsilane (Scheme 1).
2 h; (ii) ClSiR2R3 .
2
Scheme 1
der phase-transfer conditions to provide cyclopropanecar-
boxylic acids 7. This approach gave better yields of
carboxylic acids 7 than direct oxidative workup of the
ozonization mixture (see Scheme 2).
As an alternative for the synthesis of silylcyclopropanes,
cyclization of tosylated 3-silylalk-4-en-1-ols may be en-
visaged. Compounds of type 4 had been obtained previ-
ously by tosylation of alcohols obtained by ring opening
of epoxides 2 by silyl-substituted allyl anions 1b–e.8
However, they had failed to give anions with the usual
alkyllithium bases.5, 8 We have now found that the partic-
ularly efficient Schlosser9 reagent (BuLi/potassium tert-
butoxide) allows deprotonation leading to immediate in-
tramolecular displacement of tosylate to give 1-silyl-1-vi-
nylcyclopropanes 5d–j in good to very good yields.
Products 5d,e and 5g–j were isolated as mixtures of two
diastereomers, which can be distinguished by NMR spec-
troscopy. 5f was a pure diastereomer. Only 4c failed to un-
dergo the reaction (Scheme 2).
In the present work racemic epoxides were used, but opti-
cally active starting materials would provide straightfor-
ward access to non-racemic silylcyclopropane building
blocks.
All experiments were performed under dry N2. THF was distilled
from sodium benzophenone ketyl prior to use. CH2Cl2 was distilled
from CaH2. Column chromatography was carried out on Merck silica
gel (70–230 mesh). Petroleum ether (PE) with the boiling range
60–70°C was always used in the separations. Analytical TLC was
performed on Merck silica gel 60 PF254 plates (visualization with UV
light or 4-methoxybenzaldehyde spray reagent). Mps are uncorrected.
IR spectra were recorded on a Pye-Unicam SP 3-200 spectrometer
and on a Bruker Vektor 22 instrument. NMR spectra were obtained
on Bruker ARX 400 or DPX 200 spectrometers; coupling constants,
J, are given in Hz. Assignments of 13C NMR signals were supported
by broadband decoupled DEPT.
Ozonization of the vinyl group and subsequent reductive
ozonide cleavage by sodium borohydride, dimethyl sul-
fide or zinc/HOAc gave carbaldehydes 6 in good yields.
Products 6 were oxidized by potassium permanganate un-

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For the tosylation of 3c–j to give 4c–j, a protocol given previously
was used.5 Instead of pyridine, CH2Cl2 (1 mL/mmol) and Et3N (1.3
equiv) was used. Separation of a- and g-isomers was achieved at this
stage by chromatography. Products 4c–h and 4j were obtained as a
mixture of diastereomers (ratio a,a* 1.4:1, 3:1, 1.1:1, 1.3:1, 1.7, 2.9:1
and 1.5:1 for 4j), 4i was a pure diastereomer; for spectroscopic data
see Tables 1, 2.
The synthesis of sulfur-substituted precursors 4a, 5a has been report-
ed previously.5 Compounds 4b, 5b were obtained analogously as a
mixture of diastereomers (for 4b ratio 1.25:1, for 5b ratio 1.9:1). For
spectroscopic data see Tables 1, 2 (for 4b) and Tables 3, 4 (for 5b).
Desulfurization; General Procedure:
The preparation of lithium 4,4¢-di-tert-butylbiphenylide (LDBB)12
and lithium 1-(dimethylamino)naphthalenide (LDMAN)13 is de-
scribed in the literature. A solution of 5a,b (1 mmol) in THF (5 mL)
was treated with LDBB (for 5b) or LDMAN (for 5a) (3 mmol) for 2 h
at –78°C. Then a solution of a trialkylchlorosilane (4 mmol) in THF
(10 mL) was added. The mixture was allowed to warm to r.t. over-
night. Then hydrolysis was carried out with a mixture of sat. aq
NH4Cl and Et2O (50 mL). The organic layer was washed with sat.
brine (2´), dried (Na2SO4), and concentrated in vacuo. The residue
was purified by column chromatography (PE) to give 5d (13%) and
5e (16%), respectively, as single diastereomers; for spectroscopic
data see Tables 3, 4.
