Synthesis of 25-hydroxyprovitamin D3 from ergosterol: A mild method for the cleavage of hetero Diels-Alder adducts leading to steroidal 5,7-dienes

Article abstract of DOI:10.1055/s-1999-3547

A new efficient seven-step procedure is described for the preparation of 3β,25-dihydroxy-cholesta-5,7-diene (7) from ergosterol (1) in a total yield of 30%. The 3-hydroxy function of ergosterol (1) is protected as tert- butyldimethylsilyl ether and the 5,

Full text of DOI:10.1055/s-1999-3547

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Ina Scherlitz-Hofmann,a Manuela Dubs,a Richard Prousa,a Bruno Schönecker,*a Peter Droescher,b Hans Schick,c
Eberhard Schrötter†
a Institut für Organische Chemie und Makromolekulare Chemie der Friedrich-Schiller-Universität Jena, Humboldtstr. 10, D-07743 Jena,
Germany
Fax +49-3641-948292, E-mail:c8scbr@uni-jena.de
b Jenapharm GmbH & Co.KG, Otto-Schott-Str. 15, D-07745 Jena, Germany
c WITEGA Angewandte Werkstoff-Forschung g. GmbH, Rudower Chaussee 5, D-12484 Berlin, Germany
5HFHLYHGꢀꢁꢂꢀ-DQXDU\ꢀꢁꢃꢃꢃꢄꢀUHYLVHGꢀꢅꢆꢀ0DUFKꢀꢁꢃꢃꢃ
Dedicated to Professor Dirk Walther, on the occasion of his 60th birthday
The chemistry and biology of vitamin D metabolites and
$EVWUDFWꢆ A new efficient seven-step procedure is described for the
analogs is a field of extensive research1. Ergosterol ꢉꢀꢊ is
a suitable and unique starting material for the synthesis of
such compounds because it exhibits the conjugated 5,7-di-
preparation of 3b,25-dihydroxy-cholesta-5,7-diene ꢉꢈꢊ from ergos-
terol ꢉꢀꢊ in a total yield of 30%. The 3-hydroxy function of ergos-
terol ꢉꢀꢊꢂis protected as WHUWꢇbutyldimethylsilyl ether and the 5,7-
diene system as hetero Diels–Alder adduct with 1,4-dihydro- ene system (provitamin stage) necessary for photochemi-
phthalazine-1,4-dione before ozonization of the side chain double
cal isomerization to the previtamin stage, and also a side
bond. The key step of this synthesis is a very mild method for the
chain double bond, which can be cleaved by ozonization
cleavage of the hetero Diels–Alder adduct ꢄ using lithium naphtha-
after protection of the 5,7-diene system by hetero Diels–
lenide. Tosylation of the 22-hydroxy function, C–C coupling with a
Alder reaction giving functionalized C22 steroids.2–5 After
C5 copper reagent and desilylation in usual way furnished the title
deprotection of the 5,7-diene these C22 steroids can react
with suitable reagents to provide provitamins with various
side chains.6,7
compound ꢈ.
.H\ꢂZRUGVꢆ vitamin D, protecting groups, ergosterol, cleavage of
hetero Diels–Alder adducts, C–C coupling
Synthesis 1999, No. 8, 1331–1334 ISSN 0039-7881 © Thieme Stuttgart · New York

ꢀꢁꢁꢃ
I. Scherlitz-Hofmann et al.
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Recently, we described the synthesis of (245)-24,25-di- The known methods for removal of the diene-protecting
hydroxyprovitamin D3 using the above strategy with a group are either quite drastic (high temperatures, strong
metallated C-22-steroid.8,9 With an "inversed" variation basic conditions, or use of LiAlH4 or DIBAH, respective-
we have attempted to couple C22 steroids with organome- ly)11,12 or give unsatisfactory yields. Therefore, there is an
tallic reagents. The C22 steroid, used for our former syn- interest in new mild methods for cleavage of hetero Diels–
thesis as 3b-benzoate, is not stable under such conditions Alder adducts leading to the 5,7-diene system in high
and under deprotection conditions of the 5,7-diene. There- yields. Recently, we described the reaction of such a het-
fore, we looked for other protecting groups of the 3-posi- ero Diels–Alder adduct with Rieke copper,13 prepared
tion with regard to stability, crystallization and total yield from lithium 2-thienylcyanocuprate with lithium naphtha-
and for alternative methods of deprotection of the 5,7-di- lenide in THF at low temperatures (–78 or –100°C), giv-
ene system.
ing nearly quantitavely the 5,7-diene.14 Now we have
found that this deprotection reaction is also possible with
lithium naphthalenide at –78°C. From ꢋ the expected 5,7-
diene ꢄ has been obtained in very good yield. The reaction
proceeds smoothly also at room temperature. Thus, a very
mild and smooth reaction for the deprotection of the 5,7-
diene system is available.
