Synthesis of enantiopure 1-alkoxyallenes and their 3-alkylated derivatives

Article abstract of DOI:10.1055/s-2001-15225

A series of enantiopure 1-alkoxyallenes 1a-1f was prepared starting from propargyl bromide and the corresponding optically active alcohols via propargyl ethers 3a-3f as intermediates. In addition, disubstituted enantiopure allene derivatives 5a-5c were synthesized by isomerization of the corresponding alkynes 4a-4c. Allene derivative 5a was also prepared via an alternative route with 1-trimethylsilylallene derivative 6a as crucial intermediate.

Full text of DOI:10.1055/s-2001-15225

PAPER
1377
Synthesis of Enantiopure 1-Alkoxyallenes and their 3-Alkylated Derivatives
Synthesis of
E
nant
r
iopure
1
n
-
Alkoxyallen
d
es t Hausherr, Beate Orschel, Stefan Scherer, Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie – Organische Chemie, Takustr. 3, 14195 Berlin, Germany
Fax +49(30)83855367; E-mail: Hans.Reissig@Chemie.FU-Berlin.DE
Received 18 January 2001; revised 27 February 2001
metric syntheses. Indeed, we succeeded in preparing the
Abstract: A series of enantiopure 1-alkoxyallenes 1a–1f was pre-
pared starting from propargyl bromide and the corresponding opti-
cally active alcohols via propargyl ethers 3a–3f as intermediates. In
addition, disubstituted enantiopure allene derivatives 5a–5c were
enantiopure alkoxyallene 1a and in using it in hetero
Diels–Alder reactions with nitrosoalkenes. This provided
1,2-oxazine derivatives with a ratio of the two possible di-
synthesized by isomerization of the corresponding alkynes 4a–4c. astereomers higher than 95:5.7 Simultaneously with our
Allene derivative 5a was also prepared via an alternative route with
1-trimethylsilylallene derivative 6a as crucial intermediate.
investigations the group of Goré published the synthesis
of a series of enantiopure alkoxyallenes substituted with
Key words: alkynes, allenes, isomerization, carbohydrates, asym-
metric synthesis
several amino alcohol, terpene or carbohydrate derived
auxiliaries.8,9 In this paper we want to present full experi-
mental details of the preparation of enantiopure alkoxyal-
lenes 1, and we also describe first examples for synthesis
Alkoxyallenes 1 are important precursors in cycloaddi- of enantiopure 3-alkylsubstituted 1-alkoxy-1,2-propa-
tions providing carbocycles and heterocycles with inter- dienes 5 bearing carbohydrate based auxiliaries. The prep-
esting patterns of functional groups.1,2 1,2-Oxazine aration of one of these axially chiral allene derivatives
derivatives which could be converted into a large number was achieved by a multistep route with 1a as precursor.
of cyclic or acyclic products by subsequent transforma- Alternatively, a shorter path via alkylated alkynes 4 as in-
tions are of particular interest as cycloadducts.3 The CH- termediate was established furnishing disubstituted al-
acidity at C-1 of alkoxyallenes allows their smooth lenes 5 with good overall efficiency (Scheme 2).
lithiation4 and, if appropriate, transmetallation to new spe-
cies,5 thus delivering strongly nucleophilic intermediates
whose reactions with various electrophiles have been uti-
lized for many synthetic applications (Scheme 1). Metal-
lated alkoxyallenes may consequently serve as synthetic
equivalents for synthons involving an umpolung process,
such as , -unsaturated acyl anions, 1,3-zwitterions,
formylester anions and homoenolates.1,6
Scheme 2
In accordance with our preliminary publication7 and the
method reported by Goré and co-workers8,9 enantiopure
alcohols 2a–2f smoothly react with propargyl bromide in
a Williamson ether synthesis to furnish the propargyl
ethers 3a–3f in good to excellent yields. Base-catalyzed
Scheme 1
isomerization of the alkyne to the allene structure was in-
Due to the high synthetic versatility of alkoxyallenes and
their derivatives it should be of particular interest to em-
ploy enantiopure derivatives whose chirality may be
transferred to newly created stereogenic centers in asym-
duced by 1.5 equivalents to 2.0 equivalents of KOt-Bu in
refluxing toluene. Although the reaction mixture became
dark brown in most cases purification of the crude product
by column chromatography allowed isolation of enan-
tiopure alkoxyallenes 1a–1e without problems and in
moderate to good yield. The fenchol based compound 1f
is more sensitive and did not survive attempts of purifica-
tion by column chromatography (Scheme 3).
Synthesis 2001, No. 9, 29 06 2001. Article Identifier:
1437-210X,E;2001,0,09,1377,1385,ftx,en;T00901SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1378
A. Hausherr et al.
PAPER
Scheme 3
The more efficient two-step synthesis of 3-alkylated alkoxyallene 5b a 75:25 ratio in favor of the R-isomer
1-alkoxypropa-1,2-dienes 5a–5c started with the C-alkyl- with respect to the allene moiety was observed. The abso-
ation of propargyl ethers 3a–3c employing standard con- lute configuration of this isomer was determined by sub-
ditions. Thus, lithium salts of the alkynes were generated sequent reactions leading to formation of a known
when n-butyllithium, 1,2-dimethyl-2,4,5,6-tetrahydro- reference compound.11
2(1H)pyrimidone (DMPU) was employed as complexing
agent and nonyl iodide introduced as electrophile. The re-
sulting ethers 4a–4c could be transformed into alkoxyal-
For diacetone glucose based allene 1a we also examined
an alternative and longer route. Lithiation of 1a and treat-
ment with trimethylsilyl chloride afforded the expected
lenes 5a–5c by lithiation with n-butyllithium in the
1-silylated allene 6a which was subsequently lithiated at
presence of tetramethylethylenediamine (TMEDA) fol-
C3 and treated with nonyl iodide to furnish the trisubsti-
lowed by quenching with wet THF at low temperature
tuted allene derivative 7a (Scheme 5).12 Finally, desilyla-
(Scheme 4).10 Use of D2O instead of water selectively
tion of this intermediate with tetrabutylammonium
provided the deuterated compound (D)-5a. Whereas the
fluoride (TBAF) provided the desired product 5a as a
yields of these reactions were satisfying, diastereoselec-
tivities were at best moderate. For fructose derived
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Enantiopure 1-Alkoxyallenes
1379
Scheme 4
in hexane were titrated using the diphenylacetic acid method.15 All
other chemicals are commercially available and were used as re-
ceived. IR spectra were measured with Beckman IR Acculab 4,
Beckman IR 5A, Perkin Elmer IR 1420 or Perkin Elmer FT-IR
spectrometer Nicolet 5 SXC. 1H and 13C NMR spectra were record-
ed on Bruker instruments (AC 500, WM 300, WH 270, AC 250) in
CDCl3 solution. The chemical shifts are given in relative to the TMS
or to the CDCl3 signal ( H = 7.26, C = 77.0). Higher order NMR
spectra were approximately interpreted as first-order spectra if pos-
sible. Optical rotations were determined with a Perkin Elmer 141 or
Perkin Elmer 241 polarimeter at 20°C. Neutral alumina (activity III,
Fluka/Merck) was used for column chromatography. Nucleosil 50–
5 (Macherey & Nagel) was used for HPLC. Starting materials 2a–
2e were prepared by literature procedures.16–20 Compound 2f was
purchased from Fluka.
