Diastereoselective addition of organocerium(III) reagents derived from 3-substituted propargyl bromides to aldehydes

Article abstract of DOI:10.1055/s-2006-947349

Various cerium allenyl reagents were generated by trans-metallation of allenyl Grignard compounds with CeCl₃ and subsequent conversion into homopropargylic alcohols by addition to various aliphatic and aromatic aldehydes. The α-acetylenic alcoh

Full text of DOI:10.1055/s-2006-947349

LETTER
1859
Diastereoselective Addition of Organocerium(III) Reagents Derived from
3
-Substituted Propargyl Bromides to Aldehydes1
D
U
iastereoselective
l
A
dditi
r
on of
O
r
i
ganoce
c
r
ium(III
)
R
h
eagents Groth,* Christian Kesenheimer, Jürgen Neidhöfer
Fachbereich Chemie, Universität Konstanz, Universitätsstrasse 11, Postfach M-720, 78457 Konstanz, Germany
Fax +49(7531)884155; E-mail: ulrich.groth@uni-konstanz.de
Received 12 April 2006
CeCl or Ce(Oi-Pr) , no change in the regioselectivity but
an enormous improvement of the diastereoselectivity of
the carbonyl addition reaction was observed in compari-
3
3
Abstract: Various cerium allenyl reagents were generated by trans-
metallation of allenyl Grignard compounds with CeCl and sub-
3
sequent conversion into homopropargylic alcohols by addition to
various aliphatic and aromatic aldehydes. The a-acetylenic alcohols son to the Grignard reagent.
were obtained with regioselectivities and diastereoselectivities up to
Because of the outstanding diastereoselectivities often
reached with organocerium compounds in addition reac-
9
8% de in favor of the threo-diastereomers.
Key words: lanthanides, organometallic reagents, addition reac-
tions, diastereoselectivity, regioselectivity
9
tions to carbonyl groups, we investigated the suitability
of these organometallics for a diastereoselective synthesis
of b-acetylenic alcohols (Scheme 2, Table 2).
The importance of allenic anions in synthetic organic
chemistry arises from their utility in C–C bond forming
reactions such as additions to carbonyl groups. The re-
O
HO
R2
TMS
TMS
OH
TMS
R2
H
2
L2Ce
H
R2
H
sulting homopropargylic alcohols are key intermediates in
R1
R1
R1
3
the synthesis of g-butyrolactones and polyketide natural
3
a,b or 4a
5
6
4
products. As ambident nucleophiles allenic anions add to
carbonyl groups giving rise to two products, b-acetylenic
5
OH
TMS
OH
TMS
and a-allenic alcohols. Furthermore, the products can be
R2
R2
formed as mixtures of two diastereomers. Thus, to achieve
a selective reaction, it is necessary to control the regio-
and stereochemistry at the same time. Structure and reac-
tivities of the ambident anions are highly dependent on the
R1
R1
5b (erythro)
5a (threo)
Scheme 2 Reaction of organocerium(III)allenyls with aldehydes
6
nature of the counter cation (Scheme 1).
8
Based on earlier results we chose Ce(Oi-Pr) as cerium
3
Br
MgBr
R1
Mg, cat. Hg2Cl2
Et2O, 0 °C
TMS
H
reagent, whereas benzaldehyde and 3-bromo-1-(tri-
methylsilyl)but-1-yne (1) were selected as model com-
R1
10
R1
TMS
TMS
BrMg
pounds to optimize the reaction conditions. First, we
decided to study the effect of the reaction temperature on
yield and selectivity of the addition. The results are shown
in Table 1.
CeL3,
THF,
–78 °C
1
R
R
= CH3 1
1
= n-Pr
2
CeL2
R1
TMS
L2Ce
H
Addition of the benzaldehyde to the organocerium reagent
at –78 °C followed by warming to room temperature with-
in 16 hours afforded the homopropargylic alcohols 5a and
5b in 50% yield with a regioisomeric ratio of >98:2 and a
diastereomeric ratio of 66:34 (entry 1). In addition, benzyl
alcohol was formed among other by-products. The same
reaction at 0 °C followed by warming to room tempera-
ture within two hours afforded 5a and 5b in an overall
R1
TMS
1
R = CH3, L = Oi-Pr 3a
1
R = CH3, L = Cl
R1 = n-Pr, L = Cl
3b
4a
Scheme 1 Generation of the organocerium(III) allenyl compounds
In the course of our studies in natural product synthesis of yield of 72% with unchanged regioselectivity and a dia-
7
compounds such as ergosterol and its 4-substituted deriv- stereomeric ratio of 72:28. Only traces of benzyl alcohol
atives we examined the influence of different cerium(III) could be found. Using these reaction conditions, we stud-
8
species. After transmetallation of the Grignard reagent ied as next the effect of the cerium reagent.
