Zinc-catalyzed Meinwald rearrangement of tetrasubstituted 1-alkynyloxiranes to tertiary α-alkynylketones

Article abstract of DOI:10.1039/c2cy20810e

Easy access to tertiary α-alkynylketones via a Meinwald-type rearrangement of 1-alkynyloxiranes is reported. This transformation is selectively accomplished with an economical zinc catalyst.

Full text of DOI:10.1039/c2cy20810e

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Zinc-catalyzed Meinwald rearrangement of
tetrasubstituted 1-alkynyloxiranes to tertiary
a-alkynylketones†
Cite this: Catal. Sci. Technol., 2013,
3, 932
Received 22nd November 2012,
Accepted 3rd January 2013
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Mar´ıa J. Gonzalez, Jesus Gonzalez, Carmela Perez-Calleja, Luis A. Lopez* and
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Ruben Vicente*
DOI: 10.1039/c2cy20810e
www.rsc.org/catalysis
Easy access to tertiary a-alkynylketones via a Meinwald-type rearrange-
ment of 1-alkynyloxiranes is reported. This transformation is selectively
accomplished with an economical zinc catalyst.
Epoxides are readily available and versatile intermediates
in organic synthesis as they can be easily converted into
various valuable building blocks.1 Among the broad reactivity
of epoxides, one of the most useful transformations is the Mein-
wald rearrangement, which leads to industrially and synthetically
relevant a-substituted carbonyl compounds.2 It has been found
that the regioselectivity observed for a particular epoxide depends
largely on the substituents and the catalyst (Scheme 1(a)).3 Parti-
cularly, metal-catalyzed transformations involving 1-alkynyl epox-
Scheme 2 Meinwald rearrangement of epoxide 1a: screening (yields of isolated
a
b
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2a). After 5 min at 0 1C. After 24 hours at rt. After 5 days using 20 mol%.
ides have been extensively studied in the last few years, with special that gold likely behaves as an oxophilic Lewis acid. Accordingly,
emphasis on the use of precious metals such as gold,4 platinum,5 we decided to explore the ability of more economical and available
silver6 or iridium.7 These compounds do not undergo a rearrange- Lewis acid catalysts to promote this interesting transformation.
ment, yet can be converted into furan derivatives when di- or Herein we disclose the use of a cheap zinc catalyst,9 which
trisubstituted epoxides are used (Scheme 1(b)).4–7 In sharp contrast, promotes the completely selective and highly efficient rearrange-
we recently found that tetrasubstituted 1-alkynyloxiranes can be ment of tetrasubstituted 1-alkynyl epoxides into synthetically
transformed selectively into tertiary a-alkynylketone derivatives in valuable tertiary a-alkynylketones.10
the presence of gold catalysts (Scheme 1(b)).8 This study showed
Our study was commenced by subjecting epoxide 1a to various
Lewis acid catalysts (5.0 mol% catalyst, CH2Cl2, rt), as depicted in
Scheme 2. Under these reaction conditions, we found that various
catalysts were able to promote the Meinwald rearrangement to
yield ketone 2a in a selective manner. As shown in Scheme 2,
Zn(OTf)2 proved to be superior to other common metal triflate
catalysts derived from Cu(II), Fe(II), Fe(III), Sc(III) or Bi(III), as well as
to previously studied AuCl3.11 Besides, the use of a strong
Brønsted acid like TfOH or TsOH allowed the transformation to
occur although in lower yield and reproducibility. Interestingly,
phosphoric acid derived from (R)-BINOL (20 mol%) showed
catalytic activity, however, an unpractical long reaction time was
required to achieve appreciable conversion.12
Scheme 1 (a) Meinwald rearrangement. (b) Gold-catalyzed transformations of
1-alkynyl epoxides.
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Departamento de Quımica Organica e Inorganica, Universidad de Oviedo, c/Julian
With these results in hand, we next explored the scope of
this zinc-catalyzed rearrangement using various tetrasubsti-
tuted 1-alkynyloxiranes 1. The results are shown in Scheme 3.
Thus, alkynyl epoxides bearing aryl substituents (R1 = Ph,
MeO–C6H4–) gave rise to ketones 2a–b in very good yields
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Claverıa 8, 33006-Oviedo, Spain. E-mail: lalg@uniovi.es, vicenteruben@uniovi.es;
Fax: +34 985103450; Tel: +34 985106223
† Electronic supplementary information (ESI) available: Experimental proce-
dures, characterization data and NMR spectra of new compounds. See DOI:
10.1039/c2cy20810e
c
932 Catal. Sci. Technol., 2013, 3, 932--934
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Scheme 4 Unsuccessful tri- and disubstituted 1-alkynyloxiranes.
Scheme 3 Zinc-catalyzed rearrangement of epoxides 1 into ketones 2 (isolated
yield in parentheses, DCE = 1,2-dichloroethane).
Scheme 5 Proposed intermediate and mechanistic experiments.
(91 and 89%, respectively). Various alkyl substituted alkynyl
epoxides were also tested, including primary, secondary and
According to the commonly accepted mechanism for the
tertiary alkyl chains (R1 = n-Bu, n-C8H17, c-C3H7, t-Bu). Under Meinwald rearrangement,2a,3 the complete selectivity observed
the same reaction conditions, the corresponding alkynyl in these transformations can be attributed to the favoured
ketones 2c–f were generally obtained in good yields (66–94%). formation of a stabilized propargylic carbocation I (Scheme 5).