70:30 mixture of diastereomers favoring the S-isomer
with regard to the chiral axis.11
Propargyl Ethers 3 (except 3f); General Procedure 1
To a stirred solution of alcohol 2 (1 equiv) under air atmosphere in
THF (1 mL/mmol 2) were added n-Bu4NI (0.1 equiv), a 60% solu-
tion of NaOH (1 mL/mmol 2) and propargyl bromide (2.5 equiv) at
0°C. The reaction mixture was stirred (TLC control) for 3 d to 6 d
at r.t. The aqueous phase was separated, extracted with t-butyl me-
thyl ether (MTB) or Et2O (3 15 mL) and the organic extracts were
combined. The organic layer was washed with H2O (3 15 mL),
dried (Na2SO4) and the solvent was evaporated. The resulting crude
products 3a–3c were purified by column chromatography with
n-hexane–EtOAc or n-hexane–MTB as eluent. 3d and 3e were pu-
rified by Kugelrohr distillation (160°C/0.02 mbar, 170°C/0.02
mbar, respectively). IR and NMR data are given in Tables 1, 4
and 5.
Scheme 5
In summary, we have disclosed here full details of the
preparation of enantiopure 1-alkoxyallenes bearing main-
ly carbohydrate moieties as chiral substituents. The litera-
ture known base-catalyzed rearrangement of the
propargyl ethers 3 proceeded in moderate to very good
yield giving the desired 1-alkoxyallenes 1 in synthetically
useful quantities. In addition, disubstituted enantiopure
allene derivatives 5 have been synthesized via two princi-
pal routes. The isomerization of alkynes of type 4 seems
to be the more efficient way to prepare 5. Unfortunately,
the diastereoselectivity of this method is so far not satisfy-
ing.13 At best the two diastereomers are formed in a 3:1 ra-
tio. In due course we shall report on applications of the
enantiopure 1-alkoxyallenes in the stereoselective synthe-
ses of pyrrolidine derivatives.14
Allenyl Ethers 1; General Procedure 2
To a stirred solution of propargyl ether 3 (1 equiv) in toluene ( 5
mL/mmol 3) was added KOt-Bu (1.5 to 2.0 equiv) and the reaction
mixture was heated to reflux for 1 h to 4 h. The mixture was
quenched with sat. aq NaHCO3 solution. The aqueous phase was
separated and extracted with MTB or Et2O (3 20 mL). The organic
extracts were combined, washed with sat. aq NaHCO3 solution (2
20 mL) and dried (Na2SO4). The solvent was removed and the crude
products 1a-1e were purified by column chromatography with n-
hexane–EtOAc or n-hexane–MtB as eluent. Compound 1f was pu-
rified by Kugelrohr distillation (30°C, 1 mbar). IR and NMR data
are given in Tables 2, 6 and 7.
Unless otherwise stated all reactions were performed under argon
atmosphere in flame-dried reaction flasks by adding the compo-
nents via syringes. All solvents were dried using standard proce-
dures. TMEDA was distilled from KOH. TMSCl was distilled from
CaH2. KOt-Bu was sublimed prior to use. Anhyd DMPU was pur-
chased from Fluka. Commercially available 2.5 M n-BuLi solutions
Nonyl-Substituted Propargyl Ethers 4; General Procedure 3
To a stirred solution of propargyl ether 3 (1 equiv) in THF (10 mL/
mmol 3) was added n-BuLi (1.1 equiv) at –50°C dropwise. After 10
min the reaction mixture was allowed to warm to –15°C. First
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

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Table 1 Synthesis of Propargyl Ethers 3 According to General Procedure 1
20
2
g (mmol)
Reaction Conditions
g (mmol)
Yield of Product 3a IR (film)
[ ]D
g (%)
(cm–1)
(g/100 mL)b
2a
2b
2c
2d
2e
2fd
2.60 (10.0) 0.370 (1.00) n-Bu4NI
3a
3b
3c
3d
3e
3f
2.74 (92)
3260 ( C-H), 2970–2870 (C–H), 2100
(C C)
–11.4 (1.0)
3.12 (26.2) HC CCH2Br
5.21 (20.0) 0.740 (2.00) n-Bu4NI
4.64 (78)
4.10 (70)
2.56 (86)
3.44 (91)
3260 ( C-H), 2980–2870 (C–H), 2100
(C C)
–73.3 (1.2)
–39.8 (1.0)
5.95 (50.0) HC CCH2Br
5.20 (19.8) 0.731 (1.98) n-Bu4NI
3270 ( C-H), 2990–2935 (C–H), 2115
(C C)
6.18 (51.5) HC CCH2Br
c
2.60 (10.0) 0.370 (1.00) n-Bu4NI
3250 ( C-H), 2980–2780 (C–H), 2110
(C C)
-
2.97 (25.0) HC CCH2Br
c
3.41 (10.0) 0.370 (1.00) n-Bu4NI
3250 ( C-H), 2960–2840 (C–H), 2110
(C C)
-
2.97 (25.0) HC CCH2Br
c
1.54 (10.0) 0.96 (40.0) NaH
3.57 (30.0) HC CCH2Br
1.54 (81) e 3300 ( C-H), 2970–2870 (C–H), 2100
-
(C C)
a Satisfactory microanalysis obtained: C 0.35, H 0.19; exception: due to instability of 3f, no satisfactory microanalysis could be obtained
(C –1.75, H +0.74).
b Specific optical rotation determined in CHCl3.
c Not determined.
d For reaction conditions see experimental part.
e Melting point 16–18°C.
C9H19I (1.2 equiv) and then DMPU (1.5 equiv) were added. The re-
action mixture was stirred in the dark at r.t. for 12 h. The mixture
was quenched with sat. aq NaHCO3 solution, the aqueous phase was
separated and extracted with Et2O (3 20 mL). The organic extracts
were combined, washed with sat. aq NaHCO3 solution (2 20 mL)
and dried (Na2SO4). The solvent was removed and the crude prod-
uct 4 was purified by column chromatography with n-hexane–
EtOAc as eluent. IR and NMR data are given in Tables 3, 8 and 9.
Nonyl Substituted Allenyl Ethers 5; General Procedure 4
To a stirred solution of propargyl ether 4 (1 equiv) in THF (20 mL/
mmol 4) n-BuLi (1.1 to 1.2 equiv) was added at –50°C dropwise.
After 20 min the reaction mixture was cooled to –80°C to –90°C
and TMEDA (1.1 to 1.2 equiv) was added. The reaction mixture
was stirred for 1 h and then quenched with wet THF or D2O in THF.
