Visible light-induced palladium-catalyzed ring opening β-H elimination and addition of cyclobutanone oxime esters

Article abstract of DOI:10.1039/c9cc08077e

A palladium catalyst under visible light irradiation activates cyclobutanone oxime ester through single electron transfer to induce radical ring opening to generate hybrid cyanoalkyl Pd(i) radical species. Hybrid cyanoalkyl Pd(i) radical species can undergo either β-H elimination to deliver (E)-4-arylbut-3-enenitrile or undergo radical addition with silyl enol ether and enamide to generate δ-cyano ketones. A dual ligand system composed of two phosphine ligands is essential for the high reactivity.

Full text of DOI:10.1039/c9cc08077e

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Visible light-induced palladium-catalyzed ring
opening b-H elimination and addition of
cyclobutanone oxime esters†
Cite this: Chem. Commun., 2019,
55, 14291
Received 15th October 2019,
Accepted 4th November 2019
ab
a
Wei-Long Xing,a Rui Shang,
*
Guang-Zu Wanga and Yao Fu
*
DOI: 10.1039/c9cc08077e
rsc.li/chemcomm
A palladium catalyst under visible light irradiation activates cyclo- or undergo radical addition with silyl enol ether and enamide to
butanone oxime ester through single electron transfer to induce generate d-cyano ketones by tuning the ligand system that is
radical ring opening to generate hybrid cyanoalkyl Pd(I) radical composed of two types of phosphine (Fig. 1).3,4a,5a,6c The photo-
species. Hybrid cyanoalkyl Pd(I) radical species can undergo either induced palladium-catalyzed ring opening process compares
b-H elimination to deliver (E)-4-arylbut-3-enenitrile or undergo differently with the palladium-catalyzed two-electron oxidative
radical addition with silyl enol ether and enamide to generate addition process under thermal conditions reported by Nishi-
d-cyano ketones. A dual ligand system composed of two phosphine mura and Uemura in terms of reactivity and selectivity (Fig. 1).11
ligands is essential for the high reactivity.
Although the ring-opening addition of cyclobutanone oxime
esters has been reported extensively by using photoredox
Palladium-catalysis in its photoexcitation state by absorbing catalysis12 and transition-metal catalysis13 our work reported
visible light energy has received increasing attention recently.1 herein presents a new reactivity of the palladium catalyst to
Palladium phosphine complexes exhibit a blend of radical active cyclobutanone oxime esters. The reactivity control of
and organometallic reactivity after photo-excitation.1a It was hybrid cyanoalkyl Pd(I) radical species by tuning the dual ligand
recently reported that photoexcited palladium(0) phosphine system offers guidance to design and to discover new catalytic
complexes activate alkyl halides2 and alkyl N-(acyloxy)phthal- reactivity of palladium under visible light irradiation.
imide3 to generate a putative hybrid alkyl Pd(I) radical species
The optimized conditions for ring-opening elimination and
that allows alkyl Heck reaction,4 desaturation,5 and even C–H addition with silyl enol ether are shown in Scheme 1a and b,
functionalization reactions6 in high efficiency. Single electron respectively. Use of a combination of a bidentate phosphine
oxidative addition and generation of hybrid alkyl Pd(I) species ligand and a monodentate phosphine ligand is essential for
effectively overcomes several long standing problems encountered both the transformations to proceed in high efficiency (see ESI†
in thermal palladium-catalyzed alkylation, such as oxidative addi- for more details about reaction optimization).
tion to tertiary alkyl electrophiles and suppression of undesired
In the elimination reaction, the desired product could be
b-H elimination in nonproductive steps. However, the electrophile obtained in 89% isolated yield under the optimal conditions.
substrates amenable in excitation state palladium catalysis are
still limited. Herein, we found that cyclobutanone oxime esters,7 a
class of electrophile easily accessed from cyclobutanone,8–10 can
be activated by a phosphine ligated Pd(0) complex under mild
irradiation conditions to generate hybrid cyanoalkyl Pd(I) radical
species. The generated hybrid cyanoalkyl Pd(I) radical species can
either undergo b-H elimination to deliver (E)-4-arylbut-3-enenitrile
a Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key
Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of
Biomass Clean Energy, iChEM, University of Science and Technology of China,
Hefei 230026, China. E-mail: fuyao@ustc.edu.cn
b Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: rui@chem.s.u-tokyo.ac.jp
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9cc08077e
Fig. 1 Activation of cyclobutanone oxime ester by the palladium catalyst
(1) under thermal conditions through oxidative addition and (2) under irradiation
conditions through the formation of hybrid alkyl Pd(I) radical species.