The synthesis of the stable silyl ether ꢃ was carried out by
reaction of ergosterol ꢉꢀꢊ in pyridine with WHUWꢇbutyldime-
thylsilyl chloride and imidazole at room temperature in
more than 90% yield. For the hetero Diels–Alder reaction
with the ergosterol derivative ꢃ we used 1,4-dihydro-
phthalazine-1,4-dione, prepared in situ from 1,2,3,4-tet-
rahydrophthalazine-1,4-dione with Pb(OAc)4 in CH2Cl2 For further synthesis of 25-hydroxyprovitamin D3 com-
and acetic acid, as described for the synthesis of the ergos- poundꢂꢄD was tosylated in the usual way. The compound
terol 3-benzoate adduct.10 This methodology, developed ꢄE, suitable for coupling reactions with organometallic re-
by Bogoslovskii et al.,5 has the advantage of achieving agents, is available from ergosterol ꢉꢀꢊ in five steps in a
better yields in the following ozonization step in compar- yield of more than 40%. For the construction of the 25-hy-
ison to the usually employed 3,5-dioxo-4-phenyl-1,2,4- droxy side chain, the 22-tosylate ꢄE was coupled in one
triazolin-1,2-diyl group. The Diels–Alder adduct ꢁ was step with the Grignard compound from 4-chloro-2-meth-
purified by chromatography and was obtained as a yellow yl-2-[(trimethylsilyl)oxy]butane15–17 and CuBr•SMe2 in
product in good yield.
THF as described for other vitamin D derivatives, giving
78% of the silylated provitamin ꢌ. The desired 3b,25-di-
The 22-alcohol ꢋ was synthesized by ozonization of the
adduct ꢁ at –60°C followed by NaBH4 reduction in the
usual way. The reactions were monitored by TLC to avoid
side products at the end of the reactions by overoxidation
and to achieve good yield of the compound ꢋ after reduc-
tion.
6,18
hydroxycholesta-5,7-diene ꢈ
(25-hydroxyprovitamin
D3) was obtained in nearly 90% by desilylation with tet-
rabutylammonium fluoride. Thus, a very efficient route (7
steps, 30% total yield) for producing this provitamin from
ergosterol was developed, based on a new and mild meth-
od for deprotection of the 5,7-diene system.
Synthesis 1999, No. 8, 1331–1334 ISSN 0039-7881 © Thieme Stuttgart · New York

3$3(5
A Mild Method for the Cleavage of Hetero Diels–Alder Adducts Leading to Steroidal 5,7-Dienes
ꢀꢁꢁꢁ
1H NMR: d = –0.05 (s, 3 H, CH3Si), 0.06 (s, 3 H, CH3Si), 0.82 (s, 3
H, 18-CH3), 0.85 [s, 9 H, (CH3)3CSi], 0.88 (d, 3- = 6.8 Hz, 3 H, 28-
CH3), 0.98 (s, 3 H, 19-CH3), 3.56 (m, 1 H, 3-H), 5.17 (m, 2 H,
22,23-H), 6.24 (AB, d, 3- = 8.2 Hz, 1 H, 6-H), 6.64 (AB, d, 3- = 8.2
Hz, 1 H, 7-H), 7.66 and 8.10 (AA’BB’, 2 m, 2 × 2H, Harom).
Transformation of the provitamin ꢈ to the 25-hydroxyvi-
tamin D3 is possible by a procedure recently described for
the synthesis of calcitriol.19 After conversion of ꢄE into
the corresponding 22-iodide coupling with nickelalac-
tones is possible and yields products suitable for the syn-
thesis of provitamins with homologated chains.20
Anal. C42H62N2O3Si (671.0): Calcd C. 75.17; H. 9.31; N. 4.17.
