Synthesis of quinol-4-ones and chroman-4-ones via a palladium-catalysed cascade carbonylation-allene insertion

Article abstract of DOI:10.1016/S0040-4039(00)01176-X

Palladium(0)-catalysed termolecular queuing processes involving oxidative addition to aryl iodides followed by low pressure carbonylation, allene insertion and capture of the resulting π-allyl palladium(II) species by an internal O- or N-nucleophile occur in good yields. One-pot 3-methylene chromanone/quinolone synthesis-Michael addition-stereoselective reduction are also reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01176-X

Tetrahedron Letters 41 (2000) 7125±7128
Synthesis of quinol-4-ones and chroman-4-ones via a
palladium-catalysed cascade carbonylation±allene insertion
a,
b
a
a
Ronald Grigg, * Angela Liu, Duncan Shaw, Selvaratnam Suganthan,
a
a
Diane E. Woodall and Gnanamoly Yoganathan
aMolecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry,
The University of Leeds, Leeds LS2 9JT, UK
b
Chemistry Department, Pharmacia Upjohn, S-751 82 Uppsala, Sweden
Received 22 June 2000; accepted 12 July 2000
Abstract
Palladium(0)-catalysed termolecular queuing processes involving oxidative addition to aryl iodides fol-
lowed by low pressure carbonylation, allene insertion and capture of the resulting p-allyl palladium(II)
species by an internal O- or N-nucleophile occur in good yields. One-pot 3-methylene chromanone/quinolone
synthesis±Michael addition±stereoselective reduction are also reported. # 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: palladium catalysis; cascade; carbonylation; allenes; 3-methylene-4-quinolones/chromanones; amino-
alcohols.
Our recent development of a wide range of palladium-catalysed processes that allow
2
1
incorporation of both allenes and carbon monoxide in polycomponent queuing cascades o€ers
a general catalytic method for accessing quinolone and chromanone ring systems which display
3
biological activity over a wide range of areas from antibacterials such as cipro¯oxacin to
4
antifungals, e.g. 2a, and neurotrophic factors essential for survival and functioning of nerve
5
cells such as recently reported neuchromenin. As part of this programme we now report our
results on three-component aryl iodide±carbon monoxide±allene (3+1+2)-cycloaddition cascade
processes.
6
In contrast to Alper's recently reported cascades of a similar type which were carried out at
high pressures (20 atm) of carbon monoxide, we focused our studies on employing carbon
monoxide at atmospheric pressure. A study of (3+1+2)-cycloaddition reactions of o-iodophenols
and N-tosyl-o-iodoanilines was undertaken using allene (1 atm) and CO (1 atm) in a Schlenk
7
ꢀ
tube. The reactions of 1a and 1b occurred at 45 C in toluene in the presence of 5 mol%
*
Corresponding author. E-mail: r.grigg@chem.leeds.ac.uk
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01176-X

7
126
Scheme 1.
Pd(PPh ) and K CO (2 equiv.) over 16 and 35 h, respectively, to a€ord 2a (70%) and 2b (55%)
3
4
2
3
(Scheme 1).
These reactions are examples of termolecular queuing processes in which four functional
moieties, namely the aryl iodide, the nucleophile (OH or NHTs), CO and the allene, are queuing
to react at the metal centre. In the ®rst step of the catalytic cycle, the palladium(0) catalyst
undergoes oxidative addition to the aryl iodide bond followed by coordination and insertion of
CO. The acylpalladium(II) intermediate adds to the allene at the central carbon atom to furnish a
p-allylpalladium(II) species which undergoes nucleophilic attack by the internal nucleophile to
give the enone product.
Scheme 3.
The (3+1+2)-cycloaddition tolerates substituents on both the allene and the aryl iodide
allowing access to an array of heterocycles with s-cis enone moieties (Scheme 2).
The creation of the conformationally locked s-cis enone system in the quinolones and
chromanones o€ers opportunities for substantial further synthetic elaboration. A study of one-pot
chromanone synthesis±Michael addition was undertaken using o-iodophenol, nucleophile (1.2
equiv.), dimethylallene (3 equiv.) and CO (1 atm) in a Schlenk tube. The reactions occurred at

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127
ꢀ
5 C in toluene in the presence of Pd(PPh ) (5 mol%) and K CO (2 equiv.) over 48±72 h to
3 4 2 3
4
a€ord the Michael adducts. One-pot quinolone synthesis±Michael addition was performed in a
slightly di€erent manner. (3+1+2)-Cycloaddition reaction of N-tosyl-o-iodoaniline, CO (1 atm)
and allene (1 atm) was allowed to proceed for 48 h and CO was released before the addition of
the nucleophile (1.2 equiv.). The subsequent Michael addition was completed after a further 24 h
(
1
Scheme 3). Both aliphatic and heteroaromatic N-nucleophiles were e€ective and in the case of
,2,4-triazole only the 1-substituted triazole was observed. The Michael adducts proved sensitive
8
ꢀ
to retro-Michael addition and so they were reduced by LiAlH in ether at ^78 C for 1 h, without
4
prior isolation, to give the corresponding g-aminoalcohols (Table 1) as single stereoisomers.
Scheme 2.

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128
Table 1
One-pot chromanone/quinolone synthesis±Michael addition±reduction
The results reported herein demonstrate ecient termolecular queuing cascades employing CO
1 atm). The one-pot formation of g-aminoalcohols involves the formation of four bonds, two
stereocentres and one ring. Further synthetic opportunities o€ered by the 3-methylene-4-quinolone/
(
chromanone systems are elaborated in the accompanying communication.9
Acknowledgements
We thank the EPSRC, Leeds University and Pharmacia Upjohn for support.
References
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