Research Article

pubs.acs.org/acscatalysis

A Redox-Neutral Fe-Catalyzed Cycloisomerization of Enyne Acetates

Johannes Teske and Bernd Plietker*
Institut fur Organische Chemie, Universitat Stuttgart, Pfaenwaldring 55, DE-70569 Stuttgart, Germany
S Supporting Information
*

ABSTRACT: The cationic complex [(Ph3P)2Fe(CO)(NO)]BF4

catalyzes the redox-neutral cycloisomerization of enyne acetates to diastereomerically pure allenyl pyrrolidines in good to
excellent yields.

KEYWORDS: iron catalysis, allene, cycloisomerization, enyne, heterocycle, diastereoselectivity

INTRODUCTION
Generating dened molecular complexity from simple
precursor molecules is one of the major driving forces for the
development of methodology in organic chemistry. Among
the methods developed today, metal-catalyzed intramolecular
cycloadditions1 and the related cycloisomerizations2 occupy an
important place. Starting from rather simple unsaturated precursor molecules, the initial cyclization is in the case of the
cycloisomerization succeeded by a shift of functional groups, or
in case of the cycloaddition, a second cyclization takes place.
Although versatile metal catalysts and complex molecular transformations have been developed within the past years, the eld
of cycloaddition/cycloisomerization reaction is still one of the
most vigorously developing elds in catalysis. In particular,
Pd-based,3 Rh-based,4 Ir-based,5 and Ru-based6 catalysts have
been shown to promote these reactions through metal-centered
two-electron redox mechanisms.7 In the past decade, the mechanistic portfolio was broadened through the advent of novel
catalysts that act as -acids in non-redox-type cycloisomerizations/
cycloadditions. Catalysts based on Au,8 Ag,9 W,10 and Cu11 but
also on Ga12 or In13 were shown to promote these reactions.
Interestingly, depending on the catalyst employed in the reaction, dierent products arise starting from identical precursor
molecules.
Within the past 15 years, signicant progress has been made
in the eld of base metal catalysis.14 Iron as one of the most
abundant metals in the upper earth crust has attracted a great
deal of interest.15 Although a plethora of Fe-catalyzed transformations have been reported in the past years, the eld of
Fe-catalyzed atom-economic redox-neutral cycloisomerization
is comparably less well elaborated.16 To the best of our
knowledge, the only examples for this type of Fe catalysis were
reported in 2005 by the group of Furstner.17 For a couple of
years, we have been involved in the development of catalytic
transformations that rely on the use of FeNO complexes.18
Whereas initial studies concentrated on the use of the anionic
XXXX American Chemical Society

Bu4N[Fe(CO)3(NO)] in mostly allylic substitution chemistry,19 we expanded more recently our investigation to the use
of the corresponding FeH complexes of the general type
H[(phosphine)2Fe(CO)(NO)], which show good activities
in hydrosilylation reactions.20 In line with this interest in
Fe catalysis, we became interested in developing catalytic transformations that rely on the use of the corresponding cationic
Fe complexes that are derived from the FeH species by
protonation. Herein, we describe the synthesis and application
of the cationic Fe complex [(Ph3P)2Fe(CO)(NO)]BF421 as a
potent catalyst in a redox-neutral cycloisomerization of enyne
esters to allenyl pyrrolidines or tetrahydrofurans with good to
excellent diastereoselectivities and yields (Scheme 1).
Scheme 1. Fe-Catalyzed Cycloisomerizations

RESULTS AND DISCUSSION

The catalytically active species was prepared in three steps
starting from Fe(CO)5 following a procedure that was originally
Received: August 8, 2016
Revised: September 12, 2016

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described by Roustan as early as 1980.21 The 16-electron
complex 6 was obtained as an amorphous powder; however,
upon treatment with CO gas or acetonitrile, we were able to
isolate the corresponding complexes 7 and 8, from which we
could conrm the structure by X-ray analysis (Scheme 2).

Scheme 3. Scope and Limitations of Fe-Catalyzed

Cycloisomerization,

Scheme 2. Preparation of Complexes 7 and 8

We employed complex 6 in the cycloisomerization of enyne

acetate 9 and were pleased to nd that 9 reacted smoothly
to the corresponding allenyl pyrrolidine 10 with perfect
diastereoselectivity using only 10 mol % Fe complex 6 in
dichloromethane at 50 C (entry 2, Table 1).22 Importantly,
Table 1. Fe-Catalyzed Cycloisomerization of Enyne 9

no.

catalyst

conversion (%)

1
2
3
4
5
6

6
7
8
HBF4
[Bu4N][BF4]

66b

decomposition

All reactions were performed on a 0.2 mmol scale using 10 mol %

catalyst 6 in dry CH2Cl2 (1 mL) at 50 C under a N2 atmosphere for
22 h. bIsolated yield.

within the substrate core did not aect the course of the
reaction. Starting from achiral propargylic acetates, we observed
a high degree of distereoselectivity with regard to the relative
conguration of the two sp3 stereocenters. In each case, the
corresponding allenyl pyrroldine was obtained as a diastereomerically pure product with regard to the two adjacent
C(sp3) chiral centers. Interestingly, although the introduction
of chirality within the propargylic acetate motif did not aect
the diastereoselectivity of the two C(sp3) chiral centers, the
allene moiety was formed as a 1:1 mixture of stereoisomers.
Subsequently, we analyzed the inuence of the heteroatom
within the linker unit. Whereas dierent sulfonylamides have
comparable reactivities, a signicant decrease in reactivity was
observed upon using an ether linker. Finally, we prepared
starting materials possessing dierent substitutions at the
olenic moiety and were happy to see that even trisubstituted
olens are reactive. However, the higher degree of substitution
goes to the expense of reactivity. Furthermore, Z-congured
olens resulted in a sluggish reaction with only minor amounts
of the product being formed.
Subsequent test experiments were performed to shed some
light on the probable mechanism of this cycloisomerization.
Enynes 34 and 35-d3 were subjected in a cross-experiment to

