Asymmetric synthesis of (+)- and (-)-streptenol A

Article abstract of DOI:10.1002/(SICI)1099-0690(199904)1999:4<751::AID-EJOC751>3.0.CO;2-R

The asymmetric synthesis of (+)-streptenol A was carried out in ten steps and with high enantioselectivity (ee ≥ 96%). The key steps are the α- alkylation of 2,2-dimethyl-1,3-dioxan-5-one RAMP hydrazone A (1), subsequent deoxygenation and elaboration of the side chain via aldehyde B to furnish (+)-streptenol A in 23% overall yield. In analogy, the enantiomer (-)- streptenol A was synthesized using the corresponding SAMP hydrazone in 18% overall yield.

Full text of DOI:10.1002/(SICI)1099-0690(199904)1999:4<751::AID-EJOC751>3.0.CO;2-R

FULL PAPER
Asymmetric Synthesis of (؉)- and (–)-Streptenol A
Dieter Enders*[a] and Thomas Hundertmark[a]
Keywords: Asymmetric synthesis / Streptenol A / Synthetic methods / Natural products / SAMP/RAMP hydrazones
The asymmetric synthesis of (+)-streptenol A was carried out
in ten steps and with high enantioselectivity (ee Ն 96%). The
key steps are the α-alkylation of 2,2-dimethyl-1,3-dioxan-5-
one RAMP hydrazone A (1), subsequent deoxygenation and
elaboration of the side chain via aldehyde B to furnish (+)-
streptenol A in 23% overall yield. In analogy, the enantiomer
(–)-streptenol A was synthesized using the corresponding
SAMP hydrazone in 18% overall yield.
RAMP/SAMP hydrazones A.[7] In view of its biological
and chemical features we have chosen (ϩ)-streptenol A and
its enantiomer to demonstrate the applicability of our
method in asymmetric synthesis. We envisaged that this
method should allow an alternative efficient access to either
(S)- or (R)-2-(2,2-dimethyl-1,3-dioxan-4-yl)acetaldehyde (B)
depending only on the configuration of the auxiliary. A
Grignard addition and subsequent oxidation should then
furnish the title compounds after cleavage of the acetonide
protecting group.[5] In this paper we would like to report
our results on the asymmetric synthesis of (ϩ)- and (Ϫ)-
streptenol A.
Introduction
(ϩ)-Streptenol A is a secondary metabolite of several
Streptomyces species and can be obtained by fermentation
processes.[1] As the other streptenols B, C and D, (ϩ)-strep-
tenol A is a potent cholesterol biosynthesis inhibitor,[1c] but
only (ϩ)-streptenol A shows anti-tumor and immuno-sti-
mulating activity.[2] In addition to these biological features,
(ϩ)-streptenol A has been employed as a versatile chiral
building block in syntheses of several members of the im-
portant class of δ-lactones (e.g. both enantiomers of masso-
ialactone and all four stereoisomers of 3-hydroxy-5-decano-
lide).[1b,3] During these investigations, inversion of the
stereogenic center of (ϩ)-streptenol A was a major task and
was accomplished in a four-step sequence to yield (Ϫ)-
streptenol A.
Results and Discussion
The alkylation of 2,2-dimethyl-1,3-dioxan-5-one SAMP/
RAMP hydrazones is a reliable tool to synthesize chiral 4-
substituted 2,2-dimethyl-1,3-dioxan-5-ones in gram quanti-
ties and with high enantiomeric excess.[8] Thus, RAMP-hy-
drazone (R)-1 was metalated at Ϫ78°C with tert-butyllith-
ium in tetrahydrofuran for 2 h and the lithium aza-enolate
was alkylated with 2-bromo-1-tert-butyldimethylsilyloxy-
ethane at Ϫ105°C furnishing the corresponding α-alkylated
hydrazone (R,R)-2 with a diastereomeric excess of de Ն
96% as evidenced by 13C-NMR spectroscopy and GC
analysis. Hydrolytic cleavage of the hydrazone with oxalic
acid[9] afforded (R)-3 in 95% yield (two steps) and an en-
antiomeric excess of ee Ն 96%. It is worth noticing that this
mild cleavage method allows for a recycling of the auxiliary.
Reduction of the carbonyl group with sodium tetrahydro-
borate in methanol afforded a diastereomeric mixture (de ϭ
61%) of the corresponding alcohols (R,S/R)-4 in 85% yield.
Treatment of their corresponding sodium alkoxides with
carbon disulfide and iodomethane gave xanthates (R,S/R)-
5 in 94% yield after chromatography. The BartonϪMcCom-
bie deoxygenation[7] using tri-n-butyltin hydride in refluxing
toluene furnished dioxane (S)-6 in 82% yield after removal
of the tin by-products by column chromatography. Depro-
tection of (S)-6 with tetrabutylammonium fluoride (TBAF)
furnished the primary alcohol (R)-7 in 93% yield after chro-
matography. On this stage, esterification of the primary al-
cohol with (S)-Mosher chloride[10] yielded the dia-
stereomerically pure Mosher ester (S,R)-11 with de Ն 96%
Stereoselective syntheses of streptenol C and D were re-
ported in the literature.[4] The most general approach to all
members of the streptenol family was developed by Blechert
and Dollt and relies on 2-(2,2-dimethyl-1,3-dioxan-4-yl)-
acetaldehyde (B) as key building block in their syntheses of
(±)-streptenol B, C and D.[5] They used their strategy for
an elegant asymmetric synthesis of the antipode (Ϫ)-strep-
tenol A based on enantiomerically pure aldehyde (R)-B
which was obtained in eight steps using HeathcockЈs mono-
ester method.[5][6] To the best of our knowledge, an asym-
metric synthesis of natural (ϩ)-streptenol A has not been
reported.
