Tetrahedron Letters 50 (2009) 1097–1099
Tetrahedron Letters
Acyloxyetherifications mediated by lead tetracarboxylates
*
Ian F. Cottrell, Mark G. Moloney , Kirsty Smithies
The Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom
Department of Process Research, Merck Sharp and Dohme Research Laboratories, Hertford Rd, Hoddesdon, Herts EN11 9BU, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Lead(IV) tetracarboxylates are capable of reacting with unsaturated alcohols to give the products of cyclic
acyloxyetherification, usually as a mixture of tetrahydro-2H-pyranyl and tetrahydrofuranyl compounds.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 21 August 2008
Revised 24 November 2008
Accepted 9 December 2008
Available online 24 December 2008
Ligand coupling processes1 mediated by lead(IV) have recently
been demonstrated to enable synthetically useful carbon-carbon
bond forming reactions,2–7 and cyclisation reactions are beginning
to emerge which are driven by this reagent.8,9 We have reported
that the reaction of lead(IV) tetracarboxylates with carboxylic
acids containing unsaturated side chains gives acyloxylactone
products in a diastereoselective process, in which one of the car-
boxylate ligands becomes incorporated into the lactone product;10
the reaction can be extended to lead(IV) tetrazolates to give the
analogous outcome. Mechanistically, it is thought that these cycli-
4-Penten-1-ols with alkyl substituents at positions 2–4 were re-
acted with lead(IV) tetra(2-thiophenecarboxylate), readily pre-
pared by metathesis of lead tetraacetate with 4 equiv of
2-thiophenecarboxylic acid, in
a,a,a-trifluorotoluene at 90 °C
under argon.10 The reactions were monitored visually and once
the colour had changed from bright yellow to white, the reactions
were stopped, and the solvent was removed. Purification by
column chromatography gave the tetrahydropyrans 2a–e and
tetrahydrofurans 3a–e, as shown in Scheme 1 and Table 1. The best
yield was obtained for 4-methylpent-4-en-1-ol 1d which gave pre-
dominantly the tetrahydropyranyl product 2d; all other substrates
gave a mixture of tetrahydropyranyl and tetrahydrofuranyl prod-
ucts 2a–c,e and 3a–c,e, in which the former generally predomi-
nated, in moderate combined yields. The ring assignment was
made using a combination of techniques: HMBC experiments con-
firmed the pyran ring as a result of three-bond coupling between
the carbonyl carbon and H3, C6 and H2 and of C2 with H6; for
the tetrahydrofuran-type products, correlation of the carbonyl car-
bon to both methylene hydrogens and of C2 to H5 confirmed the
proposed structure (Fig. 1). Of interest is that the presence of a
double bond substituent did not hinder the closure of 4-hexenol,
leading to ethers 2e and 3e, and that products arising from 5-exo
and 6-endo cyclisation were obtained; this is in marked contrast
to plumbolactonisations31 using lead(IV) tetra(2-thiophenecarb-
oxylate), for which double bond substituents are not tolerated,
and only 5-exo cyclisations are observed. No products arising from
direct 1,2-dicarboxylation of the double bond were isolated.
The stereochemistry of the tetrahydropyran products was
established by n.O.e. analysis (Fig. 2); ether 2b was found to be
the cis-diastereomer, but 2c and 2e were found to be the trans-dia-
stereomers. The stereochemistry of the minor tetrahydrofuran
derivatives was not examined. These cyclisations appear to be
analogous to palladium chloride and mercury(II) trifluoroacetate-
mediated processes, and the observed regiochemistry is in agree-
ment with electrophile-induced cyclisations to tetrahydropyrans
and tetrahydrofurans as reported by Cardillo and Orena,32 for
which the formation of 6-membered rings proceeds under high
sations occur by initial carboxylate metathesis followed by p-com-
plexation prior to lactone formation driven by reductive
elimination from lead(IV).11 It was of interest to establish whether
this process might be extendable to other substrates, and obvious
candidates were unsaturated alcohols. Electrophilic halogen-med-
iated etherifications are known,12 and similar processes with thal-
lium(III),13,14 mercury(II)15 and palladium(II)16,17 have been
reported. The reaction of lead(IV) tetraacetate with 3-butenol has
been thoroughly investigated by Moon18–23 who identified several
fragmentation pathways that proceed through either radical or cat-
ionic intermediates, initiated by the formation of an alkoxytriace-
tate lead(IV) intermediate.24–26 However, when the chain length
is long enough (e.g., with 4-pentenol as the substrate), tetrahydrof-
uranyl and tetrahydropyranyl products are observed.23,27 Mihailo-
vic took this further and demonstrated for a range of unsaturated
alcohols that products of cyclisation could be readily formed,28
and similar cycloetherifications were identified in bicyclic tem-
plates.29 However, it was found that the distribution of products
depended strongly on the nature of the solvent and on the applica-
tion of thermal or photochemical conditions. Of interest was an
examination of this process with lead tetrathiophene carboxylate,
which has been shown to be an effective reagent for alcohol oxida-
tions30 and plumbolactonisations.10
* Corresponding author. Tel.: +44 1865 275656.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.071