Amberlyst-15-catalyzed intramolecular S(N)2' oxaspirocyclization of tertiary allylic alcohols

Article abstract of DOI:10.1016/S0040-4039(00)00390-7

A variety of substituted 1-oxaspiro[4.5]dec-6-ene and 1- oxaspiro[5.5]undec-7-ene systems have been prepared by utilizing Amberlyst- 15-catalyzed S(N)2' oxaspirocyclizations under mild reaction conditions (- 20°C) in quantitative yields. In this process,

Full text of DOI:10.1016/S0040-4039(00)00390-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3411–3413
Amberlyst-15-catalyzed intramolecular SN20 oxaspirocyclization
of tertiary allylic alcohols
Jenn-jong Young,∗ Liarng-jyur Jung and Kuang-ming Cheng
Institute of Preventive Medicine, National Defense Medical Center, PO Box 90048-700, Sanhsia, Taipei, Taiwan 237, ROC
Received 4 February 2000; revised 2 March 2000; accepted 3 March 2000
Abstract
A variety of substituted 1-oxaspiro[4.5]dec-6-ene and 1-oxaspiro[5.5]undec-7-ene systems have been prepared
by utilizing Amberlyst-15-catalyzed SN20 oxaspirocyclizations under mild reaction conditions (−20°C) in quantita-
tive yields. In this process, a tertiary allylic alcohol serves as the precursor of π-allylic carbocation and the primary,
secondary or tertiary alcohol within the same molecule serves as the nucleophile. © 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: Amberlyst-15; SN20 oxaspirocyclization; tertiary allylic alcohols; allylic oxaspirocycles.
The syntheses of oxaspirocycles 2 are available from the tertiary alcohols 1 that can form stabi-
lized carbocations under acid treatment, and internal capture by the second hydroxy group to form
oxaspirocycles1,2 (Scheme 1). Sometimes the same strategy cannot be extended to the preparation of
allylic oxaspirocycles such as 2b since the precursor 1b has a marked tendency towards elimination3 of
the tertiary and allylic alcohol. In view of this difficulty, Constantino et al.3 developed a circuitous route
for the synthesis of allylic spiro-α-lactone 3 starting from dimedone in an overall yield of 8.8% (Scheme
2).
Scheme 1.
Palladium-catalyzed oxaspirocyclization of conjugated diene4 or allylic ester5 by using alkoxides as
nucleophiles has also emerged as a synthetically versatile method for constructing allylic oxaspirocycle
systems. But tertiary alkoxides have not been widely used as nucleophiles in π-allyl palladium chemistry.
∗
Corresponding author. Fax: +886 2 26725934.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00390-7
tetl 16670

3412
Scheme 2.
In this report, we demonstrate that the route for Amberlyst-15-catalyzed intramolecular SN20 oxaspi-
rocyclizations of tertiary allylic alcohols 4–9, even in the case of sterically hindered tertiary nucleophile,
can be applied to the syntheses of allylic oxaspirocycles in quantitative yields (Scheme 3).
Scheme 3.
The syntheses of tertiary allylic alcohols 4–9 were accomplished as outlined in Scheme 4. The
sequence was initiated by the reaction of the Normant Grignard reagent6 with the vinylogous ester 3-
ethoxy-2-cyclohexen-1-one. The resulting ketoalcohols 16 and 17 were oxidized to the aldehydes 18 and
197 (PCC, CH2Cl2, room temperature) and methyl esters 20 and 21 (Jones reagent, acetone, 0°C then
CH2N2, diethyl ether, 0°C). The alcohols, aldehydes and esters were converted to their corresponding
tertiary allylic alcohols 4–9 by treatment with methyllithium in THF at −40°C in quantitative yields
without any purification.
Scheme 4. (a) PCC, CH2Cl2, room temperature; (b) Jones reagent, acetone, 0°C; (c) CH2N2, diethyl ether, 0°C; (d)
CH3Li/diethyl ether, THF, −40°C
All the tertiary allylic alcohols 4–9 underwent SN20 oxaspirocyclization on treatment with
Amberlyst-15 (CHCl3, −20°C) to produce the corresponding 1-oxaspiro[4.5]dec-6-enes 10–12 and
1-oxaspiro[5.5]undec-7-enes 13–15 in quantitative yields. Amberlyst-15 is a macroreticular sulfonic

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acid-based polystyrene cationic exchange resin, and thus the work-up procedure8 is very simple,
involving only filtration of the resin and removal of the solvent to obtain the product in a high state of
purity.
The competing elimination reaction (Scheme 5) was only observed in the case of 2-substituted 1-
oxaspiro[5.5]undec-7-ene systems at room temperature. Lowering the reaction temperature to −20°C
can prevent the elimination reaction from occurring.
Scheme 5.
In summary, allylic oxaspirocycles are readily accessible by Amberlyst-15-catalyzed intramolecular
SN20 oxaspirocyclization of tertiary allylic alcohols from simple starting materials with high yields and
easy work-up features. They can be further functionalized and should provide useful entries to the total
synthesis of oxaspirocyclic natural products (such as: theaspirane, theaspirone, vetispirane, dactyloxene
B, etc.).
General experimental procedure: Preparation of 7-methyl-1-oxaspiro[4.5]dec-6-ene (10): Amberlyst-
15 resin (20 mg) was added to a solution of tertiary allylic alcohol 4 (73 mg, 0.429 mmol) in 5 ml
of chloroform (stabilized with 2-methyl-2-butene, Merck cat. No. 2444). The mixture was then stirred
at −20°C for 1 h under nitrogen. The reaction mixture was filtered through KHCO3, and concentrated
under rotary evaporator/aspirator system to give 10 (65 mg, 0.427 mmol, 99.5%) in a high state of purity
without a purification procedure.
Acknowledgements
We thank the National Science Council (NSC86-2113-M-016-003) of the Republic of China and IPM-
NDMC (Grant No. IPM-870503) for financial support.
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