Recently, we published a protocol for the α-alkylation
and deoxygenation of 2,2-dimethyl-1,3-dioxan-5-one
[a]
Institut für Organische Chemie, Rheinisch-Westfälische Tech-
nische Hochschule Aachen,
Professor-Pirlet-Straße, D-52074 Aachen, Germany
Fax: (internat.) ϩ 49(0)241/8888-127
E-mail: Enders@RWTH-Aachen.de
Eur. J. Org. Chem. 1999, 751Ϫ756
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0404Ϫ0751 $ 17.50ϩ.50/0
751

D. Enders, T. Hundertmark
FULL PAPER
Scheme 2. Synthesis of (ϩ)- and (Ϫ)-streptenol A: a) Mg, (E)-5-
˚
bromopent-2-ene, THF; b) PCC, Celite, MS (4 A), CH2Cl2; c)
TFA, THF/H2O (4:1)
to ketone (S)-10 were screened. Pyridinium chlorochromate
(PCC)[12] in combination with Celite and ground molecular
sieves in dichloromethane was the reagent of choice giving
(S)-10 in 72% yield after chromatography. The isopropylid-
ene acetal was hydrolytically cleaved in the final step with
trifluoracetic acid in THF/water[13] to yield the natural
product (ϩ)-streptenol A in 78% yield. The antipode (Ϫ)-
streptenol A was obtained in 37% overall yield starting
1
from aldehyde (R)-8. The spectroscopic data (IR, H, 13C
NMR, EI/CI-MS) of the synthetic streptenols were in ac-
cordance with the data reported in the literature.[1a,3] How-
ever, the optical rotation values of [α]D23 ϭ ϩ21.7 (c ϭ 1.0,
23
CHCl3) for (ϩ)-streptenol A and [α]D ϭ Ϫ21.5 (c ϭ 1.0,
Scheme 1. Asymmetric synthesis of the aldehydes (S)- and (R)-8:
a) tBuLi, BrCH2CH2OTBS, THF; b) aq. oxalic acid, Et2O, 95%;
c) NaBH4, MeOH, 85%; d) NaH, MeI, CS2, THF, 94%; e)
nBu3SnH, AIBN, toluene, 82%; f) TBAF, THF, 93%; g) TPAP,
CHCl3) for (Ϫ)-streptenol A are slightly lower than the
published values of [α]D ϭ ϩ23 (c ϭ 1.0, CHCl3)[1a] and
[α]D ϭ Ϫ23 (c ϭ 1.0, CHCl3),[5] respectively. One possible
explanation for this difference is the tendency of streptenol
A to form varying amounts of diastereomeric hemi-
ketals.[1a]
˚
NMO, MS (4 A), CH2Cl2, 88%
according to HPLC analysis revealing that no racemisation
occurred. The ruthenium-catalyzed oxidation of the alcohol
(R)-7 with 7.5 mol-% tetrapropylammonium perruthenate
(TPAP) and N-methylmorpholine oxide (NMO) in di-
chloromethane according to Ley et al.[11] gave (S)-2-(2,2-
dimethyl-1,3-dioxan-4-yl)acetaldehyde [(S)-8] in 88% yield.
This key building block of all members of the streptenol
family was obtained in 51% overall yield starting from
RAMP-hydrazone (R)-1. The same reaction sequence em-
ploying SAMP-hydrazone (S)-1 gave aldehyde (R)-8 in 49%
overall yield, thus emphasizing the reliability of this ap-
proach.
With both enantiomers of aldehyde 8 in hand, we con-
tinued the synthesis sligthly modifying BlechertЈs pro-
cedure.[5] The Grignard-addition of (E)-3-penten-1-ylmag-
nesium bromide to the aldehyde (S)-8 in THF at 50°C fur-
nished the diastereomeric mixture (S/R,S)-9 in 81% yield.
Conclusion
In summary, an efficient asymmetric synthesis of (ϩ)-
and (Ϫ)-streptenol A starting from commercially available
2,2-dimethyl-1,3-dioxan-5-one was carried out in ten steps
and 23% or 18% overall yield, respectively. The applicability
of our alkylation/deoxygenation protocol for the synthesis
of polyhydroxylated compounds has been demonstrated.
The configuration at the generated stereogenic centers can
be controlled by either using SAMP or RAMP as chiral
auxiliary, which can be recycled after cleavage with oxalic
acid.
Experimental Section
General: All solvents were dried and purified prior to use. Ϫ All
Several methods for the subsequent oxidation of (S/R,S)-9 reactions were carried out under dry argon. Ϫ Column chromatog-
752 Eur. J. Org. Chem. 1999, 751Ϫ756

Asymmetric Synthesis of (ϩ)- and (Ϫ)-Streptenol A
FULL PAPER
raphy: Merck silica gel 60, 0.040Ϫ0.063 mm (230Ϫ400 mesh). Ϫ
Optical rotation values: Perkin-Elmer P 241 (254 nm); solvents
Merck Uvasol quality. Ϫ IR: Perkin-Elmer FT/IR 1750. Ϫ NMR:
IR (film): ν˜ ϭ 2988 cmϪ1 (w), 2956 (m), 2931 (m), 2884 (w), 2858
(m), 1750 (s), 1472 (w), 1464 (w), 1426 (w), 1382 (m), 1376 (m),
1362 (w), 1255 (s), 1223 (s), 1175 (w), 1158 (w), 1111 (s), 1067 (m),
Varian VXR 300 and Gemini 300 and Innova 400, TMS as internal 1007 (w), 953 (w), 940 (w), 876 (w), 861 (w), 837 (s), 812 (w), 777
standard. Ϫ MS: Finnigan MAT 212 and Finnigan SSQ 7000 (70
eV). Ϫ Microanalyses: Elementar vario EL. Ϫ THF was dried by
distillation from K/benzophenone under Ar. Diethyl ether and
toluene were dried by distillation from Na/benzophenone under Ar.
2,2-Dimethyl-1,3-dioxan-5-one,[14] 2-bromo-1-tert-butyldimethyl-
(s). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 0.05 (s, 6 H, SiCH3), 0.89
(s, 9 H, SiCH3), 1.43 [s, 3 H, C(CH3)3], 1.46 [s, 3 H, C(CH3)3],
1.61Ϫ1.72 (m,
1 H, CHHCH2OTBS), 2.07Ϫ2.18 (m, 1 H,
CHHCH2OTBS), 3.70Ϫ3.75 (m, 2 H, CH2CH2OTBS), 3.99 (d, J ϭ
17.1 Hz, 1 H, OCHHCO), 4.28 (dd, J ϭ 17.0 Hz, J ϭ 1.7 Hz, 1
silyloxyethane[15] and 2,2-dimethyl-1,3-dioxan-5-one RAMP/ H, OCHHCO), 4.49 (ddd, J ϭ 8.9 Hz, J ϭ 3.8 Hz, J ϭ 1.7 Hz,
SAMP-hydrazones[8a] were prepared according to the published 1H OCHCO). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ Ϫ5.4 (2 ϫ
procedures.
SiCH3), 18.2 [C(CH3)3], 23.6 [C(CH3)2], 24.0 [C(CH3)2], 25.9 [3 ϫ
C(CH3)3], 31.8 (CH2CH2OTBS), 58.2 (CH2CH2OTBS), 66.6
(OCH2CO), 71.3 (OCHCO), 100.8 [C(CH3)2], 210.1 (CO). Ϫ MS
(CI, isobutane); m/z (%): 289 [Mϩ ϩ 1] (100), 273 (3), 272 (5), 271
(25), 232 (5), 231 [Mϩ Ϫ 57], (33), 173 (3). Ϫ C14H28O4Si (288.46):
calcd. C 58.29, H 9.78; found C 57.92, H 9.78. Ϫ In analogy, cleav-
age of 4.9 g (12.3 mmol) of (S,S)-2 afforded 3.3 g of (S)-3 (92%).
