Diethyl zinc catalyzed diastereoselective addition of ketenes to (S)-(+)-3-hydroxytetrahydrofuran

Article abstract of DOI:10.1016/S0040-4039(01)01164-9

The reaction of (S)-(+)-3-hydroxytetrahydrofuran with phenyl methyl ketene in presence of n-BuLi and Et₂Zn results in the formation of the diastereomeric esters (SS+SR) with a high degree of diastereoselectivity (98:2).

Full text of DOI:10.1016/S0040-4039(01)01164-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5985–5987
Diethyl zinc catalyzed diastereoselective addition of ketenes to
(
S)-(+)-3-hydroxytetrahydrofuran
Vishnu K. Tandon*
Department of Chemistry, Lucknow University, Lucknow-226007, India
Received 23 April 2001; revised 5 June 2001; accepted 28 June 2001
Abstract—The reaction of (S)-(+)-3-hydroxytetrahydrofuran with phenyl methyl ketene in presence of n-BuLi and Et Zn results
2
in the formation of the diastereomeric esters (SS+SR) with a high degree of diastereoselectivity (98:2). © 2001 Elsevier Science
Ltd. All rights reserved.
1
,2
We first demonstrated the synthesis
of (S)-(+)-3-
reaction of ketenes 2 with (S)-(+)-3-hydroxytetra-
hydrofuran 4 with various bases has now been carried
out resulting in the formation of 5 with diastereoselec-
hydroxytetrahydrofuran and its stereoselective reac-
tions via chiral sulfonyl methyl isocyanides. It has been
used in 1,4-chirality transfer cycloaddition reactions as
3
4
11
tivity in the range of 8–46%.
well as in the asymmetric synthesis of (S)-(+)-atrolactic
5
acid. Both the (R)-(−)- and (S)-(+)-enantiomers of
The reaction of ketenes 2 with (−)-menthol 1 (R*, (−)-
menthyl) and (+)-borneol 1 (R*, (+)-bornyl) in the
3
-hydroxytetrahydrofuran have been used for the syn-
thesis of potent HIV protease inhibitors.
6
presence of n-BuLi and Et Zn results in the formation
2
of diastereomeric esters 3 (SS+RS) with asymmetric
induction in the range of 30–57% (Table 1, Scheme 1).
Significant improvement in asymmetric induction cata-
The catalytic asymmetric addition of an achiral alcohol
to a chiral ketene in the presence of optically active
bases is known to result in an efficient asymmetric
lyzed by Et Zn was observed with (−)-menthol and
2
7
synthesis of esters, whereas uncatalyzed addition of a
(+)-borneol compared to the reaction carried out earlier
10
chiral alcohol to a chiral ketene generally results in the
with other bases.
8
formation of esters with low asymmetric induction.
The reaction of (S)-(+)-3-hydroxytetrahydrofuran 4
9
The reaction of ketenes 2 with chiral (S)-secondary
with ketenes 2 in the presence of n-BuLi and Et Zn
2
alcohols 1 in the presence of base can result in the
formation of a mixture of diastereomeric esters 3 (RS+
SS) (Scheme 1).
results in the formation of ester 5 (SS+SR) with high
12
asymmetric induction, 80–96% d.e. (Table 2, Scheme
2). The diastereomeric excess in 5 was determined by
1
13
13
H NMR and C NMR and was found to be the
The reaction of ketenes with (−)-menthol and (+)-bor-
same. The extent of asymmetric induction in
diastereomeric esters 5 was further confirmed by
hydrolysis to the optically active acids 6. Thus, esters 5
neol in the presence of various bases, resulting in low
10
asymmetric induction, has been reported earlier. The
R1
R1
R1
O
O
base
R*OH
+
C
C
O
C
C
+
C
C
R2
H
R2
R2
H
OR*
OR*
1
2
3
(SS + SR)
Scheme 1.
*
0
Fax: +91-522-326665; e-mail: tandon vk@yahoo.com
–
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01164-9