Sat. aq NaHCO3 solution was added, the aqueous phase was sepa-
rated, extracted with Et2O (3 15 mL) and the organic extracts were
combined. The organic phase was washed with sat. aq NaHCO3 so-
lution (2 15 mL), dried (Na2SO4) and the solvent was removed.
The crude products 5a and 5c were purified by column chromatog-
raphy, 5b was purified by HPLC with n-hexane–EtOAc as eluent.
IR and NMR data are given in Tables 3, 8 and 9.
Table 2 Synthesis of Allenyl Ethers 1 According to General Procedure 2
20
3
g (mmol) Reaction Conditions
g (mmol)
Yield of Product 1a IR (film)
[ ]D
g (%)
(cm–1)
(g/100 mL)b
3a
3b
1.70 (5.7) 1.12 (10.0) KOt-Bu
1a
1b
1.36 (80)
2970–2870 (C–H), 1950 (C=C=C),
1670 (C=C)
–23.7 (1.2)
–107.0 (1.2)
–9.1 (1.1)
4.14 (13.9) 3.12 (27.8) KOt-Bu
1.91 (46)
3000–2880 (C–H), 1960 (C=C=C),
1680 (C=C)
3c
3d
3e
3f
1.85 (6.2) 1.22 (10.9) KOt-Bu
2.40 (8.0) 1.81 (16.1) KOt-Bu
3.21 (8.5) 1.91 (17.0) KOt-Bu
3.00 (15.6) 2.47 (22.0) KOt-Bu
1c
1d
1e
1f
0.83 (45)c
0.99 (41)
1.82 (57)
1.98 (66)
2990–2900 (C–H), 1955 (C=C=C)
3000–2860 (C–H), 1960 (C=C=C)
3040–2820 (C–H), 1950 (C=C=C)
d
-
d
-
d
2950–2860 (C–H), 1950 (C=C=C),
-
1690 (C=C)
a Satisfactory microanalysis obtained: C 0.40, H 0.20; exception: due to instability of 1f, no satisfactory microanalysis could be obtained
(C –2.51, H +0.32).
b Specific optical rotation determined in CHCl3.
c 500 mg of starting material was isolated, yield 61% with respect to consumed 3c.
d Not determined.
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

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Synthesis of Enantiopure 1-Alkoxyallenes
1381
Table 3 Synthesis of Nonyl-Substituted Propargyl Ethers 4 and the Corresponding Allenyl Ethers 5 According to General Procedures 3 and 4
20
3 or 4 g (mmol)
Reaction Conditions
mL (mmol)
Yield of Producta
g (%)
Ratio of IR (film)
Isomers
[ ]D
(cm–1)
(g/100 mL)b
3a
3b
3c
4a
4a
4b
4c
0.342 (1.15) 0.52 (1.3) n-BuLi, 0.27 (1.4) C9H19I,
4a
4b
4c
5a
0.350 (72)
0.704 (54)
1.04 (73)
1.11 (82)c
-
2985–2855 (C–H),
2225 (C C)
–8.5 (2.2)
–38.6 (1.1)
–28.3 (0.9)
0.21 (1.7) DMPU
0.907 (3.07) 1.40 (3.4) n-BuLi, 0.73 (3.7) C9H19I,
-
2985–2855 (C–H),
2220 (C C)
0.60 (5.1) DMPU
1.00 (3.37)
1.35 (3.18)
1.50 (3.7) n-BuLi, 0.80 (4.0) C9H19I,
0.60 (5.1) DMPU
-
2990–2855 (C–H),
2200 (C C)
d
1.60 (3.8) n-BuLi,
50:50
50:50
75:25h
55:45
2985–2855 (C–H),
1955 (C=C=C)
-
0.57 (3.8) TMEDA
0.200 (0.47) 0.24 (0.6) n-BuLi,
0.08 (0.6) TMEDA, then D2O–THF
(D)-5a 0.134 (67)e
2990–2855 (C–H),
1945 (C=C=C)
–16.9 (1.1)f
0.986 (2.32) 1.20 (2.8) n-BuLi,
5b
5c
0.670 (68)g
0.655 (62)
2985–2855 (C–H),
1955 (C=C=C)
–121.1 (1.0)f
0.42 (2.8) TMEDA
d
1.05 (2.48)
1.10 (2.7) n-BuLi,
2990–2855 (C–H),
-
0.41 (2.7) TMEDA
1955 (C=C=C)
a Satisfactory microanalysis obtained: C 0.51, H 0.24; exceptions: 4c, 5a and (D)-5a were identified by MS and HRMS.
b Specific optical rotation determined in CHCl3.
c 130 mg of starting material was isolated, yield 90% with respect to consumed 4a.
d Not determined.
e 12 mg of deuterated starting material was isolated, yield 71% with respect to consumed 4a.
f Specific optical rotation given for mixture of isomers.
g 140 mg of starting material isolated, yield 79% with respect to consumed 4b.
h Major isomer is R configurated with respect to allene moiety.11
(1S,2R,4R)-2-[(Prop-2-yn-1-yl)oxy]-1,3,3-trimethyl-
bicyclo[2.2.1]heptane (3f)
H, 4-H), 4.12–3.96 (m, 2 H, 6-H), 1.50, 1.43, 1.34, 1.31 (4 s, 3 H
each, CH3).
To a stirred suspension of NaH (0.96 g, 40.0 mmol) in THF (80 mL)
was added a solution of (+)-fenchol (2f; 1.54 g, 10.0 mmol) in THF
(20 mL) at 0°C. The reaction mixture was stirred at r.t. for 20 min,
then cooled to 0°C and propargyl bromide (2.70 mL, 30.0 mmol)
was added. The reaction mixture was stirred for 3 d at r.t. Sat. aq
NH4Cl solution (20 mL) was added, the aqueous phase was separat-
ed and extracted with MTB (3 20 mL). The organic extracts were
combined, dried (MgSO4) and the solvent was removed. The crude
product 3f was purified by Kugelrohr distillation (50–80°C/0.02
mbar); yield: 1.54 g (81%). IR and NMR data are given in
Tables 1, 4 and 5.
13C NMR (CDCl3, 67.9 MHz): (allene) = 201.7 (s, C-2), 129.3 (s,
C-1), 87.0 (t, C-3), –2.5 [q, Si(CH3)3]; (auxiliary) = 111.8, 108.8
[2 s, C(CH3)2], 105.1 (d, C-1), 82.3 (d, C-3), 80.7 (d, C-2), 80.5 (d,
C-4), 72.8 (d, C-5), 66.9 (t, C-6), 26.9, 26.6, 26.3, 25.3 (4 q, CH3).
Anal. Calcd for C18H30O6Si (370.5): C, 58.35; H, 8.16. Found: C,
58.08; H, 8.21.