(R,R)-4-(2-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}ethyl)-2,2-di-
methyl-1,3-dioxan-5-one RAMP-hydrazone [(R,R)-2]: 3.6 g (14.9
mmol, 1.0 equiv.) of (R)-1 was dissolved in 50 mL of THF and
cooled to Ϫ78°C under Ar and 10.3 mL of tert-butyllithium (1.6
 in pentane, 16.5 mmol, 1.1 equiv.) was slowly added. After stir-
ring for 2 h at Ϫ78°C, the solution was cooled to Ϫ105°C and 3.9
g (16.5 mmol, 1.1 equiv.) of 2-bromo-1-tert-butyldimethylsilyloxy-
25
Ϫ [α]D ϭ Ϫ122.6 (c ϭ 1.0, CHCl3)
ethane was added dropwise. The solution was stirred at this tem- (4R,5S/R)-4-(2-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}ethyl)-2,2-di-
perature for 4 h and then allowed to reach room temp. overnight.
Then, 5 mL of an aqueous pH-7 buffer solution and 200 mL of
diethyl ether were added. The organic phase was washed with water
and brine, dried with MgSO4 and the solvent was removed under
reduced pressure to yield (R,R)-2 as a yellow oil. An analytical
sample was obtained by column chromatography (SiO2; pentane/
methyl-1,3-dioxan-5-ol (R,S/R)-4: 4.1 g (14.2 mmol) of (R)-3 was
dissolved in MeOH and cooled to Ϫ78°C. Then 1.1 g (28.4 mmol
2.0 equiv.) of NaBH4 was added, the mixture was allowed to reach
room temp. and then stirred for 2 h. The solvent was removed
under reduced pressure and the residue was taken up in CH2Cl2
and treated with water. The organic phase was washed with a pH-
7 buffer and brine and dried with MgSO4. The solvent was removed
23
Et2O, 2:1), yield 6.1 g (quant.). Ϫ [α]D ϭ Ϫ78.8 (c ϭ 2.0, ace-
tone). Ϫ IR (film): ν˜ ϭ 2984 cmϪ1 (m), 2955 (s), 2930 (s), 2857 (s), under reduced pressure to yield the alcohol (R,S/R)-4 as a mixture
1472 (w), 1463 (m), 1450 (w), 1380 (m), 1372 (m), 1338 (w), 1255
(s), 1226 (s), 1158 (m), 1112 (s), 1091 (s), 1050 (m), 1007 (w), 972 chromatography (SiO2; pentane/Et2O, 1:1), yield 3.6 g (85%). Ϫ
(w), 954 (w), 940 (w), 908 (w), 894 (w), 864 (w), 835 (s), 813 (w),
de ϭ 61%. Ϫ IR (film): ν˜ ϭ 3424 cmϪ1 (w), 2994 (w), 2955 (s),
of diastereomers. An analytical sample was obtained by column
1
777 (s). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 0.05 (s, 3 H, SiCH3), 2930 (s), 2884 (m), 2859 (s), 1472 (w), 1464 (w), 1434 (w), 1381
0.06 (s, 3 H, SiCH3), 0.90 [s, 9 H, C(CH3)3], 1.38 [s, 3 H, C(CH3)2], (m), 1256 (s), 1228 (w), 1199 (m), 1168 (m), 1132 (w), 1088 (s),
1.39 [s, 3 H, C(CH3)2], 1.58Ϫ1.72 (m, 2 H, CH2CH2OTBS),
1.78Ϫ1.88 (m, H, NCH2CH2CH2), 2.00 (m, H,
1007 (w), 985 (w), 957 (w), 940 (w), 924 (w), 866 (w), 838 (s), 807
(w), 778 (s), 664 (w). Ϫ H NMR (300 MHz, C6D6): (R,S)-4: δ ϭ
1
2
1
NCH2CH2CHH), 2.20 (m, 1 H, NCH2CH2CHH), 2.40 (dd, J ϭ 0.01 (s, 6 H, SiCH3), 0.92 [s, 9 H, C(CH3)3], 1.37 [s, 3 H, C(CH3)2],
8.5 Hz, J ϭ 8.4 Hz, 1 H, NCHHCH2CH2), 3.02 (dt, J ϭ 8.8 Hz, 1.48 [s, 3 H, C(CH3)2], 1.67Ϫ1.84 (m, 1 H, CHHCH2OTBS),
J ϭ 6.0 Hz, NCHHCH2CH2), 3.19Ϫ3.36 (m, 2 H, CHCHHOCH3),
3.35 (s, 3 H, OCH3), 3.42 (dd, J ϭ 8.8 Hz, J ϭ 3.6 Hz, 1 H, OH), 3.44Ϫ3.55 (m,
1.89Ϫ2.04 (m, 1 H, CHHCH2OTBS), 3.30 (d, J ϭ 3.6 Hz, 1 H,
H, CHOH), 3.59Ϫ3.78 (m, H,
CH2CH2OTBS, OCH2CHOH), 3.93Ϫ4.00 (m, 1 H, OCHCHOH).
13C NMR (75 MHz, C6D6): δ ϭ Ϫ5.4 (2ϫ SiCH3), 18.4
1
4
CHCHHOCH3), 3.71Ϫ3.82 (m, 2 H, CH2CH2OTBS), 4.15 (dd,
J ϭ 15.7 Hz, J ϭ 1.9 Hz, 1 H, OCHHCN), 4.50 (d, J ϭ 15.7 Hz,
Ϫ
1 H, OCHHCN), 4.56 (m, 1 H, OCHCN). Ϫ 13C NMR (75 MHz, [C(CH3)3], 19.3 [C(CH3)2], 26.0 [3 ϫ C(CH3)3], 29.3 [C(CH3)2], 37.8
CDCl3):
δ ϭ Ϫ5.3 (2 ϫ SiCH3), 18.3 [C(CH3)3], 22.8 (CH2CH2OTBS), 60.1 (CH2CH2OTBS), 64.9 (OCH2CHOH), 67.9
(NCH2CH2CH2), 24.1 [2 ϫ C(CH3)2], 25.3 [3 ϫ C(CH3)3], 26.8
(OCHCHOH), 73.3 (CHOH), 98.4 [C(CH3)2]. Ϫ MS (EI, 70eV);
(NCH2CH2CH2), 35.1 (CH2CH2OTBS), 55.4 (NCH2CH2CH2), m/z (%): 275 [Mϩ Ϫ 15], 189 (12), 175 (31), 157 (35), 145 (65), 131
59.0 (OCH3), 59.9 (CH2CH2OTBS), 66.65 (CHCH2OCH3), 66.68 (30), 129 (10), 127 (12), 115 (9), 105 (22), 101 (43), 89 (36), 83 (34),
(OCH2CN), 67.1 (OCHCN), 75.6 (CHCH2OCH3), 100.3
77 (11), 75 (100), 73 (35), 59 (83), 57 (12), 55 (14). Ϫ C14H30O4Si
[C(CH3)2], 163.0 (CN). Ϫ MS (CI, isobutane); m/z (%): 401 [Mϩ (290.47): calcd. C 57.89, H 10.41; found C 57.43 H 10.43. Ϫ In
ϩ 1] (100), 400 [Mϩ] (7), 345 (3), 344 (12), 343 (Mϩ Ϫ 57, 47), 342 analogy, reduction of 6.1 g of (S)-3 afforded 5.3 g of (S,R/S)-4
(3). Ϫ C20H40N2O4Si (400.63): calcd. C 59.96, H 10.06, N 6.99 (87%).
