Synthesis of heterocycles via sequential Pd/Ru-catalysed allene insertion-nucleophile incorporation-olefin metathesis

Article abstract of DOI:10.1016/S0040-4039(01)01810-X

A novel sequential palladium/ruthenium-catalysed three-component process is described involving allenylation of aryl/heteroaryl iodides to generate (π-allyl) palladium species which are intercepted by nitrogen nucleophiles to afford 1,6- and 1,7-dienes. S

Full text of DOI:10.1016/S0040-4039(01)01810-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8673–8675
Synthesis of heterocycles via sequential Pd/Ru-catalysed allene
insertion–nucleophile incorporation–olefin metathesis
H. Ali Dondas,a Genevieve Balme,b Blandine Clique,a Ronald Grigg,a,* Anne Hodgeson,c
James Morrisa and Visuvanathar Sridharana
aMolecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry, Leeds University,
Leeds LS2 9JT, UK
bLaboratoire de Chimie Organique, University Lyon, Villeurbanne, France
cProcess R and D, GlaxoSmithKline, Dartford DA1 5HA, UK
Received 23 July 2001; accepted 21 September 2001
Abstract—A novel sequential palladium/ruthenium-catalysed three-component process is described involving allenylation of
aryl/heteroaryl iodides to generate (p-allyl) palladium species which are intercepted by nitrogen nucleophiles to afford 1,6- and
1,7-dienes. Subsequent ring-closing metathesis affords N-heterocycles in good yield. © 2001 Elsevier Science Ltd. All rights
reserved.
In recent years allenes have become useful building
blocks in palladium-catalysed processes.1 We have
developed a wide range of powerful and selective Pd-
catalysed molecular queuing processes2 whose potential
would be considerably enhanced by interfacing with
synthetically valuable catalytic processes mediated by
other transition metals. We have recently developed
such bimetallic cascades which include the electrochem-
ically driven Pd/Cr Nozaki–Hiyama–Kishi reaction,3
Pd/In Barbier type allylation,4,5 Pd/Ru Heck/metathe-
sis,6,7 Rh/Pd cycloaddition–cyclisation–anion capture
processes8 and Rh/Pd cycloaddition–Friedel Craft
reactions.9
tolerance and accommodate a higher density of sub-
stituents on the double bond formed in ring-closing
metathesis.
Mes
N
N
Mes
Ph
Cl
Cl
Ru
P(Cy)3
1
Our ongoing interest in designing palladium-catalysed
allenylation processes, in combination with core reac-
tions, has led to the three-component process (Scheme
1) involving Pd/Ru catalysis reported herein.
The use of ring-closing olefin metathesis in organic
synthesis has seen explosive growth over the past
decade. This is partly due to the discovery of second
generation, air stable, Ru catalysts such as 110–12 which
exhibit higher thermal stability, wider functional group
The strategy (Scheme 1) involves reaction of an aryl/
vinyl halide 2 with allene and a nucleophile 3 in the
Ar
(1)
Pd(0)
Y
Ar
Ar
+
+
Y
X
HY
4
2
3
5
Scheme 1.
* Corresponding author. Tel.: +44-113-233-6501; fax: +44-113-233-6501; e-mail: r.grigg@chem.leeds.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01810-X

8674
H. A. Dondas et al. / Tetrahedron Letters 42 (2001) 8673–8675
Table 1. Three-component allenylation–amination cascadesa,b
Table 2. Ring-closing metathesis processa
presence of Pd(0) to afford 1, v-dienes 4, capable of
undergoing a ruthenium-catalysed ring-closing metathe-
sis to give hetero- or carbo-cycles 5.

H. A. Dondas et al. / Tetrahedron Letters 42 (2001) 8673–8675
8675
Acknowledgements
We thank Leeds University, GlaxoSmithKline, the EU
and EPSRC for support.
HN
SO2Ph
CO2Me
HN
SO2Ph
References
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6
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In conclusion, we have demonstrated a novel sequential
palladium-catalysed allene insertion/nucleophile incor-
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metathesis for the synthesis of heterocycles. Further
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other nucleophiles into these processes.
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