Cobaloxime Catalysis: Selective Synthesis of Alkenylphosphine

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Cobaloxime Catalysis: Selective Synthesis of Alkenylphosphine Oxides under Visible Light Wen-Qiang Liu, Tao Lei, Shuai Zhou, Xiu-Long Yang, Jian Li, Bin Chen, Jayaraman Sivaguru, Chen-Ho Tung, and Li-Zhu Wu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b06920 • Publication Date (Web): 11 Aug 2019 Downloaded from pubs.acs.org on August 11, 2019

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Journal of the American Chemical Society

Cobaloxime Catalysis: Selective Synthesis of Alkenylphosphine Oxides under Visible Light Wen-Qiang Liu,a,b Tao Lei,a,b Shuai Zhou,a,b Xiu-Long Yang,a,b Jian Li,a,b Bin Chen,a,b Jayaraman Sivaguru,c Chen-Ho Tung,a,b and Li-Zhu Wu*,a,b aKey

Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, The Chinese Academy of Sciences, Beijing 100190, P. R. China bSchool

of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, P. R. China

cCenter

for Photochemical Sciences and Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, United States ABSTRACT: Direct activation of H-phosphine oxide to react with unsaturated carbon-carbon bond is a straightforward approach for accessing alkenylphosphine oxides, which shows significant applications in both synthetic and material fields. However, expensive metals and strong oxidants are typically required to realize the transformation. Here, we demonstrate the utility of earth-abundant cobaloxime to convert H-phosphine oxide into its reactive radical species under visible light irradiation. The radical species thus generated can be utilized to functionalize alkenes and alkynes without any external photosensitizer and oxidant. The coupling with terminal alkene generates E-alkenylphosphine oxides with excellent chem- and stereo-selectivity. The reaction with terminal alkyne yields linear E-alkenylphosphine oxide via neutral radical addition, while the addition with internal ones generates cyclic benzophosphine oxides and hydrogen. Mechanistic studies on radical trapping experiments, electron spin resonance studies and spectroscopic measurements confirm the formation of phosphinoyl radical and cobalt intermediates that are from capturing the electron and proton eliminated from H-phosphine oxide. The highlight of our mechanistic investigation is the dual role played by cobaloxime viz., both as the visible light absorber to activate the P(O)-H bond, as well as a hydrogen transfer agent to influence the reaction pathway. This synergetic feature of the cobaloxime catalyst preforming multiple functions under ambient condition provides a convergent synthetic approach to vinylphosphine oxides directly from H-phosphine oxides and alkenes (or alkynes).

INTRODUCTION Phosphine oxide represents an important class of units, in which the installation of phosphine group into a molecule significantly improves its bioavailability and inherent optical and electronic characters.1-3 As such, the development of a convenient means to access these substrates has received considerable attention across multiple disciplines. Common synthetic approaches to this type of molecules include treatment of prefunctionalized substrates with strong bases or use of expensive transition metal catalysts.4-10 Recent interest in the direct activation of H-phosphine oxide [P(O)H] to construct CP bond is more atom-economical and straightforward. However, the necessity of precious metal catalysts and oxidants remains one of fundamental limitations. With the aim of developing a suite of new methods for cost-effective chemical synthesis that is both efficient and eco-friendly, we become interested in the use of earth-abundant metal complex for this transformation with visible light.

Cobaloxime [e.g. Co(dmgBF2)2(L)2, dmg = dimethylglyoximato, L = H2O, MeCN, etc.], initially developed as a mimic of vitamin B12,11-13 was recognized early on as a powerful catalyst for either hydrogen evolution from proton14-16 or hydrogen atom transfer17-21. Rapid growth of photocatalysis in recent years has widely extended the application of cobaloxime as an efficient catalyst to carry out chemical transformations that occur efficiently under mild conditions. A particularly useful application corresponds to a Heck type coupling.22 Carreira et al reported an alkyl group derived from alkyl halide underwent intra- and inter-molecular addition23, 24 to double bond followed by unsaturation to provide a substituted olefin. The transformation proceeded upon irradiation of a reaction vessel with visible light in the presence of an amine base. Cobaloxime, combining with photosensitizers, has also shown the ability to capture the electrons and protons eliminated from the substrates for cross-coupling reactions.25-39 In this regard, we questioned whether cobaloxime could activate H-phosphine oxide (for example, diphenylphosphine oxide) [P(O)H] to afford phosphinoyl radical [P(O)·], and simultaneously

