Cobalt Dual Catalysis for Visible-Light-Mediated Alkene

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

pubs.acs.org/OrgLett

Photoredox/Cobalt Dual Catalysis for Visible-Light-Mediated Alkene−Alkyne Coupling Pramod Rai,‡ Kakoli Maji,‡ and Biplab Maji* Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India

Org. Lett. Downloaded from pubs.acs.org by UNIV OF SOUTHERN QUEENSLAND on 05/08/19. For personal use only.

S Supporting Information *

ABSTRACT: Dual photoredox transition-metal catalysis has recently emerged as a powerful tool for making synthetically challenging carbon−carbon bonds under milder reaction conditions. Herein, we report on the visible-light-mediated controlled generation of low-valent cobalt catalyst without the need for a metallic reductant. It enabled C− C bond formation via ene-yne coupling at room temperature. The generality of this dual catalysis is demonstrated via the creation of sizable molecular diversity with the accommodation of several functional groups.

T

he carbon−carbon bond construction is one of the central goals in organic synthesis.1 The intermolecular cross-coupling of easily accessible, inexpensive, and benchstable π-component systems, specifically a CC triple bond and a C=C double bond to form a linear carbon chain is an attractive strategy.2 It is particularly intriguing transformation, because of the possibility of the generation of molecular complexity resulting from different regioisomers and stereoisomers with the retention of the entire atom economy.3 From the pioneering work of Cheng,4 Montgomery,5 and others,6 several low-valent transition-metal catalysts were utilized for the ene-yne coupling reactions (Figure 1a). However, in such a thermal reaction, the low-valent metal catalysts were accessed in situ using (super) stoichiometric heterogeneous metal, Grignard reagent, triethylborane, etc. as reducing agents to circumvent the limited accessibility and bench stability of these low-valent metal complexes. Given the concerns associated with the use of dissolving metal/Grignard as reducing agents, an alternative catalytic activation mode under a benign condition capable of accommodation of large functional groups and, thus, the creation of vast molecular diversity is highly desirable. The visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic bond activation process.7 Notably, the use of a dual catalyst for the C−C bond formation in the presence of visible light has drawn much attention to the researchers over the past few years.7b,8 In this regard, recently, Rovis and co-workers have utilized visiblelight-gated cobalt catalysis for [2 + 2 + 2] cycloaddition of alkynes for the formation of arenes.9 Zhao, Wu, and coworkers have developed a visible-light-triggered iridium/cobalt catalyst system for the hydrocarboxylation and carbocarboxylation of alkynes using CO2.10 Ritter et al. have demonstrated an iridium/cobalt catalyst system for the dehydrogenative decarboxyolefination of carboxylic acids.11 However, despite such development, to best of our knowledge, visible-lighttriggered reductive coupling of an alkyne with an alkene to © XXXX American Chemical Society

Figure 1. Previous transition-metal-catalyzed C−C bond formation via the ene-yne coupling and this work. Inset shows the proposed mechanistic hypothesis. CoII= Co(dppe)2Cl2. IrIII= [Ir{dF(CF3)ppy2(dtbpy)]PF6. SET = single electron transfer.

form a trisubstituted alkene has not been developed thus far (Figure 1b). At the onset of our analysis, we have realized that a reductively quenched iridium-based photoredox catalyst [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (PC1, E1/2[IrIII/IrII] = −1.37 V vs Received: April 5, 2019

A

DOI: 10.1021/acs.orglett.9b01201 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters SCE in MeCN),12 could reduce a high-valent transition-metal catalyst (dppe)2CoCl2 (A, E1/2[CoII/CoI] = −0.88 V vs SCE in MeCN) in a controlled manner using an organic sacrificial reductant under visible-light irradiation (Figure 1, inset). The low valent-metal complex B thus generated could be intercepted by a proton donor to deliver a hydride complex C.13 The latter could then undergo hydrometalation with an olefin coupling partner 2 to produce the organometallic intermediate D. The subsequent carbometalation and protonation could deliver the ene-yne coupling product 3, where the oxidized catalyst could then be reduced back to its original state by the photocatalyst cycle. We envisioned that the key advantage of such a photodriven reaction would be milder reaction conditions and accommodation of a large number of functionalities, including aryl halides and reducible groups. It would open a new direction for visible-light-mediated lowvalent metal catalysis for the construction of C−C bonds. Based on the above hypothesis, we have started our investigation by employing 3-hexyne (1a) and n-butyl acrylate (2a) as a model substrate in the presence of a photocatalyst and transition-metal catalyst under the irradiation of blue-lightemitting diode LED (440 nm) at room temperature (Table 1).

