Regioselective synthesis of substituted cyclopenta[l]phenanthrenes

Article abstract of DOI:10.1021/acs.orglett.6b02008

A simple and efficient synthesis of cyclopenta[l]phenanthrenes from substituted acetophenones provides access to polycyclic aromatics with a variety of substitution patterns. The synthesis requires only three steps from a silyl enol ether: a Mukaiyama aldol reaction followed by McMurry coupling and then Mallory photocyclooxidation to give the target phenanthrenes. Photocyclization conditions have been found that give regioselective formation of 2,7-phenanthrenes from bis(meta-substituted) stilbenes.

Full text of DOI:10.1021/acs.orglett.6b02008

Letter
pubs.acs.org/OrgLett
Regioselective Synthesis of Substituted Cyclopenta[l]phenanthrenes
David M. Connors and Nancy S. Goroff*
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States
S
* Supporting Information
ABSTRACT: A simple and efficient synthesis of cyclopenta[l]-
phenanthrenes from substituted acetophenones provides access to
polycyclic aromatics with a variety of substitution patterns. The
synthesis requires only three steps from a silyl enol ether: a Mukaiyama
aldol reaction followed by McMurry coupling and then Mallory
photocyclooxidation to give the target phenanthrenes. Photocyclization
conditions have been found that give regioselective formation of 2,7-
phenanthrenes from bis(meta-substituted) stilbenes.
n efforts to make large, structurally well-defined aromatic
molecules and conjugated polymers, phenanthrenes repre-
sent convenient intermediates: medium in size, easily
characterized, stable, and potentially synthetically approach-
able. In particular, we have focused our efforts on cyclopenta-
[l]phenanthrenes (1, Scheme 1), because of the wide variety
formation of helices in solution.11 The cyclopentane ring also
provides an attachment point for connecting phenanthrenes to
a central scaffold as an approach to template-directed
synthesis of three-dimensional aromatic compounds such as
the elusive “buckybelts” (F).12 While there have been
numerous reports of phenanthrene synthesis in the
literature,9,10,13−17 none provides the versatility needed to
pursue these applications. Cyclopenta[l]phenanthrenes have
been prepared by condensation of ethyl acetoacetate with
phenanthroquinone18 and by intramolecular ring closure of a
phenanthrene,19 biphenyl,20 or tetrahydrophenanthrene.21 But
there are no synthetic routes in the literature to cyclopenta-
[l]phenanthrenes with substituents on the phenanthrene (R1-
R8, 1). Here we report a new and efficient approach to
prepare substituted cyclopenta[l]phenanthrenes regioselec-
tively, starting from inexpensive starting materials.
I
Scheme 1. Current and Potential Uses of
Cyclopenta[l]phenanthrenes
As shown in the retrosynthetic analysis in Scheme 2,
diphenylcyclopentene 2 provides access to phenanthrene 1 via
the Mallory photocyclization reaction.22−24 Stilbene 2 is
synthesized from a 1,5-diketone (3) via McMurry cou-
Scheme 2. Retrosynthesis of Cyclopenta[l]phenanthrenes
of compounds (A−F) that are accessible from this simple
building block. Phenanthrenocyclopentadienes (A) serve as
bulky metallocene ligands, increasing stereo- and regiocontrol
in metallocene-catalyzed reactions.1−4 The cyclopentane ring
could also allow the convenient attachment of solubilizing
groups in the synthesis of structurally well-defined graphitic
ribbons5−8 (B and E) and conjugated aromatic polymers (C
and D).9,10 Poly(3,6-phenanthrenes) such as C have garnered
interest because they allow a zigzag conformation and the
Received: July 10, 2016
© XXXX American Chemical Society
A
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Letter
pling.25,26 The desired diketone (3) can be generated via
Mukaiyama aldol27 reaction from an acetophenone (4) and
trimethyl orthoformate. As shown in Scheme 3, this route to
In the Mallory reaction, meta substituents on the stilbene
can end up either at the 2 or 4 position of the final
phenanthrene; in most circumstances, the dihydrophenan-
threne intermediates form in similar amounts, leading to a
mixture of products.29 However, Laarhoven and co-workers
have worked out photocyclization conditions that, for
stilbenes with one meta substituent, give selective formation
of the phenanthrene with the substituent at the 2 position.30
Under these conditions, when air is used as the oxidant in
place of iodine, the irreversible oxidation of the dihydrophe-
