Palladium-indium mediated Barbier-type allylation of aldehydes with allenes

Article abstract of DOI:10.1039/b001457p

A new allylation reaction of carbonyl compounds using allenes is described; homoallylic alcohols were obtained in moderate to good yields from aryl iodides, allenes and carbonyl compounds and an excellent diastereoselection was exhibited when 2-hydroxycyclohexanone was employed.

Full text of DOI:10.1039/b001457p

Palladium–indium mediated Barbier-type allylation of aldehydes with allenes
Usman Anwar, Ronald Grigg,* Marcello Rasparini, Vladimir Savic and Visuvanathar Sridharan
Molecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry, Leeds University,
Leeds, UK LS2 9JT. E-mail: R.Grigg@chem.leeds.ac.uk
Received (in Cambridge, UK) 22nd February 2000, Accepted 6th March 2000
Published on the Web 27th March 2000
A new allylation reaction of carbonyl compounds using
allenes is described; homoallylic alcohols were obtained in
moderate to good yields from aryl iodides, allenes and
carbonyl compounds and an excellent diastereoselection was
exhibited when 2-hydroxycyclohexanone was employed.
the stereochemical outcome (Table 4) of the reaction of
iodobenzene and allene following the protocol described
above.
Table 1
In the last decade indium has emerged as the metal of choice to
mediate the allylation of carbonyl compounds because of its
environmentally benign properties allied with a high degree of
chemo-, regio- and diastereo-selectivity especially in aqueous
media.1 Furthermore the reaction requires no activation of the
carbonyl group and produces few by-products.
The indium mediated allylation reaction is an aldol-type
reaction where the nucleophile is an allylindium( ) species
I
usually generated from an allylic halide and indium(0).2
Here, we describe the formation of allylindium species by
transmetallation3 of p-allylpalladium(II) complexes generated
from aryl iodides and allenes. The resultant allylindium species
subsequently add to the carbonyl compound affording homo-
allylic alcohols (Scheme 1).
There are four synthetic variants of this Pd–In mediated
reaction depending on whether the Pd or the In step are intra- or
inter-molecular.
A first set of examples (class 1 processes) where both the Pd
and the In steps are intermolecular is presented in Table 1. Aryl/
heteroaryl iodides (1.5 mmol) react (DMF, 80 °C, 18 h, Schlenk
tube) with allene (1.0 bar) and aldehydes (1.0 mmol) in the
presence of indium (100 mesh powder, 1.5 mmol), Pd(OAc)2
(0.1 mmol) and tris(2-furyl)phosphine (0.2 mmol). The use of
triphenylphosphine resulted in an incomplete conversion of the
starting materials.
Encouraged by these results we employed a substituted
allene, n-octylallene4 (1.5 mmol) in the process. A reaction time
of 24 h was necessary to achieve complete conversion of the
aldehyde. In both the cases so far explored (Table 2) only one
geometric isomer was produced and their structures were
assigned from NOE data.
A class 2 process (intermolecular p-allyl formation—
intramolecular allylation5) was explored next. The increased
rigidity of the transition state of the aldol-like addition (sub-
optimal approach trajectory) may explain the lower yield
observed in entry 1. The six membered product was obtained in
a better yield (Table 3). The catalytic system comprised
Pd(PPh3)4 (10 mol%) (entry 1) or Pd2(dba)3 (5.0 mol%) and
tris(2-furyl)phosphine (20.0 mol%) (entry 2).
A class 3 process requires an aryl/heteroaryl iodide bearing
an allenic side chain. The Pd catalysed step is then intra-
molecular and is combined with an intermolecular In mediated
reaction. Allenyl (2-iodobenzyl) ether7 (1.0 mmol) was reacted
(DMF, 90 °C, 14 h) with aldehydes (1.05 mmol) in the presence
of Pd(PPh3)4 (0.10 mmol) (Scheme 2).
We have briefly studied the effect of chelating groups a to the
carbonyl group, such as nitrogen,8 hydroxyl9 and alkoxy,10 on
Scheme 1
DOI: 10.1039/b001457p
Chem. Commun., 2000, 645–646
This journal is © The Royal Society of Chemistry 2000
645

Table 2
Table 4
Table 3
Further work on these and on the related class 4 processes
(intramolecular p-allyl formation—intramolecular aldol-like
condensation) are in hand.
We thank the EPSRC and Leeds University for support.
The preliminary results (Table 4) show that the palladium–
Notes and references
indium mediated allylation of carbonyl compounds using
allenes provides easy access to homoallylic alcohols and that
chelation clearly controls its diastereoselectivity.
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4 S. Searles, L. Yushun, B. Nassim, M. T. Robert-Lopes, P. Tran and P.
Crabbè, J. Chem Soc., Perkin Trans. 1, 1984, 747.
5 To our knowledge this is the only example of In mediated intra-
molecular Barbier reaction: L. A. Paquette and J. L. Mendez-Andino,
J. Org. Chem., 1998, 63, 9061.
6 S. E. Gibson, N. Guillo, R. J. Middleton, A. Thuilliez and M. J. Tozer,
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Schomer, J. Org. Chem., 1999, 62, 4293.
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1917.
Scheme 2
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Chem. Commun., 2000, 645–646