Rhodium(III)-catalyzed oxidative coupling through C-H bond cleavage directed by phosphinoxy groups

Article abstract of DOI:10.1021/ol4012794

A straightforward synthesis of phosphaisocoumarins is achieved by the rhodium-catalyzed oxidative coupling of diarylphosphinic and phenylphosphonic acid derivatives with alkynes. The P-OH groups effectively act as the key function for the regioselective C

Full text of DOI:10.1021/ol4012794

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Rhodium(III)-catalyzed Oxidative Coupling
through CÀH Bond Cleavage Directed by
Phosphinoxy Groups
Yuto Unoh,† Yuto Hashimoto,† Daisuke Takeda,† Koji Hirano,† Tetsuya Satoh,*,†,‡ and
Masahiro Miura*,†
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, Japan, and JST, ACT-C, 4-1-8 Honcho, Kawaguchi,
Saitama 332-0012, Japan
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
Received May 8, 2013
ABSTRACT
A straightforward synthesis of phosphaisocoumarins is achieved by the rhodium-catalyzed oxidative coupling of diarylphosphinic and
phenylphosphonic acid derivatives with alkynes. The PÀOH groups effectively act as the key function for the regioselective CÀH bond
cleavage. Related oxidative coupling of phenylphosphine oxides with alkenes can also be conducted smoothly under similar conditions.
Transition-metal-catalyzed regioselective CÀH function-
alizations with the aid of directing groups (ÀDG) have
Scheme 1
been recognized as important and environmentally benign
synthetic tools, because these procedures provide atom-
and step-economical routes to complex target molecules
from simple starting materials.1 Particularly, the oxidative
coupling reactions of aromatic substrates possessing a
directing group with internal alkynes through (i) chelation-
directed CÀH bond cleavage, (ii) alkyne insertion, and (iii)
annulation allow the straightforward syntheses of benzannu-
lated heterocycles from readily available monofunctionalized
aromatic substrates (Scheme 1).1m
As an early example, we reported the rhodium-catalyzed
biological properties. Phosphaisocoumarins have also
oxidative coupling of benzoic acids with alkynes to produce
gained much attention as a new class of inhibitors for
isocoumarin derivatives (DG = COO(H) in Scheme 1).2
pancreatic cholesterol esterase.5 Ding and co-workers
After the discovery, similar annulations of various aromatic
reported their multistep syntheses via Sonogashira cou-
substrates have also been developed by us3 and other
pling and subsequent copper-catalyzed cyclization of re-
groups.4 Produced benzannulated heterocycles are usually
sulting ortho-alkynylphenylphosphonic acids.6 A more
of interest because of their optical, electrochemical, and
simple and flexible approach toward phosphaisocoumar-
ins is the oxidative coupling of phenylphosphonic acids
with alkynes via PÀOH directed CÀH functionalization.
† Osaka University.
‡ JST.
However, the utilization of PÀOH groups as directing
r
10.1021/ol4012794
XXXX American Chemical Society

groups has been scarcely explored.7 In the context of our
studies on rhodium-catalyzed oxidative annulation,1m,3 we
succeded in finding that a series of phenylphosphinic acids
undergoes oxidative coupling with internal alkynes under
rhodium catalysis to achieve the single-step syntheses of
phosphaisocoumarin derivatives. A related oxidative cou-
pling between phosphine oxides and alkenesusing a similar
catalyst system is also disclosed herein.
Table 1. Reaction of Phenylphosphinic Acids 1 with Alkynes 2a
In an initial attempt, diphenylphosphinic acid (1a)
(0.25 mmol) was treated with 1 equiv of diphenylacetylene
(2a) (0.25 mmol) in the presence of [Cp*Rh(MeCN)3][SbF6]2
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a Reaction conditions: 1 (0.25 mmol), 2 (0.38 mmol), [Cp*Rh-
(MeCN)3][SbF6]2 (0.01 mmol), AgOAc (0.75 mmol), in solvent (3 mL)
at 120 °C under N2 for 2 h. b Isolated yield based on the amount of 1 used.
Value in parentheses indicates GC yield. c With AgOAc (1 mmol). d With
2a (0.25 mmol). e [Cp*RhCl2
]
was used as a catalyst. f With AgOAc
2
(0.5 mmol). g 3h/isomer = 93:7.
(0.01 mmol) and AgOAc (1 mmol) as catalyst and oxidant,
respectively, in diglyme (3 mL) at 120 °C for 2 h under N2.
B
Org. Lett., Vol. XX, No. XX, XXXX

