Synthesis of bulky phosphines by rhodium-catalyzed formal [2 + 2 + 2] cycloaddition reactions of tethered diynes with 1-alkynylphosphine sulfides

Article abstract of DOI:10.1021/ja071622o

The reaction of tethered diynes with 1-alkynylphosphine sulfides under rhodium catalysis provides the corresponding phosphine sulfides having a bulky aryl group. The following desulfidation yields bulky phosphines that will potentially serve as ligands in

Full text of DOI:10.1021/ja071622o

Published on Web 05/11/2007
Synthesis of Bulky Phosphines by Rhodium-Catalyzed Formal [2 + 2 + 2]
Cycloaddition Reactions of Tethered Diynes with 1-Alkynylphosphine Sulfides
Azusa Kondoh, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received March 7, 2007; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Table 1. Rh-Catalyzed Formal [2 + 2 + 2] Cycloaddition
In the modern organic synthesis, bulky phosphine ligands play
an indispensable role in preparing biologically interesting com-
pounds as well as organic functional materials.1 Synthesis of such
bulky ligands is hence quite important. However, the methods for
the synthesis are mostly limited to the reaction of a chlorophosphine
with a bulky organometallic reagent2 and the transition-metal-
catalyzed phosphination or phosphinylation of a bulky aryl halide.3
We have been focusing on 1-alkynylphosphines as precursors
of new phosphines.4 In the course of our study on the use of
1-alkynylphosphines, we report herein a conceptually different
approach to bulky phosphines. Rhodium-catalyzed formal [2 + 2
+ 2] cycloaddition reaction5 of 1,6-diynes and 1-alkynylphosphine
sulfides6 afforded benzene rings having a thiophosphinyl moiety.
When substrates are properly designed, the newly formed benzene
rings naturally have one or two substituents next to the thiophos-
phinyl group, which provide sterically congested environment
around the phosphorus.7
The reaction of 1,6-diyne 1a with 1-octynyldiphenylphosphine
sulfide (2a) proceeded smoothly in dichloromethane in the presence
of a cationic rhodium catalyst and BINAP (Table 1, entry 1). Among
the ligands we screened, BINAP was the best ligand. When DPPE,
DPPB, DPPF, or PPh3 (2 equiv) was used, the yield was moderate.
The generation of the cationic rhodium species by the action of
silver tetrafluoroborate was essential. Without the silver salt, only
1a participated in the cycloaddition reaction to form dimerized 4a
and no 3aa was obtained. The cationic rhodium center would induce
the strong coordination of 2a. Iridium catalysis, [IrCl(cod)]2 with
or without the silver salt, for instance, left 2a untouched and
provided 4a instead. The use of [Cp*RuCl(cod)] only promoted
the very slow dimerization of 1a. The reaction of trivalent
1-octynyldiphenylphosphine with 1a resulted in no conversion. The
highly coordinating nature of the trivalent phosphine would cause
deactivation of the catalyst. The reaction of 1-octynyldiphenylphos-
phine oxide with 1a provided 40% yield of the corresponding
product along with 4a. The sulfide moiety seems to properly assist
the reaction of a rhodacyclopentadiene intermediate with 2a in the
catalytic cycle.8
Reactions of Tethered Diynes with 1-Alkynylphosphine Sulfides
entry
1
Xa
R1
2
R2
3
yield
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
1b
1c
1d
1e
1c
1c
1c
1c
1c
1f
TsN
O
H
H
H
H
H
H
H
H
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
2a
2a
2b
2c
2g
C6H13
C6H13
C6H13
C6H13
C6H13
Ph
3aa
3ba
3ca
3da
3ea
3cb
3cc
3cd
3ce
3cf
71
77
97
60
93
85
83
74
E2C
CH2
CH2CH2
E2C
E2C
E2C
E2C
E2C
E2C
E2C
E2C
E2C
E2C
iPr
tBu
o-MeOC6H4
Me3Si
C6H13
C6H13
H
H
85
80
Me
Ph
Ph
iPr
iPr
3fa
87b
90b
65b,c
70b,d
77b,d
1g
1g
1h
1h
3ga
3gb
3hc
3hg
Ph
iPr
2-MeO-1-Npe
a Ts ) p-MeC6H4SO2, E ) CO2Me. b Performed in 1,2-dichloroethane
at reflux. c Performed for 12 h. d [RhCl(cod)]2 (5 mol %), AgBF4 (10 mol
%), rac-BINAP (10 mol %), 12 h. e 2-Methoxy-1-naphthyl.
The scope of 1-alkynylphosphine sulfides (entries 6-10) is wide
enough to employ not only phenyl-substituted 2b but also bulky
isopropyl- and tert-butyl-substituted 2c and 2d. The reactions of
o-methoxyphenyl-substituted 2e and trimethylsilyl-substituted 2f
proceeded smoothly. The reaction is so powerful that dialkynylphe-
nylphosphine sulfide 5a and trialkynylphosphine sulfide 5b par-
ticipated in multiple cycloadditions to yield the corresponding
products in high yields (eqs 1 and 2).
Reactions of internal diynes (R1 * H) did not proceed at all in
dichloromethane at 25 °C. Instead, performing the reactions in
refluxing 1,2-dichloroethane resulted in smooth conversion to afford
the corresponding products in good yields (entries 11-15). The
products have a 2,6-disubstituted phenyl group on the phosphorus,
which creates a considerable steric effect.9 Interestingly, the reaction
of 1h with diphenyl[(2-methoxy-1-naphthyl)ethynyl]phosphine
sulfide (2g) provided phosphine sulfide 3hg, which has a chiral
axis.10 The use of monosubstituted 1, where one R1 is H and the
other R1 is Ph, resulted in self-dimerization of the diyne.
Various combinations of tethered diynes and 1-alkynylphosphine
sulfides were examined (Table 1). Dipropargyl ether (1b) and a
diyne 1c derived from dimethyl malonate reacted smoothly with
2a. The latter provided the corresponding triarylphosphine sulfide
3ca in the highest yield of 97% (entry 3). 1,7-Octadiyne (1e) was
superior to 1,6-heptadiyne (1d) as a substrate.
1-Alkynyldicyclohexylphosphine sulfides 7 were less reactive
than the corresponding diphenyl analogues 2. The reaction of
terminal diyne 1c with 7a provided the desired product 8a in
9
6996
J. AM. CHEM. SOC. 2007, 129, 6996-6997
10.1021/ja071622o CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Application of the bulky phosphine was examined. The ligand
8b-S proved to serve as a ligand for the amination of aryl chloride
with morpholine (eq 5).12 The bulky phosphine ligands prepared
by this method will find many applications in organic synthe-
sis.
Acknowledgment. This work was supported by Grants-in-Aid
for Scientific Research from MEXT and JSPS.
moderate yield with concomitant formation of 4b (eq 3). The
reaction of internal diyne 1g with dicyclohexylphosphine sulfide
7b was successful to yield highly crowded 8b in high yield (eq 4).
The products, phosphine sulfides, were subjected to radical
desulfidation conditions11 to provide the corresponding trivalent
phosphines in high yields (Scheme 1). The desulfidation reactions
of these bulky phosphines were clean and high-yielding. Except
for triisopropyl-substituted 3hc-S, the phosphines obtained were
stable under air. We could perform the purification of the trivalent
phosphines on silica gel without any special care. The present
method offers a novel access to bulky phosphine ligands.
Supporting Information Available: Experimental details and
characterization data for new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
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Scheme 1. Desulfidation with TTMSS
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