prepared from 1-(trimethylsilyl)propargyl bromide with
Applying CeCl for synthesizing the cerium allenyl re-
3
agent out of the Grignard reagent at 0 °C gave similar
SYNLETT 2006, No. 12, pp 1859–1862
Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-947349; Art ID: G14006ST
0
1
.0
8
.2
0
0
6
results (Table 1, entry 3) as Ce(Oi-Pr) under the reaction
conditions A with benzaldehyde. Best results were
3
obtained by employing CeCl under reaction conditions B
3
©
Georg Thieme Verlag Stuttgart · New York

1
860
U. Groth et al.
LETTER
Table 1 Addition of Cerium Allenyl Compounds 3a and 3b to Benzaldehyde
Entry
Reaction conditionsa Cerium reagent
Yield (%) of 5 + 6
5:6
5a:5b
66:34
72:28
67:33
70:30
1
2
3
A
B
A
B
Ce(Oi-Pr) 3a
50
72
51
90
>98:2
>98:2
>98:2
>98:2
3
Ce(Oi-Pr) 3a
3
CeCl 3b
3
4
CeCl 3b
3
a
A: –78 °C to r.t., 16 h; B: 0 °C to r.t., 2 h.
(
Table 1, entry 4). The overall yield of 5a and 5b the organocerium reagent 4a derived from 3-bromo-1-
increased to 90% with almost the same regio- and dia- (trimethylsilyl)hex-1-yne (2)11 (entries 11–15). In accor-
stereoselectivity as in entries 1, 2 and 3. Our results with dance with former studies, moderate diastereomeric ratios
other aldehydes are summarized in Table 2.
were observed by employing benzaldehyde (entries 1, 6
and 11) and p-anisaldehyde (entries 2, 7 and 12). On the
other hand, the high diasteroselectivities of 98:2 ob-
served in the addition reactions to pivalaldehyde are
remarkable (entries 4, 9 and 14).
6
The overall yield of 5 and 6 ranges from 56% to 90%,
whereas addition to benzaldehyde, p-anisaldehyde and
pivalaldehyde afforded predominantly the respective
homopropargylic alcohols 5a and 5b with a regioselectiv-
ity of >98:2. Lower regioselectivities were observed when In summary, we have presented a useful method for the
cyclohexylcarbaldehyde (entries 3, 8 and 13) and acetal- synthesis threo-homopropargylic alcohols. An enantio-
dehyde (entries 5, 10 and 15) were employed. The influ- selective synthesis of these compounds using chiral
ence of the aldehyde on the regioselectivity of the addition modified cerium reagents is under current investigation.
has already been observed before. However, the reason
5
for this phenomenon still remains unkown.
The homopropargylic alcohols 5a were obtained with Typical Experimental Procedure
All reactions were carried out under an argon atmosphere using
threo/erythro ratios ranging from 65:35 to >98:2. Slightly
Schlenck techniques. Moisture and oxidation sensitive compounds
higher diastereoselectivities were obtained in reactions of
were stored in a glove box.
Table 2 Addition of Cerium Allenyl Compounds 3a, b and 4a to Different Aldehydes
b
Entry
Bromide R1
Me
Aldehyde R2
Ph
Yield (%) of 5 + 6
5:6
5a:5b
70:30
65:35
80:20
98:2
1
2
3
4
5
6
7
8
9
90
90
80
74
85
72
70
66
56
64
85
84
72
56
84
>98:2
>98:2
92:8
Me
4-MeOC H
6
4
4
4
Me
Cyclohexyl
Me
t-Bu
Me
Ph
>98:2
89:11
>98:2
>98:2
92:8
Me
81:19
72:28
68:32
85:15
98:2
Mea
Mea
Mea
Mea
Mea
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
4-MeOC H
6
Cyclohexyl
t-Bu
>98:2
86:14
>98:2
>98:2
90:10
>98:2
86:14
1
1
1
1
1
1
0
1
2
3
4
5
Me
79:21
72:28
68:32
82:18
>98:2
85:15
Ph
4-MeOC H
6
Cyclohexyl
t-Bu
Me
a
Ce(Oi-Pr) was used instead of CeCl .