3-O-[1-(Trimethylsilyl)dodeca-1,2-diene-1-yl]-1,2:5,6-di-O-
isopropylidene- -D-glucofuranose (7a)
To a stirred solution of 6a (893 mg, 2.41 mmol) in THF (40 mL)
was slowly added n-BuLi (1.10 mL, 2.7 mmol) at –50°C. The reac-
tion mixture was stirred for 30 min, then C9H19I (0.57 mL, 2.9
mmol) was added dropwise and the reaction mixture was allowed to
warm to –20°C within 2 h. The mixture was quenched with sat. aq
NaHCO3 solution, the aqueous phase was separated and extracted
with Et2O (2 20 mL). The organic extracts were combined, dried
(Na2SO4) and the solvent was removed. The crude product 7a was
purified by column chromatography with n-hexane–EtOAc as elu-
ent; yield: 1.21 g (90%) (dr = 70:30).
3-O-[(1-Trimethylsilyl)propadiene-1-yl]-1,2:5,6-di-O-isoprop-
ylidene- -D-glucofuranose (6a)
To a stirred solution of 1a (502 mg, 1.68 mmol) in Et2O (20 mL)
was added n-BuLi (0.89 mL, 2.2 mmol) at –50°C. The reaction
mixture was stirred for 30 min, then TMSCl (0.32 mL, 2.5 mmol)
was added and the reaction mixture was allowed to warm to –20°C
within 2 h. The reaction was quenched with sat. aq NaHCO3 solu-
tion, the aqueous phase was separated and extracted with Et2O (2
20 mL). The organic extracts were combined, dried (Na2SO4) and
the solvent was removed. The crude product 6a was purified by col-
umn chromatography with n-hexane–EtOAc as eluent; yield: 0.60 g
(95%).
IR (film): = 2990–2855 cm–1 (C–H), 1930 (C=C=C).
1H NMR (CDCl3, 250 MHz): (allene) = 5.70 (t, J = 6.3 Hz, 0.3 H,
3-H), 5.63 (t, J = 6.6 Hz, 0.7 H, 3-H), 2.15–2.00 (m, 2 H, 4-H), 1.50–
1.10 (m, 14 H, CH2), 0.85 (t, J = 6.6 Hz, 3 H, CH3), 0.07 [s, 9 H,
Si(CH3)3]; (auxiliary) = 5.83 (d, J = 3.9 Hz, 0.3 H, 1-H), 5.82 (d,
J = 3.4 Hz, 0.7 H, 1-H), 4.49 (d, J = 3.9 Hz, 0.3 H, 2-H), 4.46 (d,
J = 3.4 Hz, 0.7 H, 2-H), 4.35–4.20 (m, 3 H, 3-H, 4-H, 5-H), 4.10–
3.90 (m, 2 H, 6-H), 1.47, 1.40, 1.32, 1.27 (4 s, 3 H each, CH3).
IR (film): = 2990–2900 cm–1 (C–H), 1890 (C=C=C).
1H NMR (CDCl3, 250 MHz): (allene) = AB-system ( A = 5.30,
B = 5.23, JAB = 9.0 Hz, 2 H, 3-H), 0.12 [s, 9 H, Si(CH3)3];
(auxiliary) = 5.84 (d, J = 3.9 Hz, 1 H, 1-H), 4.52 (d, J = 3.9 Hz, 1 H,
2-H), 4.39–4.27 (m, 2 H, 3-H, 5-H), 4.25 (dd, J = 6.6 Hz, 3.2 Hz, 1
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A. Hausherr et al.
PAPER
able 4 1H NMR Data of Propargyl Ethers 3 (300 MHz, CDCl3/TMS); , J (Hz)
roduct
Alkyne
Auxiliary
a
4.28 (d, J = 2.3, 2 H, 1-H),
2.47 (t, J = 2.3, 1 H, 3-H)
5.87 (d, J = 3.7, 1 H, 1-H), 4.62 (d, J = 3.7, 1 H, 2-H), 4.35–4.22 (m, 1 H, 5-H), 4.12
(dd, J = 7.5, 3.0, 1 H, 4-H), 4.08 (d, J = 3.0, 1 H, 3-H), AB part of ABX-system
(
A = 4.07, B = 3.98, JAB = 8.6, JAX = 6.1, JBX = 5.4, 2 H, 6-H), 1.49, 1.41, 1.34, 1.30
(4 s, 3 H each, CH3)
b
ABX-system ( A = 4.54, B = 4.44,
X = 2.45, JAB = 16.0, JAX = JBX = 2.3, 3 H,
1-H, 3-H)
4.31 (dd, J = 7.5, 5.4, 1 H, 4-H), 4.24 (d, J = 8.7, 1 H, 1-H), 4.20 (dd, J = 5.4, 2.4, 1
H, 5-H), AB-system ( A = 4.13, B = 4.03, JAB = 13.5, J = 2.4, 2 H, 6-H), 3.95 (d,
J = 8.7, 1 H, 1-H), 3.76 (d, J = 7.5, 1 H, 3-H), 1.58, 1.50, 1.41, 1.37 (4 s, 3 H each,
CH3)
ca
d
ABX-system ( A = 4.23, B = 4.15,
X = 2.42, JAB = 15.7, JAX = 2.4, JBX < 1, 3
H, 1-H, 3-H)
4.60 (dd, J = 7.9, 2.5, 1 H, 4-H), 4.27 (d, J = 2.5, 1 H, 3-H), 4.26–4.23 (m, 1 H, 5-
H), AB-system ( A = 3.81, B = 3.65, JAB = 13.0, J = 1.5, 2 H, 6-H), 3.58 (s, 2 H, 1-
H), 1.54, 1.48, 1.43, 1.35 (4 s, 3 H each, CH3)
4.14 (d, J = 2.4, 2 H, 1-H),
2.42 (t, J = 2.4, 1 H, 3-H)
5.13 (s, 1 H, 1-H), 4.76 (dd, J = 5.9, 3.6, 1 H, 3-H), 4.58 (d, J = 5.9, 1 H, 2-H), X part
of ABX-system ( X = 4.36, J = 7.7, 1 H, 5-H), AB part of ABX-system ( A = 4.06,
B = 4.00, JAB = 8.7, JAX = 6.2, JBX = 4.5, 2 H, 6-H), 3.91 (dd, J = 7.7, 3.6, 1 H, 4-H),
1.43, 1.41, 1.33, 1.29 (4 s, 3 H each, CH3)
e
f
4.58 (d, J = 2.4, 2 H, 1-H),
2.46 (t, J = 2.4, 1 H, 3-H)
5.86 (d, J = 3.6, 1 H, 1-H), 4.58 (d, J = 3.6, 1 H, 2-H), 4.32–4.20 (m, 1 H, 5-H), 4.18–
4.05 (m, 2 H, 3-H, 4-H), AB part of ABX-system ( A = 4.06, B = 3.96, JAB = 8.6,
JAX = 6.1, JBX = 5.2, 2 H, 6-H), 1.75–1.47, 1.45–1.35 (2 m, 20 H, CH2)
ABX-system ( A = 4.17, B = 4.08,
X = 2.37, JAB = 16.0, JAX = JBX = 2.4, 3 H,
1-H, 3-H)
3.10 (mc, 1 H, 2-H), 1.71–0.90 (m, 7 H, 4-H, 5-H, 6-H, 7-H), 1.10, 1.05, 0.90 (3 s,
3 H each, CH3)
Recorded on 500 MHz spectrometer.
