Inter- and intramolecular [4 + 1]-cycloadditions between electron-poor dienes and electron-rich carbenes

Article abstract of DOI:10.1021/ja046344x

Inter- and intramolecular [4 + 1]-annulations between dialkoxy carbenes and electron-deficient dienes afford mono- or bicyclic products in moderate to good yield. Copyright

Full text of DOI:10.1021/ja046344x

Published on Web 07/24/2004
Inter- and Intramolecular [4 + 1]-Cycloadditions Between Electron-Poor
Dienes and Electron-Rich Carbenes
Claude Spino,* Hadi Rezaei, Kristina Dupont-Gaudet, and Francis B e´ langer
UniVersit e´ de Sherbrooke, D e´ partement de Chimie, 2500 Boul. UniVersit e´ , Sherbrooke, QC, Canada, J1K 2R1
Received June 21, 2004; E-mail: claude.spino@usherbrooke.ca
The [4 + 1]-cycloaddition between a carbene 2 and a diene 1 to
give a cyclopentene derivative is, in a sense, the five-membered
ring equivalent of the Diels-Alder reaction (eq 1).
Scheme 1. Examples of [4 + 1]-cycloadditions
Given the ubiquity of five-membered carbo- and heterocyclic
substructures in natural products, one would expect the [4 +
1]-cycloaddition, like the Diels-Alder reaction, to count among
the most powerful reactions in the arsenal of the synthetic chemist.
On the contrary, this reaction has few precedents. Lilienblum and
Hoffmann reported such an intermolecular cheletropic reaction
between dimethoxycarbene 6a and tropone 5 or tetracyclone 7
Scheme 2. Fisher Carbenes 12 Give Mostly Cyclopropane
Products with Electron-Poor Dienes
1
2
(
Scheme 1). The same carbene also added to tetrazines and to
3
4,4-bis(trifluoromethyl)-1,3-diazabutadiene. More recently, Rigby
established that 6a added to vinyl isocyanates to give five-membered
4
ring lactams. In addition, dimethoxy carbene 6a reacts with silyl-
5
substituted vinyl ketenes 10 (Scheme 1). The latter also react with
sulfur ylids or trimethylsilyldiazomethane to give 9.6
Examples of [4 + 1]-cycloadditions between a carbene and a
simple diene are rare. The main reason is the known propensity
Scheme 3. Intermolecular [4 + 1]-Cycloadditions of
Electron-Deficient Dienes with Dialkoxy Carbenes
7
of carbenes and carbenoids to give cyclopropanation products with
alkenes and 1,3-dienes.8 For example, dimethoxycarbene gave
cyclopropane derivatives in low yield with 1-phenyl- and 1,1-
1
diphenyl-1,3-butadiene. Fisher carbene complexes 12 gave mostly
cyclopropanation products with electron-poor dienes (Scheme 2).9
On the basis of the precedented rearrangement of vinylcyclopro-
panes,10 Hudlicky and Danheiser established a two-step protocol
11
12
that converted 1,3-dienes to cyclopentene derivatives.
Warkentin and co-workers studied extensively the chemistry and
mechanistic aspects of dialkoxy carbenes and related bis-heteroatom
carbenes.13 One of the easiest methods to generate such carbenes
is through the thermal decomposition of appropriately substituted
oxadiazolines 15 (Scheme 3).13,14 We were surprised to find that
dialkoxycarbenes 6a and 6b added efficiently to electron-poor diene
17 to give the corresponding cyclopentene adducts 18a and 18b in
67 and 60% yields, respectively. Cyclopropane products were not
detected, although they could be intermediates (vide infra). Dienes
9a,b gave cyclopentanone acetals 20a,b as single diastereomers
1
At this point, we were convinced that an intramolecular version
of this annulation reaction could lead to useful polycyclic structures
in improved yields. We are not aware of prior examples of such
intramolecular [4 + 1]-cycloaddition aside from a fortuitous reaction
in 38% and 29% yield, respectively. The latter reaction gave a crude
product with a clean NMR that indicated complete conversion of
the diene 19b, but the products were somewhat unstable. The two
methyl ether groups in 20a gave different 1H NMR signals,
indicating a cis stereochemistry of the two esters in 20a. The
stereochemistry of 20b was assumed to be the same as 20a. Diene
15
observed by Warkentin and co-workers.
We prepared dienes 23a-c, which were coupled to oxadiazoline
1
6
15c using an improved reaction condition (Scheme 4). Heating
to reflux the resulting oxadiazolines 24a-c in toluene in carefully
washed glassware gave good yields of the bicyclic adducts 25a-c
and 26a-c (Scheme 4). Oxadiazoline 24a gave a 5:95 mixture of
diastereomeric adducts 25a and 26a in 85% yield, while acetals
21 reacted efficiently also, as judged by NMR, but gave cyclopen-
tadiene 22 in 30% yield after purification on silica gel. Vinylcy-
clohexene and other electron-rich dienes, such as Danishefsky’s
diene, did not react with 6a.
9926
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J. AM. CHEM. SOC. 2004, 126, 9926-9927
10.1021/ja046344x CCC: $27.50 © 2004 American Chemical Society

C O MMU N I C A T I O N S
Scheme 4. Preparation of Bicyclic Adducts 25a-c and 26a-c
In conclusion, we have shown that electron poor dienes and
oxadienes participate in [4 + 1]-cycloadditions with dialkoxy
carbenes. The intramolecular reactions are the first examples of
this kind and lead to useful bicyclic structures. We are presently
expanding this methodology to include nitrogen1 and sulfur
7,18
5,19,20
atoms as well as probing into the mechanistic aspects of the reaction.
Acknowledgment. We thank the Natural Sciences and Engi-
neering Council of Canada and the Universit e´ de Sherbrooke for
financial support.
1
Supporting Information Available: Experimental and H NMR
spectra of all new compounds and syntheses and characterization of
2
3a-c (PDF, CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
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Scheme 5. Preparation of Bicyclic Acetal 28 and Orthoester 30
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