Rearrangement of p-methoxybenzyl-protected allylic alcohols to aldehydes
Johan Wennerberg, Lars Eklund, Magnus Polla and Torbjo¨rn Frejd*
Organic Chemistry 1, Department of Chemistry, Lund University, S-22100, Lund, Sweden
Allyl p-methoxybenzyl ethers undergo an acid-catalysed
1,4-rearrangement to give p-methoxyphenylbutyraldehyde
derivatives, which can be ring-closed to give substituted
naphthalene derivatives.
We have performed the reaction with four different PMB-
protected allylic alcohols. The reaction is very simple to carry
out, and easy access to allylic ethers together with the utility of
aldehydes of type 2 should make this rearrangement quite useful
in organic synthesis.† As a simple demonstration of this we
cyclized one of the products, 2c, using PPA(polyphosphoric
acid)7 to give the naphthalene derivative 3 in good yield.
Aromatisation via elimination of water followed by oxidation
(presumably due to dissolved air) took place directly in the PPA
reaction mixture. The scope and limitations, together with
various applications, of the described rearrangement will be
reported shortly.
During our work with the Lewis acid-induced carbonyl-ene
reaction,1 a key step in our studies towards the synthesis of
taxanes,2,3 we recently discovered a new type of rearrangement
(Scheme 1). When a mixture of 1c and methyl or ethyl
glyoxylate was treated with zeolite b or BF3·Et2O, the ene
reaction did not occur. Instead, 1c rearranged to give aldehyde
2c in good yield, which also occurred in the absence of the alkyl
glyoxylate. Although allylic benzyl ethers are a well known
class of compounds we were surprised to find that a literature
search did not reveal any similar reactions under acidic
conditions. One reason for this could be the fact that the reaction
does not occur when an unsubstituted benzyl group is used
instead of a p-methoxybenzyl (PMB) group. Thus, electron rich
aromatic rings seems to be necessary. Another reason is that
only zeolite b and BF3·OEt2 among fifteen Lewis acids tested
effected the rearrangement. The outcome of the reaction is
similar to a 1,4-Wittig rearrangement,4,5 although the reaction
conditions and the mechanisms are quite different. While the
1,4-Wittig rearrangement needs strongly basic conditions and is
usually a minor side reaction, the present rearrangement
proceeds under acidic conditions (zeolite b is an acidic zeolite6)
and gives moderate to good yields.
This work was financially supported by the Swedish Natural
Science Research Council, The Knut and Alice Wallenberg
Foundation and The Crafoord Foundation.
Footnote
† Typical procedure: A solution of the PMB-protected allylic alcohol (1.0
mmol) in CH2Cl2 (2 ml) was stirred together with zeolite b (125 mg
activated at 400 °C for 4 h) overnight at room temperature. The resulting
orange–red mixture was then filtered through Celite. The Celite was washed
with CHCl3 (2 3 5 ml) and the combined organic extracts were
concentrated at reduced pressure. The crude materials were purified by
column chromatography (SiO2, heptane–ethyl acetate, 95:5).
References
We propose the following mechanism; the initial step is the
coordination of the Lewis acid (or protic acid) to the ether
oxygen (A). This possibly leads to increased positive charge at
the benzylic carbon, which explains why the p-methoxy group
is necessary for the charge delocalization. Next, the p-electrons
in the double bond attack the benzylic position to form cation B,
which then undergoes a 1,2-hydride shift to give the aldehyde.
The hydride shift was indicated by essentially complete
statistical recovery of deuterium at the carbonyl a-position of 2c
after rearrangement of 1c, which was 50% deuteriated at the
allylic methylene group.
1 K. Mikami and M. Shimizu, Chem. Rev., 1992, 92, 1021.
2 M. Polla and T. Frejd, Tetrahedron, 1993, 49, 2701.
3 M. Polla, PhD Thesis, Lund University, 1993.
4 J. A. Marshall, in Comprehensive Organic Synthesis, ed. G. Pattenden,
Pergamon Press, Oxford, 1991, vol. 3, p. 975.
5 T. Nakai and K. Maikami, in Organic Reactions, ed. R. M. Joyce, Wiley
New York, 1994, vol. 46, p. 105.
6 M. Linsten, EKA Chemicals AB, personal communication.
7 T. S. Chen, P. Canonne and L. C. Leitch, Synthesis, 1973, 620.
Received, 27th November 1996; Com. 6/08020K
R
R
Me
O
O
Zeolite β
PPA
OMe
Me
OMe
OMe
1a R = H
b R = Me
c R = Pri
d R = Ph
2a R = H (77%)
b R = Me (83%)
c R = Pri (74%)
d R = Ph (54%)
3 (75%)
H
–
–
L
+
O
R
R
L
O
+
OMe
OMe
A
B
Scheme 1
Chem. Commun., 1997
445