found C 59.56, H 10.27, N 7.33. Ϫ In analogy, alkylation of 5.7 g
(4ЈR,5ЈR/S)-{4-(2-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}ethyl)-2,2-
dimethyl-1,3-dioxan-5-yl-methansulfanyl}methanethioate [(R,S/R)-
5]: To a solution of 3.6 g (12.4 mmol) of (R,S/R)-4 in 15 mL of
(23.0 mmol) of SAMP-hydrazone (S)-1 afforded 11.8 g of (S,S)-2
23
(quantitative). Ϫ [α]D ϭ ϩ78.7 (c ϭ 2.0, acetone).
(R)-4-(2-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}ethyl)-2,2-dimethyl-
1,3-dioxan-5-one [(R)-3]: 5.9 g of the crude hydrazone (R,R)-2 was
dissolved in 60 mL of diethyl ether and stirred vigorously at room
temp. with a sat. aqueous solution of oxalic acid (35 mL) for 12 h
(TLC control). The aqueous layer was separated, extracted with
diethyl ether and the organic extracts were combined, washed with
water, brine and dried with MgSO4. The solvent was removed un-
der reduced pressure to give (R)-3 as an oil. An analytical sample
THF under Ar was added imidazole (cat.) and 1.2 g (31 mmol, 2.5
equiv.) of a 60% suspension of NaH in mineral oil at 0°C. After
30 min, 2.6 mL (43 mmol, 3.5 equiv.) of CS2 was added dropwise
and stirring was continued for an additional 30 min at 0°C. Then,
3.5 g (4.4 mmol, 2.0 equiv.) of iodomethane was added and the
mixture was stirred at room temp. overnight. The reaction mixture
was hydrolysed with water and extracted with diethyl ether. The
combined organic layers were washed with a sat. aqueous NH4Cl
was obtained by column chromatography (SiO2; pentane/Et2O, solution and brine, dried (MgSO4) and concentrated under reduced
25
10:1), yield 4.1 g (95%). Ϫ [α]D ϭ ϩ122.5 (c ϭ 1.0, CHCl3). Ϫ
pressure. Purification by column chromatography (SiO2; pentane/
753
Eur. J. Org. Chem. 1999, 751Ϫ756

D. Enders, T. Hundertmark
FULL PAPER
Et2O, 2:1) afforded the xanthate (R,S/R)-5 as slightly yellow oil.
Analytical samples of both diastereomers were obtained by column
chromatography (SiO2; pentane/Et2O, 9:1), yield 4.5 g (94%). Ϫ
CH2CH2OTBS), 3.82 (ddd, J ϭ 11.8 Hz, J ϭ 5.4 Hz, J ϭ 1.7 Hz,
1 H, OCHHCH2CHO), 3.98 (td, J ϭ 12.1 Hz, J ϭ 3.0 Hz, 1 H,
OCHHCH2CHO), 4.00Ϫ4.11 (m, 1 H, OCH2CH2CH). Ϫ 13C
NMR (75 MHz, CDCl3): δ ϭ Ϫ5.4 (SiCH3), 18.3 [C(CH3)3], 19.3
25
(R,S)-5: [α]D ϭ ϩ75.0 (c ϭ 1.05, CHCl3). Ϫ IR (film): ν˜ ϭ 2991
cmϪ1 (w), 2954 (m), 2928 (m), 2856 (w), 1472 (w), 1463 (w), 1444 [C(CH3)2], 25.9 [3 ϫ C(CH3)3], 30.5 [C(CH3)2], 31.5 (OCH2CH2-
(w), 1424 (w), 1383 (w), 1371 (w), 1256 (m), 1211 (s), 1168 (m), CHO), 39.6 (CH2CH2OTBS), 58.8 (OCH2CH2CHO), 60.1
1132 (m), 1094 (s), 1069 (s), 1009 (w), 959 (w), 940 (w), 926 (w), (CH2CH2OTBS), 65.5 (OCH2CH2CHO), 98.3 [C(CH3)2]. Ϫ MS
1
866 (w), 837 (s), 807 (w), 777 (m). Ϫ H NMR (300 MHz, C6D6): (EI, 70 eV); m/z (%): 259 (12), 160 (12), 159 (100), 141 (14), 131
δ ϭ 0.04 (s, 6 H, SiCH3), 0.96 (s, 9 H, C(CH3)3], 1.32 (s, 6 H,
C(CH3)2], 1.55Ϫ1.68 (m, 1 H, CHHCH2OTBS), 1.83Ϫ1.94 (m, 1 (62), 73 (38), 67 (17), 59 (35), 58 (12), 57 (18), 55 (12). Ϫ MS (CI,
H, CHHCH2OTBS), 2.13 (s, 3 H, SCH3), 3.55Ϫ3.78 (m, 3 H,
isobutane); m/z (%): 275 [Mϩ ϩ 1] (100), 217 [Mϩ Ϫ 57] (22), 215
(49), 129 (68), 117 (13), 115 (13), 105 (11), 101 (49), 89 (45), 75
CH2CH2OTBS, OCHHCHOS), 4.08 (m, 1 H, OCHHCHOS), 4.23 (6), 159 (4). Ϫ C14H30O3Si (274.47): calcd. C 61.26 H 11.02; found
(m, 1 H, OCHCHOS), 5.63 (m, 1 H, OCHCHOS). Ϫ 13C NMR C 60.88 H 11.32. Ϫ In analogy, deoxygenation of 2.8 g (7.4 mmol)
23
(75 MHz, C6D6): δ ϭ Ϫ5.3 (SiCH3), 18.4 [C(CH3)3], 18.9 of (S,R/S)-5 yielded 1.8 g of (R)-6 (89%). Ϫ [α]D ϭ Ϫ33.9 (c ϭ
[C(CH3)2], 20.8 [C(CH3)2], 26.0 [3 ϫ C(CH3)3], 27.1 (SCH3), 36.2
(CH2CH2OTBS), 58.5 (CH2CH2OTBS), 61.5 (OCH2CHOS), 67.0
(OCHCHOS), 76.6 (OCHCHOS), 99.6 [C(CH3)2], 215.8 (CS2CH3).
Ϫ MS (CI, isobutane): m/z (%): 381 [Mϩ ϩ 1] (11), 325 (12), 324
(20), 323 [Mϩ Ϫ 57] (100), 309 (5), 291 (13), 275 (22), 273 (22), 217
(15), 215 (13), 159 (5), 157 (5).Ϫ C16H32O4S2Si (380.63): calcd. C
1.0, acetone).
(R)-2-[2,2-Dimethyl-1,3-dioxan-4-yl]ethan-1-ol [(R)-7]: To a solution
of 2.6 g (9.6 mmol) of (S)-6 in 50 mL of THF was added 14 mL
of a 1.0  THF solution of tetrabutylammonium fluoride by syr-
inge. The mixture was stirred at room temp. for 4 h and then
washed with sat. aqueous NH4Cl solution. The aqueous phase was
extracted with EtOAc three times. The combined organic phases
were washed with brine (30 mL), dried (MgSO4) and concentrated
under reduced pressure. Purification by column chromatography
(SiO2; pentane/Et2O, 4:1 to 1:1) afforded alcohol (R)-7 as colour-
28
50.49 H 8.47; found 50.33 H 8.77. Ϫ (R,R)-5: [α]D ϭ Ϫ9.6 (c ϭ
0.94, CHCl3). Ϫ IR (film): ν˜ ϭ 2991 cmϪ1 (w), 2954 (m), 2929 (m),
2882 (w), 2877 (w), 1471 (w), 1463 (w), 1426 (w), 1383 (w), 1276
(w), 1255 (m), 1225 (s), 1196 (s), 1171 (w), 1137 (w), 1069 (s), 1022
(w), 968 (w), 949 (w), 924 (w), 865 (w), 837 (m), 812 (w), 777 (m).
23
less oil, yield 1.4 g (93%). Ϫ [α]D ϭ ϩ55.5 (c ϭ 1.0, acetone). Ϫ
1
Ϫ H NMR (300 MHz, C6D6): δ ϭ 0.03 (s, 6 H, SiCH3), 0.96 [s,
IR (film): ν˜ ϭ 3422 cmϪ1 (m), 2992 (m), 2945 (s), 2873 (m), 1478
(w), 1460 (w), 1429 (w), 1382 (s), 1371 (s), 1274 (m), 1240 (m), 1201
(s), 1165 (s), 1132 (m), 1097 (s), 1059 (s), 1012 (w), 994 (w), 969
(m), 949 (w), 936 (w), 875 (w), 849 (w), 683 (w), 523 (w). Ϫ 1H
NMR (300 MHz, C6D6): δ ϭ 1.25 [s, 3 H, C(CH3)2], 1.41 [s, 3 H,
C(CH3)2], 1.43Ϫ1.67 (m, 4 H, OCH2CH2CHO, CH2CH2OTBS),
2.90 (br. s, 1 H, OH), 3.54Ϫ3.80 (m, 5 H, CH2CH2OTBS,
OCH2CH2CH, OCH2CH2CHO). Ϫ 13C NMR (75 MHz, C6D6):
δ ϭ 19.3 [C(CH3)2], 30.3 [C(CH3)2], 31.4 (OCH2CH2CHO), 39.1
(CH2CH2OTBS), 58.7 (OCH2CH2CHO), 58.8 (CH2CH2OTBS),
68.2 (OCH2CH2CH), 98.3 [C(CH3)2]. Ϫ MS (EI, 70 eV); m/z
(%):145 (63), 115 (16), 85 (12), 73 (12), 67 (82), 61 (21), 59 (100),
58 (33), 57 (42), 55 (71), 54 (19). Ϫ MS (CI, isobutane); m/z (%):
161 [Mϩ ϩ 1] (100), 159 (3), 145 (3), 103 [Mϩ Ϫ 57] (9), 85 (3). Ϫ
C8H16O3 (160.21): calcd. C 59.98 H 10.07; found C 59.98 H 9.89.
Ϫ In analogy, reaction of 1.9 g (6.9 mmol) of (R)-6 yielded 1.04 g
9 H, C(CH3)3], 1.24 [s, 3 H, C(CH3)2], 1.44 [s, 3 H, C(CH3)2],
1.64Ϫ1.76 (m,
1 H, CHHCH2OTBS), 1.87Ϫ1.98 (m, 1 H,
CHHCH2OTBS), 2.12 (s, 3 H, SCH3), 3.51Ϫ3.74 (m, 3 H,
CH2CH2OTBS OCHHCHOS), 4.00 (dd, J ϭ 13.4 Hz, J ϭ 1.9 Hz,
1 H, OCHHCHOS), 4.19 (ddd, J ϭ 8.7 Hz, J ϭ 4.4 Hz, J ϭ 1.7
Hz, 1 H, OCHCHOS), 5.40 (q, J ϭ 1.9 Hz, 1 H, OCHCHOS). Ϫ
13C NMR (75 MHz, C6D6): δ ϭ Ϫ5.3 (SiCH3), 18.5 [C(CH3)3],
18.6 [C(CH3)2], 19.0 [C(CH3)2], 26.1 [3 ϫ C(CH3)3], 29.4 (SCH3),
34.8 (CH2CH2OTBS), 58.7 (CH2CH2OTBS), 62.4 (OCH2CHOS),
66.8 (OCHCHOS), 76.9 (OCHCHOS), 98.8 [C(CH3)2], 216.4
(CSSCH3). Ϫ MS (CI, isobutane): m/z (%): 381 [Mϩ ϩ 1] (100),
367 (10), 365 (14), 335 (27), 323 (30), 291 (19), 275 (34), 217 (10),
215 (22), 75 (8). Ϫ C16H32O4S2Si (380.63): calcd. C 50.49 H 8.47;
found C 50.68 H 8.31. Ϫ In analogy, reaction of 5.3 g (18.0 mmol)
28
of (S,R/S)-4 afforded 1.3 g of (S,S)-5 (19%), [α]D ϭ ϩ9.7 (c ϭ
25
1.0, CHCl3) and 4.5 g of (S,R)-5 (66%), [α]D ϭ Ϫ75.1 (c ϭ
28
of (S)-7 (94%). Ϫ [α]D ϭ Ϫ55.4 (c ϭ 1.0, acetone).
1.05, CHCl3).
(4ЈS,1R)-2-(2,2-Dimethyl-1,3-dioxan-4-yl)ethyl
3,3,3-Trifluoro-2-
(S)-1-(tert-Butyl)-1,1-dimethylsilyl {2-[2,2-Dimethyl-1,3-dioxan-4-
yl]ethyl} Ether [(S)-6]: 5.1 g (17.6 mmol, 1.5 equiv.) of tri-n-butyltin
hydride was dissolved in 400 mL of toluene in a Schlenk flask. The
solution was purged with Ar for 10 min and was then heated to
reflux. Then, 4.5 g of the xanthate (R,S/R)-5 (1.0 equiv.), dissolved
methoxy-2-phenylpropanoate [(S,R)-11]: According to a literature
procedure[10a] to a solution of 50 mg (0.2 mmol, 1.2 equiv.) of (ϩ)-
(R)-α-trifluoromethyl-α-methoxyphenylacetic acid and 16 mg (0.2
mmol, 1.2 equiv.) of dimethylformamide in 10 mL of hexane was
added 89 µL (1.0 mmol, 5.7 equiv.) of oxalyl chloride at room temp.
in 15 mL of toluene, was added dropwise via canula over a period The resulting mixture was stirred for 1 h and the solvent was re-
of 4 h. During the addition, a sat. solution of AIBN in toluene was
added dropwise via canula (ca. 0.1 equiv.) and the solution was
stirred under reflux overnight. After conversion of the starting ma-
terial was indicated by TLC, the solvent was removed under re-
duced pressure and the residue directly subjected to column chro-
matography (SiO2; pentane/Et2O, 8:1) to give (S)-6 as a colourless
moved under reduced pressure. To the resulting colourless solid a
solution of 71 µL (0.18 mmol, 1.0 equiv.) of triethylamine, a crystal
of 4-(dimethylamino)pyridine and 28 mg (0.18 mmol, 1.0 equiv.) of
(S)-7 in 2 mL of chloroform was added. The mixture was stirred
at room temp. overnight. A sat. aqueous NH4Cl solution was ad-
ded and the organic layer was washed with brine, dried (MgSO4)
and concentrated under reduced pressure. The crude product was
23
oil, yield 2.6 g (82%). Ϫ [α]D ϭ ϩ34.1 (c ϭ 1.0, acetone). Ϫ IR
(film): ν˜ ϭ 2993 cmϪ1 (w), 2953 (s), 2930 (s), 2859 (m), 1472 (w), subjected to HPLC analysis on a stationary chiral phase (Chiracel
1463 (w), 1380 (m), 1369 (w), 1256 (m), 1198 (m), 1170 (m), 1135 OJ) and compared with an independently synthesised racemic ref-
(m), 1102 (s), 1059 (w), 1021 (w), 1007 (w), 971 (m), 961 (w), 939 erence sample (de Ն 96%). Purification by column chromatography
1
(w), 921 (w), 877 (w), 837 (s), 804 (w), 777 (m). Ϫ H NMR (300 (SiO2; pentane/Et2O, 1:1) afforded (S,R)-11 as colourless oil, yield
MHz, CDCl3): δ ϭ 0.05 (s, 6 H, SiCH3), 0.90 [s, 9 H, C(CH3)3],
1.37 [s, 3 H, C(CH3)2], 1.45 [s, 3 H, C(CH3)2], 1.53Ϫ1.76 (m, 4 H, 1750 (s), 1452 (w), 1431 (w), 1382 (w), 1371 (w), 1271 (s), 1242 (s),
45 mg (66%). Ϫ IR (film): ν˜ ϭ 2993 cmϪ1 (w), 2950 (w), 2870 (w),
OCH2CH2CHO, CH2CH2OTBS), 3.60Ϫ3.77 (m,
2
H, 1170 (s), 1122 (m), 1101 (m), 1082 (w), 1059 (w), 1022 (m), 1001
754
Eur. J. Org. Chem. 1999, 751Ϫ756

Asymmetric Synthesis of (ϩ)- and (Ϫ)-Streptenol A
FULL PAPER
(m), 969 (w), 949 (w), 857 (w), 767 (w), 720 (w), 698 (w). Ϫ 1H C(CH3)2], 1.66Ϫ1.80 (m, 5 H, OCH2CH2CH, CHCH3), 1.96 (m, 2
NMR (300 MHz, C6D6): δ ϭ 1.19 [s, 3 H, C(CH3)2], 1.42 [s, 3 H, H, CH2CHOHCH2), 2.19 (m, 2 H, CH2CHOHCH2), 2.97 (br. s, 1
C(CH3)2], 1.44Ϫ1.63 (m, 4 H, OCH2CH2CHO, CH2CH2OTBS), H, CHOH), 3.85 (m,
1
H, CHOH), 3.90Ϫ3.97 (m,
2
1
1
H,
H,
H,
3.39Ϫ3.44 (m, 3 H, OCH3), 3.49Ϫ3.62 (m, 3 H, OCH2CH2CHO, CH2CHCHCH3), 4.07 (dd,
OCH2CH2CHO), 4.12Ϫ4.34 (m, 2 H, CH2OCOR), 7.05Ϫ7.15 (m, OCHHCH2CH), 4.12 (dd,
J
ϭ
12.4 Hz, 2.8 Hz,
11.8 Hz, 2.8 Hz,
J
ϭ
3 H, H-ar), 7.65 (m, 2 H, H-ar). Ϫ 13C NMR (75 MHz, C6D6):
OCHHCH2CH), 4.22Ϫ4.34 (m, 1 H, OCHHCH2CH), 5.50Ϫ5.58
δ ϭ 19.1 [C(CH3)2], 30.2 [C(CH3)2], 31.4 (OCH2CH2CHO), 35.5 (m, 2 H, CHCHCH3). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 17.6
(CH2CH2OTBS), 55.3 (OCH3), 59.6 (OCH2CH2CHO), 59.7 (CHCH3), 18.8 [C(CH3)2], 28.3 [OCH2CH2CH), 29.6 [C(CH3)2],
(CH2CH2OCOR*), 62.7 (CCF3), 65.3 (OCH2CH2CH), 98.4 30.7 (CH2CHOHCH2), 37.0 (CH2CHOHCH2), 42.3
[C(CH3)2], 122.4 (CF3), 126.2Ϫ129.8 (C-ar), 166.6 (CO). Ϫ MS (CH2CHCHCH3), 59.5 (OCH2CH2CH), 67.0 (OCH2CH2CH), 70.2
(EI, 70 eV); m/z (%): 362 (11), 361 (64), 189 (64), 127 (16), 119 (CHOH), 98.0 [C(CH3)2], 124.7 (CHCHCH3), 130.6 (CHCHCH3).
(11), 105 (24), 85 (15), 77 (12), 68 (10), 67 (100), 59 (18), 57 (23), Ϫ MS (EI, 70 eV); m/z (%): 213 [Mϩ Ϫ Me [ (32), 115 (28), 101
55 (20). Ϫ MS (CI, isobutane); m/z (%): 377 [Mϩ ϩ 1] (100), 361
(4), 319 [Mϩ Ϫ 57] (9), 289 (4). Ϫ C18H23F3O5 (376.37): calcd. C
57.44 H 6.16; found C 57.56 H 6.31.
(29), 99 (19), 81 (36), 74 (28), 59 (94), 57 (40), 55 (100), 46 (28). Ϫ
MS (CI, isobutane); m/z (%): 229 [Mϩ ϩ H] (100), 211 (4), 171 (7),
153 (2). Ϫ In analogy, reaction of 752 mg (4.7 mmol) of (R)-8
yielded 782 mg of (R/S,R)-9 (73%).
(S)-2-(2,2-Dimethyl-1,3-dioxan-4-yl)ethanal (S)-8: In 15 mL of di-
chloromethane a mixture of 500 mg (3.1 mmol, 1.0 equiv.) of (R)-
(S)-1-(2,2-Dimethyl-1,3-dioxan-4-yl)-hept-5-en-2-one [(S)-10]: To a
7, 78 mg (7.5 mol-%) of tetrapropylammonium perruthenate, 620 solution of 345 mg of (S/R,S)-9 in 50 mL of dichloromethane at
mg (4.6 mmol, 1.5 equiv.) 4-methymorpholine oxide and 1.2 g of
ground molecular sieves (4 A) were stirred 72 h at room temp. After mmol) of pyridinium chlorochromate, 970 mg of Celite and 970
room temp. was slowly added a mixture of 967 mg (967 mg, 4.5
˚
˚
complete conversion of the starting material was indicated by TLC,
the mixture was directly subjected to column chromatography
(SiO2; pentane /Et2O, 1:1) to yield a colourless oil (volatile!), yield
mg of ground molecular sieves (4 A). The suspension was stirred
for 4 h (TLC control) and then filtered through a pad of silica gel
which was eluted with 500 mL of ethyl acetate. The solvent was
removed under reduced pressure and the residue was purified by
column chromatography (SiO2; pentane/Et2O, 4:1) to yield (S)-10
23
435 mg (88%). Ϫ [α]D ϭ ϩ11.9 (c ϭ 1.0, CH2Cl2). Ϫ IR (film):
ν˜ ϭ 2991 cmϪ1 (s), 2952 (vs), 2877 (s), 1726 (s), 1432 (m), 1382
(vs), 1267 (s), 1242 (s), 1200 (vs), 1166 (vs), 1100 (vs), 1062 (vs), as a colourless oil, yield 244 mg (72%). Ϫ [α]D23 ϭ ϩ12.8 (c ϭ 1.0,
1027 (vs), 991 (vs), 972 (vs), 912 (m), 888 (m), 872 (m), 848 (m), CH2Cl2). Ϫ IR (film): ν˜ ϭ 3520 cmϪ1 (w), 3411 (w), 2992 (vs),
816 (m), 750 (w), 640 (w), 526 (w). Ϫ 1H NMR (300 MHz, CDCl3): 2869 (vs), 2723 (w), 1713 (vs), 1433 (s), 1409 (s), 1381 (vs), 1316
δ ϭ 1.37 (s, 3 H, CH3), 1.48 (s, 3 H, CH3), 1.52Ϫ1.74 (m, 2 H, (m), 1272 (vs), 1242 (vs), 1198 (vs), 1161 (vs), 1132 (vs), 1102 (vs),
OCH2CH2CH), 2.49 (ddd, J ϭ 16.8 Hz, 4.9 Hz, 1.7 Hz, 1 H, 1047 (vs), 971 (vs), 948 (s), 911 (s), 875 (s), 839 (m), 822 (m), 735
1
CHHCHO), 2.64 (ddd, J ϭ 16.8 Hz, 7.2 Hz, 2.2 Hz, 1 H,
CHHCHO), 3.85 (ddd, J ϭ 11.8 Hz, 5.2 Hz, 1.7 Hz, 1 H,
(m), 648 (w), 638 (w), 525 (m), 484 (m), 439 (w). Ϫ H NMR (300
MHz, CDCl3): δ ϭ 1.28 [s, 3 H, C(CH3)2], 1.39 [s, 3 H, C(CH3)2],
H, 1.43Ϫ1.53 (m, 2 H, OCH2CH2CH), 1.53Ϫ1.58 (m, 3 H, CHCH3),
OCHHCH2CH), 4.02 (dt,
J
ϭ
11.8 Hz, 3.0 Hz,
1
OCHHCH2CH), 4.40Ϫ4.50 (m, 1 H, OCH2CH2CH), 9.79 (t, J ϭ 2.18 (m,
2
H, CH2COCH2CH2), 2.30Ϫ2.40 (m,
2
H,
H,
1.9 Hz, 1 H, CHO). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.6
CH2COCH2CH2), 2.43 (dd,
J
ϭ
7.1 Hz, 2.7 Hz, 1
(CH3), 29.3 (CH3), 30.5 (OCH2CH2CH), 49.4 (CH2CHO), 59.2 COCH2CHH), 2.60 (dd, J ϭ 16.1 Hz, 7.1 Hz, 1 H, COCH2CHH),
(OCH2CH2CH), 64.1 (OCH2CH2CH), 98.1 [C(CH3)2], 200.4 3.74 (ddd, J ϭ 11.8 Hz, 4.8 Hz, 2.1 Hz, 1 H, OCHHCH2CH), 3.92
(CHO). Ϫ MS (EI, 70 eV); m/z (%): 143 [Mϩ Ϫ Me] (62), 115 (17),
(td, J ϭ 11.5 Hz, 3.7 Hz, 1 H, OCHHCH2CHO), 4.28 (m, 1 H,
83 (23); 61 (15), 59 (68), 55 (100). Ϫ MS (CI, isobutane); m/z (%): OCH2CH2CHO), 5.31Ϫ5.43 (m, 2 H, CHCHCH3). Ϫ 13C NMR
159 [Mϩ ϩ H] (100), 143 (4), 115 (9), 101 (14). Ϫ HRMS (75 MHz, CDCl3): δ ϭ 17.9 (CHCH3), 19.2 [C(CH3)2], 26.6
(C7H11O3): calcd. 143.0708; found 143.0708. Ϫ In analogy, oxi-
dation of 800 mg (5.0 mmol) of (S)-7 yielded 679 mg of (R)-8
(OCHHCH2CHO), 29.9 [C(CH3)2], 31.2 (CH2COCH2CH2), 43.8
(CH2COCH2CH2), 49.4 (CH2COCH2CH2), 59.8 (OCH2CH2-
CHO), 65.7 (OCH2CH2CHO), 98.5 [C(CH3)2], 125.9 (CHCH3),
129.6 (CHCHCH3), 208.5 (CO). Ϫ MS (EI, 70 eV); m/z (%): 226
[Mϩ], 211 [Mϩ Ϫ Me] (19), 168 (15), 150 (6), 115 (16), 97 (80), 73
(12), 69 (100), 59 (30), 55 (34). Ϫ In analogy, oxidation of 276 mg
(1.2 mmol) of (R/S,R)-9 yielded 194 mg of (R)-10 (71%). Ϫ
23
(86%). Ϫ [α]D ϭ Ϫ12.0 (c ϭ 1.0, CH2Cl2) {ref.[5]: [α]D ϭ Ϫ12.8
(c ϭ 1.1, CH2Cl2)}.
(4ЈS,2R/S)-1-(2,2-Dimethyl-1,3-dioxan-4-yl)hept-5-en-2-ol (S/R,S)-
9: According to the literature[6] 158 mg (6.5 mmol, 2.5 equiv.) of
freshly ground magnesium was placed in a flame-dried 100-mL
Schlenk flask. Then 10 mL of THF was added and 968 mg (6.5
mmol, 2.5 equiv.) of (E)-5-bromo-2-pentene was slowly added via
syringe. The reaction mixture was heated to 50°C for 30 min. The
23
[α]D ϭ Ϫ12.9 (c ϭ 1.0, CH2Cl2) {ref.[5]: [α]D ϭ Ϫ13.7 (c ϭ
1.05, CH2Cl2)}.
(؉)-Streptenol A: 100 mg (0.44 mmol) of (S)-10 was dissolved in 2
mixture was allowed to reach room temp. and 410 mg (2.6 mmol, mL of THF and 1 mL of water. The mixture was cooled to 0°C
1.0 equiv.) of (S)-8 was slowly added. After stirring for 2 h at and 0.1 mL of trifluoracetic acid was added via syringe. Stirring
50Ϫ60°C, a sat. aqueous NH4Cl solution was slowly added, the was continued at 0°C for 3 h until TLC control indicated complete
organic phase was diluted with diethyl ether and washed with conversion of the starting material. Then, 1 mL of an aqueous
water. The aqueous phase was extracted with EtOAc three times ammonia solution and 3 mL of water were added. The aqueous
and the combined organic phases were washed with brine, dried
(MgSO4) and concentrated under reduced pressure to give (S/R,S)-
solution was extracted three times with CH2Cl2 and the combined
organic phases were washed with brine and dried with MgSO4.
9 as a sligthly yellow oil, yield 480 mg (81%). Ϫ IR (film): ν˜ ϭ Evaporation of the solvent under reduced pressure and filtration
3449 cmϪ1 (s), 2993 (vs), 2939 (vs), 2865 (s), 2728 (w), 1452 (m),
through a pad of Florisil yielded the title compound as a colour-
23
1438 (m), 1381 (vs), 1311 (m), 1269 (s), 1241 (s), 1201 (vs), 1163 less oil, yield 63 mg (78%). Ϫ [α]D ϭ ϩ21.7 (c ϭ 1.0, CHCl3)
(vs), 1137 (s), 1102 (vs), 1053 (m), 969 (vs), 947 (m), 909 (m), 872 {ref.[1a]: [α]D ϭ ϩ 23 (c ϭ 1.0, CHCl3)}. Ϫ In analogy, deprotection
(m), 853 (m), 815 (m), 748 (w), 639 (w), 524 (m), 501 (w). Ϫ 1H of 180 mg (0.80 mmol) of (R)-10 yielded 106 mg of (Ϫ)-streptenol
23
NMR (300 MHz, CDCl3): δ ϭ 1.58 [s, 3 H, C(CH3)2], 1.61 [s, 3 H, A (72%). Ϫ [α]D ϭ Ϫ21.5 (c ϭ 1.0, CHCl3) {ref.[5]: [α]D ϭ Ϫ23
Eur. J. Org. Chem. 1999, 751Ϫ756
755

D. Enders, T. Hundertmark
FULL PAPER
[4a] M. Franck- Neumann, P. Bissinger, P. Geoffroy Tetrahedron
[4]
[5]
(c ϭ 1.0, CHCl3)}. The spectroscopic data are in accordance with
[4b]
Lett. 1995, 38, 4469. Ϫ
M. Hayashi, H. Kaneda, N. Oguni,
previously published data.[1a,3]
Tetrahedron: Asymmetry 1995, 6, 2511.
S. Blechert, H. Dollt, Liebigs Ann. 1996, 2135.
[6] [6a]
P. D. Theisen, C. H. Heathcock, J. Org. Chem. 1988, 53,
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58, 142.
Acknowledgments
[7] [7a]
D. H. R. Barton, S. W. J. McCombie, J. Chem. Soc., Perkin
Our work was generously supported by the Deutsche For-
schungsgemeinschaft (Leibniz award, Sonderforschungsbereich
380) and the Fonds der Chemischen Industrie. We thank the De-
gussa AG, BASF AG, Bayer AG and Wacker Chemie for the do-
nation of chemicals. T. H. is indebted to Ms. Melanie Neugebauer
and Mr. Mario Kraft for their excellent contributions as under-
graduate students.
[7b]
Trans. 1 1975, 1574. Ϫ
D. Enders, T. Hundertmark, C.
Lampe, U. Jegelka, I. Scharfbillig, Eur. J. Org. Chem. 1998,
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[8] [8a]
[8b]
D. Enders, B. Bockstiegel, Synthesis 1989, 493. Ϫ
D.
Enders, W. Gatzweiler, U. Jegelka, Synthesis 1991, 1137. Ϫ
[8c]
D. Enders, O. F. Prokopenko, Liebigs Ann. 1995, 1185. Ϫ
[8d]
M. Majewski, P. Nowak, Tetrahedron: Asymmetry 1998, 9,
2611.
[9]
D. Enders, T. Hundertmark, R. Lazny, Synlett 1998, 721.
[10] [10a]
[10b]
D. E. Ward, C. K. Ree, Tetrahedron Lett 1991, 34, 7165. Ϫ
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J. A. Dale, D. L. Dull, S. H. Mosher, J. Org. Chem. 1969,
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34, 2543. Ϫ
J. A. Dale, S. H. Mosher, J. Am. Chem. Soc.
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Y. Romeyke, M. Keller, H. Kluge,
[1c]
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S. Grabley, P. Hammann, Tetrahedron 1991, 47, 3335. Ϫ
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W. P. Griffith, S. V. Ley, G. P. Whitecombe, A. D. White, J.
Grabley, P. Hammann, H. Kluge, J. Wink, J. Antibiotics 1991,
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Chem. Soc., Chem. Commun. 1989, 1625. Ϫ
S. V. Ley, J.
Norman, W. P. Griffith, S. P. Marsden, Synthesis 1994, 639.
E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 2647.
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[Chem. Abstr. 1990, 112, 75317y]. Ϫ
A. Arone, R. Cardillo,
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[15]
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