TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4127–4129
Direct conversion of a,b-unsaturated nitriles into cyanohydrins
using Mn(dpm)3 catalyst, dioxygen and phenylsilane
Philip Magnus,* David A. Scott and Mark R. Fielding
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
Received 2 April 2001; revised 23 April 2001; accepted 24 April 2001
Abstract—Treatment of a,b-unsaturated nitriles with Mn(dpm)3 (3 mol%), PhSiH3 in isopropyl alcohol in the presence of oxygen
resulted in reduction and a- and b-hydroxylation. © 2001 Elsevier Science Ltd. All rights reserved.
The use of cyanohydrins in synthesis has a long history
starting with the Lapworth benzoin reaction.1
Cyanohydrin O-ethers have also been used to imple-
ment reversed-polarization reactions of aldehydes
(umpolung), and also serve as a protecting group for
the carbonyl function.2 While the oxidative conversion
of nitriles to carbonyl functionality is known, there are
no reports of the direct transformation of an a,b-unsat-
urated nitrile into a cyanohydrin.3 We recently reported
the conversion of a,b-unsaturated ketones into a-
hydroxy ketones using tris(dipivaloylmethanato) man-
ganese(III) [abbreviated to Mn(dpm)3],4 phenylsilane
and oxygen. The application of this system to other
functional groups has provided a new synthetic route to
cyanohydrins (Scheme 1) from a,b-unsaturated nitriles.
Examples are shown in Table 1.
in the cases of entries b, c, and e. The substituents at
the b-position affected the product distribution. A sin-
gle aliphatic group resulted in only a-hydroxylation.
Cinnamonitrile (1e) gave a 2:1 mixture of b-hydroxy
and a-hydroxy nitriles. Mukaiyama obtained a 6:1 mix-
ture of b-:a-hydroxy esters upon treatment of ethyl
cinnamate with Mn(dpm)3, phenylsilane and oxygen.5
Similarly, as we had observed for the corresponding
unsaturated ester,4 treatment of unsaturated nitrile 1f
gave a mixture of products, although 3f was not iso-
lated. For the cyclooctyl substrate 1g, the ratio of
b-:a-hydroxylation was again around 2:1.
We had previously found that treatment of b-ionone
with Mn(dpm)3, phenylsilane and O2 resulted in 1,6
reduction and hydroxylation at the g-position.4 Similar
results were obtained for the analogous nitriles (Scheme
2). Compound 4, with an extended conjugated system,
gave 5 (24%), but since this initial product is also a
substrate for the reaction, 6 (21%, 1:1 diastereomers)
was also obtained. Similarly, 7 gave 8 (11%), but also 9
(15%, 1:1 diastereomers).
The substrates 1a–1g (listed in Table 1) were prepared
from the corresponding aldehydes and cyano-
methylphosphonate, and where applicable, were
approximately 1:1 mixtures of the E- and Z-isomers.
Treatment of 1a–1g with Mn(dpm)3 (3 mol%) in isopro-
pyl alcohol and phenylsilane under an oxygen atmo-
sphere resulted in complete conversion of the starting
materials (the volatility of some products may have
diminished the isolated yields). Small amounts of the
conjugate reduction products were observed (1H NMR)
In the absence of oxygen, no reaction was observed for
compound 1a, whereas the conjugate reduction of
unsaturated ketones proceeds well in the absence of
air.4
OH
3 mol% Mn(dpm)3
CN
CN
CN
+
R
R
R
O2/PhSiH3/i-PrOH
OH
2
1
3
Scheme 1.
Keywords: reduction; oxidation; cyanohydrin; manganese; phenylsilane.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00693-1