nanthrene intermediate is much slower. Because of this
change in rate-determining step, and with the reaction carried
out at elevated temperature, the initial photocyclization
reaction becomes reversible, favoring formation of the
intermediate dihydrophenanthrene that leads to product 1e.
Under these conditions, phenanthrene 1e is formed selectively
in 40% yield. These photocyclization conditions also allowed
us to synthesize 2,7-dibromophenanthrene (7e) in two steps
(Scheme 4). To our knowledge, these reactions are the first
reported examples of regioselective photocyclization to a 2,7-
phenanthrene.31
Scheme 3. Synthesis of Symmetric Phenanthrenes 1a−e
Scheme 4. Synthesis of 2,7-Dibromophenanthrene
The approach described here can also be used to prepare
unsymmetric cyclopenta[l]phenanthrenes (Scheme 5), by
using 1 equiv of silyl enol ether in the initial reaction with
trimethyl orthoformate and then allowing the resulting
dimethyl acetal (e.g., 8a or 8b) to react with a different
silyl enol ether in a second, analogous step. The succeeding
two steps remain unchanged, so the unsymmetric phenan-
threnes can each be synthesized in four linear steps from the
silyl enol ether. Phenanthrenes 1f−i were each synthesized by
this method. Phenanthrenes 1g and 1i, with substituents in
the bay region, particularly demonstrate the versatility of this
method. Further functionalization at the halide substituents
provides a route to additional phenanthrenes.
This approach provides each cyclopenta[l]phenanthrene as
a methyl ether. Hydrolysis of the ether with sodium iodide
and aluminum chloride generates the free alcohol.32 We have
demonstrated this hydrolysis for phenanthrenes 1a and 1b,
preparing alcohols 9a and 9b (Scheme 6). The hydrolysis of
the methyl ether can also be performed at the stilbene stage if
preferred for solubility reasons.
In conclusion, we have developed a versatile regioselective
route to cyclopenta[l]phenanthrenes. A wide range of
commercially available and inexpensive acetophenones can
act as starting materials. This approach allows access to either
symmetric or unsymmetric phenanthrenes with control over
the substituents at the outer rings. The reactions tolerate
chloride and methyl substituents, and m- or p-bromide
substituents, with no major change in yields. We have also
demonstrated conditions that selectively transform meta-
substituted stilbenes into 2,7-phenanthrenes. The new
symmetric phenanthrenes is straightforward, starting from an
acetophenone with the desired substituents. The Mukaiyama
aldol reaction is performed in the presence of bis-
(trifluoromethane)sulfonimide as an acid catalyst27 with yields
between 40% and 80%. The resulting diketones (3a−e) are
then cyclized, with yields between 48% and 95%, via
McMurry coupling under Mukaiyama’s conditions, using Zn
and TiCl4.26 Photocyclization of diarylcyclopentenes 2a and
2b, in the presence of iodine and excess propylene oxide,
produces phenanthrenes 1a and 1b, respectively, in high yield.
Unfortunately, in the case of o-bromoacetophenone, the
photocyclization reaction to give phenanthrene 1c was
unsuccessful. Reaction under irradiation at 300 nm returned
only starting material. Using a shorter wavelength for
irradiation did lead to cyclization to a phenanthrene but
also to loss of one or both of the bromines. The steric
hindrance of the o-bromine substituents slows the photo-
cyclization to where the rate of photodehalogenation is
competitive. Nevertheless, o-chloroacetophenone gives access
to phenanthrene 1d, one of only a few successful examples of
the Mallory reaction on a stilbene with this substitution
pattern.28
B
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Scheme 5. Synthesis of Unsymmetric Phenanthrenes 1f−i
Experimental details, compound characterization, and
NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: nancy.goroff@stonybrook.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Stony Brook Foundation for funding of this
research and Lawrence Scott (Boston College), Frank Mallory
(Bryn Mawr College), and Clelia (Sally) Mallory (University
of Pennsylvania) for helpful discussions.
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phenanthrene derivatives described here have potential use as
starting materials for polymerization and as precursors to new
cyclopentadienyl ligands.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b02008.
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