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capture the electron and proton eliminated from P(O)H functionality. The generated intermediates such as CoIII-H or CoII enabled transfer the hydrogen in situ in the subsequent radical addition with alkene or alkyne, thus providing us a new and direct strategy for the construction of important phosphine oxides. With this in mind, we carried out reaction of diphenylphosphine oxide [P(O)H] and alkene in the presence of cobaloxime (in dark), but unfortunately no reaction was observed. However, visible light irradiation of the same reaction vessel realized the activation of P(O)H bond by cobaloxime. In contrast to well established photocatalytic systems,40-42 the reaction proceeded smoothly without external photosensitizer and sacrificial oxidant. Cobaloxime directly initiated the photocatalytic reaction of H-phosphine oxide [P(O)H] with alkene and alkyne to selectively produce alkenylphosphine oxides in good to excellent yields. In these transformations, both alkene and alkyne were all well tolerated to afford alkenylphosphine oxides. The high yields, excellent selectivity, wide substrate scopes, mild reaction conditions and the absence of external photosensitizer and sacrificial oxidant demonstrated the great photocatalytic activity of cobaloxime.

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Scheme 1. Optimization of cobaloxime catalysts O Ph P H + Ph Ph

1a

Cobaloxime Ph

pyridine, blue LEDs RT, 16 h, argon, DCM (6 mL)

O Ph P

Cl O H N Me O N Co N O Me N H O Me

Ph

O + Ph P

Ph

Cl O H N Me O N Co N O Me N H O Me Me

4-CO2Mepy

py

Ph Ph

Ph

3a

2a

Me

Ph

3a' Cl O H N Me O N Co N Me H O N H O Me Me

Co(dmgH)2pyCl

Co(dmgH)2(4-CO2Mepy)Cl

Cl Co(dmgH)(dmgH2)Cl2

>99%, 2:1

>99%, 2:1

>99%, 2:1

F MeCN O B F N Me O N Co N O Me N F B O Me F MeCN

F MeOH O B F N Me O N Co N O Me N F B O Me F MeOH

Co(dmgBF2)2(MeCN)2

Co(dmgBF2)2(MeOH)2

Co(dmgBF2)2(H2O)2

90%, 9:1

40%, >20:1

36%, >20:1

Me

Me

Me

F

H 2O

F N O N Co N O Me N B O F Me F H 2O

Me

O

B

Reaction conditions: A solution of 1a (0.1 mmol), 2a (0.3 mmol), cobaloxime (10 mol %) and pyridine (0.2 mmol) in DCM (6 mL) was irradiated with 3 W blue LEDs for 16 hours at room temperature under argon atmosphere. The ratio is 3a to 3a’ detected by 1H NMR analysis.

RESULTS AND DISCUSSION Cobaloxime catalyzed reaction of H-phosphine oxide and terminal alkene. To evaluate our strategy, we investigated the reaction of diphenylphosphine oxide 1a and 1,1-diphenylethene 2a in the presence of 10 mol % Co(dmgH)2pyCl, pyridine (2 equiv.) in CH2Cl2 at room temperature. Upon irradiation with blue LEDs (450 ± 10 nm) for 16 hours, the reaction occurred smoothly with > 99% isolated yield of 3a and 3a’. The products were characterized by NMR spectroscopy (1H, 13C and 31P NMR) as well as high resolution mass spectroscopy (HRMS). Careful analysis of the reaction mixture revealed a 2:1 ratio of alkenylphosphine oxide 3a and hydrophosphorylation product 3a’ (Scheme 1). Further variations on the ligands of cobaloxime complexes showed that different cobaloximes with CoIII (Co(dmgH)2pyCl, Co(dmgH)(dmgH2)Cl2), Co(dmgH)2(4CO2Mepy)Cl) and CoII (Co(dmgBF2)2(L)2, L = MeCN, MeOH, H2O) were all suitable for carrying out the chemical transformation. Among the investigated cobaloxime, Co(dmgBF2)2(MeCN)2 displayed the best photocatalytic activity that resulted in 90% yield with a 3a:3a’ ratio of 9:1 (Further optimization of condition see Table S1). It became clear that cobaloxime itself was able to promote the reaction to access alkenylphosphine oxide 3a without additional/sacrificial oxidant. This is unprecedented in the reported reaction of H-phospine oxide and olefins by metal catalysis43 or visible light catalysis (Rhodmaine B)40 to afford hydrophosphorylation product (alkylphosphine oxide 3a’). Our results for the first time highlight the photo-catalytic ability of cobaloxime in H-phosphine oxide reaction with alkene, and opens up an efficient synthetic route to access vinyl phosphine oxides,

