Neighboring nucleophilic group assisted rearrangement of allylic esters under Eu(fod)3 catalysis

Article abstract of DOI:10.1016/S0040-4039(01)00708-0

The acetate 13a and methoxyacetate 13b of (E)-3-hydroxy-4-(arylmethylidene)cyclodeca-1,5-diyne possessing a free hydroxy group underwent an allylic rearrangement at 20°C in the presence of catalytic Eu(fod)₃ to give the enediyne 14 in excellent yields. In contrast, the acetate 10a with a silyloxy group failed to rearrange under the same conditions. These results demonstrated that an internal nucleophilic group promotes the Eu(fod)₃-catalyzed rearrangement of allylic esters under mild conditions.

Full text of DOI:10.1016/S0040-4039(01)00708-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4215–4218
Neighboring nucleophilic group assisted rearrangement of allylic
esters under Eu(fod)3 catalysis
Wei-Min Dai,* Anxin Wu, Mavis Yuk Ha Lee and Kwong Wah Lai
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon,
Hong Kong SAR, China
Received 4 January 2001; accepted 27 April 2001
Abstract—The acetate 13a and methoxyacetate 13b of (E)-3-hydroxy-4-(arylmethylidene)cyclodeca-1,5-diyne possessing a free
hydroxy group underwent an allylic rearrangement at 20°C in the presence of catalytic Eu(fod)3 to give the enediyne 14 in
excellent yields. In contrast, the acetate 10a with a silyloxy group failed to rearrange under the same conditions. These results
demonstrated that an internal nucleophilic group promotes the Eu(fod)3-catalyzed rearrangement of allylic esters under mild
conditions. © 2001 Elsevier Science Ltd. All rights reserved.
Recently, we reported a general synthesis of 3-substi-
tuted 10-membered ring enediynes as illustrated in
Scheme 1.1 It took advantage of the Ln(fod)3-catalyzed
rearrangement of allylic alkoxyacetates to migrate the
exocyclic double-bond into the cyclic skeleton.2 The
mild reaction conditions used were crucial to minimize
decomposition of the 10-membered ring enediynes
which are known to readily undergo cycloaromatiza-
tion at physiological temperature.3 It was reported that
allylic esters lacking the a oxygen functionality in the
acyloxy units failed to rearrange at room tempera-
ture.2a,b Therefore, we planned to equip an internal
nucleophilic group in the esters 2 to facilitate the rear-
rangement through combined ‘pushing and pulling’
interactions (Scheme 2). When the acyloxy group
(RCO2) is activated by complexation with a lan-
thanide(III) catalyst, the hydroxyl group would attack
at the exocyclic double bond in an SN2% fashion to form
the enediynes 1. Alternatively, in the case where an
allylic cation 3 would be generated from 2 by het-
erolytic cleavage of the acyloxy group, the internal
hydroxy group is also ideal for attack at the g position
O
2 steps
RO
10 mol % Ln(fod)3
O
O
CHCl3 20 °C, 24-48 h
(57-79%)
CHO
RO
Ar
O
Ar
Ln(fod)3 =Pr(fod)3, Eu(fod)3, Er(fod)3, Yb(fod)3
R = Me, Bn, PMB; Ar = Ph, 1-Naph, 2-Naph
Ar
I
Scheme 1.
internal nucleophile-
promoted allylic
rearrangement
α
RCO2
H
H
O
O
O
γ
Ar
Ar
Ar
1
2
3
Scheme 2.
Keywords: benzofurans; diynes; lanthanides; rearrangement.
* Corresponding author. Fax: +852 2358 1594; e-mail: chdai@ust.hk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00708-0