result, providing the coupling product in 84% isolated yield with perfect stereoselectivity (Table 1, entry 1). The more strongly reducing photoredox catalysts, such as Ir(ppy)2(dtbbpy)PF6 (PC2) or Ir(ppy)2(bpy)PF6 (PC3) having a potential of E1/2[IrIII/IrII] = −1.51 V and −1.38 vs SCE in MeCN, respectively were less active than the fluorinated catalyst PC1, which gave higher yields from increased longevity (Table 1, entries 2 and 3). Among the phosphine ligands, PPh3 displayed similar reactivity as that of dppe (Table 1, entry 4), whereas the use of other phosphine ligands was found less useful (Table 1, entry 5). Furthermore, the transition-metal precatalysts FeBr2 and NiCl2 with dppe as ligand was found to be moderately active and low yields of the products were obtained (Table 1, entries 6 and 7). The choice and the stoichiometry of the sacrificial reducing agent was found to be crucial, because i-Pr2NEt or Hantzsch ester alone or in a different ratio were less effective (Table 1, entries 8−11). Only a trace amount of product was detected when pivalic acid was used as a proton source (Table 1, entry 12).14 No product was detected in the absence of the light, photocatalyst, cobalt catalyst, or iPr2NEt/Hantzsch ester (Table 1, entries 13−16). They are thus demonstrating the requirement of all of the components. The coupling reaction did not proceed under the thermal condition (80 °C, 20 h) (Table 1, entry 17). Further optimization, in terms of solvents, the wavelength of the employed light, the stoichiometry of the reactants, and catalyst loading were also performed and are detailed in the Supporting Information. We have then explored the substrate scope of this photodriven cobalt-catalyzed reductive coupling reactions (Scheme 1). Initially, the scope of various alkenes was tested using 1a as the coupling partner, and we are pleased to find that the conditions for the model reaction could be applied for a large number of alkenes furnishing the desired products in moderate to good yields and all cases the (E)-stereoisomer was formed selectively. We account the observed stereoselectivity as the manifestation of syn-carboacobaltation as shown in Figure 1. Under the standard reaction conditions, readily available aliphatic acrylates like n-butyl (2a), ethyl (2b), and methyl acrylate (2c) gave the corresponding products in 68%− 84% yields. Also, acrylates bearing benzyl group (2d) and biphenyl methyl group (2e) were tolerated. To further extend the scope of this reductive coupling reaction various functionalized substrates were tested. Substrates bearing functional groups such as aryl ether (2f), trifluoromethyl (2g), and nitrile (2h) groups reacted efficiently to give the corresponding coupling products (3af−3ah) in 74%−80% yields with exclusive stereoselectivity. Importantly, the substrates containing aryl halide moieties such as fluoro (2i), chloro (2j), and bromo (2k), which are less compatible with metal reductants, were found to be viable coupling partners under the milder photodriven conditions and the products were obtained in good to excellent yields with the complete retention of the halide functional groups. Substrates containing pyridine heterocycle (2l) were also tested under the dual photoredox conditions which provide the desired product in moderate 49% yields. Interestingly, menthyl (2m) and bioactive molecules such as estrone (2n) and cholesterol (2o) were also derivatized with complete stereoselectivity using the reductive coupling method, affording the desired products (3am−3ao) in good yields (Scheme 1). Besides, acrylamide (2p) derived from natural amino acids like (L)-phenyl alanine could also undergo

Table 1. Reaction Development: Key Optimizationsa

entry

deviation

1 2

none Ir(ppy)2(dtbpy)PF6 (PC2) instead of [Ir{dF(CF3) ppy}2(dtbpy)]PF6 (PC1) Ir(ppy)2(bpy)PF6 (PC3) instead of [Ir{dF(CF3) ppy}2(dtbpy)]PF6 (PC1) PPh3 instead of dppe dppp or dppm or dppf or xantphos or dppbz instead of dppe FeBr2 instead of CoCl2 NiCl2 instead of CoCl2 i-Pr2NEt (3 equiv) instead of HE (2 equiv), i-Pr2NEt (1 equiv) NEt3 (3 equiv) instead of HE (2 equiv), i-Pr2NEt (1 equiv) HE (3 equiv) instead of HE (2 equiv), i-Pr2NEt (1 equiv) HE (1 equiv), i-Pr2NEt (2 equiv) instead of HE (2 equiv), i-Pr2NEt (1 equiv) PivOH (1 equiv) instead of H2O (1 equiv) no light no [Ir{dF(CF3)ppy}2(dtbpy)]PF6 no CoCl2/dppe no HE, i-Pr2NEt no light at 80 °C

