A one-pot esterification of chiral O-trimethylsilyl-cyanohydrins with retention of stereochemistry

Article abstract of DOI:10.1016/S0040-4039(02)01200-5

Enantiomerically enriched O-TMS cyanohydrins have been transformed directly into O-acyl-cyanohydrins using various anhydrides or acid chlorides in the presence of catalytic amounts of scandium(III) triflate. The reaction occurs with full retention of ster

Full text of DOI:10.1016/S0040-4039(02)01200-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5715–5717
A one-pot esterification of chiral O-trimethylsilyl-cyanohydrins
with retention of stereochemistry
Stephanie Norsikian, Ian Holmes, Franz Lagasse and Henri B. Kagan*
Laboratoire de Synthe`se Asyme´trique, ESA 8075, Institut de Chimie Mole´culaire d’Orsay, Universite´ Paris-Sud, 91405 Orsay,
France
Received 21 June 2002; accepted 24 June 2002
Abstract—Enantiomerically enriched O-TMS cyanohydrins have been transformed directly into O-acyl-cyanohydrins using
various anhydrides or acid chlorides in the presence of catalytic amounts of scandium(III) triflate. The reaction occurs with full
retention of stereochemistry and allows the convenient measurement of enantiomeric excesses by chiral HPLC. © 2002 Elsevier
Science Ltd. All rights reserved.
Recently, we described a novel method of preparing
O-TMS cyanohydrins 1 from aromatic aldehydes and
TMSCN using asymmetric base catalysis.1,2 The related
Lewis acid catalytic asymmetric trimethylsilylcyanation
of aldehydes and ketones has been widely investi-
gated.3–8 During our work we frequently needed to
derivatise the O-TMS cyanohydrins generated in order
to store the compounds and to improve the peak
separation for chiral HPLC analysis. This was initially
achieved by the standard, two-step, literature protocol
Table 1. Direct transformation of O-TMS cyanohydrins 1 into O-acylcyanohydrins 3
Entry
1, R (ee%)
Acylating agenta
Reaction time
Ester 3, yield%b (ee%)
1
2
3
4
5
6
7
8
C6H5 (84)
C6H5 (84)
Ac2O
Ac2O (1 equiv.)
Ac2O
Ac2O
Ac2O
Ac2O
Ac2O (5 equiv.)
Ac2O
CH3COCl
t-BuCOCl
PhCOCl
PhCH2COCl
Ac2O
(PhCO)2O
PhCOCl
Ac2O
15 min
30 min
15 min
15 min
15 min
12 h
98 (83)
98 (82)
98 (85)
98 (82)
98 (77)
92 (0)
3-MeC6H4 (89)
2-OMeC6H4 (84)
p-ClC6H4 (80)
p-NO2C6H4 (55)
p-NO2C6H4 (55)
p-CF3C6H4 (77)
C6H5 (86)
C6H5 (86)
C6H5 (83)
C6H5 (84)
CH3(CH2)6 (73)
CH3(CH2)6 (73)
CH3(CH2)6 (73)
C6H5CHꢀCH (88)
4 (49)
30 minc
45 min
1 h
94 (0)
98 (78)
98 (83)
98 (84)
70 (83)
96 (84)
98 (73)d
96 (70)
98 (71)
98 (88)
5a 98 (47)
7 90 (44)
9
10
11
12
13
14
15
16
17
18
2 h
1 h
2 h
15 min
3 h
3 h
15 min
2 h
Ac2O
Ac2O
6 (43)
5 h
a Reaction in acetonitrile at rt. 1/acylating agent/Sc(OTf)3=1:2:0.01, unless stated. [1]=1.0 M−1. Ee measured by HPLC, unless stated (Table 2).
b Isolated yield, after flash chromatography (silica gel).
c 5 mol% Sc(OTf)3.
d Measured by chiral GC.
Keywords: O-trimethylsilyl-cyanohydrins; O-acyl-cyanohydrins; esterification; scandium triflate; ee measurement.
* Corresponding author. Fax: +33 (0)1 69 15 46 80; e-mail: kagan@icmo.u-psud.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01200-5

