Spontaneous resolution upon crystallization of allenyl-bis-phosphine oxides

Article abstract of DOI:10.1039/c5cc00232j

The first example of 'spontaneous resolution by crystallization' in allene chemistry, by means of crystal structures and solid state CD spectra of the R and S enantiomers, is presented. These allenes are prepared by the simple reaction of Ph₂PC

Full text of DOI:10.1039/c5cc00232j

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Spontaneous resolution upon crystallization of
allenyl-bis-phosphine oxides†
Cite this: Chem. Commun., 2015,
51, 7168
G. Gangadhararao, R. N. Prasad Tulichala and K. C. Kumara Swamy*
Received 10th January 2015,
Accepted 17th March 2015
DOI: 10.1039/c5cc00232j
www.rsc.org/chemcomm
The first example of ‘spontaneous resolution by crystallization’ in
allene chemistry, by means of crystal structures and solid state CD
spectra of the R and S enantiomers, is presented. These allenes are
prepared by the simple reaction of Ph2PCl with o-nitro functionalized
propargyl alcohols.
Allenes, in particular optically active allenes, are important
building blocks in organic synthesis due to the transfer of axial
to central chirality in the final pharmaceutically useful products.1
Since chiral allenes are present in many natural products,
pharmaceuticals2 and molecular materials,3 their synthesis and
reactivity is a prime area of research activity.4 Allenylphosphonates/
allenylphosphine oxides, a subclass of allenes, are also versatile
precursors in synthetic chemistry.5 An interesting case of asymmetric
addition of arylboronic acids to a-keto esters using phosphine
containing chiral allenes as ligands to Rh(I) has also been reported
recently.6 Several methods for the synthesis of chiral allenes,7
including phosphorylated allenes,8 by using a chiral auxiliary/
source have been developed. In order to obtain chiral allenes
from propargylic substrates, there are primarily two major
approaches: one by chirality transfer from the chiral propargylic
substrate (Scheme 1a),9 and the other from the racemic propargylic
substrate by using a chiral ligand (Scheme 1b).10 In these cases,
a chiral source is a must to obtain chiral allenes. A third possibility
is spontaneous resolution by crystallization (Scheme 1c) with-
out using any chiral source, a point not mentioned in the
literature so far. Spontaneous resolution through crystallization
itself is an important topic in organic synthesis and origin of
life.11,12 Herein we disclose our results on the formation of bis-
phosphinoylated allenes by using achiral substrates Ph2PCl (1)
Scheme 1 Formation of chiral allenes using propargylic substrates.
Chart 1 Precursors 1–4 used in the present study.
School of Chemistry, University of Hyderabad, Hyderabad 500 046, Telangana,
India. E-mail: kckssc@uohyd.ac.in, kckssc@yahoo.com; Fax: +91-40-23012460;
Tel: +91-40-231348560
and o-nitro functionalized propargyl alcohols 2a–f, 3a–c and 4
(Chart 1). More importantly, in the reaction using propargyl
alcohols 2a, 2d and 3a, the chiral allene crystallized
spontaneously and in one case both the enantiomers could
be successfully separated.
† Electronic supplementary information (ESI) available: Experimental details,
X-ray structures of the compounds 5–6 and 9–13, UV-Visible spectra of com-
pounds 9 and 12, copies of 1H/13C NMR spectra, and CIF data. CCDC 1041550–
1041557 and 1051469. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c5cc00232j
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Scheme 2 Reaction of 1 with 2a leading to allenes 5 and 6.
The normal reaction of P(III)–Cl with an equimolar quantity of
functionalized propargyl alcohols is expected to lead to mono-
phosphinoylated allenes.13 However, the presence of o-functionality
leads to novel cyclization leading to rather unexpected heterocycles/
fused carbocycles.14 Interestingly, when we performed the reaction
between Ph2PCl (1) and o-nitro functionalized propargyl alcohol
(2a) using 2 : 1 molar stoichiometry (Scheme 2), the resulting
product was allene 5, with a phosphinoyl group at the a position
and a phosphine group at the g position [X-ray, Fig. S1, ESI†]. We
could not get good 1H/13C NMR spectra for this compound,
because of its oxidative instability that led to the bis-phosphinoyl-
allene 6 (X-ray, Fig. S1, ESI†).15 Both compounds 5 and 6 crystal-
lized in the chiral space group P212121 and showed absolute
configurations of R and S respectively (Fig. 1). However we were
unable to separate both the enantiomers in this case.
Scheme 3 Formation of allenyl-bis-phosphine oxides 6–15.
alcohols 2a–f, 3a–c and 4 with Ph2PCl (1) (Scheme 316) to obtain
the allenyl-(bis)phosphine oxides (6–15). Among these struc-
tures, 9 and 12 crystallized in the chiral space group P212121.
More interesting is the fact that for compound 12, we were able
to isolate both the enantiomers (R and S). These two forms were
separated by hand-picking. This separation was facilitated by a
slightly different morphology of these crystals. The overall yield
(including R and S forms) was 480%. The presence of two sterically
interactive tetrahedral Ph2P(O)C and electron-withdrawing o-nitro
groups may be responsible for the separation of enantiomers with
axial chirality. Some carbon atoms of the phenyl groups corres-
ponding to the two phosphorus moieties do come close enough
(B3.5 Å). In the general case, it may be possible to observe a
similar phenomenon wherein sterically interacting substituents
are present on the allene. Judgement regarding this effect may
have to come from more analogous systems. In the case of
compound 12, we could obtain the CD spectra in the solid state
for both the R and S enantiomers (Fig. 2 and 3). However, we were
not able to get significant optical rotation in solution, mainly
because of the difficulty in separating enough pure crystals. Use of
Because of the possibility of spontaneous resolution of
enantiomeric allenes by crystallization in cases similar to the
above, this topic attracted our interest. Hence we synthesized
some more derivatives. In addition, it may be noted that the
substitution of allenic CH by a phosphorus moiety is not
common. Thus, we treated o-nitro functionalized propargyl
¨
an additional chiral base like Troger’s base [(5R,11R)-enantiomer]
in the case of 10, however, did not produce chiral samples.
The bis-phosphinoylated allenes of the type described above
have not been reported so far in the literature. Hence we
wanted to check whether the o-NO2 group on propargyl alcohol
is essential for the second substitution. However, the 2 : 1
stoichiometric reaction of 1 with propargyl alcohols 16 or 18
Fig. 1 A diagram showing the (R)-configuration for compound 5 and
(S)-configuration for 6. Note: the view taken is along the CQCQC axis.
Numbers 1, 2 and 3 on the structures show the ordering of atoms for
deciphering the configuration.
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We acknowledge DST and UGC (both in New Delhi) for
funding and equipment. GGR thanks D. S. Ramakrishna for help
in UV spectra and CSIR for fellowship. RNPT thanks UGC for a
fellowship. KCK also thanks DST for the J. C. Bose fellowship.
Notes and references
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5 (1041550), 6 (1041551), 9
(1041552), 10 (1041553), 11 (1041554), (R)-12 (1041555), (S)-12
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