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

yield (%) 84 59 52 80 up to 56 41 38 60 40 50 65 nd nd nd nd trace trace

a

Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), PC1 (1 mol %), CoCl2 (10 mol %), dppe (20 mol %), i-Pr2NEt:HE (1:2, 0.3 mmol), H2O (1 equiv), blue LED (440 nm) in MeCN (0.5 mL) at room temperature under Ar. Yield of the isolated product was given. HE = Hantzsch ester.

After sizable optimizations, we have found that the combination of PC1 (1 mol %) as the photocatalyst, CoCl2 (10 mol %), in combination with dppe 1,2-bis(diphenylphosphino)ethane, (20 mol %) as the transitionmetal catalyst, water (1 equiv). as the proton source in the presence of iPr2NEt/Hantzsch ester (1:2) furnished the best B

DOI: 10.1021/acs.orglett.9b01201 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Scheme 1. Visible-Light-Driven Cobalt-Catalyzed Ene-Yne Couplinga

a

Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol), PC1 (1 mol %), CoCl2 (10 mol %), dppe (20 mol %), i-Pr2NEt:HE (1:2, 0.3 mmol), H2O (1 equiv), Blue LED (440 nm) in MeCN (0.5 mL) at room temperature under Ar. The yields of the isolated products are given. b77% yield in 1 mmol scale 20 h. cNMR yield. dRatios of (Z)-3:(E)-3 are given in parentheses. eRatios of (E)-3:(Z)-3:r-(E)-3 are given in parentheses.

generation of a broad molecular diversity resulting not only from E/Z isomerization but also from different regioselectivity. Gratifyingly, for the studied reactions, the regioselectivity is found to be controlled by the cobalt catalyst, and, in all cases, the r-(E)-3 product is obtained only in a small amount. In fact, in some cases, they are not even observed. For example, ethyl propiolate (1f) was found to couple with ethyl acrylate (2a) and ethyl vinyl ketone (2r) in 53%−65% yield in exclusive stereoselectivity. In the case of prop-1-yn-1-ylbenzene (1g), minor E/Zisomerization product was observed. Interestingly, in addition to acrylates (2a, 2b), enones (2r), and acrylonitrile (2s) are also accommodated as a suitable substrate. Notably, bocprotected acrylamide (2t) could also be very compatible with this method. Similarly, a variety of unsymmetrical alkynes (1h−1m) were tolerated with the reaction conditions, providing the respective cross-coupling products in good to

this reaction affording the coupled product in moderate yield. Phenyl vinyl sulfone (2q) which is known to be the Michael acceptor also undergoes the reaction very smoothly. In all these cases, the reducible functional groups such as an alkene, keto, amide, sulfone groups were retained in the product. Furthermore, we have investigated the scope concerning the alkyne coupling partner (Scheme 1). In addition to 3-hexyne (1a), the symmetrical aliphatic alkynes such as 4-octyne (1b) was converted to the corresponding product 3ba in 91% yield with complete stereoselectivity. However, in the case of diarylacetylenes (1c−1e), a stereoisomeric mixture due to E/Z isomerization via a triplet−triplet energy transfer process is observed.15 In these cases, the products were obtained in 56%−90% yield with Z/E ratio up to 3:1. A large variety of unsymmetrical alkynes were then tested to further expand the scope of this photodriven ene-yne coupling reaction (Scheme 1). In such cases, we have anticipated the C