Preparation of Vinylcyclopropanes 5 from Tosylates 4 Using Bu-
tyllithium/Potassium tert-Butoxide; General Procedure:
t-BuOK (3 equiv) in anhyd THF (5 mL/mmol) was mixed with 1.6 M
BuLi in hexane (3.3 equiv) at –95°C. The solution was stirred for
15 min and transferred via transfer syringe into a solution of tosylate
4 in THF (5 mL/mmol) at –95°C. The mixture was allowed to warm
to –78 °C, and consumption of the tosylate was followed by TLC (PE/
Et2O 5:1). After the completion of the reaction, the solution was
poured into sat. aq NH4Cl/pentane/Et2O (1:1:1). The organic layer
was washed with sat. brine (2´), dried (Na2SO4), and concentrated in
vacuo. The crude product was purified by column chromatography
(PE). Products 5d,e and 5g–j were obtained as a mixture of
diastereomers (ratio 1.6:1, 2.6:1, 2.5:1, 3:1, 4:1 and 2:1, respectively).
The minor isomer was not obtained free of the major isomer. 5f was
a pure diastereomer for which trans-orientation of the silyl and R1
substituents is assumed; for spectroscopic data see Tables 3, 4.
Ozonization of 5e–g,i,j; General Procedure:
A stirred solution of 5 in MeOH (10 mL/mmol) was treated with
ozone at –78°C. After complete consumption of the starting material,
NaBH4 (1.5 equiv) (for 6b,c,e) or DMS (1.5 equiv) (for 6a) or Zn/
HOAc (1.5 equiv) (for 6d) was added at the same temperature. The
mixture was allowed to warm to r.t. and stirred overnight. The solu-
tion was poured into a two-phase system of H2O and Et2O. The organ-
ic layer was separated, washed with sat. brine (2´), dried (Na2SO4),
and concentrated in vacuo. The crude product was purified by column
chromatography (PE/EtOAc). Products 6a–c and 6e were obtained as
a mixture of diastereomers (ratio 1.8:1, 1.9:1, 1.7:1 and 1.8:1 for 6e);
6d was a pure diastereomer. For spectroscopic data of 6a (mp
127–129°C) and 6b–e see Tables 3, 4.
a: (i) BuLi, (for 1d, 1e), or s-BuLi, TMEDA (for 1b, 1c), THF, –78°C,
4 h; (ii) 2, –78°C, 4 h. b: Et3N, 4-DMAP, TosCl, CH2Cl2, –20°C,
48 h. c: BuLi, t-BuOK, THF, –78°C, 3 h. d: O3, MeOH, –78°C,
NaBH4 (for 6b, 6c, 6e) or Zn, HOAc (for 6d), –78°C, to r.t. e: KMnO4,
H2O, CH2Cl2, PTC (methyltrioctylammonium chloride), r.t.
Scheme 2
Oxidation of Carbaldehydes 6; General Procedure:
Oxirane 2a is commercially available, (benzyloxymethyl)oxirane
(2b) was prepared from epichlorohydrin by conventional methods.10
Silylalkenols 3 were prepared according to a general procedure.5
Products 3c,g,i8 and 3f,h11 have been reported before. Products 3d,e,j
were obtained as a mixture of diastereomers (ratio a,a* 1.1:1, 1.3:1,
1.5:1, respectively). Separation of a,a*-isomers and minor g-
isomers5, 8 (ratio a,g5:1, 5:1, 4.5:1) was not achieved by chromatog-
raphy; for spectroscopic data see Tables 1, 2. Alkenols 3a,b were gen-
erated only in situ.
To a solution of 6 (1 mmol) in H2O (1.5 mL)/CH2Cl2 (2.5 mL) and
methyltrioctylammonium chloride (3 drops) was added KMnO4
(316.1 mg, 2 mmol). The mixture was stirred overnight at r.t. and then
treated with sodium bisulfite solution, followed by 2 N H2SO4 (5
mL). The organic layer was separated, dried (Na2SO4), and concen-
trated in vacuo. Purification of the crude product was achieved by re-
crystallization. Products 7a–c were obtained as a mixture of
diastereomers (ratio 1.2:1, 1.2:1, 1.3:1, respectively). For spectro-

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scopic data of 7a (mp 132–134°C), 7b (mp 135–137 °C), and 7c (mp
192–194°C) see Tables 3, 4.
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(9) Schlosser, M. J. Organomet. Chem. 1967, 8, 9.
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K.; Takahashi, M.; Ogasawara, K. Heterocycles 1990, 31, 1715.
(11) Flörke, H. Dissertation, Universität Clausthal, 1993.
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(13) Cohen, T.; Sherbine, J. P.; Hutchins, R. R.; Lin, M.-T. Organo-
met. Synth. 1986, 3, 361.
Support of this work by Fonds der Chemischen Industrie, Frankfurt,
is gratefully acknowledged.
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(2) Wells, G. J.; Yan, T.-H.; Paquette, L. A. J. Org. Chem. 1984, 49,
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(4) Burgess, K.; Ho, K.-K.; Moye-Sherman, D. Synlett 1994, 575.
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