Palladium-catalyzed intramolecular selenocarbamoylation of alkynes with carbamoselenoates: Formation of α-alkylidene-β-lactam framework

Article abstract of DOI:10.1021/ja052175k

Pd-catalyzed intramolecular selenocarbamoylation of alkynes leading to α-alkylidene-β-lactams was developed. This reaction can be applied to thiocarbamoylation and to the synthesis of δ- and ε-lactams and a cyclobutanone. Copyright

Full text of DOI:10.1021/ja052175k

Published on Web 06/15/2005
Palladium-Catalyzed Intramolecular Selenocarbamoylation of Alkynes with
Carbamoselenoates: Formation of r-Alkylidene-â-lactam Framework
Masashi Toyofuku,† Shin-ich Fujiwara,*,‡ Tsutomu Shin-ike,‡ Hitoshi Kuniyasu,† and
Nobuaki Kambe*,†
Department of Molecular Chemistry, Graduate School of Engineering, Osaka UniVersity, Suita, Osaka 565-0871,
Japan, and Department of Chemistry, Osaka Dental UniVersity, Hirakata, Osaka 573-1121, Japan
Received April 5, 2005; E-mail: fujiwara@cc.osaka-dent.ac.jp; kambe@chem.eng.osaka-u.ac.jp
Transition-metal-catalyzed addition of organochalcogen com-
pounds to alkynes with cleavage of bonds such as RS-SR′, RS-
BR′2, RSe-P(O)(OR′)2, etc. is a promising synthetic route to
functionalized alkenes. This chemistry has been studied extensively.1-3
Although the more attractive and challenging theme of interest
first step in this process is oxidative addition of the Se-CON bond
would be the insertion of C-C unsaturated units across chalcogen-
of 3 to Pd(0) giving 5 via 4 or 4′. Subsequent insertion of alkyne
carbon bonds that can construct new chalcogen-carbon and
into the Se-Pd bond affords the five-membered palladacyle 6.13
carbon-carbon bonds in one step, this transformation remains much
Reductive elimination leads to the cyclized products 7 and
regenerates the Pd(0) species.
When Se-phenyl N-methyl-N-prop-2-ynyl carbamoselenoate 3a
(0.4 mmol) was treated with Pd(PPh3)4 (5 mol %) in toluene (0.5
less explored.4-8 To the best of our knowledge, the first example
of this type of reactions was found by Ando and co-workers, who
reported Pd-catalyzed insertion of dimethyl acetylenedicarboxylate
(DMAD) into the S-C bond of allene episulfides to give cyclic
mL) at reflux, the corresponding R-alkylidene-â-lactam 7a was
formed in 74% yield within 1 h with excellent regio- and
stereoselectivity (Table 1, run 1).14 The results obtained using
several carbamoselenoates are also summarized in Table 1. This
reaction proceeds efficiently even when the amount of Pd(PPh3)4
is reduced to 1 mol % (run 2). Bulkier alkyl substituents on nitrogen,
e.g., butyl or benzyl, did not affect the reaction (runs 3 and 4). In
contrast to the fact that internal alkynes are sluggish in thioesteri-
fication reactions,6a carbamoselenoates 3d and 3e having an internal
alkyne moiety readily undergo intramolecular selenocarbamoylation
to afford the desired lactams 7d and 7e in high yields (runs 5 and
6, respectively). The structures of products were confirmed by either
NOE experiments or X-ray analysis, and the E/Z ratios were
products in low yields.4 Meng and co-workers reported Cu-catalyzed
seleno- and telluroacylation of alkynes with selenol and tellurol
esters (ArSe-C(O)R and ArTe-C(O)R), respectively, via nucleo-
philic addition of in situ generated copper acetylides to chalcogeno
esters.5 Tanaka and co-workers revealed Pd-catalyzed thioesterifi-
cation of alkynes through oxidative addition of thiocarbonate (PhS-
C(O)OMe) to Pd in the presence of a bulky trialkyl phosphine.6
We also have shown that thiol esters (ArS-C(O)R)7 and selenol
esters8 undergo decarbonylative addition to alkynes in the presence
of Pt catalysts. These transformations produce vinyl chalcogenides;
this work also demonstrates that selenoacylation proceeds com-
petitively in the case of some selenol esters.
Here we disclose that Pd catalyzes intramolecular selenocar-
bamoylation of alkynes to give R-alkylidenelactams.
1
determined by H NMR.
This reaction was also applied successfully to the construction
of the R-alkylidene-δ-lactam and -ꢀ-lactam frameworks.15 When
carbamoselenoates 8 having a 4-pentynyl or a 5-hexynyl group on
the N atom were treated under similar conditions, six- and seven-
membered lactams 9 were obtained in high yields (eq 3).
Since it has been reported that the reaction of a carbamothioate,
PhS-C(O)NMe2, with 1-pentyne does not proceed efficiently in
the presence of Pd(PPh3)4,9a we first examined the possibility of
selenocarbamoylation by reacting a carbamoselenoate, PhSe-C(O)-
NMe2 (1), with an alkyne. When toluene (0.3 mL) containing 1
(0.5 mmol), 1-octyne (3 equiv), and Pd(PPh3)4 (5 mol %) was heated
at reflux for 14 h, the selenocarbamoylation product, â-seleno
acrylamide 2, was obtained in 40% yield with high regio- and
stereoselectivity (eq 2).
This finding led us to examine the construction of the R-alky-
lidene-â-lactam framework, a core structure of several antibiotics
and various synthetic intermediates, by applying this reaction using
an intramolecular cyclization strategy.10-12 Our working hypothesis
for R-alkylidene-â-lactam synthesis is shown in Scheme 1. The
Very interestingly, when carbamoselenoate 10 having both
2-propynyl and 4-pentynyl groups on the N atom was employed,
the more strained four-membered lactam 11a was obtained pre-
dominantly (50%) over the more thermodynamically stable six-
membered lactam 11b (10%) (eq 4). This result indicates that
formation of the four-membered ring is kinetically favored.
† Osaka University.
‡ Osaka Dental University.
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J. AM. CHEM. SOC. 2005, 127, 9706-9707
10.1021/ja052175k CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. A Proposed Pathway for R-Alkylidene-â-lactam 7
Acknowledgment. The authors gratefully acknowledge the
support for this work by a Grant-in-aid for Scientific Research,
Ministry of Education, Culture, Sports, Science and Technology
of Japan.
Supporting Information Available: Experimental details and
characterization data of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
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3
R
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′
of 7
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3a
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Me
Me
nBu
Bn
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59% (84%)
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11/89
a Conditions: 3 (0.4 mmol), Pd(PPh3)4 (5 mol %), toluene (2 mL), reflux,
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In summary, Pd(PPh3)4 catalyzes intermolecular selenocarbam-
oylation of 1-octyne with carbomoselenoate 1 to afford a â-seleno
acrylamide in a moderate yield. This catalytic system can success-
fully be applied to intramolecular systems giving rise to the
conjugated lactams and a cyclobutanone having seleno and thio
substituted exo methylene groups at the R-carbon. A significant
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