Figure 1. UV-vis absorption spectra in DCM at room temperature: 1a (green), 2a (gray), Co(dmgBF2)2(MeCN)2 (red), 1a and Co(dmgBF2)2(MeCN)2 (blue), irradiation with blue LEDs of 1a and Co(dmgBF2)2(MeCN)2 for 60 s (purple). [1a] = 1.0 × 10-3 M, [2a] = 1.0 × 10-3 M, [Co(dmgBF2)2(MeCN)2] = 1.0 × 10-4 M.

which could be further functionalized, for example, to give alkenyl phosphine (see Supporting Information, part 5). As no reaction occurred in the absence of visible light and cobaloxime, essential to this transformation was the activation of P(O)-H bond by cobaloxime under visible light irradiation. To confirm the interaction between Hphosphine oxide and cobaloxime, both electrochemical and spectroscopic studies were carried out. According to electrochemical study, the oxidative potential of 1a was E1a+/1a  1.0 V vs SCE40 and reductive potential of Co(dmgBF2)2(CH3CN)2 was EII/I = -0.76 V vs SCE (Figure S1). Obviously, this couple is unlikely to proceed electron transfer from 1a to cobaloxime. However, photoexcited


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Journal of the American Chemical Society cobaloxime (excitation energy E00 = 2.67 eV; Figure S2) featured a reductive potential of 1.91 V vs SCE (EII*/I = EII/I + E00) that enabled single electron transfer from 1a to excited cobaloxime. UV-vis absorption spectra showed that two reactants 1a and 2a do not absorb above 400 nm light and only Co(dmgBF2)2(CH3CN)2 absorbs visible light with an absorption maximum at 440 nm (Figure 1). When diphenylphosphine oxide 1a was added into the solution of cobaloxime, a strong peak at 320 nm was generated along with the decrease at 440 nm. Subsequent irradiation of this solution for 1 minute led to the formation of a new signal at 620 nm indicative of CoI species 35 (Figure 1). This result affirmed a photoinduced electron transfer from diphenylphosphine oxide 1a to cobaloxime under visible light irradiation. Moreover, irradiating solution of 1a, 5,5-dimethyl-1-pyrroline Noxide (DMPO) and Co(dmgBF2)2(CH3CN)2 in DCE for 10 seconds and analyzing the sample by electron spin resonance (ESR) provided a characteristic signal of phosphinoyl radical44 (Scheme 2, Figure S7). Besides, TEMPO and MNP as free radical trapping agents significantly decreased the yields of target alkenylphosphine oxide 3a from 99% to 34% and 23%, respectively (Scheme 2, Scheme S1). A coupling product of diphenylphosphine oxide and MNP was detected by 1H NMR and HRMS, directly revealing the formation of phosphinoyl radical. Scheme 2. Radical-capture experiments O Ph P H