13C NMR (CDCl3, 67.9 MHz): (major isomer, allene) = 195.6 (s,
C-2), 128.8 (s, C-1) 103.7 (d, C-3), 31.9, 31.1, 29.5, 29.4, 29.3, 29.0,
28.9, 22.6 (8 t, CH2), 14.1 (q, CH3), –2.3 [q, Si(CH3)3];
(auxiliary) = 111.6, 108.7 [2 s, C(CH3)2], 105.1 (d, C-1), 81.9 (d, C-
3), 80.5 (d, C-2), 79.9 (d, C-4), 72.6 (d, C-5), 66.6 (t, C-6), 26.8,
26.6, 26.1, 25.3 (4 q, CH3); (minor isomer, allene) = 195.1 (s, C-
2), 129.0 (s, C-1), 104.1 (d, C-3), 33.5, 31.9, 31.1, 30.8, 30.5, 29.5,
29.4, 22.6 (8 t, CH2), 14.1 (q, CH3), -2.3 [q, Si(CH3)3];
(auxiliary) = 111.7, 108.6 [2 s, C(CH3)2], 105.2 (d, C-1), 82.5 (d, C-
3), 80.6 (d, C-2), 80.0 (d, C-4), 72.9 (d, C-5), 66.6 (t, C-6), 26.8,
26.6, 26.1, 25.3 (4 q, CH3).
Due to the instability of 7a, no satisfactory microanalysis could be
obtained. The product was fully characterized after conversion into
5a.
able 5 13C NMR Data of Propargyl Ethers 3 (75.5 MHz, CDCl3);
roduct
Alkyne
Auxiliary
a
79.3 (s, C-2), 75.0 (d, C-3), 58.1 (t, C-1)
111.8, 109.0 [2 s, C(CH3)2], 105.2 (d, C-1), 82.8, 82.5, 81.0 (3 d, C-2, C-3, C-4),
72.5 (d, C-5), 67.2 (t, C-6), 26.8,a 26.2, 25.4 (3 q, CH3)
b
cb
d
e
79.5 (s, C-2), 74.7 (d, C-3), 58.3 (t, C-1)
79.3 (s, C-2), 74.5 (d, C-3), 58.9 (t, C-1)
79.0 (s, C-2), 75.0 (d, C-3), 54.1 (t, C-1)
79.5 (s, C-2), 74.9 (d, C-3), 58.3 (t, C-1)
112.0, 109.1 [2 s, C(CH3)2], 104.2 (s, C-2), 77.6 (d, C-4), 74.0, 73.9 (2 d, C-3, C-5),
71.7 (t, C-1), 60.0 (t, C-6), 28.1, 26.7, 26.3, 25.9 (4 q, CH3)
108.9, 108.5 [2 s, C(CH3)2], 102.5 (s, C-2), 71.0 (t, C-1), 70.9 (d, C-5), 70.2, 70.1
(2 d, C-3, C-4), 60.9 (t, C-6), 26.5, 25.8, 25.2, 24.0 (4 q, CH3)
112.7, 109.3 [2 s, C(CH3)2], 105.0 (d, C-1), 85.1 (d, C-2), 80.7 (d, C-4), 79.8
(d, C-3), 73.1 (d, C-5), 66.9 (t, C-6), 26.9, 25.9, 25.2, 24.6 (4 q, CH3)
112.5, 109.6 [2 s, C(O)2], 104.9 (d, C-1), 82.6, 82.5, 81.8, 72.2 (4 d, C-2, C-3, C-4,
C-5), 67.1 (t, C-6), 36.5, 36.4, 35.7, 34.7, 25.4, 25.1, 24.8, 24.0, 23.8, 23.5 (10 t,
CH2)
f
81.0 (s, C-2), 73.4 (d, C-3), 58.8 (t, C-1)
92.1 (d, C-2), 49.0, 39.2 (2 s, C-1, C-3), 48.8 (d, C-4), 41.4, 26.1, 25.9 (3 t, C-5, C-
6, C-7), 31.4, 20.7, 19.7 (3 q, CH3)
Double intensity.
Recorded on 125.8 MHz spectrometer.
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Enantiopure 1-Alkoxyallenes
1383
Table 6 1H NMR Data of Allenyl Ethers 1 (300 MHz, CDCl3/TMS); , J (Hz)
Product
Allene
Auxiliary
1aa
ABX-system ( X = 6.70, A = 5.58,
B = 5.52, JAB = 8.6, JAX = JBX = 6.0, 3 H,
1-H, 3-H)
5.87 (d, J = 3.7 Hz, 1 H, 1-H), 4.59 (d, J = 3.7, 1 H, 2-H), 4.38–4.30 (m, 1 H, 5-H),
4.25 (d, J = 2.8, 1 H, 3-H), 4.18 (dd, J = 7.6, 2.8, 1 H, 4-H), AB part of ABX-system
(
A = 4.09, B = 4.00, JAB = 8.7, JAX = 5.6, JBX = 5.0, 2 H, 6-H), 1.51, 1.43, 1.36, 1.31
(4 s, 3 H each, CH3)
1ba
1ca
6.88 (t, J = 6.1, 1 H, 1-H),
5.48 (d, J = 6.1, 2 H, 3-H)
4.34 (dd, J = 7.8, 5.4, 1 H, 4-H), 4.25–3.90 (m, 5 H, 1-H, 5-H, 6-H), 3.86 (d, J = 7.8,
1 H, 3-H), 1.54, 1.50, 1.41, 1.37 (4 s, 3 H each, CH3)
6.79 (t, J = 6.0, 1 H, 1-H),
5.46 (d, J = 6.0, 2 H, 3-H)
4.61 (dd, J = 7.8, 2.4, 1 H, 4-H), 4.38 (d, J = 2.4, 1 H, 3-H), 4.24 (br d, J 7.8, 1 H,
5-H), AB-system ( A = 3.92, B = 3.75, JAB = 12.8, J = 1.7, 2 H, 6-H), AB-system
(
A = 3.73, B = 3.64, JAB = 10.7, 2 H, 1-H), 1.55, 1.47, 1.42, 1.34 (4 s, 3 H each,
CH3)
1d
1e
1f
ABX-system ( X = 6.55, A = 5.41,
B = 5.38, JAB = 8.9, JAX = 6.1, JBX = 6.0,
3 H, 1-H, 3-H)
5.20 (s, 1 H, 1-H), 4.79 (dd, J = 5.9, 3.6, 1 H, 3-H), 4.69 (d, J = 5.9, 1 H, 2-H), 4.48–
4.35 (m, 1 H, 5-H), AB part of ABX-system ( A = 4.09, B = 4.01, JAB = 8.7,
JAX = 6.1, JBX = 4.3, 2 H, 6-H), 3.97 (dd, J = 8.0, 3.6, 1 H, 4-H), 1.45, 1.43, 1.36,
1.32 (4 s, 3 H each, CH3)
ABX-system ( X = 6.68, A = 5.54,
5.84 (d, J = 3.8, 1 H, 1-H), 4.54 (d, J = 3.8, 1 H, 2-H), 4.32–4.20 (m, 1 H, 5-H), 4.24
(d, J = 3.0, 1 H, 3-H), 4.13 (dd, J = 7.8, 3.0, 1 H, 4-H), AB part of ABX-system
( A = 4.04, B = 3.97, JAB = 8.6, JAX = 6.0, JBX = 5.3, 2 H, 6-H), 1.70–1.20 (m, 20 H,
B
=5.49, JAB = 8.5, JAX = JBX = 6.0, 3 H,
1-H, 3-H)
CH2)
ABX-system ( X = 6.71, A = 5.39,
B = 5.35, JAB = 7.6, JAX = JBX = 5.8, 3 H,
1-H, 3-H)
3.32 (mc, 1 H, 2-H), 1.30–0.86 (m, 7 H, 4-H, 5-H, 6-H, 7-H), 1.08, 1.03, 0.88 (3 s,
3 H each, CH3)
a Recorded on 270 MHz spectrometer.
3-O-(Dodeca-1,2-diene-1-yl)-1,2:5,6-di-O-isopropylidene- -D-
glucofuranose (5a)
Acknowledgement
Generous support by the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie (Kekulé fellowship for A. H.) is
most gratefully acknowledged.
To a stirred solution of 7a (860 mg, 1.73 mmol) in THF (20 mL)
was added a 1 M solution of TBAF (3.5 mL, 3.5 mmol) of at –10°C.
The reaction mixture was stirred at r.t. overnight. Sat. aq NaHCO3
solution was added, the aqueous phase was separated and extracted
with Et2O (2 20 mL). The organic extracts were combined, dried
(Na2SO4) and the solvent was removed. The crude product 5a was
purified by column chromatography with n-hexane–EtOAc; yield:
705 mg (62%) (dr = 70:30). IR data are identical with the data given
in Table 3. NMR data are given in Tables 8 and 9.
Table 7 13C NMR Data of Allenyl Ethers 1 (75.5 MHz, CDCl3);
Product
Allene
Auxiliary
1a
200.3 (s, C-2), 119.9 (d, C-1), 91.7 (t, C-3)
111.6, 111.5 [2 s, C(CH3)2], 105.0 (d, C-1), 81.9, 80.1, 80.0 (3 d, C-2, C-3, C-4),
73.0 (d, C-5), 67.4 (t, C-6), 26.6, 26.5, 26.0, 25.9 (4 q, CH3)
1b
1ca
1d
1e
200.5 (s, C-2), 122.9 (d, C-1), 91.9 (t, C-3)
200.8 (s, C-2), 121.8 (d, C-1), 91.4 (t, C-3)
201.1 (s, C-2), 117.2 (d, C-1), 89.9 (t, C-3)
200.5 (s, C-2), 120.3 (d, C-1), 91.9 (t, C-3)
111.9, 108.9 [2 s, C(CH3)2], 103.9 (s, C-2), 75.8, 75.3, 73.7 (3 d, C-3, C-4, C-5),
71.3 (t, C-1), 60.0 (t, C-6), 27.8, 26.7, 26.0, 25.7 (4 q, CH3)
108.8, 108.5 [2 s, C(CH3)2], 101.9 (s, C-2), 70.8, 70.1, 70.0 (3 d, C-3, C-4, C-5),
69.5 (t, C-1), 60.9 (t, C-6), 26.4, 25.7, 25.2, 23.9 (4 q, CH3)
112.9, 109.3 [2 s, C(CH3)2], 105.0 (d, C-1), 84.8, 80.9, 79.3, 72.8 (4 d, C-2, C-3,
C-4, C-5), 66.9 (t, C-6), 26.9, 25.8, 25.1, 24.5 (4 q, CH3)
112.5, 109.6 [2 s, C(O)2], 104.7 (d, C-1), 81.8, 80.5, 80.2, 71.9 (4 d, C-2, C-3, C-4,
C-5), 66.7 (t, C-6), 36.5, 36.3, 35.7, 34.7, 26.8, 25.1, 24.9, 24.0, 23.8, 23.5 (10 t,
CH2)
1f
201.9 (s, C-2), 122.4 (d, C-1), 90.5 (t, C-3)
90.4 (d, C-2), 49.0, 39.4 (2 s, C-1, C-3), 48.7 (d, C-4), 41.4, 26.3, 26.2 (3 t, C-5,
C-6, C-7), 30.1, 20.1, 19.7 (3 q, CH3)
a Recorded on 67.9 MHz spectrometer.
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

1384
A. Hausherr et al.
PAPER
able 8 1H NMR Data of Propargyl Ethers 4 and Allenyl Ethers 5 (270 MHz, CDCl3/TMS); , J (Hz)
roduct
Alkyne or Allene, respectively
Auxiliary
a
4.25 (br. s, 2 H, 1-H), 2.25–2.17 (m, 2 H,
4-H), 1.58–1.21 (m, 14 H, CH2), 0.88
(t, J = 7.0, 3 H, CH3)
5.88 (d, J = 3.9, 1 H, 1-H), 4.63 (d, J = 3.9, 1 H, 2-H), 4.34–4.25 (m, 1 H, 5-H), 4.16
(dd, J = 7.3, 3.0, 1 H, 4-H), AB part of ABX-system ( A = 4.08, B = 4.00, JAB = 8.8,
JAX = JBX = 8.0, 2 H, 6-H), 4.00 (d, J = 3.0, 1 H, 3-H), 1.50, 1.43, 1.35, 1.31 (4 s, 3 H
each, CH3)
ba
ca
ab
AB-system ( A = 4.50, B = 4.42,
JAB = 15.6, 2 H, 1-H), 2.19 (t, J = 7.0, 2 H,
4-H), 1.50–1.20 (m, 14 H, CH2), 0.88
(t, J = 6.8, 3 H, CH3)
4.30 (dd, J = 7.3, 5.6, 1 H, 4-H), 4.27 (d, J = 8.6, 1 H, 1-H), 4.19 (dd, J = 5.6, 2.0,
1 H, 5-H), AB-system ( A = 4.12, B = 4.02, JAB = 13.4, J = 2.0, 2 H, 6-H), 3.93 (d,
J = 8.6, 1 H, 1-H), 3.78 (d, J = 7.3, 1 H, 3-H), 1.58, 1.50, 1.41, 1.37 (4 s, 3 H each,
CH3)
AB part of ABX-system ( A = 4.28,
4.63–4.56 (m, 1 H, 4-H), 4.38 (dd, J = 2.5, 1.5, 1 H, 3-H), 4.25–4.20 (m, 1 H, 5-H),
AB-system ( A = 3.91, B = 3.74, JAB = 13.0, 2 H, 6-H), 3.65 (s, 2 H, 1-H), 1.54, 1.48,
1.43, 1.34 (4 s, 3 H each, CH3)
B = 4.19, JAB = 13.7, JAX = JBX < 1, 2 H, 1-
H), 2.24–2.14 (m, 2 H, 4-H), 1.50–1.22
(m, 14 H, CH2), 0.88 (t, J = 6.2, 3 H, CH3)
6.60–6.55 (m, 1 H, 1-H), 5.99–5.91 (m,
0.3 H, 3-H), 5.90–5.83 (m, 0.7 H, 3-H),
2.16–2.05 (m, 2 H, 4-H), 1.50–1.20 (m,
14 H, CH2), 0.86 (t, J = 6.4, 3 H, CH3)
5.85 (d, J = 3.9, 0.3 H, 1-H), 5.84 (d, J = 3.4, 0.7 H, 1-H), 4.58 (d, J = 3.4, 0.7 H,
2-H), 4.56 (d, J = 3.9, 0.3 H, 2-H), 4.36–4.26 (m, 1 H, 5-H), 4.25–4.15 (m, 2 H,
3-H, 4-H), 4.10–3.99 (m, 2 H, 6-H), 1.48, 1.41, 1.34, 1.28 (4 s, 3 H each, CH3)
D)-5a
6.56 (t, J = 2.2, 1 H, 1-H), 2.15–2.03 (m, 2
H, 4-H), 1.55–1.20 (m, 14 H, CH2), 0.85
(t, J = 6.7, 3 H, CH3)
5.83 (d, J = 3.7, 1 H, 1-H), 4.56 (d, J = 3.7, 0.5 H, 2-H), 4.53 (d, J = 3.7, 0.5 H, 2-H),
4.35–4.25 (m, 1 H, 5-H), 4.23–4.13 (m, 2 H, 3-H, 4-H), 4.08–3.97 (m, 2 H, 6-H),
1.46, 1.39, 1.31, 1.26 (4 s, 3 H each, CH3)
bc
6.81–6.74 (m, 1 H, 1-H), 5.91–5.81 (m, 1
H, 3-H), 2.12–2.01 (m, 2 H, 4-H), 1.47–
1.21 (m, 14 H, CH2), 0.88 (t, J = 6.6, 3 H,
CH3)
4.32 (dd, J = 7.5, 5.5, 1 H, 4-H), 4.22 (dd, J = 5.5, 2.5, 1 H, 5-H), AB-system
(
A = 4.13, B = 4.01, JAB = 13.4, 1.5 H, 6-H), AB-system ( A = 4.12, B = 4.02,
JAB = 13.4 Hz, 0.5 H, 6-H), AB-system ( A = 4.10, B = 3.90, JAB = 8.8, 2 H, 1-H),
3.86 (d, J = 7.5, 1 H, 3-H), 1.53, 1.50, 1.40, 1.37 (4 s, 3 H each, CH3)
c
6.69 (t, J = 2.4, 0.45 H, 1-H), 6.67 (t,
J = 2.7, 0.55 H, 1-H), 5.90–5.78 (m, 1 H,
3-H), 2.10–1.97 (m, 2 H, 4-H), 1.50–1.20
(m, 14 H, CH2), 0.86 (t, J = 6.6, 3 H, CH3)
4.62–4.55 (br d, J = 7.8, 1 H, 4-H), 4.38 (d, J = 2.4, 0.55 H, 3-H), 4.36 (d, J = 2.4,
0.45 H, 3-H), 4.22 (br d, J = 7.8, 1 H, 5-H), AB-system ( A = 3.91, B = 3.73,
JAB = 13.0, J = 1.7, 2 H, 6-H), AB-system ( A = 3.69, B = 3.57, JAB = 10.7, 1.1 H,
1-H), AB-system ( A = 3.66, B = 3.61, JAB = 10.7, 0.9 H, 1-H), 1.52, 1.45, 1.41, 1.32
(4 s, 3 H each, CH3)
Recorded on 500 MHz spectrometer.
Major isomer is S configurated with respect to allene moiety.11,
Major isomer is R configurated with respect to allene moiety.11
References and Notes
(6) Reissig, H.-U.; Hormuth, S.; Schade, W.; Okala Amombo,
M.; Watanabe, T.; Pulz, R.; Hausherr, A.; Zimmer, R. J.
Heterocycl. Chem. 2000, 37, 597.
(7) (a) Arnold, T.; Orschel, B.; Reissig, H.-U. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 1033. (b) Arnold, T.; Orschel, B.;
Reissig, H.-U. Angew. Chem. 1992, 104, 1084.
(8) (a) Rochet, P.; Vatèle, J.-M.; Goré, J. Synlett 1993, 105.
(b) Rochet, P.; Vatèle, J.-M.; Goré, J. Synthesis 1994, 795.
(9) (a) Recently several 3-O-allenyl-substituted furanoses have
been synthesized and their conformations were studied by
NMR spectroscopy: Lysek, R.; Krajewski, P.; Urbanczyk-
Lipkowska, Z.; Furman, B.; Kaluza, Z.; Kozerski, L.;
Chmielewski, M. J. Chem. Soc., Perkin Trans. 2 2000, 61.
(b) Other applications: Harrington, P. E.; Tius, M. A. Org.
Lett. 2000, 2, 2447.
(1) General review: Zimmer, R. Synthesis 1993, 165.
(2) For recent synthetic work, see: (a) Pirrung, M. C.; Zhang, J.;
Morehead, A. T. Tetrahedron Lett. 1994, 35, 6229.
(b) Gröschl, D.; Niedermann, H.-P.; Meier, H. Chem. Ber.
1994, 127, 955. (c) Hojo, M.; Aihara, H.; Ito, H.; Hosomi,
A. Tetrahedron Lett. 1996, 37, 9241.
(3) For typical applications, see: (a) Unger, C.; Zimmer, R.;
Reissig, H.-U.; Würthwein, E.-U. Chem. Ber. 1991, 124,
2279. (b) Zimmer, R.; Reissig, H.-U.; Homann, K. J. Prakt.
Chem. 1995, 337, 521. (c) Angermann, J.; Homann, K.;
Reissig, H.-U.; Zimmer, R. Synlett 1995, 1014. (d)Zimmer,
R.; Hiller, F.; Reissig, H.-U. Heterocycles 1999, 50, 393.
(e) Zimmer, R.; Homann, K.; Angermann, J.; Reissig, H.-U.
Synthesis 1999, 1223.
(10) (a) Tius, M. A.; Hu, H.; Kawakami, J. K.; Busch-Petersen, J.
J. Org. Chem. 1998, 63, 5971. (b) Verkrujisse, H. D.;
Verboom, W.; Van Rijn, P. E.; Brandsma, L. J. Organomet.
Chem. 1982, 232, C1.
(11) The predominating configuration has been established by
subsequent transformation into a literature known amino
acid derivative and comparison of optical rotations:
Hausherr, A.; Reissig, H.-U. unpublished results.
(4) Hoff, S.; Brandsma, L.; Arens, J. F. Recl. Trav. Chim. Pays-
Bas 1968, 87, 916.
(5) (a) Hormuth, S.; Reissig, H.-U.; Dorsch, D. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1449. (b) Hormuth, S.; Reissig, H.-
U.; Dorsch, D. Angew. Chem. 1993, 105, 1513.
(c) Hormuth, S.; Schade, W.; Reissig, H.-U. Liebigs Ann.
Chem. 1996, 2001. .
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Enantiopure 1-Alkoxyallenes
1385
Table 9 13C NMR Data of Propargyl Ethers 4 and Allenyl Ethers 5 (67.9 MHz, CDCl3); , J (Hz)
Product
Alkyne or Allene, respectively
Auxiliary
4a
87.5, 75.4 (2 s, C-2, C-3), 58.6 (t, C-1),
31.8, 29.4, 29.3, 29.1, 28.9, 28.5, 22.6,
18.7 (8 t, CH2), 14.1 (q, CH3)
111.7, 108.8 [2 s, C(CH3)2], 105.2 (d, C-1), 82.8 (d, C-3), 81.1, 81.0 (2 d, C-2,
C-4), 72.6 (d, C-5), 67.0 (t, C-6), 26.8, 26.8, 26.2, 25.4 (4 q, CH3)
4ba
4ca
87.5, 75.6 (2 s, C-2, C-3), 59.0 (t, C-1),
31.8, 29.4, 29.2, 29.1, 28.8, 28.6, 22.6,
18.6 (8 t, CH2), 14.1 (q, CH3)
112.0, 109.0 [2 s, C(CH3)2], 104.4 (s, C-2), 77.7 (d, C-4), 73.9 (d, C-5), 73.4 (d,
C-3), 71.7 (t, C-1), 60.0 (t, C-6), 28.1, 26.8, 26.4, 26.0 (4 q, CH3)
87.2, 75.5 (2 s, C-2, C-3), 59.6 (t, C-1),
33.5, 30.5, 29.4, 29.1, 28.8, 28.6, 22.6,
18.7 (8 t, CH2), 14.1 (q, CH3)
108.8, 108.4 [2 s, C(CH3)2], 102.6 (s, C-2), 70.9 (d, C-5), 70.7 (t, C-1), 70.2, 70.1
(2 d, C-3, C-4), 60.9 (t, C-6), 26.5, 25.8, 25.2, 24.0 (4 q, CH3)
5ab
(major)
192.7 (s, C-2), 119.2 (d, C-1), 108.6 (d,
C-3), 31.9, 31.5, 31.1, 29.5, 29.3, 29.1,
28.5, 22.6 (8 t, CH2), 14.1 (q, CH3)
111.7, 109.0 [2 s, C(CH3)2], 105.0 (d, C-1), 81.8 (d, C-3), 80.3 (d, C-2), 79.4 (d,
C-4), 72.4 (d, C-5), 66.8 (t, C-6), 26.8, 26.7, 26.1, 25.3 (4 q, CH3)
5a
Identical with 5a (major), except: 192.4 (s,
111.8, 108.9 [2 s, C(CH3)2], 105.1 (d, C-1), 82.3 (d, C-3), 80.3 (d, C-2), 79.6 (d,
(minor)
C-2), 119.5 (d, C-1), 108.7 (d, C-3)
C-4), 72.5 (d, C-5), 66.8 (t, C-6), 26.8, 26.7, 26.1, 25.3 (4 q, CH3)
(D)-5ac
192.6, 192.4 (s, C-2), 119.5, 119.2 (d,
C-1), 108.6, 108.3 (t, JCD 25.0, C-3),
31.8, 31.3, 31.0, 29.5, 29.3, 29.1, 28.4,
22.6 (8 t, CH2), 14.1 (q, CH3)
111.7, 111.6, 109.0, 108.9 [2 s, C(CH3)2], 105.1, 105.0 (s, C-1), 82.3, 81.7 (d, C-3),
80.2, 80.2, 79.5, 79.3 (2 d, C-2, C-4), 66.8, 66.8 (t, C-5), 26.8, 26.6, 26.1, 25.3 (4 q,
CH3)
5b d
(major)
192.1 (s, C-2), 122.3 (d, C-1), 108.8 (d,
C-3), 31.8, 31.4, 29.5, 29.4, 29.2, 29.1,
28.5, 22.6 (8 t, CH2), 14.1 (q, CH3)
111.9, 109.0 [2 s, C(CH3)2], 104.1 (s, C-2), 75.8, 75.0, 73.7 (3 d, C-3, C-4, C-5),
71.4 (t, C-1), 60.1 (t, C-6), 28.1, 26.9, 26.1, 25.8 (4 q, CH3)
5b
Identical with 5b (major), except: 192.0
112.1, 109.2 [2 s, C(CH3)2], 104.3 (s, C-2), 76.0, 74.3, 73.9 (3 d, C-3, C-4, C-5),
(minor)
(s, C-2), 122.4 (d, C-1)
71.4 (t, C-1), 60.1 (t, C-6), 28.0, 26.9, 26.2, 25.9 (4 q, CH3)
5c e
192.6 (s, C-2), 121.2 (d, C-1), 108.0 (d,
C-3), 31.8, 31.3, 29.5, 29.4, 29.3, 29.2,
28.4, 22.6 (8 t, CH2), 14.1 (q, CH3)
108.9, 108.6 [2 s, C(CH3)2], 102.1 (s, C-2), 70.9 (d, C-5), 70.2, 70.2 (2 d, C-3, C-4),
69.2 (t, C-1), 61.0 (t, C-6), 26.5, 25.8, 25.2, 24.0 (4 q, CH3)
a Recorded on 125.8 MHz spectrometer.
b Major isomer is S configurated with respect to allene moiety.11
c Mixture of two diastereomers (50:50).
d Major isomer is R configurated with respect to allene moiety.11
e Mixture of two diastereomers (55:45), signals of both diastereomers completely identical.
(12) This route is based on transformations as described by:
Clinet, J.-C.; Linstrumelle, G. Tetrahedron Lett. 1980, 21,
3987.
(13) Deprotonation of 4a with n-BuLi in the presence of 1.2
equivalents of (–)-sparteine followed by aqueous workup
furnished 5a as a 50:50 mixture of diastereomers. Thus,
addition of this chiral complexing agent does not seem to
exert a noticeable influence on the diastereoselectivity of
this process.
(16) Singh, P. P.; Gharia, M. M.; Dasgupta, P.; Scrivastara, H. C.
Tetrahedron Lett. 1977, 439.
(17) Fayet, C.; Gelas, J. Carbohydr. Res. 1986, 155, 99.
(18) Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Gould, R. O.;
Hodgson, P. K. G.; McDougall, D. Tetrahedron 1998, 54,
9765.
(19) Copeland, C.; McAdam, D. P.; Stick, R. V. Aust. J. Chem.
1983, 36, 1239.
(20) Hockett, R. C.; Miller, R. E.; Scattergood, A. J. Am. Chem.
Soc. 1949, 71, 3072.
(14) Hausherr, A.; Reissig, H.-U. manuscript in preparation.
(15) Kofron, W. G.; Baclawski, L. M. J. Org. Chem. 1976, 41,
1879.
Synthesis 2001, No. 9, 1377–1385 ISSN 0039-7881 © Thieme Stuttgart · New York