Found C. 74.87; H. 9.23; N. 4,18.
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅꢃꢃꢅK\GUR[\ꢅꢄaꢇꢍaꢅꢉꢀꢇꢋꢅGLR[Rꢅ
ꢀꢇꢃꢇꢁꢇꢋꢅWHWUDK\GURSKWKDOD]LQHꢅꢃꢇꢁꢅGL\OꢊꢅꢃꢁꢇꢃꢋꢅELVQRUFKROꢅꢌꢅHQHꢂ
ꢉꢋꢊ
Melting points: Boëtius micromelting point apparatus, corrected
values. Elemental analyses: CHN-O-Rapid (HERAEUS) or CHNS-
932 (LECO) instruments. Optical rotations were measured at 20°C
in CHCl3 with a photoelectronic polarimeter Polamat A (Carl Zeiss
Jena) at 546 and 578 nm and extrapolated to 589 nm, Fꢂin g .100–1
mL–1. 1H and 13C NMR spectra: 200, 250 or 400 MHz with Bruker
AC 200F, AC 250 and DRX 400 instruments, respectively, in
CHCl3 with TMS as internal standard. Signals were assigned by
DEPT, C,H-COSY, HMQC. All reactions were monitored by TLC
aluminium sheets, silica gel 60 F254 (Merck), layer thickness 0.2
mm, detection by UV (254 nm) and sprayed with a solution of con-
cd H2SO4 (80 mL), EtOH (20 mL) and vanilline (200 mg) and heat-
ed to 170 °C. Silica gel 60 (0.2–0.5 mm; Merck) was used for
column chromatography. Solvents were distilled and dried before
use according to conventional methods. THF and Et2O were freshly
distilled under argon from sodium and benzophenone prior to use.
A mixture of O3 and O2 (40 L/h) was introduced into a solution ofꢂꢁ
(10.1 g, 15.0 mmol) in CH2Cl2 (400 mL) and pyridine (10 mL)
while stirring at –60 °C over 35 min. The reaction was monitored by
TLC (hexane/EtOAc, 5:1). After almost quantitative consumption
of the starting material stirring was continued for 5 min, followed
by the addition of NaBH4 (4.50 g, 119 mmol) and subsequently
MeOH (370 mL) so that the temperature did not rise above –50°C.
Then the mixture was stirred for 1 h and kept overnight at r. t. The
solvents were removed under reduced pressure and the residue was
dissolved in EtOAc (200 mL) and washed with aq sat. NH4Cl (100
mL) and brine (100 mL). The organic phase was dried (Na2SO4), the
solvent evaporated and the residue was purified by column chroma-
tography with silica gel (320 g). Elution with hexane/EtOAc (1:1)
gives the alcohol ꢋ as a yellow crystalline product; yield: 7.30 g
(81%); mp 154–156°C (EtOAc); [α]D –101 (F = 0.91).
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅHUJRVWDꢅꢄꢇꢈꢇꢃꢃꢅWULHQHꢂꢉꢃꢊ
Imidazole (6.00 g, 88.1 mmol) and WHUW-butyldimethylsilyl chloride
(6.00 g, 39.8 mmol) were added to a stirred solution of ꢀ (8.00 g,
20.2 mmol) in anhyd pyridine (150 mL). The reaction was moni-
tored by TLC (hexane/EtOAc, 20:1). After 2 h, H2O (500 mL) was
added, the solid material was filtered off, washed with H2O and
MeOH and dried (Na2SO4). The crude product was used for the fol-
lowing steps. For analysis the reaction product was crystallized with
MeOH; yield: 10.0 g (97%); mp 150–154°C (MeOH); [α]D –68 (F
= 1.00).
1H NMR: d = –0.05 (s, 3 H, CH3Si), 0.04 (s, 3 H, CH3Si), 0.81 [s,
12 H, (CH3)3CSi and 18-CH3], 0.97 (s, 3 H, 19-CH3), 1.02 (d, 3- =
6.3 Hz, 3 H, 21-CH3), 3.31, 3.46 and 3.62 (3 m, 3 H, 3a-H and 22-
CH2), 6.20 (AB, d, 3- = 8.2 Hz, 1 H, 6-H), 6.61 (AB, d, 3- = 8.2 Hz,
1 H, 7-H), 7.64 and 8.06 (AA’BB’, 2 m, 2 × 2 H, Harom).
Anal. C36H52N2O4Si (604.9): Calcd C. 71.48; H. 8.66; N. 4.63.
