A [2+2+2] cyclization strategy for the synthesis of phosphorus embedding [6]helicene-like structures

Article abstract of DOI:10.1039/c3cc48943d

A Ni(0) promoted intramolecular [2+2+2] cyclotrimerization of triynes provides suitable access to a new series of phosphorus embedding helicenes. [6]Oxahelicenes in which the helical sequence terminates with a phosphole oxide unit have been prepared in both racemic and enantiopure forms and characterized by X-ray diffraction studies. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc48943d

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A [2+2+2] cyclization strategy for the synthesis
of phosphorus embedding [6]helicene-like
structures†
Cite this: Chem. Commun., 2014,
50, 2199
Received 22nd November 2013,
Accepted 17th December 2013
Paul Aillard, Pascal Retailleau, Arnaud Voituriez* and Angela Marinetti*
DOI: 10.1039/c3cc48943d
www.rsc.org/chemcomm
A Ni(0) promoted intramolecular [2+2+2] cyclotrimerization of triynes
provides suitable access to a new series of phosphorus embedding
helicenes. [6]Oxahelicenes in which the helical sequence terminates
with a phosphole oxide unit have been prepared in both racemic and
enantiopure forms and characterized by X-ray diffraction studies.
Helical structures with embedded phosphorus functions have been
largely neglected so far in spite of the recognized importance of
analogous carbo- and heterohelicenes, or helicene-like molecules,
in extremely diverse fields and applications.1 This is especially
surprising when considering that the peculiar features of phos-
phorus functions have the potential of extensively modulating the
properties of helical structures and consequently expanding the
scope of such applications. Notably, the various oxidation states and
coordination degrees existing for phosphorus, combined with its
coordinating ability toward transition metals, would offer almost
infinite opportunities for tuning the physicochemical properties and
reactivity of helical derivatives.2 So, it can be reasonably postulated
that the underdevelopment of this area results from the lack of
suitably diverse and general synthetic approaches, since only a very
few synthetic strategies have been described in the pioneering work
of Tanaka et al.3 and Nozaki et al.4 Thus, with the aim of filling this
gap we have recently started extensive systematic studies on
synthetic approaches to phosphorus containing helicenes.5
Our strategy involves the use of phosphindoles or dibenzo-
phospholes as the key structural units, since, in principle, these
fragments can be easily integrated into helical scaffolds through
their condensed aromatic rings. So far, these synthons have been
adapted successfully to the synthesis of phosphahelicenes6 via
one of the oldest and most classical method for the synthesis of
Scheme 1 Photochemical synthesis of phosphorus embedding helicenes.5
carbohelicenes, i.e. the oxidative photocyclization of diarylolefins.7
This strategy is presented in Scheme 1.
A well-known alternative for the synthesis of helical derivatives
is the metal mediated [2+2+2] cyclotrimerization of alkynes.8 The
´
method has been introduced in helicene chemistry by Stara and
co-workers9a and applied extensively by the same authors and
others.9b–p Especially, intermolecular rhodium-promoted cyclo-
trimerizations have been used recently by Tanaka et al. to access
the first series of phosphahelicenes.3 We believe that this
cyclotrimerization method, when combined with our strategy of
using phosphindoles as starting materials, as shown in Scheme 2,
has the potential of widely expanding the range of phosphorus
embedding helical structures.
Institut de Chimie des Substances Naturelles, CNRS UPR 2301 – Centre de
Recherche de Gif – 1, av. de la Terrasse, 91198 Gif-sur-Yvette, France.
E-mail: angela.marinetti@cnrs.fr, arnaud.voituriez@cnrs.fr
† Electronic supplementary information (ESI) available: Experimental procedures
and characterization data; X-ray crystal structures of 5a0 and 5b. CCDC 960385
and 960386. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c3cc48943d
Scheme 2 Phosphorus embedding helicenes through metal promoted
[2+2+2] cyclotrimerization (this work).
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Fig. 1 X-ray crystal structure of (SP*-M*)-5a0 (major isomer), CCDC 960385.
Starting from the epimeric P-l-menthyl-substituted triynes
(SP)-4b and (RP)-4c, the [2+2+2] cyclizations afford the product
distributions as shown in Scheme 4: the (SP)-4b epimer affords
the M-configured helical compound (SP,M)-5b0 ([a]D25 = ꢀ902
(c = 1, CHCl3)) as the major isomer, in a 67 : 33 ratio to the
minor P-configured helicene.12 Fig. 2 displays the X-ray crystal
structure of the minor isomer (SP,P)-5b. On the other hand, the
