Isonitrile-nitrile rearrangement promoted by samarium(II) iodide

Article abstract of DOI:10.1039/a700570i

A samarium(II) iodide-promoted rearrangement of isonitriles to nitriles, which requires an α-alkoxycarbonyl group at the carbon atom bearing the isonitrile group, occurs under very mild conditions and contrasts with the thermal version of the rearrangement, which usually requires high temperature.

Full text of DOI:10.1039/a700570i

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Isonitrile–nitrile rearrangement promoted by samarium(ii) iodide
Han-Young Kang,*a Ae Nim Pae,b Yong Seo Cho,b Hun Yeong Koh*b and Bong Young Chung*c
a Department of Chemistry, Chungbuk National University, Cheongju 361-763, Korea
b Department of Applied Science, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Korea
c Department of Chemistry, Korea University, Seoul 136-701, Korea
A samarium(II) iodide-promoted rearrangement of iso-
nitriles to nitriles, which requires an a-alkoxycarbonyl group
at the carbon atom bearing the isonitrile group, occurs under
very mild conditions and contrasts with the thermal version
of the rearrangement, which usually requires high tem-
perature.
The results of the isonitrile–nitrile rearrangement promoted
by samarium(ii) iodide are summarized in Table 1. The
rearrangement proceeds under very mild conditions in contrast
to the thermal version, in which a temperature of up to 300 °C
is required. The samarium(ii) iodide-promoted isonitrile–nitrile
rearrangement tolerates various types of functionality as shown
in Table 1. Yields are variable, and usually formation of the
corresponding reduced products 5 is also observed.
Decyanation of a-cyanocarboxylic esters promoted by
samarium(ii) iodide was reported by us.9 Conversion of nitriles
4 to the reduced products 5 is precluded since this process in the
presence of samarium(ii) iodide requires higher temperature
(room temperature). Therefore, the reduced products 5 are
believed to be formed directly from the isonitrile substrate and
not via the rearranged compounds, nitriles 4. Under our
conditions (SmI2, THF–HMPA, 278 °C) the rearranged
products 4 are usually formed predominantly. The substrate 3d,
having an isocyano group at the benzylic position, produced
only the corresponding reduced product 5d. Importantly, the
isonitrile substrate has to be activated by an alkoxycarbonyl
group for successful rearrangement. In the case of 3e only the
isonitrile group attached to the carbon a to the carbonyl group
was isomerized, as expected.
Generally, 1.2–1.5 equiv. of samarium(ii) iodide are suffi-
cient for the rearrangement. However, in some cases, 2.5 equiv.
were employed to complete the reaction. It is also appropriate to
note that this process, which provides a-cyanocarboxylates and
the corresponding reduced (deaminated) products, can be
understood as an efficient method for deamination of a-amino
acid derivatives, since the isonitriles prepared were made from
the corresponding a-amino acids and at higher temperature
a-cyanocarboxylates are known to undergo decyanation in the
presence of samarium(ii) iodide.9
The isonitrile–nitrile rearrangement, which has been known for
about ninety years, proceeds thermally with retention of
stereochemistry at the migrating carbon [eqn. (1)].1–3 This
(1)
R
NC
R CN
implies that the bond-forming and -breaking steps occur
simultaneously and that there is little development of charge in
the transition state. This rearrangement occurs at high tem-
perature (250–280 °C) and is believed to take place via a radical
intermediate. When the migrating carbon atom contains deloc-
alizing groups such as alkoxycarbonyl or phenyl, then re-
arrangement also takes place but with low retention of
configuration.4 This reaction has also been the focus of
theoretical investigation.5
Samarium(ii) iodide is a useful tool for synthetic organic
chemists since it is known for promoting various organic
transformations.6 Among the useful reactions of this reagent,
reductive cleavage of a-heteroatom-substituted carbonyl sub-
strates, involving deoxygenation of the functionality containing
heteroatoms such as oxygen, sulfur and halogen, has been one
of the most utilized.7 However, in the case of functional groups
containing a nitrogen atom, reductive cleavage has rarely been
studied despite the importance of the transformation. The first
systematic study of the reductive cleavage of aziridines adjacent
to a carbonyl group has recently been reported.8
From the view-point of the synthetic potential of this
rearrangement, we investigated the possibility of utilization of
the reaction for asymmetric synthesis (Table 2). We prepared
During the course of investigations on reactions promoted by
samarium(ii) iodide we had an opportunity to study the reaction
of penicillanate 1 in the presence of this powerful single
electron-transferring agent [eqn. (2)].
+
–C
N
N
C
O
Table 1 Isonitrile–nitrile rearrangement promoted by samarium(ii) iodide
S
S
SmI2, HMPA
THF, –78 °C
Me
Me
Me
Me
(2)
N
N
O
O
O
O
R1
R1
+
SmI2, HMPA
THF, –78 o
CO2CHPh2
R1
CO2CHPh2
OR2
OR2
OR2
1
2
C
CN
NC
We anticipated a reduced product. However, to our surprise,
a nitrile 2 was obtained in 70% yield (contained 5% of the
reduced product). The diastereoisomers of 1 were separated,†
and each was treated under the same reaction conditions. Both
diastereoisomers (a-NC and b-NC) provided approximately the
same ratio of 2 (a-CN:b-CN = 1:1.5), which indicated that the
stereoselection induced by the migrating NC group and/or the
b-lactam nucleus is low.
5
3
4
Product (% yield)
SmI2
(equiv.)
Isonitrile R1
R2
4
5
3a
3b
3c
3d
3e
3f
H
PMBa
PMBa
Me
Me
PMBa
PMBa
1.2
1.2
1.0
2.5
2.5
1.8
4a (50)
5a (11)
4b (50) 5b (10)
(CH3)2CHCH2
Bn
Ph
CN(CH2)4
PMBO2CCH2
4c (57)
4d (0)
4e (50)
4f (40)
5c (12)
5d (46)
5e (20)
5f (11)
In order to investigate the generality and limitations of this
isonitrile–nitrile rearrangement, various carboxylic acid deriva-
tives with an a-isonitrile group were prepared. Synthesis of the
substrates was easily achieved in a straightforward manner
starting from the corresponding a-amino acids.‡
a PMB = p-methoxybenzyl.
Chem. Commun., 1997
821

