Photoredox-Catalyzed Hydroacylation of Olefins Employing

Letter pubs.acs.org/OrgLett

Photoredox-Catalyzed Hydroacylation of Olefins Employing Carboxylic Acids and Hydrosilanes Muliang Zhang,† Rehanguli Ruzi,† Junwei Xi,† Nan Li,† Zhongkai Wu,† Weipeng Li,† Shouyun Yu,*,† and Chengjian Zhu*,†,‡ †

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China ‡ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, China S Supporting Information *

ABSTRACT: A hydroacylation reaction of alkenes has been achieved employing readily available carboxylic acids as the acyl source and hydrosilanes as a hydrogen source via photoredox catalysis. The combination of both single electron transfer and hydrogen atom transfer steps has dramatically expanded new applications of carboxylic acids in organic synthesis. The protocol also features extremely mild conditions, broad substrate scope, and good functional group tolerance, affording a novel and convenient approach to hydroacylation of alkenes.

T

insertion of the unsaturated substrate into the M−H bond and C−C bond-forming reductive elimination processes enable this transformation deliver branched and linear products.3 Consequently, the availability of a predictable regio- and chemoselective strategy for olefin hydroacylation will continue to have a significant impact on chemical synthesis. An alternative protocol is to search for a suitable acyl source in place of an aldehyde for achieving hydroacylation. Carboxylic acids are versatile synthons for the preparation of numerous commodity chemicals.4 Carboxylic acids have several advantages for synthetic organic chemistry: (1) most carboxylic acids are abundant, inexpensive, structurally diverse feedstocks; (2) compared with aldehydes as an acyl source, carboxylic acids are more stable. Recently, Shi and co-workers developed Pdcatalyzed hydroformylation of olefins with formic acid in the presence of Ac2O (Scheme 1B).5 However, a general reaction for the intermolecular hydroacylation of olefins with advanced carboxylic acids has yet to be achieved. The continuing studies and successful applications of such a reaction would offer a complement to the conventional aldehyde-based hydroacylation and access to synthetically useful products. From a synthetic point of view, direct addition of the acyl radical onto the double bond is very promising for achievement of olefin hydroacylation. Caddick and co-workers reported hydroacylation of α,β-unsaturated esters via aerobic C−H activation, and production of acyl radicals is a key step in this reaction.6 However, compared with the development of simple alkyl and even vinyl radicals, the application of acyl radicals in modern organic synthesis has largely dropped behind.7 Recently, different strategies have been developed for the formation of acyl radicals by single electron transfer (SET) oxidation8 or reduction9 processes. Meanwhile, seminal work

he hydroacylation of unsaturated hydrocarbons is a highly versatile reaction, which provides a direct approach to valuable ketones.1 This transformation is traditionally carried out with the addition of aldehydes to carbon−carbon multiple bonds catalyzed by transition metals (Scheme 1A).1a,d Scheme 1. Metal-Catalyzed Olefin Hydroacylation

Transition-metal-catalyzed hydroacylation of alkenes with aldehydes often requires high temperature,1a,d which restricts the regioselectivity and functional group tolerance of this reaction. Because the acylmetal intermediate tends to undergo an undesired decarbonylation process, in particular for rhodium-catalyzed systems, substrates must frequently have additional coordinating groups.2 In addition, migratory © 2017 American Chemical Society

Received: May 9, 2017 Published: June 14, 2017 3430

DOI: 10.1021/acs.orglett.7b01391 Org. Lett. 2017, 19, 3430−3433

Letter

Organic Letters

photocatalyst and a light source in this olefin hydroacylation reaction (entries 12 and 13). With the optimized reaction conditions in hand, we then examined the scope of the hydroacylation with respect to the alkenes. Representative examples are shown in Scheme 2.

on radical-mediated hydrofunctionalization of olefins has also provided strong evidence that carbon radical intermediates are quenched well by abstraction of a hydrogen atom.10 Prompted by the effectiveness of these two types of catalytic modes, we postulated that the combination of SET and hydrogen atom transfer (HAT) steps in a single mechanism would be an attractive protocol for creating more valuable chemical transformations. To the best of our knowledge, photocatalytic intermolecular acyl−olefin reductive coupling reactions are currently unknown. We wondered whether reduction of carboxylic acids might be used for the generation of acyl radicals via an SET pathway, followed by regioselective addition of the acyl radicals to olefin acceptors and a subsequent HAT process (Scheme 1C). This would undoubtedly be a particularly powerful approach to achieve the hydroacylation of diverse olefins. We describe herein the first olefin hydroacylation reaction employing readily available carboxylic acids with tris(trimethylsilyl)silane (TTMSS) as the hydrogen source and reducing agent. Our initial investigation focused on the reaction between benzoic acid (1a) and styrene (2a) in the presence of dimethyl dicarbonate (DMDC), which gives a mixed anhydride serving as an oxidative quencher of a photocatalyst.9a As shown in Table 1, different solvents were examined using 2.0 mol % fac-