we have (RP)-4c epimer affords the P-configured helical compound
Scheme 3 Synthesis of the phosphorus embedding [6]-helicene-like
derivatives 5.
9a,b,d,e
´
Thus, inspired by the work of Stara et al.,
devised phosphindoles, with the general formula I0, as the key (RP,P)-5c ([a]D25 = +844 (c = 0.3, CHCl3)) as the major isomer, in
substrates and triynes V as the helicene precursors to test the a 86 : 14 ratio to the minor M-configured helicene 5c0.13
feasibility of a [2+2+2] strategy. In these initial studies, the
All the structural and stereochemical assignments mentioned
5-hydroxy-substituted phosphindole oxides 1a–c.5a,c have been above are based on the crystal structure of the (SP,P)-5b isomer
selected as starting materials (Scheme 3). In compound 1a the shown in Fig. 2, combined with the observed [a]D values which
phosphorus substituent is a phenyl group, while 1b and 1c are the
two epimers of the P-l-menthyl-substituted phosphindole displaying
opposite configurations of the chirogenic phosphorus atom.
The hydroxyl function of 1 enables the selective iodination of
the 6-position by reaction with N-iodosuccinimide in DMF,
then alkylation of the phenol with a TIPS-protected propargylic
bromide affords phosphindole 2 which displays the desired
alkyne unit. The second step of the reaction sequence shown in
Scheme 3 takes advantage of the iodine function of 2 to link the
phosphorus fragment to diyne 39d via a palladium catalysed
Sonogashira coupling.
After in situ removal of the TIPS protecting groups, the desired
triynes 4a–c have been isolated in good yields at a 300–500 mg scale.
For the final [2+2+2] cyclization step, several catalysts can be
envisioned, including Co(I),9a,g,h,l,m,10 Rh(I),3,9f,i,k,o Ir(I)9n and
Ni(0)9b,p,11 derivatives. In this work, only Rh(I) and Ni(0) cata-
Scheme 4 Product distribution in the nickel(0)-catalysed [2+2+2] cyclo-
lysts have been tested: a 1 : 2 mixture of Ni(cod)2/PPh3 proved to
be the best catalyst, which afforded the desired helicenes 5 after
reaction for only 15 min at room temperature, at a 20 mol%
catalyst loading. The final phosphine oxides 5a–c have been
obtained as diastereomeric mixtures, due to the presence of
both a stereogenic phosphorus centre and a helically chiral
scaffold. The isomer pairs have been separated easily by flash
chromatography on silica gel columns.
trimerization of the P-menthyl substituted phosphindole oxides (SP)-4b
and (RP)-4c.
The diastereoselectivity of the cycloisomerization step depends
on the nature of the phosphorus substituent R1, and also, for the
epimeric triynes (SP)-4b and (RP)-4c, on the stereochemistry of
phosphorus. Thus, starting from 4a, in which R1 = Ph, a 40:60
ratio of the diastereomeric (RP*,M*)-5a and (SP*,M*)-5a0 has been
obtained. The structure of the major isomer (SP*,M*)-5a0 has been
assigned by X-ray diffraction studies (Fig. 1).
Fig. 2 X-ray crystal structure of (SP-P)-5b (minor isomer), CCDC 960386.
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5 (a) K. Yavari, S. Moussa, B. Ben Hassine, P. Retailleau, A. Voituriez
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6 In the strict sense, the term ‘phosphahelicene’ should denote helical
polyaromatic sequences with ortho-fused phosphorus containing
rings. For simplicity reasons, the term phosphahelicenes is used
in this paper to designate both polyaromatic and partially saturated
helical structures with embedded phosphole units, irrespective of
the linking mode of the phosphorus heterocycle.
are diagnostic of the helical configurations (positive [a]D values
for P-configured helicenes).
From the above results it appears that the Ni(cod)2/PPh3
promoted cycloisomerization of triynes 4a–c always favors
isomers in which the PQO functions occupy the external faces
of the helical scaffolds (‘‘exo’’-isomers) while the phenyl or
menthyl groups are oriented toward the internal faces. The
same trend was observed in our previous work on the photo-
chemical synthesis of phosphahelicenes: the photochemical
reactions resulted in almost exclusive formation of the ‘‘exo’’-
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structure. It involves however total chemoselectivity, as far as a
single phosphahelicene scaffold is formed from the designed
precursors 4. This was not the case for the oxidative photocycliza-
tion of diarylolefins which usually afforded mixtures of the two
isomeric helical compounds III and IV (Scheme 1). In the end, the
[2+2+2] cyclotrimerization strategy proves to be at least as efficient
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oxides has been ascertained: no epimerization of the helical
structure was observed after heating (SP-P)-5b overnight at 100 1C
in toluene.
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Chem. Commun., 2014, 50, 2199--2201 | 2201