A direct conversion of alkenes to isocyanides

Article abstract of DOI:10.1055/s-1999-2615

Treatment of alkenes with silver salts (AgClO₄, AgBF₄, or AgOTf) and trimethylsilyl cyanide (TMSCN) in dichloromethane followed by hydrolysis affords the corresponding isocyanides directly in high yields. The addition of the isocyano function is carried out in accordance with Markovnikov's rule.

Full text of DOI:10.1055/s-1999-2615

288
LETTER
A Direct Conversion of Alkenes to Isocyanides
Yoshikazu Kitano,* Kazuhiro Chiba, Masahiro Tada
Laboratory of Bio-organic Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
Fax 81(42)360-8830; E-mail: kitayo@cc.tuat.ac.jp
Received 16 November 1998
The reactions were carried out with 3.0 equivalents of
Abstract: Treatment of alkenes with silver salts (AgClO4, AgBF4,
TMSCN and 2.0 equivalents of silver salts (AgX), respec-
or AgOTf) and trimethylsilyl cyanide (TMSCN) in dichlo-
romethane followed by hydrolysis affords the corresponding isocy-
anides directly in high yields. The addition of the isocyano function
is carried out in accordance with Markovnikov’s rule.
tively.6 Results for the reaction of 6-methyleneundecane 1
are summarized in Table 1. These results showed that 6-
isocyano-6-methylundecane was obtained with
2
AgClO4, AgBF4, or AgOTf as a Lewis acid. The addition
of the isocyano function was carried out in accordance
with Markovnikov’s rule. In all cases, 2 was obtained with
no significant byproducts, but the reaction proceeded
more rapidly with AgClO4 than with AgBF4 or AgOTf.
Nitrile was not observed under these conditions.7 Howev-
er, it turned out that other silver salts such as AgF, AgCl,
AgBr, AgI, AgO2CCF3, AgNO3, and AgIO3 were either
unreactive or caused partial decomposition.
Key words: addition reactions, alkenes, isocyanides
Tertiary isocyanide is a versatile compound because bio-
logically active isocyanoterpenes from which marine or-
ganisms have been isolated have tertiary isocyanide as a
main component.1 Isocyanides are commonly prepared by
dehydration of formamides.2 However, the preparation of
tertiary isocyanides presents some difficulties. Harsh con-
ditions are generally required in order to prepare tertiary
alkyl amines as precursors of formamides. In addition,
product yield is low throughout the process. Recently, we
reported a new method for preparing tertiary isocyanides
from tertiary alcohols directly.3 This method was accom-
plished by performing the Ritter-type reaction4 under an-
hydrous conditions with TMSCN as a cyano source.
TMSCN is often utilized as a useful reagent for the prep-
aration of tertiary isocyanides.3, 5 However, to the best of
our knowledge, no published research indicates how to
prepare tertiary isocyanides directly from alkenes. For this
reason, we developed a milder, direct conversion method
to prepare tertiary isocyanides from alkenes. We thought
the desired conversion might be achieved by activating
alkenes with an appropriate Lewis acid followed by nu-
cleophilic attack with TMSCN. After some examination,
the desired conversion was achieved by using silver salts.
We describe herein a direct conversion method of alkenes
to isocyanides by using TMSCN and silver salts.
Reactions of other alkenes with TMSCN and AgClO4 are
summarized in Table 2. It can be seen that 1,1-di-substi-
tuted, tri-substituted, and tetra-substituted alkene afforded
the corresponding tertiary isocyanides in high yields (en-
tries 1, 2, and 3). In entries 4-7, the substrates which pos-
sess substituents at the 4-position were examined. In all
cases, the stereochemistry of the major isomer was the
isocyano substituent axially oriented. Moreover, 1,1-di-
substituted and tri-substituted alkenes, which afforded the
same product, revealed that stereoisomers were obtained
at approximately the same ratio. The addition of the iscy-
ano function was particularly observed in high stereose-