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Table 1 Scope of ring-opening elimination of a-arylated cyclobutanone
oxime estersa
a
Reaction conditions: oxime ester (0.5 mmol), Pd(OAc)2 (5 mol%),
Xantphos (6 mol%), PPh3 (10 mol%) and i-Pr2NH (0.5 mmol) in dioxane
(3 mL) at room temperature under irradiation with blue LEDs (Kessil,
40 W, 440 nm) for 12 h. Yields of isolated products were reported.
of a-arylated cyclobutanone oxime ester (Table 1). Several
2-aryl substituted cyclobutanone oxime esters with both
electron-donating (3, 4) and electron-withdrawing substituents
(5, 8) were suitable substrates for providing (E)-4-arylbut-3-
enenitrile products in 54–87% yields. 2-Thienyl (6) and
2-naphthyl (7) substituted cyclobutanone oxime esters were
Scheme 1 Key reaction parameters: (a) ring opening elimination, reaction
conditions: oxime ester (0.5 mmol), Pd(OAc)2 (5 mol%), Xantphos (6 mol%),
PPh3 (10 mol%) and i-Pr2NH (0.5 mmol) in dioxane (3 mL) at room
temperature under irradiation with blue LEDs (Kessil, 40 W, 440 nm). (b)
Addition with silyl enol ether, reaction conditions: oxime ester (0.2 mmol),
silyl enol ether (0.3 mmol), PdCl2 (5 mol%), dppf (6 mol%), PPh3 (10 mol%) amenable substrates. 2-Alkyl substituted cyclobutanone oxime
and Na2HPO4 (0.2 mmol) in dioxane (2 mL) at room temperature under
irradiation with blue LEDs (Kessil, 40 W, 456 nm). Yield determined by
esters were not suitable substrates under the optimized reac-
tion conditions.
The reaction scope for ring opening addition with silyl enol
ether with respect to different cyclobutanone oxime esters is
GC with diphenylmethane as an internal standard. TMS = trimethylsilyl.
Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. BINAP =
(+/ꢀ)-2,20-bis(diphenylphosphino)-1,10-binaphthyl. 1,10-Phen = o-phenan-
throline. dppf = 1,10-Bis(diphenylphosphino)ferrocene. dppp = 1,3-Bis(diphenyl- demonstrated in Table 2. Cyclobutanone oxime esters bearing
phosphino)propane. DPEphos = Bis(2-diphenylphosphinophenl)ether.
various functional groups, such as ester (9) and protected
amine (10) at the 3-position, were well tolerated to afford the
expected products in good yields. The cyclobutanone oxime
Control experiments revealed that the dual ligand system and esters derived from spiro-cyclobutanones containing a piper-
irradiation are essential for the ring-opening elimination reac- idine ring also showed comparable reactivity (11, 87% yield).
tivity. The wavelength of the light source was also crucial for Furthermore, heterocyclobutan-3-one oxime esters (O, S, N)
high efficiency. Compared with the result using 440 nm blue participated in the reaction well to deliver products with good
LEDs, irradiation sources of other irradiation wavelengths yields (12–15, 65–77% yields). Cyclobutanone oxime esters
(390 nm, 427 nm and 456 nm) resulted in reduced yields (see possessing substituents at the 2-position delivered the ring
ESI† for details). For ring opening addition with silyl enol ether opening addition products with carbon–carbon bond cleavage
(Scheme 1b), control experiments revealed that the combi- occurring selectively at the more hindered position (16–21).
nation of dppf and PPh3 is essential for the high catalytic This ring opening selectivity suggested a radical process rather
efficiency. The desired product could only be obtained in a than a pure organometallic mechanism through b-carbon
moderate yield when dppf was used alone. Irradiation also elimination. In addition, benzocyclobutenone derivatives also
played a crucial role in ring opening addition, and it was found worked well under the standard conditions to deliver benzo-
that 456 nm LEDs were the optimal irradiation source (Schemes nitrile products (22) in 78% yields. Ring strain is the main driving
1b, 1). Oxime esters other than trifluoromethyl benzoate were force for the radical ring opening process, as less-strained
also investigated (Scheme 1b, 2), benzoate, 4-methoxybenzoate, substrates turned out to be unreactive, such as cyclopentanone
and pentafluorobenzoate were all amenable to deliver the oxime ester. 2-Aryl substituted cyclobutanone oxime esters were
desired product, but with lower efficiency. The results of testing not suitable substrates for ring-opening addition with silyl enol
other bidentate phosphine ligands and bidentate nitrogen ether, probably because of the stability of the generated benzylic
ligands showed that dppf was the most suitable ligand for ring radical species after ring-opening.
opening addition with silyl enol ether.