+

Ph

Standard Conditions Ph

1a O Ph P H

2a +

Ph


1a O Ph P H Ph

1a

Ph

Ph

TEMPO / MNP


Ph

2a

Ph Ph

Ph 3a + 3a', 94%, 9:1 Ph O Ph Ph P Ph 3a + 3a', 34% / 23%

2a +

O Ph P

MNP

O Ph P N Ph OH

Detected by 1HNMR, MS

alkenylphosphine oxide 3a and the multi-substituted process for product was unlikely. Interestingly, reductive product of 1,1-diphenylethene 2a in the reaction was detected as the byproduct by gas chromatography-mass spectrometry (GC-MS) and 1H NMR spectroscopy (Scheme S3), revealing a selective hydrogen-transfer of reduced cobaloxime into terminal alkene. Isotopic experiment for deuterated 1,1-diphenylethene D-2a further manifested the hydrogen transfer pathway (Scheme S4). Thus, the cobaloxime performs a dual role in the reaction mechanism, 1) as a photocatalyst to activate [P(O)H] bond and 2) as a metal catalyst to capture the electron and proton eliminated from Hphosphine oxide and subsequently transfer the hydrogen to terminal alkene. With this conjecture, we have developed a mechanistic model shown in Scheme 3. Photoexcitation of cobaloxime generated phosphinoyl radical I that reacts with terminal olefin 2a affording radical intermediate II. This intermediate II combined with another CoII catalyst to form metallic intermediate III. After removal of CoIIIH intermediate via β-H elimination, the product 3a was obtained. As mentioned above, the generated CoIIIH intermediate selectively reduced 2a to 1,1-diphenylethane 2a’ (with a subsequent formation of CoIII complex) rather than alkenyl phosphine oxide 3a to hydrophosphorylation product 3a’, thus leading to the high selectivity for alkenylphosphine oxide. The very small amount of hydrophosphorylation product probably came from the protonation of metallic intermediate III. It is also plausible that the CoIII intermediate can be reduced by intermediate II to return its initial state and convert the latter into carbocation intermediate, with removal of a proton to provide the final vinyl product 3a. One cannot exclude the regeneration of ground-state cobaloxime from photoinduced oxidation of substrate 1a by in situ generated CoIII intermediate or disproportionation of CoIII and CoI species. Scheme 3. A plausible mechanism for the reaction of H-phosphine oxide and terminal alkene O Ph P H

O Ph P

Ph II 1a *[Co]

[Co]I

I Ph

H+ h

Based on the above evidences, it is reasonable to consider that visible light irradiation of cobaloxime activated H-phosphine oxide leading to the generation of phosphinoyl radical that reacts with alkene. Under our optimized conditions, high selectivity for alkenyl product 3a was obtained instead of the expected hydrophosphorylation product 3a’. In order to confirm this selectivity, the mixture of product 3a and Hphosphorylation [P(O)-H] 1a was irradiated in the presence of Co(dmgBF2)2(MeCN)2 that did not result in H-phosphorylation and diphosphorous substituted products (Scheme S2). The control study revealed that the minor saturated Hphosphorylation product 3a’ did not come from the further hydrogenation of generated

[Co]III II

O Ph P

2a

Ph

[Co]III-H

[Co]II

Ph

Ph Ph

Ph

O Ph Ph P 2a' Ph

O Ph P Ph

Ph Ph II [Co]II

Ph Ph [Co]III H

III

Ph 3a

With understanding on the reaction mechanism, we explored the generality of this cobaloxime catalyzed reaction involving H-phosphine oxides and terminal olefins. Scheme 4 summarizes the scope of this strategy that highlights the following: a) Styrene derivatives 2 undergo phosphorylation with the retention of double bond in good to excellent yields ranging from 52% to 99% with high selectivity; b) For 1,1-diphenylethene derivatives, substituents such as methyl, methoxy, fluoro, chloro and



bromo on the aromatic ring were well tolerated (3b-3f) to afford the desired products in good to excellent yields (7599%); c) Besides 1,1-diphenylethene derivatives, this transformation is applicable to common monosubstituted styrene derivatives. Moderate to good yields (52-64%) were obtained with up to 20:1 selectivity (ratio of alkenylphosphine oxide : alkylphosphine oxide) irrespective of the steric and electronic variations (3g-3n). The successful formation of 3e-3f and 3m-3n in good yields with intact chloride and bromide provides a good opportunity for post-synthetic functionalization; d) Eisomer was exclusively obtained in the vinyl product; e) With regard to H-phosphine oxides, diphenylphosphine oxides bearing methyl or halogen gave the desired products (3o-3s) in good yields although diethyl phosphite was not suitable in this reaction. As exception, para-methyl substituted one gave the desired product (3o) only in 31% yield but > 20:1 selectivity. f) A large-scale synthesis has been accomplished with 78% isolated yield of 3a and > 20:1 (3a:3a’) selectivity, establishing its great potential of the cobaloxime catalysis in organic synthesis. Scheme 4. Substrate Scope for the reaction of Hphosphine oxide and terminal alkene O Ar P H

+

Ar

1 (0.1 mmol)

Co(dmgBF2)2(MeCN)2 (10 mol %) Ph

Ph

pyridine (1 equiv.), blue LEDs RT, 16 h, argon, DCM (2 mL)

Cl

Ph Ph

Ar

2 (0.3 mmol)