lectivity (entries 4, 5, and 6). The ester group was not
affected under these conditions (entries 6 and 7). In entry
8, intramolecular chemoselectivity was examined with the
substrate which possesses two different types of substitut-
ed olefinic bonds. The addition of isocyano only occurred
at the 1,1-di-substituted olefinic bond with complete
chemoselectivity. As regards our other results, cyclohex-
ene, 1-tetradecene, and 2-tetradecene, which afforded a
Synlett 1999, No. 3, 288–290 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Direct Conversion of Alkenes to Isocyanides
289
secondary isocyanide, were inert under these conditions.
Therefore, we consider that this reaction proceeds selec-
tively with the alkenes which afforded tertiary isocyanide.
Scheme 1
Scheme 2
Scheme 3
occurred after 1,1-di-substituted alkene had been trans-
formed to tri-substituted alkene.
The reaction mechanism is proposed in Scheme 3. It is
considered that this reaction involves the anti-parallel
electrophilic addition of AgClO4 and TMSCN to the ole-
finic bond (intermediate A). The initial attack by AgClO4
occurs from a less hindered site through a conformation
where the substituent of the 4-position is equatorially ori-
ented. A complex of silver salt and carbanion (intermedi-
ate B) is then hydrolyzed to isocyanide. From the above
proposed reaction mechanism, the high steroselectivity of
this method is clearly understood.
Similar reactions with 3 and 4 by hydrolysis with D2O are
summarized in Scheme 1. These results showed that ob-
taining deuterium introduced products was possible, but
obtaining products with deuterium being introduced into
their methyl group was hardly likely with 3. The reaction
of 3 with AgClO4 in the absence of TMSCN is summa-
rized in Scheme 2. This result showed that 1,1-di-substiut-
ed alkene 3 was rearranged to internal trisubstituted
alkene 4 rapidly. It was suggested that isocyano addition
In summary, we have developed a new method which di-
rectly converts alkenes into the corresponding isocya-
nides. We believe this method provides a convenient and
useful way to synthesize tertiary isocyanides.
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290
Y. Kitano et al.
LETTER
(6) General Procedure: TMSCN (1.5 mmol) and silver salt (1.0
mmol) under argon were added to a solution of alkene (0.5
mmol) in 2 ml of dry dichloromethane. The reaction mixture
was adequately stirred at ambient temperature, and then satu-
rated aq. NaHCO3 (2 ml) was added. After stirring for an ad-
ditional 10 min, the mixture was then analyzed by GLC or
poured into saturated aq. NaHCO3 and extracted with diethyl
ether. The combined organic extracts were washed with water
and brine and dried over MgSO4. The crude product was puri-
fied by silica gel column chromatography.
References and Notes
(1) Okino, T.; Yoshimura, E; Hirota, H; Fusetani, N. Tetrahedron
1996, 52, 9447. Fusetani, N.; Hirota, H.; Okino, T.; Tomono,
Y.; Yoshimura, E. J. Nat. Toxins 1996, 5, 249. König, G. M.;
Wright, A. D. J. Org. Chem. 1996, 61, 3259.
(2) Creedon, S. M.; Crowley, H. K.; McCarthy, D. G. J. Chem.
Soc., Perkin Trans. 1 1998, 1015. Baldwin, J. E.; O’Neil, I. A.
Synlett 1990, 603, and references cited therein.
(3) Kitano, Y.; Chiba, K.; Tada, M. Tetrahedron Lett. 1998, 38,
1911.
(4) Bishop, R. In Comprehensive Organic Synthesis, Heteroatom
Manipulation; Winterfeldt, E., Ed.; Pergamon Press: Oxford,
1991; Vol. 6. Chapter 1.9.
(5) Corey, E. J.; Magriotis, P. A. J Am. Chem. Soc. 1987, 109,
287. Sasaki, T.; Nakanishi, A.; Ohno, M. J. Org. Chem. 1981,
46, 5445.
(7) Tertiary isocyanides are rearranged to the corresponding nitri-
les in the presence of tin tetrachloride (SnCl4). Reetz, M. T.;
Chatziiosifidis, I.; Künzer, H.; Müller-Starke, H. Tetrahedron
1983, 39, 961.
Synlett 1999, No. 3, 288–290 ISSN 0936-5214 © Thieme Stuttgart · New York