The stability of the alkynylcyclopropane moiety in ketone 2e Further studies were directed toward finding evidence for the
is noteworthy, whose reactivity might be further exploited. presence of this key intermediate. First, we accomplished the
Interestingly, a silyl group (R1 = TMS) on the alkyne was capture of the proposed intermediate using a simple nucleophile
tolerated as well, providing ketone 2g in 77% yield. The use such as MeOH (Scheme 5(a)). Thus, when the reaction was
of a terminal alkyne on the epoxide also proved suitable, giving conducted in MeOH as solvent, a separable mixture of the
rise to ketone 2h in 83% yield. As these transformations alkynol 3a and the ketone 2a was obtained in good yield after
involved a 5-to-6 ring enlargement, we subsequently proceeded a long reaction time (72 h, 3a = 41%; 2a = 35%; 3a : 2a =
with other tetrasubstituted alkynyl epoxides. Thus, epoxide 1i 1.2 : 1).15 Interestingly, the formation of alkynol 3a occurred
bearing a cyclohexane spiro core was converted into the regio- and chemoselectively, as it was the only addition product
a-alkynyl cycloheptanone 2i in a moderate yield of 66% only observed. On the other hand, the formation of the ketone 2a
when the reaction was accomplished at 70 1C.13 Similarly, might be explained by assuming a similar reaction rate between
acyclic substrates were also studied as exemplified by epoxides the nucleophile addition and the Meinwald rearrangement.
1j–k, which gave rise to acyclic a-alkynyl ketones 2j–k, respectively. Nonetheless, a pinacol-type rearrangement on alkynol 3a could
It should be noted that the transformation involving epoxide also account for the formation of the alkynylketone 2a. To
1j required again slightly stronger reaction conditions.13 Inter- exclude this possibility, we stirred isolated 3a in the presence of
estingly, ketone 2k was obtained under mild conditions and catalytic amounts of Zn(OTf)2 at room temperature in dichloro-
with complete selectivity (preference for the migration of the methane. The typical catalyst loading (5.0 mol%) did not give rise
benzyl group).
to the ketone 2a and most of the alkynol 3a was recovered (80%),
We also studied the reactivity of the corresponding tri- or while when using a higher catalyst loading (20 mol%) 2a was
disubstituted 1-alkynyloxiranes under zinc catalysis (Scheme 4). obtained in very low yield (12%) (Scheme 5(b)). Additionally, we
Unfortunately, only a complex mixture of various inseparable wanted to study if the possibility that the adventitious presence of
products14 along with decomposition of the starting substrate water, which would form a 1,2-diol intermediate prior to the
was observed, even when the experiments were carried out at rearrangement, could play a role in these reactions. Thus, we tried
lower reaction temperatures.
to prepare the corresponding diol analogous to alkynol 3a.
c
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However, all attempts using various catalysts and moisture
conditions led to the formation of 2a. Conversely, we were able
to prepare diol 4i from alkynyl epoxide 1i by treatment with
TsOHÁH2O (see ESI† for details). When alkynol 4i was subjected
to various reaction conditions only trace amounts of ketone 2i
were observed in the crude mixture (Zn(OTf)2, 20 mol%, 70 1C,
DCE) (Scheme 5(c)). These experiments likely support a Mein-
wald-type rearrangement to be the operating mechanism,
excluding the participation of diol species.
In summary, we have disclosed herein the preparation of
synthetically valuable tertiary a-alkynylketones10 by means of
a completely selective Meinwald-type rearrangement of tetra-
substituted 1-alkynyloxiranes. This transformation is efficiently
promoted by an inexpensive zinc catalyst. The origin of the
selectivity of this rearrangement resides on the superior stabi-
lity of the propargylic carbocation over other possible species.3
Further studies concerning the enantioselective version of
this transformation enabling the enantiopure generation of
quaternary stereogenic carbons, by using metal or Brønsted
acid catalysis, are ongoing in our laboratories.
7 J. Y. Kang and B. T. Connell, J. Org. Chem., 2011, 76, 2379.
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8 M. J. Gonzalez, J. Gonzalez and R. Vicente, Eur. J. Org.
Chem., 2012, 6140.
9 For recent examples of zinc catalysis, see: (a) R. Vicente,
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J. Gonzalez, L. Riesgo, J. Gonzalez and L. A. Lopez, Angew.
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We thank Ministerio de Economıa y Competitividad of Spain
(MINECO; Project CQT-201020517-C02) for financial support.
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R.V. is a Ramon y Cajal Fellow.
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salts (including zinc halides) were much less effective.
12 HPLC chromatography indicated o5% ee.
13 No conversion was observed after prolonged time (72 h) at
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14 The formation of furan derivatives as described for other
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15 When the same reaction was accomplished with 20 mol%
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934 Catal. Sci. Technol., 2013, 3, 932--934
This journal is The Royal Society of Chemistry 2013