3

Me O Ph P Ph

O Ar P

F

MeO

O O O Me F OMe Ph P Ph P Ph P Ph Ph Ph 3b, 98%, 9:1 3c, 99%, 9:1 3d, 75%, 5:1 Br Me O Me O Ph P O Ph P Br Cl Ph Ph P Ph Ph 3f, 77%, 10:1 3g, 59%, >20:1 3h, 60%, >20:1

3a, 94%, 9:1; 78%; >20:1a

O Ph P Ph 3e, 88%, 5:1

which reacted with alkenes with no additional photosensiter and oxidant under mild condition. Cobaloxime catalyzed reaction of H-phosphine oxide and alkyne. Considering the excellent ability of cobaloxime to promote the reaction of H-phosphine oxides and alkenes, we envisioned that this straightforward and environmentally friendly strategy offered considerable advantages in both simplicity and efficiency for the addition reaction of H-phosphine oxides [P(O)-H] and alkynes. To our delight, via simple trials the combination of cobaloxime and visible light was found to catalyze the radical addition of [P(O)H] bond to alkynes. As shown in Scheme 5, with 10 mol % Co(dmgH)2pyCl as catalyst and 2 equivalent pyridine as base in 2 mL of DCE/MeOH (v/v = 3/1), H-phosphine oxides and terminal alkynes reacted smoothly to produce linear alkenylphosphine oxides with good E-selectivity (more details for condition optimization see Table S2). From the analysis of products (Scheme 5), following conclusions could be obtained: a) For terminal alkynes, most phenylacetylene derivatives bearing either electrondonating or electron-withdrawing groups could obtain their corresponding alkenylphosphine oxides with good E-selectivity (5a-5p). Methoxyl (5h), halogen (5k-5m) and strong electron-withdrawing groups such as cyano (5n), ester (5o), trifluoromethyl (5p) were all compatible to afford the corre Scheme 5. Substrate Scope for the reaction of Hphosphine oxide and terminal alkyne O Ar P H + R Ar 1 (0.1 mmol) 4 (0.2 mmol) O Ph P Ph

O Ph P Ph

O Ph P Ph 3i, 52%, >20:1

3j, 58%, >20:1

O Ph P Ph

Cl

O Ph P Ph

3m, 63%, >20:1 Me

Ph O P

OMe

Ph

F

Ph

Me 3o, 31%, >20:1 Ph O Ph Cl P

Me Me

Me

3q, 58%, >20:1

aThe

F 3r, 68%, 9:1

Bu

O Ph P Ph

F

3k, 54%, >20:1 3l, 64%, >20:1 Ph Me Ph O Ph O Ph Me P Br P

3n, 54%, >20:1 Ph O P

O Ph P Ph

Cl 3s, 86%, 14:1

Ph

5a, 83%, 13:1

Me t

O Ph P Ph

G

5i, 71%, 7:1b

Ph O EtO P OEt

5m, 45%, 4:1a

Ph

Me

O P

Bu

O Ph P Ph

O Ph P Ph

5n, 75%, 13:1

OMe

5h, 68%, 11:1a F

O Ph P Ph

5k, 60%, 7:1a CN

Ph

t

O Ph P Ph

Me

5d, 61%, 17:1a

5g, 68%, 14:1a

O Ph P Ph 5j, 84%, >20:1

O Br Ph P Ph

O Ph P Ph

5c, 40%, >20:1

5f, 68%, 13:1a

O Ph P Ph

Ph 5, yield, E/Z

O Ph P Ph

Ph

R

O Ph P

24 h, argon, RT DCE/MeOH (2 mL, v/v = 3/1)

O Ph P Ph

Me

O Ph P Ph

O Ph P Ph

Co(dmgH)2pyCl (10 mol %) pyridine (2 equiv.), blue LEDs

5b, 55%, 20:1

5e, 56%, 8:1a

Me

3p, 77%, 9:1

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Cl

5l, 56%, 8:1a

O O CO2Me CF3 Ph P Ph P Ph Ph 5o, 77%, >20:1 5p, 41%, 17:1

O P

Ph

O P

MeO

Ph

3t, 0%

reaction was carried out in 1 mmol 1a.

5q, 78%, 17:1

Thus the selective installation of phosphine oxide onto alkene scaffold opens up an important transformation in synthetic and medicinal chemistry. By employing cobaloxime as an efficient photocatalyst, we developed a molecular catalytic system for alkenylphosphine oxide, driven by visible light that forms phosphinoyl radicals,

F

O P

F 5t, 76%, 17:1

aToluene

Ph Cl

O P

Ph O EtO P OEt

Cl 5u, 64%, 10:1

was used as the solvent. carbazol-9-yl substitution.