All reactions were performed on a 0.2 mmol scale using 10 mol %

catalyst in dry dichloromethane at 50 C under a nitrogen atmosphere
for 22 h. bIsolated yield.

the use of catalytic amounts of HBF4 that might be formed

from complex 6 by reaction with water led to a fast degradation
of 9 to a mixture of dierent products (entry 5, Table 1).
A catalytic impact of the BF4 anion was excluded by
employing [Bu4N][BF4] in catalytic amounts in the absence of
the Fe complex to the test reaction under otherwise identical
conditions (entry 6, Table 1). As for the reaction in the absence
of any catalyst (entry 1, Table 1), no conversion was observed.
Importantly, 18-electron complexes 7 and 8 did not show any
activity under the given reaction conditions (entries 3 and 4,
respectively, Table 1).
With these results in hand, a screening of the scope and
limitation of this transformation was performed (Scheme 3).
A broad set of dierent densely functionalized tri- and
tetrasubstituted allenyl pyrrolidines were prepared. The cycloisomerization shows good functional group tolerance. Halides,
esters, ethers, and amides are tolerated. Additional olenic moieties
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corresponding Fe-catalyzed transformation of enyne 9, they

could be potential intermediates from which allenyl pyrrolidine 10
might be formed. However, neither 36 nor 37 gave the corresponding allene 10 when either was subjected to the Fe catalysis
conditions (eqs 2 and 3, Scheme 4).
Importantly, treating the isoprenyl-substituted amide 38 with
either Fe complex 6 or Echavarrens Au catalyst 39 under
otherwise identical conditions (eqs 4 and 5, Scheme 4) gave
product 30 in 87 or 69% yield, respectively.26 Finally, enantiomerically pure enyne acetate 40 was tested using Fe catalyst
6 (eq 6, Scheme 4) and Au complex 39 (eq 7, Scheme 4).
In both cases, no transfer of chirality was observed. A racemic
mixture of allenes was observed in the presence of Fe catalyst 6,
and the two C(sp3) chiral centers were formed with exclusive
diastereoselectivity. Treatment of enantiopure enyne acetate 40
with Au catalyst 39 led to the formation of the corresponding vinylcyclopropane 41 as a single diastereomer as a racemic
mixture.
On the basis of these results, we propose a mechanism that
involves -activation of the alkyne moiety to III that sets the
stage for the 1,2-attack of the carboxyl group at the activated
alkyne moiety to give the corresponding vinylFe species IV.
This species is in equilibrium with Fecarbene species V.
At this point, any stereochemical information within the starting
material is lost.24 The subsequent [2+2]-cycloaddition yields
the corresponding metallacyclobutane VI, which in contrast to
Au catalysis does not undergo a fast reductive elimination to
vinylcyclopropane VII but rather an acetyl migration to give
nal product VIII (Figure 1).

Scheme 4. Control Experiments

analyze the level of deuterium scrambling (eq 1, Scheme 4).

Approximately 20% scrambling was observed; however, control
experiments indicate the scrambling to be a Fe-catalyzed
follow-up reaction between the two products, 13 and 29-d3.
This result indicates an intramolecular acyl group transfer to be
part of the mechanism. Propargylic acetates are a frequently
used structural motif in Pt as well as Au catalysis.23,24 Dierent
mechanisms for the mode of activation have been discussed,
i.e., the formal [3,3]-acyl rearrangement to allenyl acetates as
well as a [1,2]-acyl shift to vinylAu complexes or Aucarbene
complexes and the subsequent cyclopropanation of adjacent
double bonds.24 To obtain some indication of a probable
mechanistic scenario, we screened dierent noble metal-based
catalysts in the isomerization using enyne 9. Whereas Pt(II)
complexes catalyze a rearrangement of enyne acetate 9 to the
corresponding allene 36, catalytic amounts of either AuCl3 or
Echavarrens Au(I) complex [(o-Ph)C6H4Pt-Bu2]Au(CH3CN)PF6 3925 result in the formation of cyclopropane 37. Despite
the fact that both 36 and 37 were not observed in the

Figure 1. Mechanistic proposal.

CONCLUSION
Herein, we report that cationic FeNO complex 6 is reactive
in the redox-neutral cycloisomerization of 1,6-enyne acetates.
A variety of substrates underwent reaction to the corresponding
allenyl pyrrolidines27 with exclusive diastereoselectivities regarding the two new C(sp3) chiral centers. This novel reactivity
opens a new eld in Fe catalysis and adds an interesting feature
to the steadily growing area of base metal catalysis.

ASSOCIATED CONTENT

S Supporting Information
*

The Supporting Information is available free of charge on the

ACS Publications website at DOI: 10.1021/acscatal.6b02260.
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Additional observations and data (PDF)

Crystallographic information (CIF)
Crystallographic information (CIF)
Crystallographic information (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: bernd.plietker@oc.uni-stuttgart.de.
Notes

The authors declare no competing nancial interest.

ACKNOWLEDGMENTS
The authors are grateful to the Deutsche Forschungsgemeinschaft for nancial support and to Dr. Wolfgang Frey for X-ray
analysis.

DEDICATION
Dedicated to Prof. Dr. Dieter Hoppe on the occasion of his
75th birthday.
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DOI: 10.1021/acscatal.6b02260
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