Found C. 71.23; H. 8.44; N. 4.60.
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅꢃꢃꢅK\GUR[\ꢅꢃꢁꢇꢃꢋꢅELVQRUFKRODꢅ
ꢄꢇꢈꢅGLHQHꢂꢉꢄDꢊ
1H NMR: d = 0.06 [s, 6 H, (CH3)2Si], 0.62 (s, 3 H, 18-CH3), 0.80
3
and 0.82 (2 d, - = 6.7 Hz, 6 H, 26- and 27-CH3), 0.89 [s, 9 H,
Lithium naphthalenide was prepared from lithium (51 mg, 7.35
mmol) and naphthalene (1.0 g, 7.80 mmol) in THF (10 mL) as de-
scribed.13 The resulting green solution was slowly added to a stirred
solution of ꢋꢂ(1.27 g, 2.10 mmol) in THF (20 mL) at 0°C. After 15
min the mixture lost its colour and the reaction was finished as in-
dicated by TLC (heptane/EtOAc, 1:1). The solution was treated
with aq sat. NH4Cl (20 mL).The organic phase was separated and
the aqueous phase extracted with Et2O (3 × 20 mL). The combined
organic layers were dried (Na2SO4). After removal of the solvents
under reduced pressure the crude product was purified by column
chromatography on silica gel (30 g). Elution with heptane and then
with heptane/EtOAc (5:1) and recrystallization from CH2Cl2 gave
ꢄD as a colourless solid; yield 820 mg (88%); mp 148–150°C
(CH2Cl2); [α]D –83 (F = 0.50).
1H NMR: d = 0.04 [s, 6 H, (CH3)2Si], 0.62 (s, 3 H, 18-CH3), 0.87 [s,
9 H, (CH3)3CSi], 0.91 (s, 3 H, 19-CH3), 1.05 (d, 3- = 6.5 Hz, 3 H,
21-CH3), 3.36 (m, 1 H, 22-CH2), 3.58 (m, 1 H, 3a-H), 3.63 (m, 1 H,
22-CH2), 5.36 (m, 1 H, 7-H), 5.53 (d, 3- = 5.4 Hz, 1 H, 6-H). After
addition of trichloroacetyl isocyanate: d = 3.59 (m, 1 H, 3-H), 4.00
(m, 1H, 22-CH2), 4.32 (m, 1 H, 22-CH2), 8.36 (s, 1H, NH).
(CH3)3CSi], 0.89 (d, 3 H, 28-CH3), 0.93 (s, 3 H, 19-CH3), 1.04 (d,
3- = 6.6 Hz, 3 H, 21-CH3), 3.59 (m, 1 H, 3a-H), 5.20 (m, 2 H, 22,23-
H), 5.38 (AB, m, 1 H, 7-H), 5.55 (AB, d, 3- = 5.5 Hz, 1 H, 6-H).
13C NMR: d = –4.6 [(CH3)2Si], 12.0 (C-18), 16.3 (C-19), 17.6 (C-
28), 19.6 (C-21), 20.0 (C-26), 21.1 (C-27), 23.0 (C-15), 25.9
[(CH3)3CSi], 28.3 (C-12), 32.4 (C-2), 33.1 (C-25), 37.1 (C-10), 38.6
(C-1), 39.1 (C-16), 40.4 (C-20), 41.3 (C-4), 42.8 (C-24), 46.3 (C-9),
54.6 (C-14), 55.7 (C-17), 71.3 (C-3), 116.3 (C-7); 119.2 (C-6);
131.9 (C-22); 135.6 (C-23), 140.7 (C-8), 141.2 (C-5).
Anal. C34H59OSi (511.9): Calcd C. 79.77; H. 11.62. Found C. 79.55;
H. 11.28.
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅꢄaꢇꢍaꢅꢉꢀꢇꢋꢅGLR[RꢅꢀꢇꢃꢇꢁꢇꢋꢅWHWUDK\ꢅ
GURꢅSKWKDOD]LQHꢅꢃꢇꢁꢅGL\OꢊHUJRVWDꢅꢌꢇꢃꢃꢅGLHQHꢂꢉꢁꢊ
Powdered and dried 1,2,3,4-tetrahydrophthalazine 21,22 (11.4 g, 70.3
mmol) was added while stirring to a cooled solution of ꢃ (7.6 g, 14.8
mmol) in CH2Cl2 (450 mL) (0 to –5°C). A solution of Pb(OAc)4
(11.4 g, 25.7 mmol) in HOAc (80 mL) was added dropwise for 20
min. The reaction was monitored by TLC (hexane/EtOAc, 20:1).
After 1 h neutral Al2O3 (30 g) was added and the mixture was stirred
at 0°C for a further 30 min. The yellow solid product was filtered
off and washed with CH2Cl2. The organic layer was separated and
washed with aq sat. NaHCO3 and H2O. The solution was dried
(Na2SO4) and the solvent was removed under reduced pressure. The
crude product was purified by column chromatography with silica
gel (230 g). Elution with hexane/EtOAc (20:1) afforded ꢁ as a yel-
low solid; yield: 7.3 g (73%); mp 108-112°C (CH2Cl2); [α]D –135
(Fꢀ= 1.00).
Anal. C28H48O2Si (444.8): Calcd C. 75.61; H. 10.88. Found C.
75.38; H. 10.69.
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅꢃꢃꢅWRV\OR[\ꢅꢃꢁꢇꢃꢋꢅELVQRUFKRODꢅ
ꢄꢇꢈꢅGLHQHꢂꢉꢄEꢊ
Tosyl chloride (12.6 g, 67.1 mmol) was added to a stirred solution
of ꢄD (3.80 g, 8.50 mmol) in pyridine (62 mL) under Ar at –5°C. The
mixture was stirred for 4 h at this temperature. When the reaction
was finished, indicated by TLC with hexane/EtOAc (5:1), the mix-
Synthesis 1999, No. 8, 1331–1334 ISSN 0039-7881 © Thieme Stuttgart · New York

ꢀꢁꢁꢋ
I. Scherlitz-Hofmann et al.
3$3(5
ture was poured onto ice (400 g) and extracted with EtOAc (3 × 50
mL). The combined organic layers were dried (Na2SO4) and the sol-
vent was removed under reduced pressure. The crystalline residue
was filtered off and washed with EtOAc; yield of ꢄE: 4.40 g (86%);
mp 163–167°C (EtOAc); [α]D –64 (F = 0.48)
$FNQRZOHGJHPHQW
We gratefully acknowledge the financial support by Jenapharm
GmbH.
1H NMR: d = 0.06 [s, 6 H, (CH3)2Si], 0.57 (s, 3 H, 18-CH3), 0.88 [s,
9 H, (CH3)3CSi], 0.90 (s, 3 H, 19-CH3), 1.01 (d, 3- = 6.5 Hz, 3 H,
21-CH3), 2.45 (s, 3 H, C+3C6H5), 3.59 (m, 1 H, 3a-H), 3.98 (m, 2
H, 22-CH2), 5.36 (AB, m, 1 H, 7-H), 5.53 (AB, d, 3- = 5.5 Hz, 1 H,
6-H), 7.34 and 7.78 (AA’BB’, 2 d, 3- = 8.1 Hz, 2 × 2 H, Harom).
5HIHUHQFHV
(1) Norman, A.W.; Bouillon, R.; Thomasset, M.; Eds. 9LWDPLQꢀ'ꢇ
&KHPLVWU\ꢈꢀ%LRORJ\ꢀDQGꢀ&OLQLFDOꢀ$SSOLFDWLRQVꢀRIꢀWKHꢀ6WHURLGꢀ
+RUPRQH; University of California: Riverside, California,
1997; p 1.
(2) Barton, D. H. R.; Shiori, T.; Widdowson, D. A. -ꢉꢀ&KHPꢉꢀ6RFꢉꢂ
ꢀꢎꢈꢀ, 1968.
Anal. C35H54O4SiS (599.0): Calcd C. 70.19; H. 9.09; S. 5.35. Found
C. 70.13; H. 8.94; S. 5.49.
(3) Barton, D. H. R.; Lusinchi, X.; Ramirez, J. S. %XOOꢉꢀ6RFꢉꢀ&KLPꢉꢀ
ꢁbꢅWHUWꢅ%XW\OGLPHWK\OVLO\OR[\ꢅꢃꢄꢅWULPHWK\OVLO\OR[\FKROHVWDꢅꢄꢇꢈꢅ
GLHQHꢂꢉꢌꢊ
)UDQFHꢀ,, ꢀꢎꢍꢄ, 849.