As a result, the oxidative annulation effectively proceeded
to afford 1,3,4-triphenyl-1H-2,1-benzoxaphosphorin-1-oxide
(3a) in 79% yield (entry 1 in Table 1). In other solvents such
as dioxane, DMF, and o-xylene, the product yield decreased
(entries 2À4). Increasing the amount of 2a (0.38 mmol) led
to enhancement of the product yield to 94% (entry 5). The
use of [Cp*RhCl2]2 (0.005 mmol) as catalyst in place of
[Cp*Rh(MeCN)3][SbF6]2 reduced the reaction efficiency
(entry 6). With a slightly decreased amount of AgOAc
(0.75 mmol), 3a was obtained almost quantitatively (entry 7).
However, further decrease in the amount of AgOAc
reduced the product yield (entry 8). Under the optimized
conditions, the reactions of various phenylphosphinic
acids 1 with alkynes 2 were next examined. Bis(para-
substituted phenyl)phosphinic acids 1b and 1c underwent
coupling with 2a to afford the corresponding phosphaiso-
coumarins 3b and 3c (entries 9 and 10). In these cases, 1:2
coupling products were also detected by GC-MS. There-
fore, the yields of desired 1:1 coupling product 3 seem to
somewhat decrease for the overreaction. As expected, the
use of sterically hindered bis(ortho-methylphenyl)phosphinic
acid (1d) was found to suppress the overreaction to give 3d
selectively in 86% yield (entry 11). The reaction of phenyl-
phosphonic acid monoethyl ester (1e) with 2a proceeded
smoothly to produce 3e in 78% yield (entry 12). It should
be noted that this compound is an important intermediate
and their hydrolysis and alcoholysis with or without ring-
opening have been established.8 para-Methoxy- and chloro-
substituted diphenylacetylenes 2b and 2c also coupled with
1a to produce the corresponding phosphaisocoumarins 3f
and 3g (entries 13 and 14). The reaction of unsymmetrical
1-phenyl-1-propyne (2d) gave 3h predominantly, along with
minor amounts of an isomer and a separable 1:2 coupling
product (entry 15).
Figure 1. Time course of the yields of formed 3a-d0 (diamonds)
and 3a-d9 (squares) during the early stages of the reactions of
1a-d0 and 1a-d10 with 2a.
Table 2. Reaction of Phenylphosphine Oxides 4 with Acrylates 5a
A plausible mechanism for the reaction of diphenylpho-
sphinic acid (1a) with alkyne 2 is illustrated in Scheme 2, in
which neutral ligands are omitted. Coordination of 1a to a
RhIII center and subsequent cyclorhodation on one of the
phenyl groups of a resulting intermediate A take place to
form a five-membered rhodacycle intermediate B. Then,
alkyne insertion to form C and reductive elimination may
Scheme 2
a Reaction conditions: 4 (0.25 mmol), 5 (2 mmol), [Cp*Rh(MeCN)3]-
[SbF6]2 (0.02 mmol), AgOAc (1 mmol), in o-dichlorobenzene (3 mL) at
120 °C under N2 for 6 h. b Isolated yield based on the amount of 4used. c With
5a (0.75 mmol) and [Cp*Rh(MeCN)3][SbF6]2 (0.01 mmol). d In diglyme.
occur to release 3. The RhI species seems to be oxidized by
AgI to regenerate RhIII.
Org. Lett., Vol. XX, No. XX, XXXX
C

Forproviding additional mechanisticinformation, deut-
erated diphenylphosphinic acid (1a-d10) was treated with
2a under standard reaction conditions. During the early
stage (∼13min), the reactionof1a-d10 (squares in Figure 1)
proceeded significantly more slowly than that of 1a-d0
(diamonds). The observed kinetic isotope effect (KIE)
was 6.8. This fact suggests that the rate-determining step
involves CÀH(D) bond cleavage (A to B in Scheme 2).
Next, we examined the oxidative coupling using alkenes
in place of alkynes as coupling partners. Treatment of 1a
with 2 equiv of butyl acrylate (5a) in the presence of a
[Cp*Rh(MeCN)3][SbF6]2/AgOAc system and subsequent
methylation with MeI and K2CO3 gave a trace amount of
alkenylated product along with a significant amount of
methyl ester of recovered 1a. Interestingly, phenylpho-
sphine oxides 4 were found to react with alkenes 5. Thus,
dicyclohexyl(phenyl)phosphine oxide (4a) (0.25 mmol)
reacted with 5a (0.75 mmol) in the presence of [Cp*Rh-
(MeCN)3][SbF6]2 (0.01 mmol) and AgOAc (1 mmol) in
diglyme at120°C toaffordortho-alkenylatedproduct6ain
15% yield (entry 1 in Table 2). This reaction was found to
proceed more smoothly in o-dichlorobenzene (entry 2).
With the increased amounts of [Cp*Rh(MeCN)3][SbF6]2
(0.02 mmol) and 5a (2 mmol), the product yield was
improved up to 64% (entry 3). Under similar condtions,
related acrylates, such as ethyl (5b), cyclohexyl (5c), iso-
butyl (5d), and tert-butyl (5e) acrylates also underwent the
coupling with 4a to produce 6bÀe in 42À67% yields
(entries 4À7). The reaction of dicyclohexyl(biphenyl-2-yl)-
phosphine oxide (4b), which is readily available by simple
oxidation of Cy-JohnPhos, similarly proceeded to produce
6f (entry 8). In the case with sterically less hindered di-
methyl(phenyl)phosphine oxide (4c), dialkenylation took
place to selectively produce 7 in 71% yield (entry 9).
In summary, we have demonstrated that the rhodium-
catalyzed oxidative coupling of phenylphosphinic acids
with alkynes proceeds efficiently to give phosphaisocou-
marin derivatives selectively. Under similar rhodium cat-
alysis, phenylphosphine oxides couple with alkenes to
form the corresponding ortho-alkenylated products. These
represent rare but effective examples involving CÀH bond
cleavage directed by phosphinoxy groups.
(5) Li, B.; Zhou, B.; Lu, H.; Ma, L.; Peng, A.-Y. Eur. J. Med. Chem.
2010, 45, 1955.
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Chem. Soc. 2003, 125, 15006.
Acknowledgment. This work was partly supported by
Grants-in-Aid from MEXT, JSPS, and JST, Japan.
(7) During the preparation of this manuscript, Kim and co-workers
reported the palladium-catalyzed oxidative coupling of benzyl- and
phenoxyphosphonic acids with alkenes: (a) Meng, X.; Kim, S. Org.
Lett. 2013, 15, 1910. (b) Chan, L. Y.; Kim, S.; Ryu, T.; Lee, P. H. Chem.
Commun. 2013, 49, 4682.
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2008, 5277. (b) Peng, A.-Y.; Li, B.; Yang, X.; Lin, J. Synthesis 2008,
2412.
Supporting Information Available. Standard experi-
mental procedure and characterization data of products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX