Diphosphination of Arynes with Diphosphines

Article abstract of DOI:10.1021/acs.orglett.8b01470

A diphosphination of arynes with diphosphines has been developed. The reaction of stable aryne precursors, 2-(trimethylsilyl)aryl triflates, with tetraaryldiphosphines proceeds in the presence of fluorine- or carbonate-based activators to deliver the corresponding diphosphinated products, sterically and electronically tuned 1,2-bis(diphenylphosphino)benzene (dppbz) derivatives, which can find wide application in transition metal catalysis and material science. Additionally, preliminary computational studies on the reaction mechanism are also reported.

Full text of DOI:10.1021/acs.orglett.8b01470

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Diphosphination of Arynes with Diphosphines
Yuto Okugawa,† Yoshihiro Hayashi,‡ Susumu Kawauchi,‡ Koji Hirano,*,† and Masahiro Miura*,†
†Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
‡Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan
S
* Supporting Information
ABSTRACT: A diphosphination of arynes with diphosphines
has been developed. The reaction of stable aryne precursors, 2-
(trimethylsilyl)aryl triflates, with tetraaryldiphosphines proceeds
in the presence of fluorine- or carbonate-based activators to
deliver the corresponding diphosphinated products, sterically
and electronically tuned 1,2-bis(diphenylphosphino)benzene
(dppbz) derivatives, which can find wide application in
transition metal catalysis and material science. Additionally,
preliminary computational studies on the reaction mechanism
are also reported.
isphosphines are indispensable organic compounds in
underdeveloped. A related stannylphosphination of arynes with
Bmodern synthetic chemistry because they are promising stannylphosphines was reported by Studer, but strongly basic
conditions (i-PrMgCl) and careful temperature control (−78
°C) were still necessary, and aryne precursors were limited to
1,2-di(pseudo)halogenated benzenes.10
bidentate ligands in transition metal catalysis and can greatly
affect the selectivity as well as the efficiency of catalytic
reactions.1 Particularly, 1,2-bis(diphenylphosphino)ethanes and
-ethenes constitute a prevalent class of ligands, owing to their
uniquely rigid chelating nature to the metal center. Thus, rapid
and concise synthesis of the above-mentioned chelate-type
ligands has been a long-standing research subject in the
synthetic community. Among numerous reported procedures,
the diphosphination of C−C multiple bonds with diphosphines
(R2P−PR2) is one of the most attractive and straightforward
approaches since the readily available hydrocarbons can be used
as the starting substrates.2 To date, several reaction systems
based on metal catalysts, radicals, and photochemistry have
been developed for the diphosphination of alkynes3 and
alkenes.4 On the other hand, the diphosphination of highly
reactive and unstable arynes5 remains undescribed in the
literature in spite of the advantage of such an approach.6 Given
the recent wide application of expected products, that is, 1,2-
bis(diphenylphosphino)benzenes (dppbzs) in homogeneous
catalysis7 and material science,8 development of new, effective
strategies for the diphosphination of arynes is highly desirable.
Herein, we report a simple and, thus, practical method for the
diphosphination of arynes: TBAT (Bu4NSiPh3F2) or Cs2CO3/
18-crown-6-promoted diphosphination of stable aryne pre-
cursors, 2-(trimethylsilyl)phenyl triflates with diphosphines, is
described. The newly developed protocol allows for preparation
of electronically and sterically diverse dppbz-type ligands, some
of which are inaccessible by conventional methods. Although
synthesis of phosphorus-substituted arenes via aryne inter-
mediates has been recently developed by several research
groups,9 direct introduction of the P(III) group remains
Our study commenced by identification of an appropriate
aryne precursor with tetraphenyldiphosphine (Ph2P-PPh2; 2a)
as the coupling reagent. After extensive screening of activators
and reaction parameters as well as aryne precursors, we were
pleased to find that the 2-(trimethylsilyl)phenyl triflate (1a,
0.25 mmol) was the promising substrate, and the desired
diphosphination reaction proceeded in the presence of
Bu4NPh3SiF2 (TBAT) and MS 4 A in DCE at 60 °C
(conditions A; Scheme 1). For ease of handling, the
diphosphinated product was analyzed and isolated as the
corresponding phosphine sulfide 3aa-S (85% 31P{1H} NMR
yield and 79% isolated yield) after treatment with elemental
Scheme 1. Optimal Conditions for Diphosphination of 2-
(Trimethylsilyl)phenyl Triflate (1a) with
Tetraphenyldiphosphine (2a)
Received: May 10, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01470
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
sulfur S8. The reaction could be easily conducted on a 1.0 mmol
scale, and a 350 mg quantity of the product was obtained (68%
isolated yield), thus indicating the good reproducibility and
practicality of this process. Additionally, the Cs2CO3/18-crown-
6/THF-promoted conditions (conditions B)11 were also good
candidates to deliver 3aa-S in a comparable yield (71% 31P{1H}
NMR yield).12
decomposition of the aryl-Bpin bond. Conditions A generally
showed better results, but conditions B were specifically
effective in the case of 3da-S, 3ea-S, and 3na-S.
Owing to the ready availability of functionalized diary-
ldiphosphines, we then focused our attention toward synthesis
of dppbz-type ligands with electronically modified aryl
substituents on phosphorus (Figure 1). Pleasingly, conditions
With the optimal conditions in hand, we performed the
diphosphination of a variety of 2-(trimethylsilyl)aryl triflates 1
with 2a. Representative products are illustrated in Scheme 2.
Scheme 2. Diphosphination of Various 2-
(Trimethylsilyl)aryl Triflates 1 with Tetraphenyldiphosphine
a
(2a)
Figure 1. Structure and yields of diphosphinated products 3-S from
substituted tetraaryldiphosphines 2 under Conditions A.
A were applicable to electron-rich and -deficient tetraaryl-
diphosphines, giving electronically diverse dppbz derivatives
3hb-S−3hd-S in acceptable yields (formed C−P bonds are
illustrated with bold lines). To the best of our knowledge, they
are novel dppbz ligands that are otherwise difficult to synthesize
by other means.13 Additionally, the chiral bisphosphine ligand
with point chirality on phosphorus was also accessible (3je-S),
albeit as a 1:1 diastereomixture.
As mentioned above, the diphosphinated products were
isolated in the more stable phosphine sulfides, but the direct
isolation of P(III) products without S8 quenching was also
feasible (Scheme 3, 3aa and 3ma). Furthermore, the
Scheme 3. Direct Isolation of P(III) Products 3 and
Desulfidation of Phosphine Sulfide Products 3-S
a
Conditions: see Scheme 1. Conditions employed (A or B) in
b
parentheses. Isolated yields are given. Modified conditions B:
Cs2CO3/18-crown-6 (2.4 equiv), 2a (3.0 equiv), B2pin2 (1.0 equiv),
̊
THF, 60 C, 39 h
The reaction was compatible with electron-donating (methyl,
tert-butyl, methoxy) and -withdrawing (trifluoromethyl, chloro)
groups at the ortho and meta positions and the corresponding
backbone-modified dppbz-type ligands 3ba-S−3ha-S in good
yields (46−79%). The more sterically demanding doubly ortho-
substituted substrate was also tolerated under identical
conditions (3ia-S). Additionally, the fused ring systems,
including methylenedioxy and naphthyl groups, could be
converted into the desired diphosphines 3ja-S−3la-S in
synthetically useful yields. The heteroaromatic pyridine
derivative also underwent the diphosphination (3ma-S).
Notably, the present strategy accommodated the potentially
reactive Bpin moiety (3na-S), which can be a good handle for
further modifications toward new ligand design. In this case, the
addition of pinB−Bpin improved the yield to some extent:
although the detailed role is unclear at this stage, it can be a
scavenger of excess fluoride anions to avoid the undesired
desulfidation of 3ga-S to 3ga could be easily conducted by
using a Schwartz reagent.3g,14 Thus, the present diphosphina-
tion reaction can provide new and facile access to bidentate
ligands.
Reaction mechanisms of arynes with some nucleophiles have
been studied experimentally5 and theoretically,10,15 but details
about diphosphination with diphosphines still remains elusive.
Thus, to gain some mechanistic insight, we performed
computational studies with DFT calculations. Three plausible
reaction paths were assumed, as shown in Figure S3: (a) the
formation of a zwitterionic intermediate by addition of Ph2P−
PPh2 to benzyne, (b) (2 + 1) addition of benzyne with Ph2P−
PPh2, (c) radical addition of PPh2−PPh2 to benzyne. The
results of the reaction path search for the three paths show that
B
DOI: 10.1021/acs.orglett.8b01470
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the path (a) is the most kinetically and thermodynamically
favorable mechanism for the diphosphination.16
The energy diagram of the path (a) is shown in Figure 2. The
relative enthalpy is based on benzyne and Ph2P−PPh2 at 0 kcal
the 1,2-bis{(diphenylphosphino)methyl}benzene 7-S in 51%
yield, while the 2:1 diphosphinated product 8-S (CCDC
1827236) was selectively formed under TBAT/MS 4 A-
mediated conditions.
In conclusion, we have developed simple and practical
strategies for diphosphination of arynes with diphosphines. The
reaction of stable and readily prepared aryne precursors, 2-
(trimethylsilyl)aryl triflates, proceeds in the presence of
fluorine- or carbonate-based activators to form the sterically
and electronically tuned 1,2-bis(diphenylphosphino)benzene-
type bidentate ligands of great potential in transition metal
catalysis and material science. Additionally, the present work
can provide new insight into the reactivity of arynes with
heteroatom nucleophiles. More detailed mechanistic studies
and further development of related phosphination chemistry
are ongoing in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figure 2. Energy profile of the zwitterionic mechanism at the ωB97X-
D/6-311+G(d,p) in DCE solvent treated as IEFPCM.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b01470.
mol−1. The reaction enthalpy (ΔH) in the process where
Ph2P−PPh2 is added to benzyne and the zwitterionic
intermediate is formed was −32.5 kcal mol−1. In this process,
no transition state was found, although we searched carefully.
The activation enthalpy (ΔH‡) in the process from the
zwitterionic intermediate to the diphosphinated product was
2.7 kcal mol−1, and ΔH was −84.3 kcal mol−1. This low ΔH‡
value indicates that the zwitterionic intermediate rapidly
isomerizes to the diphosphinated product. Therefore, the
diphosphination of benzyne by the path (a) is thought to
proceed rapidly.
Finally, we focused on recent advances in the hexadehydro-
Diels−Alder (HDDA) reaction15a,17 and attempted to combine
this chemistry with the diphosphination. Gratifyingly, upon
simple heating of a mixture of tetrayne 4 and tetraphenyl-
diphosphine (2a) in THF-d8, the expected dppbz derivative 5-
O was formed in 29% yield (Scheme 4a). Additionally, the
Procedures, characterization data, and details of DFT
studies (PDF)
Accession Codes
CCDC 1827236 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: k_hirano@chem.eng.osaka-u.ac.jp.
*E-mail: miura@chem.eng.osaka-u.ac.jp.
ORCID
Scheme 4. Diphosphination of Additional Strained
Molecules
Koji Hirano: 0000-0001-9752-1985
Masahiro Miura: 0000-0001-8288-6439
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by JSPS KAKENHI Grant Nos. JP
15H05485 (Grant-in-Aid for Young Scientists (A)) to K.H. and
JP 17H06092 (Grant-in-Aid for Specially Promoted Research)
to M.M. We thank Dr. Yuji Nishii (Osaka University) for his
assistance in obtaining X-ray diffraction data. The numerical
calculations were carried out on the TSUBAME 3.0 super-
computer at the Tokyo Institute of Technology, Tokyo, Japan,
and on the supercomputer at the Research Center for
Computational Science, Okazaki, Japan. This computational
work was partly supported by a JST CREST (Grant Number
JPMJCR1522 to S.K.) and Grant-in-Aid for Young Scientists
(B) (JSPS KAKENHI Grant Number JP 17K17720 to Y.H.).
diphosphination could be extended to 2-[(trimethylsilyl)-
methyl]benzyl phenyl carbonate 6, a well-known ortho-
quinodimethane precursor, which is among the representative
strained and highly reactive molecules similar to arynes
(Scheme 4b).18 In this case, condition-dependent unique
divergent reactivity was observed: a combination of KF and 18-
crown-6 promoted the usual 1:1 coupling reaction to furnish
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D
DOI: 10.1021/acs.orglett.8b01470
Org. Lett. XXXX, XXX, XXX−XXX