(4) Georghiou, P. E.; Just, G. -ꢉꢀ&KHPꢉꢀ6RFꢉꢈꢀ3HUNLQꢀ7UDQVꢉꢀ, ꢀꢎꢈꢁ,ꢂ
888.
(5) Bogoslovskii, N. A.; Litvinova, G. E.; Samochvalov, G. I.
-ꢉꢀ*HQꢉꢀ&KHPꢉꢀ8665 ꢀꢎꢈꢍ, ꢊꢂ, 828.
(6) Eyley, S. C.; Williams, D. H. -ꢉꢀ&KHPꢉꢀ6RFꢉꢈꢀ3HUNLQꢀ7UDQVꢉꢀꢁ
ꢀꢎꢈꢌ,ꢂ727.
Under Ar, 1,2-dibromomethane (0.10 mL) was added to Mg (780
mg, 32.1 mmol) in THF (10 mL) with stirring. A mixture of 4-chlo-
ro-2-methyl-2-[(trimethylsilyl)oxy]butane16 (4.42 g, 22.7 mmol)
and 1,2-dibromomethane (0.69 mL, 22.7 mmol) in THF (45 mL)
was added. The resulting mixture was stirred for 30 min. at r.t. and
then refluxed for 1 h. Subsequently, it was cooled to –20°C and Cu-
Br•SMe2 adduct (112 mg, 0.55 mmol) and ꢄE (1.30 g, 2.17 mmol)
were added. The mixture was allowed to stand overnight and warm-
ing to r.t. After quenching with aq sat. NH4Cl (25 mL) and stirring
for 30 min the mixture was extracted with CH2Cl2 (3 × 40 mL). The
organic layer was separated, washed with aq satd NH4Cl solution
(40 mL) and H2O (40 mL) several times and dried (Na2SO4). Finally
the solvent was removed under reduced pressure and the afforded
oil dissolved in acetone to give a colourless solid: yield 0.99 g
(78%); mp 118–121°C (acetone).
(7) Morris, D. S.; Williams, D. H.; Norris, A. F. -ꢉꢀ2UJꢉꢀ&KHPꢉ
ꢀꢎꢍꢀ, ꢊꢋꢈꢀ3422.
(8) Schrötter, E.; Schönecker, B.; Hauschild, U.; Droescher, P.;
Schick, H. 6\QWKHVLV ꢀꢎꢎꢏ, 193.
(9) Schrötter, E.; Landmann, E.; Schick, H.; Schönecker, B.;
Hauschild, U.; Droescher, P. -ꢉꢀ3UDNWꢉꢀ&KHP. ꢀꢎꢍꢍ, ꢆꢆꢌ, 501.
(10) Schönecker, B.; Hauschild, U.; Schrötter, E.; Schick, H.
3KDUPD]LHꢀꢀꢎꢍꢌ, ꢊꢁ, 597.
(11) Kubodera, N.; Miyamoto, K.; Watanabe, H. -ꢉꢀ2UJꢉꢀ&KHP.
ꢀꢎꢎꢃ, ꢍꢎ, 5019, and references cited.
1H NMR: d = 0.07 [s, 6 H, (CH3)2Si], 0.10 [s, 9 H, (CH3)3Si], 0.62
(s, 3 H, 18-CH3), 0.89 [s, 9 H, (CH3)3CSi], 0.93 (s, 3 H, 19-CH3),
0.96 (d, 3- = 7.4 Hz, 3 H, 21-CH3), 1.20 (s, 6 H, 26,27-CH3), 3.60
(m, 1 H, 3a-H), 5.38 (d, 3- = 5.5 Hz, 1 H, 7-H), 5.55 (d, 3- = 5.5 Hz,
1 H, 6-H).
Kondo, F.; Miyashita, M.; Konno, K.; Takayama, H. -ꢉꢀ&KHPꢉꢀ
6RFꢉꢈꢀ3HUNLQꢀ7UDQVꢉꢀ, ꢀꢎꢎꢄ, 2679.