Reaction conditions: 0 °C to r.t., 2 h; isolated yield.
3
3
b
Synlett 2006, No. 12, 1859–1862 © Thieme Stuttgart · New York

LETTER
Diastereoselective Addition of Organocerium(III) Reagents
1861
6
Mg (0.61 g, 25.0 mmol) and Hg Cl (5.0 mg, 0.01 mmol) were sus-
erythro-1-Cyclohexyl-2-methyl-4-trimethylsilylbut-3-yn-1-ol
2
2
1
pended in Et O (20 mL) at r.t. and 1,2-dibromoethane (0.1 mL) was
H NMR (250 MHz, CDCl ): d = 0.15 (s, 9 H, TMS), 0.88–2.00 (m,
15 H, cyclohexyl, CH , OH), 2.66 (dq, 1 H, H-2, J = 10.0, 7.0 Hz),
2
3
added. The mixture was stirred for 1 h and then cooled to 0 °C.
Within 1 h compound 1 (1.0 g, 4.7 mmol) or compound 2 (1.1 g, 4.7
mmol) was added by use of a syringe pump while the temperature
was maintained between 0 °C and 5 °C. After stirring for an addi-
tional hour at r.t. the mixture was added at 0 °C to a suspension of
the cerium(III) compound (4.7 mmol) in THF via cannula. The re-
sulting solution was stirred then at 0 °C for 1 h. Subsequently, 3
mmol of the aldehyde were added and the mixture was allowed to
warm up to r.t. within 2 h. The solvent was removed in vacuo
3
3.33 (dq, 1 H, H-1, J = 10.0, 3.8 Hz).
threo-2,2,4-Trimethyl-6-trimethylsilylhex-5-yn-3-ol
1
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 0.95 (s, 9 H,
t-Bu), 1.29 (d, 3 H, CH , J = 7.0 Hz), 1.96 (d, 1 H, OH, J = 10.7 Hz),
2.82 (dq, 1 H, H-4, J = 10.7, 7.0 Hz), 2.97 (dd, 1 H, H-3, J = 10.7,
1.4 Hz). C NMR (62.5 MHz, CDCl ): d = –0.03 (-TMS), 21.24
(-CH ), 26.32 [-C(CH ) ], 29.97 (C-4), 36.11 [C(CH ) ], 81.41 (C-
3), 89.68 (C-6), 107.44 (C-5). GCMS: m/z (%) = 212 (<1) [M ], 197
(<1) [M – CH ] , 159 (21), 126 (30), 73 (100) [TMS] . Anal. Calcd
3
3
1
3
3
3
3
3
3 3
+
(
20 °C, 15 mbar) and the residue was suspended in Et O (150 mL).
2
+
+
After addition of 1 M HCl (50 mL), the layers were separated and
3
the aqueous layer was extracted with Et O (3 × 50 mL). The com-
for C H OSi: C, 67.86; H, 11.39. Found: C, 66.68; H, 10.82.
2
12 24
bined organic layers were extracted with sat. NaHCO solution (50
3
mL) and brine (50 mL) and dried over Na SO . The solvent was
then removed in vacuo (20 °C, 15 mbar) again. The crude products
were purified by flash chromatography on silica gel (eluent: PE–
erythro-2,2,4-Trimethyl-6-trimethylsilylhex-5-yn-3-ol
2
4
1
H NMR (250 MHz, CDCl ): d = 0.13 (s, 9 H, TMS), 0.99 (s, 9 H,
3
t-Bu), 1.23 (d, 3 H, CH , J = 7.0 Hz), 1.75 (d, 1 H, OH, J = 4.5 Hz),
3
Et O, depending on the product). The regioisomeric and diastereo-
meric ratios were determined by GCMS analysis of the crude prod-
ucts.
2.69 (dq, 1 H, H-4, J = 7.0, 5.4 Hz), 3.38 (dd, 1 H, H-3, J = 5.4, 4.5
2
1
3
Hz). C NMR (62.5 MHz, CDCl ): d = –0.03 (TMS), 20.94 (CH ),
3
3
26.22 [C(CH ) ], 30.05 (C-4), 36.11 [C(CH ) ], 81.41 (C-3), 89.68
3
3
3 3
(
C-6), 107.44 (C-5). GCMS: identical to the threo-compound. Anal.
