A novel 1,2-migration of acyloxy, phosphatyloxy, and sulfonyloxy groups in allenes: Efficient synthesis of tri- and tetrasubstituted furans

Article abstract of DOI:10.1002/anie.200353535

Heading south: The 1,2-migration of the acyloxy, phosphatyloxy, and sulfonyloxy groups in allenyl systems has been discovered. This migration, combined with the transition-metal-catalyzed cycloisomerization reaction, leads to the efficient synthesis of tr

Full text of DOI:10.1002/anie.200353535

Communications
Furan Synthesis
The recently discovered Cu-catalyzed cycloisomerization
of alkynyl ketones and imines is an efficient method for the
synthesis of up to trisubstituted heterocycles.[5] While
attempting to expand the scope of this cycloisomerization
reaction, we explored the possibility of utilizing [3,3] acyloxy
migration to proceed from 1 to allene 2 en route to acyloxy-
substituted furan 3 (Scheme 1). As expected, furan 3 was
A Novel 1,2-Migration of Acyloxy, Phosphatyloxy,
and Sulfonyloxy Groups in Allenes: Efficient
Synthesis of Tri- and Tetrasubstituted Furans**
Anna W. Sromek, Alexander V. Kel'in, and
Vladimir Gevorgyan*
[3,3] Migrations of propargylacyloxy, phosphatyloxy, and
sulfonyloxy groups are important transformations in organic
synthesis.[1] In addition to these sigmatropic migrations,
radical 1,2-acyloxy and -phosphatyloxy migrations [Eq. (1)]
Scheme 1. Formation of the unexpected regioisomer 4.
have been used extensively in carbohydrate and nucleoside
chemistry.[2] 1,2-Acyloxy migration has also been proposed as
a key step in the Pd-catalyzed propargyl–propenyl isomer-
ization [Eq. (2)].[3] In both cases, 1,2-migration of acetate or
formed, albeit in moderate yields; however, it was accom-
panied by traces of the unexpected regioisomer 4. Addition of
triethylamine to the reaction mixture shifted the product
distribution toward predominant formation of furan 4. It was
rationalized that 4 arises from initial base-assisted propargyl–
allenyl isomerization 5!6[5] (Scheme 2), as opposed to a [3,3]
phosphate proceeds from an sp3 carbon. To the best of our
knowledge, no 1,2-migrations of the acyloxy, phosphatyloxy,
and sulfonyloxy groups from an sp2 carbon have been
disclosed. Herein we wish to report a novel 1,2-migration of
the acyloxy, phosphatyloxy, and sulfonyloxy groups in the
allenyl system [Eq. (3)]. This unprecedented migration,
incorporated into the cycloisomerization reaction, is the key
to an efficient synthesis of valuable tri- and tetrasubstituted
furans.[4]
Scheme 2. Rationale for the formation of the unexpected regioisomer
4.
acyloxy shift (Scheme 1). Allene 6 undergoes intramolecular
nucleophilic attack to form the aromatic dioxolenylium
zwitterion 7,[6] which is transformed into furan 4 by a
subsequent intramolecular AdN-E process (Scheme 2).[7]
We were pleased to find that by using phenyl and tert-
butyl alkynyl ketones, we were able to dramatically improve
the regioselectivity and yields of this unusual reaction. Thus,
when we employed a series of alkynyl ketones 5 possessing
different acyloxy groups, selective cycloisomerization occur-
red to produce furans 4 as single regioisomers in high yields
(Table 1)!
To gain additional support for the proposed allenic
intermediate 6 in the formation of furan 4 (Scheme 2), we
attempted approaching allenes of type 6 by an independent
route. An attractive possibility would be to access acyloxy
allene 9 by the [3,3] sigmatropic shift of 8 (Scheme 3). In the
event that the sequential cascade transformation of 8 into 9
proves successful, it would not only offer strong support for
[*] A. W. Sromek, A. V. Kel'in, Prof. V. Gevorgyan
Department of Chemistry
University of Illinois at Chicago
845 West Taylor Street, Room 4500
Chicago, IL 60607-7061 (USA)
Fax: (+1)312-355-0836
E-mail: vlad@uic.edu
[**] We are grateful to the NIH (GM 64444) for financial support of this
work. We also thank D. Yap for technical assistance.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200353535
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Angewandte
Chemie
Table 1: Cu-catalyzed synthesis of trisubstituted furans.[a]
Table 2: Ag-catalyzed synthesis of tetrasubstituted furans.[a]
Substrate
t [h]
Product
Yield [%][b]
82[c]
5a
5b
5c
5d
5e
5 f
22
4a
4b
4c
4d
4e
4 f
4g
Substrate
t [min]
Product
Yield [%][b]
1
9
81
69
90
86
80
80
8a
8b
8c
8d
8e
2
10a
10b
10c
10d
10e
>99
15
15
15
10
73