DOI: 10.1021/acs.orglett.9b01201 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

under standard reaction condition for 4 h. As expected, the E/ Z ratio was changed from 12:1 to 5:1, indicating that the isomerization is occurring after the C−C bond formation (Scheme 2b). Meanwhile, to understand the role of water, deuterium labeling studies were performed using D2O as the external proton source. The 1H NMR analysis of the product showed that one of the α-methylene proton and the vinyl proton were deuterated in 44% and 52%, respectively (Scheme 2c). This suggests that (i) both the oxidized HE and i-Pr2NEt might act as the proton source, along with added H2O, and iPr2NEt might additionally facilitate the formation of pyridine from HE by abstracting the H+, (ii) the proton source is involved not only in the formation of the cobalt hydride C but also for the release of product from the intermediate E, and (iii) the cobalt hydride C underwent anti-Markovnikov hydrometalation for the formation of D (see Figure 1, inset). Along this direction, no deuterium incorporation occurred when the reaction is performed using CD3CN as the solvent (Scheme 2d). Furthermore, premature quenching of the reaction revealed the formation of n-butyl propionate, confirming the intermediacy of the cobaltacycle D. The oxidized HE can be observed as the byproduct of this reaction. In conclusion, we have demonstrated a visible-light-driven dual Ir/Co-catalysis for the C−C bond formation via reductive coupling of an alkene with alkynes at room temperature. The catalysis bypasses the use of stoichiometric organometallic reductants. It exhibits a wide range of functional groups tolerance and generates a sizable molecular library from simple starting materials. Detailed mechanistic studies including deuterium labeling experiments, radical quenching experiments, quantum yield measurements, and Stern−Volmer quenching experiments have been presented to validate the proposed mechanistic pathway.

excellent yields and selectivities. Thiophene containing heterocycles (1n) was also tolerated, as demonstrated by the generation of 3na. Finally, to further validate the proposed mechanistic hypothesis, some control experiments were conducted. Initially, a light-dark experiment (up to 12 h) was performed to examine the role of visible light (Figure 2). Following our

Figure 2. Reaction profile with the light on/off over time.

mechanistic hypothesis, the cobalt-catalyst system is found to be activated under the irradiation and deactivated in darkness. The quantum-yield measurement (Φ = 0.91) by chemical actinometry at 440 nm under the reaction conditions further supports the temporal control of the cobalt catalyst under visible light irradiation (see the Supporting Information for details). Moreover, Stern−Volmer quenching experiments were performed to determine the quenching efficiency of the reagents.16 As anticipated, we have found that 1a and 2a does not quench the luminescence of PC1. Whereas both HE and iPr2NEt quenches the luminescence of PC1 at very high rates (kq(HE) = 2.69 × 108 M−1 s−1 and kq(i-Pr2NEt) = 1.49 × 108 M−1 s−1) and HE was found to be only slightly faster. This indicated that both HE and i-Pr2NEt could act as the terminal reductant. In addition, we have determined the quenching fraction Q, following the method described by Yoon,16b and it reveals that 99% of the photon absorbed by the PC1 participates in a productive electron transfer process. Under the standard reaction condition, the presence of 1 equiv of (2,2,6,6-tetramethylpiperidine-1-yl)oxyl (TEMPO) does not suppress the product formation (83% isolated yield), further indicating free radicals do not involve in the reaction pathway (Scheme 2a). Furthermore, to validate that the isomerization is occurring off-catalytic cycle via a triplet−triplet energy transfer,15 the isolated product 3ga was again treated

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b01201.

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Experimental details, compound characterizations, and NMR spectra of the products (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected].

Scheme 2. Control Experiments

ORCID

Biplab Maji: 0000-0001-5034-423X Author Contributions ‡

These authors contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The author thanks DST INSPIRE Faculty Award [DST/ INSPIRE/04/2015/002518] for financial support. P.R. thanks INSPIRE and K.M. thanks IISER K for a Ph.D. fellowship. Helpful discussions with Dr. P. K. Mondal (Indian Institute of Science Education and Research Kolkata), Dr. M. Baidya (Indian Institute of Technology Madras), Dr. A. Jana (Tata D

DOI: 10.1021/acs.orglett.9b01201 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

(15) Metternich, J. B.; Artiukhin, D. G.; Holland, M. C.; von Bremen-Kühne, M.; Neugebauer, J.; Gilmour, R. J. Org. Chem. 2017, 82, 9955−9977. (16) (a) Mukherjee, S.; Maji, B.; Tlahuext-Aca, A.; Glorius, F. J. Am. Chem. Soc. 2016, 138, 16200−16203. (b) Cismesia, M. A.; Yoon, T. P. Chem. Sci. 2015, 6, 5426−5434.

Institute of Fundamental Research Hyderabad), and Dr. S. Lakhdar (CNRS−ENSI Caen) were gratefully acknowledged.

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REFERENCES

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DOI: 10.1021/acs.orglett.9b01201 Org. Lett. XXXX, XXX, XXX−XXX