Analytical Data
Calcd for C H OSi: C, 67.86; H, 11.39. Found: C, 66.96; H, 10.28.
1
2
24
6
threo-2-Methyl-1-phenyl-4-trimethylsilylbut-3-yn-1-ol
1
H NMR (250 MHz, CDCl ): d = 0.17 (s, 9 H, TMS), 1.18 (d, 3 H,
3
threo-3-Methyl-5-trimethylsilylpent-4-yn-2-ol
3
1
CH , J = 7.0 Hz), 2.24 (d, 1 H, OH, J = 3.5 Hz), 2.87 (quint, 1 H, H-
H NMR (250 MHz, CDCl ): d = 0.15 (s, 9 H, TMS), 1.18 (d, 3 H,
3
3
2
, J = 7.0 Hz), 4.47 (dd, 1 H, H-1, J = 7.0, 3.5 Hz), 7.30–7.43 (m, 5
CH , J = 7.0 Hz), 1.23 (d, 3 H, H-1, J = 6.2 Hz), 1.95 (d, 1 H, OH,
H, Ph).
J = 5.0 Hz), 2.47 (dq, 1 H, H-3, J = 7.0, 6.0 Hz), 3.60 (m, 1 H, H-2).
1
3
C NMR (62.5 MHz,CDCl ): d = 0.11 (TMS), 17.08 (CH ), 22.66
3
3
6
erythro-2-Methyl-1-phenyl-4-trimethylsilylbut-3-yn-1-ol
(C-1), 35.80 (C-3), 70.50 (C-2), 87.48 (C-5), 107.65 (C-4). GCMS:
1
+
H NMR (250 MHz, CDCl ): d = 0.12 (s, 9 H, TMS), 1.07 (d, 3 H,
3
m/z = 153 (1) [M – OH] , 126 (35), 117 (15), 111 (24), 97 (18), 73
3
+
CH , J = 7.0 Hz), 2.50 (d, 1 H, OH, J = 3.5 Hz), 2.79 (m, 1 H, H-2),
(100) [TMS] . Anal. Calcd for C H OSi: C, 63.47; H, 10.65.
9
18
4
.76 (dd, 1 H, H-1, J = 6.5, 3.5 Hz), 7.28–7.41 (m, 5 H, Ph).
Found: C, 62.25; H, 9.43.
threo-1-(4-Methoxyphenyl)-2-methyl-4-trimethylsilyl-
erythro-3-Methyl-5-trimethylsilylpent-4-yn-2-ol
1
but-3-yn-1-ol
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 1.14 (d, 3 H,
3
1
H NMR (250 MHz, CDCl ): d = 0.18 (s, 9 H, TMS), 1.04 (d, 3 H,
3
CH , J = 7.0 Hz), 1.23 (d, 3 H, H-1, J = 6.2 Hz), 2.18 (d, 1 H, OH,
3
3
CH , J = 7.0 Hz), 2.61 (d, 1 H, OH, J = 3.0 Hz), 2.67–2.75 (quint, 1
J = 5.0 Hz), 2.59 (dq, 1 H, H-3, J = 7.0, 5.5 Hz), 3.71 (m, 1 H, H-2).
1
3
H, H-2, J = 7.0 Hz), 3.80 (s, 3 H, OCH ), 4.20 (dd, 1 H, H-1, J = 7.0,
C NMR (62.5 MHz, CDCl ): d = 0.11 (TMS), 16.17 (CH ), 19.47
3
3
3
3
.0 Hz), 6.87 (d, 2 H, H-3¢ and H-5¢, J = 9.3 Hz), 7.28 (d, 2 H, H-2¢
(C-1), 35.14 (C-3), 70.26 (C-2), 86.34 (C-5), 108.20 (C-4). GCMS:
1
3
and H-6¢, J = 9.3 Hz). C NMR (62.5 MHz, CDCl ): d = 0.08
identical with the threo-compound. Anal. Calcd for C H OSi: C,
63.47; H, 10.65. Found: C, 62.53; H, 9.42.