OMe 5s, 80%, 14:1

5r, 72%, 11:1

Ph

5v, 0%

bG

group represented 9H-

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Journal of the American Chemical Society sponding alkenylphosphine oxides; b) Sterically hindered 2-ethynyl-1,1'-biphenyl (5b) gave a lower yield compared with 4-ethynyl substitution one (5a). Different location of methyl group in phenylacetylene resulted in similar yields of products (5d-5f). Bulky substituents like tert-butyl group (5g) were compatible to afford the corresponding products in a 68% yield; c) Alkyne substrates with heterocycle and extended conjugation were also compatible in this reaction. Carbazole (5i) and naphthalene derivatives (5j) gave isolate yields of 71% and 84%, respectively; d) In terms of diphenylphosphine oxide derivatives, electron-donating and electron-withdrawing groups on the phenyl ring were all compatible with our reaction conditions. The substrates bearing p-methyl, 2,5dimethyl, p-methoxyl, p-fluoro, p-chloro performed well with yields ranging from 64%-80% (5q-5u).

and subsequently cyclized to generate intermediate VI rather than direct hydrogenation, probably due to the reactivity of internal triple bond.4, 7, 41, 49 Then hydrogen atom abstraction by CoII complex produced the cyclic product 7a and CoIIIH complex. In the absence of external oxidant, the captured proton and electron by cobaloxime (CoIIIH) was released as hydrogen (detected by GC, Scheme S7). Although cobaloximes are able to mediate some photoredox cycles, 22-39 all examples known so far (i) do not use the cobaloxime as the light harvesting moiety and (ii) include H2 evolution mediated by hydridocobaloxime. Our method afforded a novel and efficient approach for cyclic benzophosphole oxide without any external oxidant, which is different from previous works using strong oxidant like Nmethoxypyridinium salts.41

A unique aspect of our methodology when compared to previous reports is that such reactions mostly relied on metal catalyzed oxidative addition/insertion/reductive elimination pathway(s). 45, 46 As an alternative, free radical addition process of H-phosphine oxides to alkynes only limited to benzoyl peroxide,47 and Eosin Y42 systems, which provided a Z/E mixture or Z isomer. Our photochemical result by coblaoxime, however, is highly Eselective as showed by the reaction cycle depicted in Scheme 6 (left). Photoexcitation of cobaloxime activates P(O)H bond resulting in phosphinoyl centered radical I that was characterized by ESR (Figure S8) and radical trapping experiment (TEMPO as radical capture, Figure S5). Subsequent addition of phosphinoyl intermediate I to 4a gave rise to carbon center radical IV48 (Figure S8), which combined with CoII intermediate to form intermediate V. Protonation of intermediate V finally provided H-phosphorylation product 5a, accompanied with the regeneration of initial CoIII complex which closed the catalytic cycle without the need for external oxidant and reductant.

By employing 15 mol % Co(dmgH)2pyCl as photocatalyst and 2 equivalent sodium formate as base in DCM, we examined the generality of this reaction (more details for condition optimization see Table S3-S4). As shown in Scheme 7, this cobaloxime catalyzed cyclization was also robust and efficient for H-phosphine oxide and internal alkyne substrates. It was found that electron-withdrawing internal aryl alkynes (p-FPh, p-ClPh, p-CF3Ph) showed higher reactivity than donating ones (7b-7c, 7f). Long carbon chain nBu and sterically hindered tBu groups in diarylacetylenes had no/minimal effect on the transformation, producing the desired products 7d and 7e in good yields. Bromo-substituted diarylacetylene reacted with diphenylphosphine oxide gave 43% yield, likely due to its poor solubility in DCM. In addition to aryl alkynes, aliphatic alkynes also showed good reactivity under our optimized conditions. Both hex-3-yne 6k and dodec-6yne 6l reacted with diphenylphosphine oxide smoothly to give corresponding products in 62% and 56% yields respectively. Significantly, the reaction with unsymmetrical phenylacetylenes like silylethynylbenzene and methyl cinnamate exhibited high regioselectivity, converting into single isomer 7m and 7n with yields of 90% and 53% respectively. With regard to the exploration of H-phosphine oxide, para-substitution of aryl group led to partial rearrangement. For example, bis(4methylphenyl)phosphine oxide and diphenylacetylene under the standard conditions gave both the normal product (7o, 5’) and the isomer (7o, 6’) in 1:1 ratio with 64% yield. A similar result of 7p (5’:6’ = 2:1) was observed for the reactivity of bis(4-fluorophenyl)phosphine oxide and diphenylacetylene leading to 7p and 7p', respectively.