5
986
V. K. Tandon / Tetrahedron Letters 42 (2001) 5985–5987
Table 1.
Entry
Reaction conditions
R*
R1
R2
Ester 3
2
2
Yield (%)
[h] (acetone c=1.5)
d.e. (%) (SS\SR)
D
1
n-BuLi
CH3
Me
Et
Me
Ph
Ph
Ph
Cl
Br
82
78
83
73
−32.5
−28.4
−22.5
−28.3
62
60
48
45
Et Zn
2
2
n-BuLi
Me
Me
Me
Me
Et
Me
Ph
Ph
Ph
Cl
Br
62
59
71
63
+15.6
+12.3
+18.5
+13.4
58
49
52
48
Et Zn
2
Table 2.
Entry
Reaction conditions
R*OH
R1
R2
Ester 6
Acid 7
2
2
22
D
Yield (%)
(SS: SR)
[h]
e.e. (%)
[h]
D
1
2
3
n-BuLi–Et Zn
4
4
4
Me
Et
Br
Ph
Ph
Me
78
72
80
98:2
94:6
90:10
+22.58
+16.33
−9.35
96
84
80
+69.2
+77.6
−20.0
2
n-BuLi–Et Zn
2
n-BuLi–Et Zn
2
R1
C
O
O
C
R2
H
HO
R1
R1
SS-5
O
O
a
b
+
C
C
O
+
R2
C
C
R1
R2
O
O
R2
O
H
OH
C
C
4
2
H
6
SR-5
O
1
2
1
2
1
Scheme 2. Reagents and conditions: (a) n-BuLi/Et Zn; (b) HCl/THF, (R =Me, R =Ph; (ii) R =Et, R =Ph; (iii) R =Me,
R =Br.
2
2
1
2
(
R =CH , R =Ph) on hydrolysis with conc. HCl in
to a high degree of diastereoselectivity, possibly due to
chelation control with Zn.
3
THF for 48 h at room temperature gave (S)-(+)-2-
phenylpropanoic acid in 82% yield, e.e. 96% [[h] =
22
D
+
69.2 (c=1.4, CHCl )]. The absolute configuration was
3
assigned to the 2-phenylpropanoic acid by comparison
Acknowledgements
14
with the specific rotation of (S)-(+)-enantiomer.
The proton transfer at C2 in ketene 2 from 4 is the key
The author wishes to thank RSIC facilities of CDRI,
Lucknow, India and Dr. H. Junjappa for his helpful
discussions.
and crucial step for induction of stereoselectivity. Reac-
tions carried out in the presence of catalytic Et Zn lead
2

V. K. Tandon / Tetrahedron Letters 42 (2001) 5985–5987
5987
References
DBU. The d.e. ranges are from 8–46% with the maximum
d.e. obtained with Dabco and the minimum with pyridine
8%.
1
. Tandon, V. K.; VanLeusen, A. M.; Wynberg, H. J. Org.
Chem. 1983, 48, 2767.
. (a) Brown, H. C.; Vara Prasad, J. V. N. J. Am. Chem.
Soc. 1986, 108, 2049; (b) Brown, H. C.; Gupta, A. K.;
Rangaishenvi, M. V.; Vara Prasad, J. V. N. Heterocycles
12. Reaction conditions: A solution of 4 (88 mg, 1 mmol) in
dry toluene (10 ml) at −78°C was treated with l ml of
n-BuLi (2.48 M hexane solution, 1 equiv.) under a N2
atmosphere. The solution was stirred for 15 min then
methyl phenyl ketene 2 (i) (from 168 mg of n-propanonyl
2
1
989, 28, 283.
3
4
5
6
. Hundscheid, F. J. A.; Tandon, V. K.; Rouwette, H. F.
M.; Van Leusen, A. M. Tetrahedron 1987, 43, 5073.
. Stanssens, D.; Keukeleire, D. D.; Vandewalle, M. Tetra-
hedron Lett. 1987, 28, 4197.
. Tandon, V. K.; Agarwal, V.; Van Leusen, A. M. Indian J.
Chem. 1994, 33, 200.
. Thompson, W. J.; Ghosh, A. K.; Holloway, M. K.; Lee,
H. K.; Munson, P. M.; Schwering, J. E.; Wai, J.; Darke,
P. L.; Jugay, J.; Emini, E. A.; Schleif, W. A.; Huff, J. R.;
Anderson, P. S. J. Am. Chem. Soc. 1993, 115, 801.
. (a) Pracejus, H. Tetrahedron Lett. 1966, 3809; (b) Prace-
jus, H. Forsch. Chem. Forsch. 1967, 8, 493.
chloride, 1 equiv.) and 5.80 ml of Et Zn (1 M toluene
2
solution, 2.2 equiv.) were added. The reaction was stirred
at this temperature for 1 h and then for 12 h at 0°C.
Saturated brine solution (25 ml) added and extracted
with ether (3×25 ml), the ether extract dried (MgSO ) and
4
concentrated in vacuo to yield 5 as an oil which was
purified by flash chromatography over Al O (benzene).
2
3
1
3. The structures of all the compounds were confirmed by
1
13
IR, H and C NMR. For 5 (Table 2, entry 2) NMR
data are as follows:
7
8
9
1
H (CDCl , 200 MHz, l ppm): 0.89, 0.91 (3H, 2t, J=7.5
3
Hz, CH (4)), 1.90 (4H, m, CH , (3,4%)), 3.39, 3.41 (1H,
3
2
. Morrison, J. D.; Mosher, H. S. Asymmetric Organic
Reactions; Prentice Hall: Engelwood Cliffs, NY, 1971.
. Ketenes were generated in situ from the corresponding
2
t, J=7.5 Hz, CH (2)), 3.80 (4H, m, CH (2%, 5%)), 5.25
2
(
1H, m, CH (3%)), 7.12, 7.15 (5H, 2s, Ph).
13
1
Assignment of resonances. C, H correlations for 5
(
acid chlorides and Et N. The pale yellow colored ketenes
3
13
SS+RS): C (CDCl , 100 MHz, l ppm): C =52.907,
3
2
were used immediately for the addition reactions.
5
7
6
2.969; C =26.166, 26.263, C =11.662, C%=72.567,
1
1
0. McKenzie, A.; Christie, E. W. J. Chem. Soc. 1934, 1070.
1. A solution of (S)-(+)-3-hydroxy tetrahydrofuran 4 (176
mg, 2 mmol) in anhydrous toluene was prepared at
3 4 2
2.429, C%=74.528, 74.547, C%=32.179, 32.441, C%=
3
4
5
6.404, 66.434. The ratio of peaks at 3.39 and 3.41 for
1
CH-2 in the H NMR and at 52.907 and 52.969 for C in
−
90°C (5 mol) in dry toluene under a N atmosphere.
2
2
13
1
2
C NMR was used to estimate the diastereomeric excess
in 5.
14. An optically pure sample of (S)-(+)-2-phenylpropanoic
Ketene 2 (R =C H and R =Ph) prepared from 2-
2
5
phenylbutyroyl chloride (364 mg, 2 equiv.) was added
and stirred for 12 h at 0°C. Saturated brine solution (50
ml) was added and the reaction mixture extracted with
2
0
acid from Aldrich, Milwaukee, WI, USA, had [h] =+72
(c=1.6, CHCl ); (S)-(+)-2-phenyl butyric acid had [h] =
19
ether (3×50 ml), dried (MgSO ), concentrated (in vacuo)
3
4
to yield 5 (d.e. 45%). The reaction was carried out in the
presence of different bases: pyridine, KO Bu, Dabco and
+92 (c=0.9, toluene) and (S)-(−)-2-bromopropionic acid
had [h] =−25 (neat).
t
20
.