Phosphazene bases and the anionic oxy-Cope rearrangement

Article abstract of DOI:10.1016/S0040-4039(99)02123-1

Compounds containing a 1,5-hexadien-3-ol system undergo anionic oxy-Cope rearrangement when treated with the phosphazene super-base, P₄-t-Bu. The [3,3] sigmatropic rearrangement occurs in hexane as well as in THF. The weaker phosphazene base, P

Full text of DOI:10.1016/S0040-4039(99)02123-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 747–749
Phosphazene bases and the anionic oxy-Cope rearrangement
∗
Hassan T. Mamdani and Richard C. Hartley
Department of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK
Received 18 October 1999; accepted 10 November 1999
Abstract
Compounds containing a 1,5-hexadien-3-ol system undergo anionic oxy-Cope rearrangement when treated with
the phosphazene super-base, P4-t-Bu. The [3,3] sigmatropic rearrangement occurs in hexane as well as in THF. The
weaker phosphazene base, P2-Et fails to induce rearrangement. This is the first example of the use of a metal-free
base to induce anionic oxy-Cope rearrangement. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: phosphazenes; rearrangements; alcohols; ketones.
1
The anionic oxy-Cope (AOC) rearrangement is the [3,3] sigmatropic rearrangement of an alkoxide
1
0
1
generated from a 1,5-dien-3-ol 2 to give an enolate 3 (Scheme 1). The alkoxide 1 rearranges 10
1
7
to 10 times faster than alcohol 2 due to weakening of the C(3)–C(4) bond in the ground state by n-
donation from the oxyanion. The n-donation is greatest and the rearrangement fastest when the oxyanion
is completely naked; consequently, potassium salts rearrange faster than sodium salts, which rearrange
2
faster than lithium salts. Crown ethers and polar aprotic solvents are often used to reduce association
between the oxyanion and the cation. However, metal-free bases have never been used for this reaction.
Scheme 1.
3
The phosphazene super-bases 4 and 5, developed by Reinhard Schwesinger, are extremely strong,
uncharged, metal-free bases (Fig. 1). We here report that P -t-Bu 4 completely deprotonates alcohol 2 to
4
3
give alkoxide 1 and a huge ‘soft’ cation, which is known to have its positive charge delocalised over a
3
volume of ca. 500 Å , and that this alkoxide is sufficiently naked to undergo AOC rearrangement.
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02123-1
tetl 16051

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Fig. 1.
In our optimised procedure (see below), a THF solution of alcohol 6, 7, or 8 was added to P -t-Bu 4
4
in THF–hexane at low temperature (Scheme 2). Any precipitates dissolved during the slow warming to
room temperature. Rearrangement occurred at room temperature and quenching with phosphate buffer
1
gave the ketone 9, 10 or 11 as essentially the only product visible in the H NMR spectrum of the crude
mixture. When the alcohol 6, 7, or 8 was added to a solution of the base 4 at room temperature, the
reaction was not clean. Furthermore, if the 1 M solution of P -t-Bu 4 in hexane was added by syringe to
4
the cooled alcohol, the base crystallised in the needle blocking it. Interestingly, alcohol 6 also rearranged
in pure hexane (0.5 M), and side-products could be minimised by adding the alcohol to P -t-Bu 4 at 0°C
4
(the base precipitates at lower temperature).
Scheme 2.
Alcohols 6–8 were recovered unchanged when phosphazene P -Et 5 was used instead of P -t-Bu 4.
2
4
Potassium hydride, which is generally supplied as a dispersion in mineral oil and is insoluble in organic
solvents, is the base most commonly used for AOC rearrangements. P -t-Bu 4 is soluble in organic
4
solvents and is available (Fluka) as an easy to handle 1 M solution in hexane; consequently, we expect
that phosphazene base 4 will be widely used for AOC rearrangements.
Standard procedure: Dry THF (0.8 ml) was added to a stirred solution of phosphazene base P -t-Bu 4
4
(700 µL of a 1 M solution in hexane ex Fluka, 700 µmol, 1.07 equiv.) under argon, and the solution was
cooled to −78°C. A solution of alcohol 7 (164 mg, 655 µmol, 1 equiv.) in dry THF (1 ml) was added
dropwise over 10 min and any residue in the syringe was washed out with more dry THF (1 ml). After
3
0 min, the pale yellow solution was allowed to warm to 0°C over 2 h 40 min. The mixture was stirred
for 17 h at room temperature and then injected into the vortex of rapidly stirring pH 7 phosphate buffer
5 ml). The mixture was extracted into diethyl ether (4×5 ml) and the combined extracts were washed
with brine (5 ml), dried (Na SO ) and concentrated under vacuum. The residue was chromatographed
(
2
4
4
on silica [20 g, dichloromethane–hexane (0.5:1 then 1:1)] to give the pure ketone 10 (95 mg, 58%) as
crystals.

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Acknowledgements
We thank SmithKline Beecham for funding and Professor Dieter Seebach (Laboratorium für Organi-
sche Chemie, Eidgenössische Technische Hochschule, 8092 Zürich, Switzerland) for helpful suggestions.
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