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W.-M. Dai et al. / Tetrahedron Letters 42 (2001) 4215–4218
of 3 in a regiospecific manner to give the enediynes.4
We report here on the synthesis of the cyclic alcohol 9
possessing an ortho substituted phenyl group and the
rearrangement reactions of its esters 10b and 13a,b
under Eu(fod)3 catalysis.
Treatment of the alcohol 9 with acetic anhydride in the
presence of DMAP (CH2Cl2, 20°C) gave the acetate 10a
in 82% yield (Scheme 4).5 Condensation of 9 with
methoxyacetic acid under the DCC–DMAP conditions
(CH2Cl2, 20°C) formed the methoxyacetate 10b in 71%
yield. The latter ester underwent an allylic rearrange-
ment catalyzed by 10 mol% Eu(fod)3 (CHCl3, 20°C, 40
h) to furnish the enediyne 11 in 62% yield. The result is
comparable with that of the phenyl analog1 and indi-
cated that the bulky ortho substituent in 10b does not
interfere with the rearrangement. Removal of the silyl
group in 11 under weakly acidic conditions (PPTS,
MeOH, 20°C, 72%) afforded the hydroxy ester 12
which did not convert into the 2,5-dihydro-2-benzofuryl
enediyne 14 under the reaction conditions. Upon expo-
sure of the hydroxy methoxyacetate 13b, prepared by
deprotection of 10b, to 10 mol% Eu(fod)3 (CHCl3,
20°C, 48 h), an intramolecular nucleophilic group
assisted allylic rearrangement took place to form the
enediyne 14 in 95% yield. We carefully monitored the
course of the reaction by TLC and did not observe the
formation of compound 12 during the conversion of
13b into 14. The result clearly indicated that the neigh-
boring hydroxyl group in 13b participated in the double
bond migration presumably in an SN2% fashion.11 More-
over, activation of the methoxyacetate group by Eu(III)
is essential for the rearrangement because 13b survived
the weak acidic conditions used for removal of the silyl
group in 10b. In our earlier work on synthesis of acyclic
enediynes, we found that allylic acetates rearranged at
high temperature (132°C in PhCl).2b To our surprise,
the hydroxy acetate 13a converted into the enediyne 14
in 91% yield at 20°C (CHCl3, 72 h). The pushing force
Synthesis of the cyclic alcohol 9 started with phthalic
dicarboxaldehyde
4
(Scheme 3).5 Selective mono
Horner–Wadsworth–Emmons olefination of 4 followed
by reduction (NaBH4, aq. MeOH) gave the hydroxy
ester 5 in 55% overall yield from 4.4a Protection of the
hydroxy group in 5 as the silyl ether and addition of
Br2 to the double bond followed by the triethylamine-
mediated elimination of HBr furnished the a-bro-
moester 6 as a mixture of the Z and E isomers. This
mixture was used in the selective mono cross-coupling
reaction with 1,7-octadiyne under Sonogashira
conditions6 to form the eneyne ester in 40% yield. This
ester was reduced to the alcohol (Dibal-H, PhMe,
−78°C, 77%), which was subjected to the iodination
conditions (3 equiv. of I2, 8 equiv. of morpholine,
PhMe, 60°C) to provide the hydroxy iodoalkyne 7 in
85% yield.1,7,8 Oxidation of the mixture of 7 using PCC
gave a single E aldehyde 8 in 88% yield. Isomerization
of the initially formed aldehyde Z-8 from the alcohol
Z-7 occurred under the PCC oxidation conditions,
presumably due to the presence of a trace of acidic
residue.1 Finally, the intramolecular Nozaki–Hiyama–
Kishi reaction1,9,10 of 8 under high dilution conditions
formed the cyclic alcohol 9 in 25% isolated yield.
Compared to the para-methoxyphenyl analog,1 the
bulky ortho substituent in 8 has no influence on the
efficiency of the ring-closure reaction.
CO2Me
1. (MeO)2P(O)CH2CO2Me
nBuLi, THF
-78 ~ 20 °C, 5 h
1. tBuMe2SiCl, imidazole
DMF, 20 °C, 15 min (96%)
CHO
OHC
HO
2. NaBH4, aq. MeOH
2. Br2, CH2Cl2, 0 °C
then Et3N, 20 °C, 2 h
(40%)
0 ˚C, 2 h (55% from 4)
4
5
1. 1,7-octadiyne
Pd(PPh3)4, CuI, Et3N
THF, 20 °C, 15 h (40%)
HO
CO2Me
Br
2. Dibal-H, PhMe
tBuMe2SiO
tBuMe2SiO
I
-78 °C, 1 h (77%)
3. I2, morpholine, PhMe
60 °C, 18 h (85%)
6 (Z:E = 40:60)
7 (Z:E = 67:33)
PCC, 4Å MS
CH2Cl2, 20 °C, 20 h
(88%)
HO
CHO
CrCl2 (3 equiv.)-NiCl2 (1 equiv.)
THF, 20 °C, 8 h (0.005 M)
(25%)
tBuMe2SiO
tBuMe2SiO
I
8
9
Scheme 3.

W.-M. Dai et al. / Tetrahedron Letters 42 (2001) 4215–4218
4217
Ac2O, DMAP
CH2Cl2, 20 °C, 15 min (82%)
HO
O
R
O
or MeOCH2CO2H
DCC, DMAP, CH2Cl2
20 °C, 12 h (71%)
tBuMe2SiO
tBuMe2SiO
9
10a: R = H
10b: R = MeO
for R = MeO
(62%)
10 mol% Eu(fod)3
CHCl3, 20 °C, 40 h
O
R
O
O
HO
MeO
O
13a: R = H (83% from 10a)
13b: R = MeO (46% from 10b)
RO
10 mol% Eu(fod)3
CHCl3, 20 °C
11: R = tBuMe2Si
12: R = H
PPTS, MeOH,
20 °C, 22 h (72%)
O
14 from 13a: 72 h, 91%
from 13b: 48 h, 95%
Scheme 4.
provided by the free hydroxyl group in 13a accounts
for the enhanced reactivity of the allylic acetate
toward the Eu(fod)3-catalyzed rearrangement. This
example demonstrated that a combined ‘pushing and
pulling’ effect resulted in an efficient and high yield-
ing chemical transformation. The longer reaction time
observed for the acetate 13a may be explained by the
non-chelation interation with Eu(III) or the relatively
lower stability of the acetate anion compared to the
methoxyacetate anion.12
Acknowledgements
We thank the Department of Chemistry, HKUST for
a post-doctoral fellowship to A. Wu. Financial sup-
port to M. Y. H. Lee from HKUST Post-Doctoral
Fellowship Matching Fund (PDF99/00) is also
acknowledged.
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