Tetrahedron Letters
Evaluation of tuned phosphorus cavitands on catalytic
cross-dimerization of terminal alkynes
Naoki Endo a, Mao Kanaura a, Michael P. Schramm b, Tetsuo Iwasawa a,
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a Department of Materials Chemistry, Faculty of Science and Technology, Ryukoku University, Otsu, Shiga 520-2194, Japan
b Department of Chemistry and Biochemistry, California State University Long Beach, 1250 Bellflower Blvd., Long Beach, CA 90840, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of four new bis-phosphorus cavitands is described, including a description of their catalytic use
on cross-dimerization of terminal alkynes. The commercially available P[N(CH2CH3)2]3, PhP[N
(CH2CH3)2]2, P(OCH3)3, and in situ generated P(NMeBn)3 were reacted with a tetra-ol cavitand platform
to provide new phosphorus ligands. These ligands readily formed bis-Au complexes that were examined
to generate a reactivity profile for the catalytic cross-dimerization of terminal alkynes. We found that the
ligand derived from P[N(CH3)2]3 gave best product selectivity.
Received 11 August 2016
Revised 3 September 2016
Accepted 8 September 2016
Available online 13 September 2016
Keywords:
Ó 2016 Elsevier Ltd. All rights reserved.
Introverted functionality
Supramolecular catalysis
Metallo-cavitands
Phosphorus cavitands
Resorcin[4]arene
Mother nature is a master of chemical transformations. She
serves as an incredibly well-organized chemical transformation
machine, performing countless cascades of catalysis giving prod-
ucts with breathtaking molecular diversity. Recently, enzymes
with multiple metals that activate otherwise inert substrates
inside an enforced cavity have caught our attention.1 Development
of artificial catalysts of comparable ability to such enzymes is a
vital matter, especially from the viewpoint of green chemistry.2
Using principles from the fields of both supramolecular and
organometallic chemistry, we have sought to develop active metal
centers embedded inside cavities.3 However, such ‘‘introverted”
functionalized cavitands have not yet attained the status associ-
ated with what we consider a powerful synthetic scaffold.4 The
shortcomings we have encountered continued to challenge us.
The synthetic difficulty not only to install a metal center, but also
to fine-tune its substructure has hindered these efforts.5 Within a
confined space there has been little room for a metal, a ligand
set, let alone a substrate. Overcoming these drawbacks will allow
cavitands to be utilized as efficient chemical catalysts.6
enforced cavity was not only large enough to accommodate multi-
ple metals, more importantly this new entity entices two different
reaction partners inside AND carries out a coupling between them.
While yields still remained modest we were greatly encouraged.
We think the tuning of the metal centers through remote elec-
tronic effects might further influence the reaction efficiency.8,9
Thus, we have systematically manipulated the phosphorous
ligands of 1 while simultaneously maintaining the enforced cavity.
Herein we present a preparation of new bis-phosphorus cavitands
2–5 that are synthetic variants of 1. For 2–5 different substituents
were induced onto the two phosphorus atoms (Scheme 2). We
anticipated that these fine-tuned ligands would regulate both the
fitting of two guests into the space, as well as have some electronic
effect, thus influencing both the yields and selectivity in the cross-
dimerization of terminal alkynes.
We began our investigation from synthesis of 2 and 4 in accor-
dance with the experimental procedure of 1 (Scheme 3).10 The
tetra-ol cavitand 6 reacted with commercially available P[N(CH2-
CH3)2]3 and PhP[N(CH2CH3)2]2 in 64% and 38% yields, respectively.
The phosphonite 4 was prepared three times and every sample
decomposed 1 month later despite storage in the dark under an
argon atmosphere; thus, 4 proved to be unexpectedly fragile.11
For the synthesis of 3 in Scheme 4, the corresponding P
(NMeBn)3 was not commercially available, and we explored an
access to in situ generation of P(NMeBn)3 and the following reac-
tion with the tetra-ol cavitand 6. Among several attempts, the
use of 9.6 equiv of PCl3 and 35 equiv of HNMeBn was best for
We recently reported the synthesis of an introverted bis-Au
species tethered to a cavitand of diquinoxaline-spanned resorcin
[4]arene (Scheme 1).7 The arrangement of two Au atoms, pointing
inward and flanked by 2 aromatic walls, provided a new architec-
ture for catalytic cross-dimerization of terminal alkynes: the
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Corresponding author. Tel.: +81 77 543 7461; fax: +81 77 543 7483.
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