Scheme 6. A plausible mechanism for the reaction of H-phosphine oxide and alkyne CoIII H

CoIII O Ph P V Ph

O Ph P Ph Ph-4-Ph

H+ Ph

O Ph P

Ph-4-Ph h 5a

7a

*CoIII

Ph 1a Terminal Alkyne

4a Ph 4-Ph

e- , H+

O Ph P H Ph 1a

CoII

Internal Alkyne

O Ph P I Ph

6a Ph

O Ph P

Ph Ph H VI

Ph-4-Ph IV

CoIII-H

Ph

O Ph P H CoII

O Ph P Ph

H2

+

Ph

In terms of internal alkynes, the same cobaloxime catalysis indicated a radical addition yielding cyclic benzophosphole oxide rather than linear hydrophosphorylation product. As shown in Scheme 6 (right), phosphinoyl radical I reacted with internal alkyne

CONCLUSION In summary, we have developed a straightforward strategy for the synthesis of alkenylphosphine oxides via free radical pathway under extremely mild reaction conditions, by using inexpensive and easily accessible cobaloxime complex as the photocatalyst. Our methodology is compatible with a variety of terminal alkenes, terminal alkynes and internal alkynes with high yields and selectivity. Mechanistic studies demonstrated



that cobaloxime not only absorbs the visible light to activate the [P(O)-H] functionality, but also realizes the hydrogen capture and transfer in situ for selective synthesis of alkenylphosphine oxide under redox-neutral condition. Integrity of multiple functions into this single cobaloxime offers a unique alternative to existing procedures. We believe the present work not only provides a uniform strategy from H-phosphine oxide and unsaturated carbon bonds for the simple and practical preparation of alkenylphosphine oxides, but also manifests the value-added potential of cobaloxime in photocatalysis. Scheme 7. Substrate Scope for the reaction of Hphosphine oxide and internal alkyne O Ar P H

+

Ar

R1

R

60 oC, 20 h, argon, blue LEDs

R2

1 (0.1 mmol)

R2

Co(dmgH)2pyCl (15 mol %) HCOONa (2 equiv.), DCM (2 mL)

R1

P

O

Ar 7

6 (0.2 mmol) Me

n

Me

Bu

Me P

O

Ph

P Ph

O

P Ph

P

O

Ph

7b, 60%

7c, 62%

7d, 69%

t

OMe

F

Cl

t

P Ph

Bu

O

OMe

P

O

Ph

Ph

7e, 69%

7f, 54%

Br

CF3

P

Br O

7i, 43%

P Ph

P

F O

P Ph

7g, 79%

P

CF3

Ph

O

P Ph

7k, 62%

P Ph

Ph Si

O

P Ph

Me CO2CH3

5' 6'

P

Ph Ph

O

F

5' 6'

P

Ph O

O Me

7m, 90%

O

7l, 56%

Ph Ph

Cl O

7h, 77%

O

7j, 62%

Bu

O

7a, 80% Bu

Ph

n

Me

7n, 53%

7o, 64%, 5':6' = 1:1

F

7p, 72%, 5':6' = 2:1

ASSOCIATED CONTENT Supporting Information. The experimental procedure, characterization data, and copies of 1H, 13C, 19F, and 31P NMR spectra. The Supporting Information is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author *[email protected]

ACKNOWLEDGMENT This work was supported by the Ministry of Science and Technology of China (2017YFA0206903), the National Natural Science Foundation of China (21861132004), the Strategic Priority Research Program of the Chinese Academy of Science (XDB17000000), Key Research Program of Frontier Sciences of the Chinese Academy of Science (QYZDY-SSW-

Page 6 of 8

JSC029), and K. C. Wong Education Foundation. Jayaraman Sivaguru is grateful to the Chinese Academy of Sciences President’s International Fellowship (2018VCA0001). We thank Professor Wenguang Wang at Shandong University for stimulating discussion on the reaction mechanism.

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Cobaloxime Catalysis: Selective Synthesis of Alkenylphosphine

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