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the substrates shown in Table 2 having chiral oxazolidinone
auxiliaries.§
rangement should be included in the list of useful organic
transformations promoted by samarium(ii) iodide.
We are grateful to the Korea Ministry of Science and
Technology and the Organic Chemistry Research Center
(sponsored by the Korea Science and Engineering Foundation)
for generous financial support.
The efficiency of the differentiation of the diastereotopic
faces by Evans’ chiral auxiliaries (3g and 3h) was first tested.
Both cases show reasonable diastereoselectivities. Hoping to
enhance the effectiveness of shielding to achieve a better de, a
recently reported chiral auxilary (c = CHPh2; 3i in Table 2) was
also introduced.10 However, in this case, no further increase in
de was observed. Although only limited cases were tested, the
results from Table 2 indicate that diastereoselectivity might be
achieved if an appropriate chiral environment can be main-
tained. However, the systems considered here are not effective
enough to obtain the desired level of diastereoselectivity. The
reason could be either that the stereocentres responsible for the
stereoselection are located far away from the carbon bearing the
isocyano group or that the isocyano and cyano groups are linear,
and thus are unable to provide efficient shielding of one
diastereotopic face compared with the other.¶
Ito and co-workers have reported their investigation of the
reaction of samarium(ii) iodide with an isonitrile group.11 In
their cases, samarium(ii) iodide promotes a-addition reactions
of isonitriles. In our cases it is, however, probably reasonable to
conclude that the reaction starts with an electron-transfer to the
carbonyl group since no reaction was observed with a substrate
without an a-alkoxycarbonyl group. The next step would
involve breaking the bond between the migrating carbon atom
and the nitrogen atom of the isocyano group, although the exact
nature of the intermediate is not clear at the moment. At this
stage, when benzylic stabilization is possible, return of the
removed isonitrile moiety is not allowed and this results in
exclusive formation of the reduced product. Otherwise the
removed isonitrile moiety returns, with rearrangement, to the
migrating carbon atom or, if this process cannot compete, the
carbon atom previously bearing the isocyano group is captured
by a hydrogen atom.
Footnotes
† Lichrosorb Si60 Semi-prep column, hexane–ethyl acetate = 3:1.
‡ The required isonitrile substrates were prepared by one of the following
routes from the corresponding a-amino acids. Method A: i, SOCl2, MeOH;
ii, HCO2H, Ac2O, pyridine; iii, triphosgene, Et3N, CH2Cl2, 278 °C.
Method B: i, HCO2H, Ac2O; ii, p-Methoxybenzyl chloride, K2CO3, DMF;
iii, triphosgene, Et3N, CH2Cl2, 278 °C.
§ The purity of the substrates in Table 2 was checked by NMR spectroscopy.
The isonitriles 3g–i were all pure single diastereoisomers. For compounds
3g–i the absolute stereochemistry of the carbon atom bearing the isonitrile
group is, however, not clear at this point since epimerization could take
place during the synthesis from the corresponding amino acids under the
reaction conditions described in ref. 10. In all cases in Table 2, formation of
the reduced products (corresponding to 5) was not observed.
¶ The de values could be affected by epimerization during purification.
References
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In conclusion, the samarium(ii) iodide-promoted rear-
rangement of isonitriles to nitriles has been discovered and
investigated. This rearrangement occurs under very mild
conditions, in contrast to the thermal version of this rearrange-
ment, which usually requires high temperature. This rear-
Table 2 Rearrangement of substrates with chiral auxiliaries
O
O
O
O
H
NC
Ph
CN
Ph
SmI2, HMPA
THF, –78 °C
N
O
7 G. A. Molander, Org. React., 1994, 46, 211.
N
O
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H
χ
χ
3
4
Product
Isonitrile
c
SmI2 (equiv.)
(% yield)
De(%)
3g
3h
3i
CH(CH3)2
CH2Ph
CHPh2
1.2
1.2
1.2
4g (60)
4h (55)
4i (48)
65
68
68
Received in Cambridge, UK, 24th January 1997; Com.
7/00570I
822
Chem. Commun., 1997