The scope with respect to functional group tolerance on
With the optimal reaction conditions established, we trimethyl((1-phenylvinyl)oxy)silane for ring opening addition
evaluated the reaction scope of the ring-opening elimination is summarized in Table 3. Both para- and meta-substituents
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Table 2 Reaction scope with respect to oxime esters for ring opening
addition with silyl enol ethera
Table 3 Reaction scope with respect to silyl enol ether for ring-opening
additiona
a
Reaction conditions: oxime ester (0.5 mmol), PdCl2 (5 mol%), dppf
(6 mol%), PPh3 (10 mol%) and Na2HPO4 (0.5 mmol) in dioxane (4 mL)
at room temperature under irradiation with blue LEDs (Kessil, 40 W,
456 nm) for 12 h. Enol silyl ether (2 equiv.). Boc = tert-butoxycarbonyl.
a
b
Reaction conditions: oxime ester (0.5 mmol), PdCl2 (5 mol%), dppf
(6 mol%), PPh3 (10 mol%) and Na2HPO4 (0.5 mmol) in dioxane (4 mL)
at room temperature under irradiation with blue LEDs (Kessil, 40 W,
456 nm) for 12 h. Yields of isolated products were reported.
Cbz = benzyloxycarbonyl. i-Pr = isopropyl. Yields of isolated products
were reported.
were tolerated (23, 24). An ortho-substituent on trimethyl((1-
phenylvinyl)oxy)silane (25) slightly lowers the reactivity. phosphine and monodentate phosphine ligand activates oxime
Functional groups such as methyl sulfide (26), ether (27), esters through light-induced single electron transfer to form a
trifluoromethyl (28), halides (29–32), ester (33), and sulfone hybrid iminyl radical Pd(I) intermediate B. Intermediate B
(35) were well tolerated. a-Heteroaryl silyl enol ethers, including undergoes ring-opening cleavage of the carbon–carbon bond
thienyl (37), pyridyl (38), and furanyl (39) were also reactive to to generate a hybrid cyanoalkyl radical Pd(I) intermediate C.
afford the desired products in good yield.
For ring opening addition with silyl enol ether, intermediate C
interacts with silyl enol ether to produce a new hybrid benzyl
radical Pd(I) species D, which is prone to undergo benzyl
association to form benzyl-Pd(II) species (E) with the dissocia-
tion of PPh3. b-H elimination on E generates F. Rebinding of
PPh3 to F releases alkylated silyl enol ether, which generates a
ketone product after hydrolysis, and regenerates A for the next
catalytic cycle. The process of C to G to H shown in pale color
demonstrates the mechanism of forming the ring opening
elimination product. Xantphos showed a better efficacy for ring
(1)
In addition to the enol-type substrate, we found that N-acetyl opening elimination compared with dppf (20% GC yield of 1)
protected enamine also reacted with oxime esters (eqn (1)) to probably because radical recombination to Pd in hybrid inter-
give d-cyanoketone as a product after hydrolysis.
mediate C is facilitated by using Xantphos as a supporting
Based on our experimental evidence and the literature,3,4a,5a,6c ligand. From the proposed mechanism, the two phosphine
a proposed mechanism that accounts for the palladium- ligands work synergistically to facilitate inner-sphere single
catalyzed ring opening b-H elimination and ring-opening addi- electron transfer from Pd(0) to substrates and also stabilize
tion of cyclobutanone oxime esters is depicted in Fig. 2. The the generated hybrid iminyl and alkyl radical Pd(I) inter-
palladium(0) complex A coordinated with both bidentate mediates (B and C).
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Notes and references
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a photo-excited Pd(0) complex to induce radical ring opening/
carbon–carbon cleavage to generate hybrid cyanoalkyl Pd(I) radical
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induced palladium-catalyzed ring opening b-H elimination and
addition reaction to silyl enol ether of cyclobutanone oxime
esters under mild conditions, to deliver b-aroyl hexanenitriles
and (E)-4-arylbut-3-enenitriles, respectively. A dual phosphine
ligand system, in which a bidentate phosphine ligand and a
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for the high reactivity. This work presents a new synthetic
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We are grateful for the support from National Key R&D
Program of China (2018YFB1501600), National Natural Science
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Strategic Priority Research Program of CAS (XDB20000000),
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Conflicts of interest
The authors declare no competing interests.
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