3
9
18
(
TMS), 17.17 (C2-CH ), 36.54 (C-2), 55.25 (OCH ), 76.5 (C-1),
3
3
8
7.92 (C-4), 107.88 (C-3), 113.6 (C-3¢ and C-5¢), 127.87 (C-2¢ and
C-6¢), 133.40 (C-1¢), 159.30 (C-4¢). MS (GCMS): m/z (%) = 137
threo-1-Phenyl-2-propyl-4-trimethylsilylbut-3-yn-1-ol
–
1
1
(
100), 73 (12). IR (hexane): 2163 (C≡C) cm . Anal. Calcd for
H NMR (250 MHz, CDCl ): d = 0.17 (s, 9 H, TMS), 0.86 (t, 3 H,
3
C H O Si: C, 68.65; H, 8.45. Found: C, 68.75; H, 7.96.
H-3¢), 1.21–1.65 (m, 4 H, H-1¢ and H-2¢), 2.62–2.79 (m, 2 H, H-2
and OH), 4.52 (dd, 1 H, H-1, J = 6.6, 4.0 Hz), 7.24–7.37 (m, 5 H,
Ph). C NMR (62.5 MHz, CDCl ): d = 0.09 (TMS), 13.79 (C-3¢),
1
5
22
2
1
3
erythro-1-(4-Methoxyphenyl)-2-methyl-4-trimethylsilyl-
3
but-3-yn-1-ol
20.53 (C-2¢), 33.24 (C-1¢), 42.51 (C-2), 75.98 (C-1), 89.41 (C-4),
106.36 (C-3), 126.64 (C-4¢¢), 127.82 (C-2¢¢ and C-6¢¢), 128.19 (C-3¢¢
and C-5¢¢), 141.73 (C-1¢¢). GCMS: m/z (%) = 139 (100), 73 (12)
1
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 1.11 (d, 3 H,
3
CH , J = 7.0 Hz), 2.23 (d, 1 H, OH, J = 3.3 Hz), 2.75–2.99 (m, 1 H,
3
+
–1
H-2), 3.83 (s, 3 H, OCH ), 4.68 (m, 1 H, H-1), 6.88 (d, 2 H, H-2¢ and
H-6¢, J = 9.3 Hz), 7.32 (d, 2 H, H-3¢ and H-5¢, J = 9.3 Hz). C NMR
[TMS] . IR (hexane): 2167 (C≡C) cm . Anal. Calcd for C H OSi:
3
16 24
1
3
C, 73.79; H, 9.29. Found: C, 73.20; H, 8.66.
(
5
62.5MHz, CDCl ): d = 0.05 (TMS), 15.82 (C2-CH ), 35.45 (C-2),
3
3
5.26 (OCH ), 76.23 (C-1), 87.36 (C-4), 108.31 (C-3), 113.35 (C-3¢
erythro-1-Phenyl-2-propyl-4-trimethylsilylbut-3-yn-1-ol
3
1
and C-5¢), 127.71 (C-2¢ and C-6¢), 133.54 (C-1¢), 159.11 (C-4¢).
H NMR (250 MHz, CDCl ): d = 0.12 (s, 9 H, TMS), 0.89 (t, 3 H,
3
GCMS: identical to the threo-compound. IR (hexane): 2165 (C≡C)
H-3¢, J = 7.0 Hz), 1.26–1.71 (m, 4 H, H-1¢ and H-2¢), 2.38 (d, 1 H,
OH, J = 4.0 Hz), 2.76–2.85 (m, 1 H, H-2), 4.52 (dd, 1 H, H-1,
J = 5.0, 4.0 Hz), 7.26–7.41 (m, 5 H, Ph). C NMR (62.5 MHz,
–
1
cm . Anal. Calcd for C H O Si: C, 68.65; H, 8.45. Found: C,
1
5
22
2
1
3
6
8.91; H, 8.42.
CDCl ): d = 0.03 (TMS), 13.85 (C-3¢), 20.52 (C-2¢), 31.86 (C-1¢),
3
6
threo-1-Cyclohexyl-2-methyl-4-trimethylsilylbut-3-yn-1-ol
41.24 (C-2), 75.63 (C-1), 89.23 (C-4), 106.94 (C-3), 126.66 (C-4¢¢),
127.59 (C-2¢¢ and C-6¢¢), 128.89 (C-3¢¢ and C-5¢¢), 141.55 (C-1¢¢).
GCMS: identical to the threo-compound. IR (hexane): 2169 (C≡C)
1
H NMR (250 MHz, CDCl ): d = 0.16 (s, 9 H, TMS), 0.93–2.05 (m,
5 H, cyclohexyl, CH , OH), 2.73 (dq, 1 H, H-2, J = 7.0, 4.8 Hz),
3
1
3
–
1
3
.07 (dq, 1 H, H-1, J = 7.0, 4.8 Hz).
cm . Anal. Calcd for C H OSi: C, 73.79; H, 9.29. Found: C,
16 24
7
3.07; H, 9.97.
Synlett 2006, No. 12, 1859–1862 © Thieme Stuttgart · New York

1
862
U. Groth et al.
LETTER
+
+
–1
threo-1-(4-Methoxyphenyl)-2-propyl-4-trimethylsilyl-
[M – Et, Me] , 73 (100) [TMS] . IR (hexane): 2166 (C≡C) cm .
but-3-yn-1-ol
Anal. Calcd for C H OSi: C, 66.60; H, 11.18. Found: C, 66.46; H,
1
2
24
1
H NMR (250 MHz, CDCl ): d = 0.19 (s, 9 H, TMS), 0.87 (t, 3 H,
10.86.
3
H-3¢, J = 7.0 Hz), 1.19–1.62 (m, 5 H, H-1¢, H-2¢ and OH), 2.66–2.74
(
m, 1 H, H-2), 3.82 (s, 3 H, OCH ), 4.63 (m, 1 H, H-1), 6.89 (d, 2
erythro-3-Propyl-5-trimethylsilylpent-4-yn-2-ol
3
1
H, H-3¢¢ and H-5¢¢, J = 9.3 Hz), 7.29 (d, 2 H, H-2¢¢ and H-6¢¢, J = 9.3
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 0.92 (t, 3 H,
C-3¢, J = 7.0 Hz), 1.24 (d, 3 H, H-1, J = 6.0 Hz), 1.28–1.62 (m, 4 H,
H-1¢, H-2¢ and OH), 2.49–2.58 (m, 1 H, H-3), 3.67–3.80 (m, 1 H, H-
2). C NMR (62.5 MHz, CDCl ): d = 0.11 (TMS), 16.17 (C-3¢),
19.47 (C-2¢), 20.83 (C-1), 35.14 (C-1¢), 41.42 (C-3), 70.26 (C-2),
86.34 (C-5), 108.20 (C-4). GCMS: identical to the threo-compound.
IR (hexane): 2167 (C≡C) cm . Anal. Calcd for C H OSi: C,
6.60; H, 11.18. Found: C, 66.03; H, 10.66.
3
Hz). 13C NMR (62.5 MHz, CDCl ): d = 0.12 (-TMS), 13.80 (C-3¢),
3
2
8
0.50 (C-2¢), 33.18 (C-1¢), 42.52 (C-2), 55.24 (OCH ), 75.70 (C-1),
3
1
3
9.23 (C-4), 106.67 (C-3), 113.63 (C-3¢¢ and C-5¢¢), 127.84 (C-2¢¢
3
and C-6¢¢), 133.81 (C-1¢¢), 159.26 (C-4¢¢). GCMS: m/z (%) = 209
+
–1
(
15), 73 (100) [TMS] . IR (hexane): 2167 (C≡C) cm . Anal. Calcd
–
1
for C H O Si: C, 70.29; H, 9.02. Found: C, 72.61; H, 8.87.
1
7
26
2
12 24
6
erythro-1-(4-Methoxyphenyl)-2-propyl-4-trimethylsilyl-
but-3-yn-1-ol
1
Acknowledgment
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 0.88 (t, 3 H,
3
H-3¢, J = 7.0 Hz), 1.21–1.70 (m, 4 H, H-1¢ and H-2¢), 2.23 (d, 1 H,
This work was supported by the EU Commission, Directorate Ge-
neral XII. We are thankful to the Merck KGaA and the Wacker AG
for the generous donation of reagents.
OH, J = 6.8 Hz), 2.77–2.85 (m, 1 H, H-2), 3.83 (s, 3 H, OCH ), 4.68
3
(
7
t, 1 H, H-1, J = 4.3 Hz), 6.88 (d, 2 H, H-3¢¢ and H-5¢¢, J = 9.3 Hz),
1
3
.32 (d, 2 H, H-2¢¢ and H-6¢¢, J = 9.3 Hz). C NMR (62.5 MHz,
CDCl ): d = 0.06 (TMS), 13.89 (C-3¢), 20.53 (C-2¢), 32.05 (C-1¢),
3
4
1
1
1.31 (C-2), 55.26 (-OCH ), 75.24 (C-1), 88.58 (C-4), 107.03 (C-3),
13.32 (C-3¢¢ and C-5¢¢), 127.83 (C-2¢¢ and C-6¢¢), 133.81 (C-1¢¢),
59.11 (C-4¢¢). GCMS: identical to the threo-compound. IR (hex-
3
References and Notes
(1) Lanthanides in Organic Synthesis, part 6. For part 5, see:
Fischer, S.; Groth, U.; Jeske, M.; Schütz, T. Synlett 2002,
1922.
–
1
ane): 2169 (C≡C) cm . Anal. Calcd for C H O Si: C, 70.29; H,
9
1
7
26
2
.02. Found: C, 71.81; H, 8.91.
(
2) For reviews, see: (a) Moreau, J. L. In The Chemistry of
Ketenes, Allenes, and Related Compounds, Part 1; Patai, S.,
Ed.; Wiley-VCH: New York, 1980, 363–413.
threo-1-Cyclohexyl-2-propyl-4-trimethylsilylbut-3-yn-1-ol
1
H NMR (250 MHz, CDCl ): d = 0.15 (s, 9 H, TMS), 0.87–2.00 (m,
3
1
3
1
2
7
9 H, cyclohexyl, H-1¢, H-2¢, H-3¢ and OH), 2.62 (m, 1 H, H-2),
(b) Yamamoto, H. In Comprehensive Organic Synthesis,
Vol. 2; Trost, B. M.; Fleming, I.; Heatchcock, C. H., Eds.;
Pergamon Press: Oxford, 1991, 81–98. (c) Marshall, J. A.;
Gung, B. W.; Grachan, M. L. In Modern Allene Chemistry;
Krause, N.; Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim,
2004, 493–592.
.10 (m, 1 H, H-1). 13C NMR (62.5 MHz, CDCl ): d = 0.17 (TMS),
3
3.88 (C-3¢), 20.04 (C-2¢), 26.43 (C-4¢¢), 26.7 (C-3¢¢ and C-5¢¢),
8.35 (C-2¢¢), 29.66 (C-6¢¢), 34.31 (C-1¢), 36.84 (C-2), 42.13 (C-1¢¢),
8.14 (C-1), 88.64 (C-4), 106.59 (C-3). GCMS: m/z (%) = 266
+
+
+
(
<1.0) [M ], 265 (<1.0) [M – H] , 248 (<1.0) [M – H O] ), 233
2
+
(
(
<1.0), 185 (29.0), 154 (53), 73 (100.0) [TMS] . IR (hexane): 2167
C≡C) cm . Anal. Calcd for C H OSi: C, 72.11; H, 11.34. Found:
(3) (a) Zweifel, G.; Hahn, G. J. Org. Chem. 1984, 49, 4565.
(b) Trost, B. M.; Rhee, Y. H. J. Am. Chem. Soc. 1999, 121,
11680.
–1
1
6
30
C, 71.87; H, 11.17.
(
4) Marshall, J. A.; Xie, S. J. Org. Chem. 1995, 60, 7230.
erythro-1-Cyclohexyl-2-propyl-4-trimethylsilylbut-3-yn-1-ol
(5) (a) Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Org. Chem.
1982, 47, 2225. (b) Kobayashi, S.; Nishio, K. J. Am. Chem.
Soc. 1995, 117, 6392. (c) Kurono, N.; Sugita, K.; Tokuda,
M. Tetrahedron 2000, 56, 847.
1
H NMR (250 MHz, CDCl ): d = 0.14 (s, 9 H, TMS), 0.88–2.00 (m,
3
1
2
9 H, cyclohexyl, H-1¢, H-2¢, H-3¢ and OH), 2.50–2.60 (m, 1 H, H-
13
), 3.36 (t, 1 H, H-1, J = 6.0 Hz). C NMR (62.5 MHz, CDCl ):
3
d = 0.16 (-TMS), 13.99 (C-3¢), 20.64 (C-2¢), 26.07 (C-4¢¢), 26.34 (C-
(6) Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto,
H. Bull. Chem. Soc. Jpn. 1984, 57, 2768.
(7) Groth, U.; Richter, N.; Kalogerakis, A. Synlett 2006, 905.
(8) Eckenberg, P.; Groth, U.; Köhler, T. Liebigs Ann. Chem.
1994, 673.
3
¢¢ and C-5¢¢), 27.51 (C-2¢¢), 29.72 (C-6¢¢), 31.05 (C-1¢), 36.88 (C-2),
0.12 (C-1¢¢), 78.01 (C-1), 87.56 (C-4), 108.22 (C-3). GCMS: iden-
4
–
1
tical to the threo-compound. IR (hexane): 2167 (C≡C) cm . Anal.
Calcd for C H OSi: C, 72.11; H, 11.34. Found: C, 71.78; H, 10.89.
16
30
(
9) For reviews, see: (a) Imamoto, T. In Comprehensive
Organic Chemistry, Vol. 1; Trost, B. M.; Fleming, I.;
Schreiber, S. L., Eds.; Pergamon Press: Oxford, 1991, 231–
249. (b) Molander, G. A. Chem. Rev. 1992, 92, 29.
(c) Imamoto, T. In Lanthanides in Organic Chemistry;
Academic Press: New York, 1994, 81–95.
threo-2,2-Dimethyl-4-propyl-6-trimethylsilylhex-5-yn-3-ol
1
H NMR (250 MHz, CDCl ): d = 0.18 (s, 9 H, TMS), 0.92 (t, 3 H,
3
H-3¢, J = 7.0 Hz), 0.94 (s, 9 H, -t-Bu), 1.24–1.79 (m, 4 H, H-1¢ and
H-2¢), 2.09 (d, 1 H, OH, J = 10.7 Hz), 2.68 (m, 1 H, H-2), 3.06 (dd,
1
–
CH ), 34.87 (C-2), 36.12 (C-1¢), 37.14 (C-4), 79.74 (C-3), 90.66 (C-
6
1
3
H, H-1, J = 10.7, 1.2 Hz). C NMR (62.5 MHz, CDCl ): d =
3
0.02 (TMS), 13.79 (C-3¢), 20.58 (C-2¢), 26.32 (C-1 and 2 × C2-
(10) 3-Bromo-1-(trimethylsilyl)but-1-yne (1) was synthesized in
analogy to a procedure for the preparation of 3-bromo-1-
(trimethylsilyl)prop-1-yne: Wu, R.; Schramm, J. S.;
Pearson, D. L.; Tour, J. M. J. Org. Chem. 1996, 61, 6906.
(11) 3-Bromo-1-(trimethylsilyl)hex-1-yne (2) was prepared by
addition of lithium(trimethylsilyl)acetylide to
3
+
), 106.41 (C-5). GCMS: m/z (%) = 154 (7) [M – t-Bu, C H ] , 73
100) [TMS] . IR (hexane): 2166 (C≡C) cm . Anal. Calcd for
2 5
+
–1
(
C H OSi: C, 69.93; H, 11.73. Found: C, 69.13; H, 11.10.
1
4
28
threo-3-Propyl-5-trimethylsilylpent-4-yn-2-ol
butyraldehyde, tosylation of the resulting alcohol and
nucleophilic substitution of the tosylate by bromide under
Finkelstein conditions. See: (a) Wenkert, E.; Leftin, M. H.;
Michelotti, E. J. Org. Chem. 1985, 50, 1122. (b) Wipf, P.;
Aoyama, Y.; Benedum, T. Org. Lett. 2004, 6, 3593.
(c) Darresh, S.; Grant, A. S.; Magee, D. I.; Valenta, Z. Can.
J. Chem. 1991, 69, 712.
1
H NMR (250 MHz, CDCl ): d = 0.16 (s, 9 H, TMS), 0.93 (t, 3 H,
3
H-3¢, J = 7.4 Hz), 1.24 (d, 3 H, H-1, J = 6.0 Hz), 1.30–1.65 (m, 4 H,
H-1¢ and H-2¢), 1.91 (br s, 1 H, OH), 2.34–2.42 (m, 1 H, H-3), 3.61–
3
1
6
.71 (m, 1 H, H-2). 13C NMR (62.5 MHz, CDCl ): d = 0.17 (TMS),
3.91(C-3¢), 20.67 (C-2¢), 21.25 (C-1), 33.51 (C-1¢), 41.74 (C-3),
9.19 (C-2), 88.70 (C-5), 106.45 (C-4). GCMS: m/z (%) = 154 (25)
3
Synlett 2006, No. 12, 1859–1862 © Thieme Stuttgart · New York