5716
S. Norsikian et al. / Tetrahedron Letters 43 (2002) 5715–5717
of hydrolysis of 1 to give cyanohydrins 2 and then
esterification, into 3 using an acid chloride.6 Herein we
disclose that O-TMS cyanohydrins 1 can be conveniently,
and directly, esterified using anhydrides or acid chlorides
in the presence of catalytic amounts of scandium trifl-
uoromethanesulfonate using the methodology previously
described for the acylation of various alcohols.9,10 With
such a methodology, we have found that it is possible to
avoid aqueous conditions during ester formations that
can pose significant practical problems with water-soluble
cyanohydrins.11
Working in anhydrous conditions, using acetic anhydride
in the presence of 1 mol% Sc(OTf)3,12–14 we were very
satisfied to find that this simple and expedient procedure
for O-acetylation worked for a range of O-TMS cyanohy-
drins and occurred with full retention of stereochemistry
(Tables 1 and 2).15 It has also been demonstrated that
esterification by various acid chlorides (phenylacetyl
chloride, pivaloyl chloride) may be carried out under such
conditions. The procedure also applies to enantiomeri-
cally enriched cyanohydrins derived from ketones as in
the transformation of 4 to 5 or 6 to 7 (Scheme 1).
Table 2. Measurement of ee of O-acylcyanohydrins 3, 5 and 7
Entry
R1
R2
Eluent,a hexane/i-PrOH
Retention timeb (min)
1
2
3
4
5
6
7
8
C6H5
Ac
Ac
Ac
Ac
Ac
Ac
t-Bu
PhCO
PhCH2CO
Ac
PhCO
Ac
95/5
95/5
100/1
90/10
98/2/5
98/2
100/1
100/1
90/10
GC, 120°C isoth.
100/1
98/2
100/1
200/1
20.85; 22.63
6.96; 7.87
13.45; 15.13
7.97; 9.41
3-MeC6H4
2-OMeC6H4
p-ClC6H4
p-NO2C6H4
p-CF3C6H4
C6H5
C6H5
C6H5
CH3(CH2)6
CH3(CH2)6
C6H5CHꢀCH
23.43; 24.26d
9.83; 12.49c
12.0; 12.92
11.47; 12.61
8.89; 11.54
104.4; 118.54
7.15; 7.87
9
10
11
12
13
14
13.43; 16.41
10.44; 11.88
16.74; 25.23c
5
7
a HPLC on Chiralcel OD-H, unless entries 5 and 12 ((S,S)-Whelk-01). Flow: 1 mL min−1 except entry 1 (0.4 mL min−1) and entry 7 (0.5 mL
min−1).
b The major enantiomer is always of (S)-configuration, and is the second peak, except in entries 3, 8 and 14.
c Isohexane instead of hexane.
d Hexane/i-PrOH/dichloromethane=98:2:5. Poor peak separation.
R2COX
O
R2
CN
OTMS
OH
CN
O
CN
R1
R1
R1
1
2
3
OAc
CN
Me
OTMS
CN
Me
4
5
Me OTMS
CN
Me OAc
CN
6
7
Scheme 1. Direct O-acylation of O-TMS cyanohydrins.

S. Norsikian et al. / Tetrahedron Letters 43 (2002) 5715–5717
5717
Conclusion
7. Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North, M.;
Tararov, V. I. Tetrahedron Lett. 1999, 40, 8147–8150.
8. Hamashima, Y.; Kanai, M.; Shibasaki, M. Tetrahedron
Lett. 2001, 42, 691–694.
9. Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima, Y.;
Kanai, M.; Du, W.; Curran, D. P.; Shibasaki, M. J. Am.
Chem. Soc. 2001, 123, 9908–9909.
10. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H.
J. Org. Chem. 1996, 61, 4560–4567.
11. Barrett, A. G.; Braddock, D. C. J. Chem. Soc., Chem.
Commun. 1997, 351–352.
O-TMS cyanohydrins can be easily transformed into
their corresponding esters in a clean and fast one-pot
reaction. The process is of interest for analytical pur-
poses and may also be scaled up.16 This method, using
non-aqueous conditions, is especially useful as it deliv-
ers O-acyl cyanohydrins, which are more stable than
their O-TMS precursors, and are generally readily
analysed by chiral HPLC.
12. The one-step conversion of silyl-protected alcohols into
their corresponding acetates has been described in the
presence of SnBr2 or TiCl4 as catalysts.14,15
Acknowledgements
We thank the INCO-Copernicus program, Universite´
Paris-Sud and the Fondation Servier for providing
fellowships (I.H., S.N. and F.L., respectively). We
acknowledge Universite´ Paris-Sud and CNRS for their
financial support.
13. Oriyama, T.; Oda, M.; Gono, J.; Koga, G. Tetrahedron
Lett. 1994, 35, 2027–2030.
14. Iranpoor, N.; Zeynizadeh, B. Synth. Commun. 1999, 29,
2123–2128.
15. To a solution of O-silylated cyanohydrin (1 mmol, 1
equiv.) in 1 mL of acetonitrile was added acetic anhy-
dride (2 mmol, 2 equiv.) and Sc(OTf)3 (4.9 mg, 1 mol%).
The resulting solution was stirred for 15 min at rt, then
the solvent evaporated and the residue purified by
column chromatography (silica gel). Isolated yields are
almost quantitative. Enantiomeric excesses of 1 and 3–7
were measured by chiral HPLC (Chiralcel OD-H, hex-
ane/isopropanol or chiral GC). Enantioenriched O-TMS
cyanohydrins 1, 4 and 6 were obtained by trimethylsilyl-
cyanation of the corresponding aldehydes in the presence
of the catalysts described in Refs. 2 and 4.
16. (S)-3 (1.5 g, 7.3 mmol, R=H, 85% ee) in acetonitrile (7.3
mL) was treated with acetic anhydride (14.6 mmol) and
Sc(OTf)3 (35.7 mg, 1 mol%). After stirring for 60 min at
rt, the solvent was evaporated and the residue purified by
column chromatography. The acylated product was iso-
lated in quantitative yield and 85% ee.
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