New synthesis of α-acyl imines by radical-mediated group-transfer imidoylation of acyl tellurides with isonitriles

Article abstract of DOI:10.1016/S0040-4039(00)01287-9

Acyl radicals generated from either acyl tellurides or alkyl tellurides and carbon monoxide react with isonitriles to give α-acyl-substituted imidoyl tellurides in good to excellent yield. Hydrolysis of the product under oxidative conditions provides the corresponding α-acyl amides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01287-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7517–7520
New synthesis of a-acyl imines by radical-mediated
group-transfer imidoylation of acyl tellurides with isonitriles
Shigeru Yamago,* Hiroshi Miyazoe, Takashi Sawazaki, Ryuta Goto and
Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, Japan
Received 27 June 2000; revised 21 July 2000; accepted 24 July 2000
Abstract
Acyl radicals generated from either acyl tellurides or alkyl tellurides and carbon monoxide react with
isonitriles to give a-acyl-substituted imidoyl tellurides in good to excellent yield. Hydrolysis of the product
under oxidative conditions provides the corresponding a-acyl amides. © 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: radicals and radical reactions; carbonylation; isocyanides; imidic acids and derivatives.
The synthesis of a-acyl carbonyl compounds, e.g. a-acyl ketones, esters and amides, has
attracted considerable interest because these compounds not only serve as versatile building
blocks in organic synthesis, but also exhibit broad biological activity.1 Although direct introduc-
tion of C1 carbonyl synthons to organic molecules is an attractive approach, only a few
examples have been reported so far in electrophilic reactions of isonitriles2 or metal-mediated
double carbonylations and imidoylations.3,4 The attractive possibility of using a radical-medi-
ated process5 was problematic as carbonylation of acyl radicals by carbon monoxide (CO) does
not proceed even under extremely high CO pressure.6 Until Ryu and Kim found recently that
sulfonyl oximes could serve as excellent C1 acceptors for acyl radicals,7 the synthetic utility of
such radical methodology was unknown. We have already shown that isonitriles are better C1
carbonyl synthons than carbon monoxide in reacting with stabilized radicals, such as a-alkoxy
radicals.8 These results prompted us to investigate the reaction of acyl radicals with isonitriles.
We chose acyl tellurides as the acyl radical precursors, because Crich in his pioneering work had
shown that they are excellent acyl radical precursors,9,10 and found that isonitriles are excellent
acceptors for acyl radicals. We report here a new synthesis of a-acyl imines by thermal radical
reaction of the acyl tellurides 1 and isonitriles to give the a-acyl-substituted imidoyl tellurides 4,
* Corresponding authors. Fax: +81-75-753-5911; e-mail: yamago@sbchem.kyoto-u.ac.jp
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01287-9

7518
which are hydrolyzed to the a-acyl amides in good yield (Eq. (1)). We also observed the trapping
of isonitriles with in situ generated acyl radicals from alkyl radicals and CO. These results
clearly show that isonitriles serve as efficient C1 units for radical-mediated 1,2-dicarbonyl
syntheses.
(1)
The feasibility of the present imidoylation reaction of acyl radicals was first examined using
p-methylphenyl 3-methyltellurobutyrate (1a); the reaction took place smoothly under ambient
thermal conditions. Thus, a 0.6 M C6D6 solution of 1a and 2,6-dimethylphenylisonitrile (2.0
equiv.) was heated at 100°C for 6 h, and the imidoylated product 4a was formed in 87% yield
(Table 1, entry 1). While the decarbonylation of acyl radicals potentially competes with the
coupling reaction, no such products were detected. Although photo-irradiation has been
reported to accelerate the radical generation from acyl tellurides, irradiation using simple UV
lamps (6 W×6) or a high pressure Hg lamp (250 W) resulted in lower yield (74 and 41% yield,
respectively). Since the consumption of 1a was accelerated by UV irradiation, the observed
result was presumably due to the instability of the product under UV irradiation. The reaction
could also be carried out in various solvents, e.g. hexane, EtCN, EtOH and H2O, and the
desired product was obtained in good to excellent yield in all cases. The observed insensitivity
of the reaction to solvent is consistent with a radical chain mechanism, which involves the
generation of the acyl radical 2 from 1, the reaction of 2 with the isonitrile to form 3 and the
subsequent group-transfer reaction of 3 with 1 (Eq. (1)). While the reaction in H2O gave the best
results, we chose the aromatic solvent for the reaction because of the high solubility of the
substrates.
The synthetic scope of the reaction has been examined with various acyl tellurides, and the
results are summarized in Table 1. Acyl tellurides bearing alkyl, aryl, and alkenyl carbon
residues are found to react with 2,6-dimethylphenylisonitrile to give the desired products in good
to excellent yields under moderate thermal conditions (entries 1–10). In the reaction of acyl
tellurides bearing secondary and tertiary alkyl carbon residues, decarbonylation of CO from the
acyl radicals was found to be a serious side reaction (entries 4 and 5). However, we found that
the decarbonylation reaction could be avoided by carrying out the reaction under CO pressure
(50 atm), because the application of high CO pressure retards the decarbonylation reaction.5 It
is noteworthy that decarbonylation did not take place in the cyclopropyl-substituted acyl
telluride (entry 3). This is probably because cyclopropyl radicals, which possess sp3 radical
character, are less stable than the conformationally unrestrained secondary alkyl radicals,11 since
the rate of the decarbonylation becomes faster when the decarbonylated radical becomes more
stable.12 The acyl tellurides bearing olefin and acetylene moieties also afforded the simple
imidoylated products without undergoing intramolecular radical cyclization from the imidoyl
radical intermediates (entries 2 and 6).13 The decarbonylation reaction of the aryl- and
alkenyl-substituted acyl tellurides did not take place at all, and the desired coupling reaction
proceeded in good yield (entries 7–10).
We next examined the imidoylation of acyl radicals generated in situ from alkyl radicals and
CO. Thus, t-butyl p-tolyl telluride (5) and 2,6-dimethylphenylisonitrile in C6H6 were heated at
100°C under 50 atm of CO pressure in the presence of the radical initiator V-40 [1,1%-azobis(cy

7519
Table 1
Imidoylation reaction of acyl telluride with 2,6-dimethylphenylisonitrile
clohexane-1-carbonitrile)]. The desired product formed in 19% yield (26% yield based on
conversion) together with the imidoylated product of t-butyl tolyl telluride in 36% yield (Eq.
(2)).

7520
(2)
Since various synthetic transformations of the reactive CꢀTe bond are known,14 the products
4 would be useful precursors for a variety of 1,2-dicarbonyl compounds and their equivalents.
For example, electrochemical oxidation of 4a in the presence of water afforded the corresponding
a-acyl amide in quantitative yield (Eq. (3)). Further synthetic exploration is currently underway.
(3)
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