84
90
86
2
17
23
32
5g
[a] Reactions carried out on a 1-mmol scale. [b] Yields of isolated
products.
5h
46
4h
83[c,d]
[a] All reactions carried out on a 1-mmol scale. [b] Yields of isolated
products. [c] Reactions carried out at 808C. [d] TBS=tert-butyldimethyl-
silyl.
Scheme 3. Different approach to acyloxy allenyl ketones.
Scheme 4. 1,2-Phosphatyloxy migration. DCE=dichloroethane.
involvement of allenic intermediates 6/9, but would also allow
expansion of our cycloisomerization methodology to the
synthesis of tetrasubstituted furans 10. We were thrilled to
find that in the presence of AgBF4,[8,9] ketones 8 smoothly
underwent the postulated [3,3] shift/1,2-migration/cycloiso-
merization sequence to directly[10] afford tetrasubstituted
furans[11] 10 in excellent yields (Table 2)! Most remarkably,
this new mode of cyclization enables facile access to the fused
furan 10e, which was inaccessible by our standard cyclo-
isomerization techniques.[5]
that attempts to synthesize 14[12] led directly to the formation
of tosyl allene 15, apparently through a thermal [3,3] tosyloxy
shift. Allene 15 underwent smooth cycloisomerization at
608C in the presence of 1% AgBF4 to produce tosyl furan
16[13] in 82% yield (Scheme 5). Thus, the successful employ-
Encouraged by these results, we attempted incorporation
of hetero migrating groups into the [3,3] shift/1,2-migration/
cycloisomerization cascade. It was found that the phosphatyl-
oxy analogue of 8a, ketone 11, underwent cycloisomerization
at 608C in the presence of 5% AgBF4 to afford furanyl
phosphate 12 in 65% yield (Scheme 4). When the reaction
was conducted at room temperature, the allenyl phosphate
intermediate 13 was isolated in 56% yield. Subjecting the
latter to the same conditions as those used for the trans-
formation 11!12 led to formation of furan 12 in 77% yield
(Scheme 4).
Scheme 5. 1,2-Tosyloxy migration.
ment of the phosphatyloxy and sulfonyloxy groups not only
expands the scope of the recently found cycloisomerization
reaction, but also provides strong support for the involvement
of the acyloxy allene intermediate in the formation of acyloxy
furans 4 and 10.
In conclusion, a novel 1,2-migration of the acyloxy,
phosphatyloxy, and sulfonyloxy groups in allenyl systems
has been discovered. Incorporation of this transformation in a
Next, we attempted the analogous transformation with
propargyl tosylates 14. We were pleasantly surprised to find
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[11] For a related AgBF4-catalyzed cycloisomerization of allenic
alcohols into 2,5-dihydrofurans, see: a) L.-I. Olsson, A. Claes-
son, Synthesis 1979, 743; for the metal-catalyzed cyclization of
allenyl ketones into furans, see: b) J. A. Marshall, X. Wang, J.
Org. Chem. 1991, 56, 960; c) J. A. Marshall, G. S. Bartley, J. Org.
Chem. 1994, 59, 7169; d) S. Ma, J. Zhang, Chem. Commun. 2000,
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Hashmi, L. Schwarz, J. H. Choi, T. M. Frost, Angew. Chem. 2000,
112, 2382; Angew. Chem. Int. Ed. 2000, 39, 2285.
cycloisomerization sequence led to the development of an
efficient method for the synthesis of tri- and tetrasubstituted
furans.
Received: December 15, 2003 [Z53535]
Keywords: cyclization · furans · homogeneous catalysis ·
.
rearrangement · synthetic methods
[12] See the Supporting Information for details.
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reactions. For the Pd-catalyzed cross-coupling of aryl tosylates,
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Soc. 2003, 125, 11818; b) A. H. Roy, J. F. Hartwig, J. Am. Chem.
Soc. 2003, 125, 8704.
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[7] For 1,2-migration of the thio group proceeding through a
thiirenium intermediate, see ref. [5c].
[8] AgBF4 may participate in either or all steps of the sequence, as
silver salts are known to catalyze propargylacyloxy [3,3]-
sigmatropic shifts (see ref. [1]) as well as the cycloisomerization
of allenyl ketones into furans.[11b,c]
[9] Following a referee's suggestion, we tested the cyclization of 8d
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[10] Most likely, in keeping with earlier proposals (see ref. [5]), the
formation of allene 9 is the rate-determining step; therefore, 9
has never been observed in the reaction mixtures.
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Angew. Chem. Int. Ed. 2004, 43, 2280 –2282