(12) Tachibana, Y. &KHPꢉꢀ3KDUPꢉꢀ%XOOꢉ ꢀꢎꢎꢍ, ꢊꢋ, 1454.
(13) Rieke, R. D.; Wu, T. C.; Stinn, D: E.; Wehmeyer, R. M. 6\QWKꢉꢀ
&RPPXQ. ꢀꢎꢍꢎ, ꢁꢃ, 1833, and references cited.
(14) Scherlitz-Hofmann, I.; Bößneck, U.; Schönecker, B. /LHELJVꢀ
$QQꢉꢀ&KHP. ꢀꢎꢎꢌ, 217.
(15) Schönecker, B.; Droescher, P.; Adam, G.; Marquardt, D.;
Walther, D.; Fischer, R.; Prousa, R. DE Patent 4 105 505;
Chem. Abstr. ꢀꢎꢎꢀ, ꢁꢁꢂ, 124879.
(16) Chorvat, R. J.; Desai, B. N.; Radak, S. E.; McLaughlin, K. T.;
Miller, J. E.; Jett, C.; Rohrbacher, E. -ꢉꢀ0HGꢉꢀ&KHPꢉ ꢀꢎꢍꢄ, ꢅꢂ,
194.
Anal. C36H66O2Si2 (587.1): Calcd C. 73.65; H. 11.33. Found C.
72.31; H. 11.45.
ꢁbꢇꢃꢄꢅ'LK\GUR[\FKROHVWDꢅꢄꢇꢈꢅGLHQHꢂꢉꢈꢇꢂ3URYLWDPLQꢂRIꢂꢃꢄꢅ+\ꢅ
GUR[\YLWDPLQꢂ' ꢊ
Compound ꢌ (0.20 g, 0.34 mmol) and Bu4NF•3H2O (1.60 g, 5.10
mmol) in THF (8 mL) were stirred under Ar at 40 °C for 2.5 h. Then
CH2Cl2 (10 mL) was added and the mixture washed with brine (10
mL). The organic phase was separated, dried (Na2SO4) and the sol-
vent removed under reduced pressure. The residue was crystallized
from MeOH; yield 0.12 g (88%); mp 157–159°C.
(17) Andrews, D. R.; Barton, D. H. R.; Hesse, R. H.; Pechet, M. M.
-ꢉꢀ2UJꢉꢀ&KHP. ꢀꢎꢍꢌ, ꢍꢁ, 4819.
(18) Moreau, J.; Aberhart, D. J.; Caspi, E. -ꢉꢀ2UJꢉꢀ&KHP. ꢀꢎꢈꢋ, ꢆꢃ,
2018.
1H NMR: d = 0.60 (s, 3 H, 18-CH3), 0.92 (s, 3 H, 19-CH3), 0.94 (d,
3- = 7.4 Hz, 3 H, 21-CH3), 1.19 (s, 6 H, 26,27-CH3), 3.62 (m, 1 H,
3a-H), 5.38 (d, 3- = 5.5 Hz, 1 H, 7-H), 5.55 (d, 3- = 5.5 Hz, 1 H. 6-
H). After addition of trichloroacetyl isocyanate: d = 1.50 (s, 6 H,
26,27-CH3), 4.75 (m, 1 H, 3a-H), 8.20 and 8.33 (2 × s, 2 H, 2 NH).
The 1H NMR data correspond to those known from the literature.6,17
(19) Reichenbächer, M.; Gliesing, S.; Lange, C.; Gonschior, M.;
Schönecker, B. -ꢉꢀ3UDNWꢉꢀ&KHPꢉ ꢀꢎꢎꢌ, ꢆꢆꢂ, 634.
(20) Fischer, R.; Schönecker, B.; Walther, D. 6\QWKHVLV ꢀꢎꢎꢁ,
1267.
(21) Drew, H.; Hatt, H. -ꢉꢀ&KHPꢉꢀ6RFꢉ ꢀꢎꢁꢈ, 16.
(22) Försterling, H. -ꢉꢀ3UDNWꢉꢀ&KHP. ꢀꢍꢎꢄ, ꢅꢍꢁ, 371.
Article Identifier:
1437-210X,E;1999,0,08,1331,1334,ftx,en;H00599SS.pdf
Synthesis 1999, No. 8, 1331–1334 ISSN 0039-7881 © Thieme Stuttgart · New York