Scheme 2. Scope of Olefins in the Hydroacylation Reactiona

Table 1. Optimization of the Reaction Conditionsa

entry

photocatalyst

base

H source

solvent

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13c

fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 fac-Ir(ppy)3 − fac-Ir(ppy)3

K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2HPO4 K3PO4 Cs2CO3 K3PO4 K3PO4

TTMSS TTMSS TTMSS TTMSS TTMSS (Ph)3SiH (Et)3SiH PMHSd TTMSS TTMSS TTMSS TTMSS TTMSS

DMF dioxane DMSO DCE CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN

0 0 0 0 38 8 7 12 60 68 14 0 0

a

Reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol, 2.0 equiv), DMDC (0.3 mmol, 3.0 equiv), TTMSS (0.2 mmol, 2.0 equiv), fac-Ir(ppy)3 (0.002 mmol, 2 mol %), K3PO4 (0.2 mmol, 2.0 equiv), and CH3CN (2 mL) at room temperature using 5 W blue LEDs for 20−24 h.

Various styrenes, including para-substituted (methyl, methoxy, fluoro, and chloro) styrenes, reacted with good efficiency (3ab−ae). The substituent position on the aryl group had no obvious impact on the reactivity, as m- and o-chlorostyrene gave the targeted ketones in moderate yields (3af, 3ag). Because acyl radical addition to electron-poor alkenes is usually facile, Michael acceptors showed better reactivity in this system. A variety of vinyl esters worked well with good efficiency, constructing γ-carbonyl compounds possessing valuable electron-withdrawing functional groups (3ah−aj).Vinyl sulfone was also suitable (3ak). Substituents on either the α-position (3an) or the β-position (3al, 3am) of the Michael acceptor were also well-tolerated in this alkene hydroacylation reaction. A simple aliphatic olefin was also found to be compatible in this reaction, although with lower efficiency (3ap). This visible-light photocatalytic single-electron reduction process with HAT allows the application of complex molecules under our standard reaction conditions. Some alkenes derived from biologically important molecules such as estrone and light ester IB could undergo this hydroacylation reaction to give the corresponding products with a γ-carbonyl functional group incorporated (3aq, 3ar).

a

The reactions were carried out with 1a (0.1 mmol), 2a (0.2 mmol, 2.0 equiv), DMDC (0.3 mmol, 3.0 equiv), base (0.2 mmol, 2.0 equiv), photocatalyst (0.002 mmol, 2 mol %), solvent (2 mL), and H source (0.2 mmol, 2.0 equiv) at room temperature using 5 W blue LEDs for 6 h. bIsolated yields. cThe reaction was performed in the absence of light. dPMHS = polymethylhydrosiloxane.

Ir(ppy)3 as the photoredox catalyst and TTMSS as the hydrogen source11 in the presence of K2CO3. The desired product 3aa was isolated in 38% yield in CH3CN (Table 1, entry 5), showing that this novel olefin hydroacylation approach is feasible. Other hydrogen sources, such as (Ph)3SiH, (Et)3SiH, and PMHS could not improve the result (entries 6−8), which implied that the choice of hydrogen source is very important in the system. We then screened a series of bases, such as K2HPO4, K3PO4, and Cs2CO3. A 68% yield was achieved when K3PO4 was used as the base (entry 10). Control experiments confirmed the requirement of a 3431

DOI: 10.1021/acs.orglett.7b01391 Org. Lett. 2017, 19, 3430−3433

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Organic Letters Next, we directed our attention to delineating the scope of carboxylic acid coupling partners (Scheme 3). A broad range of

Scheme 4. Proposed Mechanism

Scheme 3. Scope of Carboxylic Acids in the Hydroacylation Reactiona

product 3aa. Finally, another SET step could occur between 10 and Ir, regenerating the ground-state photocatalyst. In conclusion, we have developed the first photocatalytic reaction for the coupling between alkenes and carboxylic acids with HAT. The disclosed photoredox-catalyzed selective reduction of carboxylic acids represents a mild and general olefin hydroacylation pathway, which could offer a powerful new strategy for the preparation of versatile small molecules of potential pharmaceutical relevance. The reaction has good substrate suitability and functional group tolerance, with alkenes spanning the broad range from styrenes to unactivated aliphatic alkenes and electron-poor alkene substrates. We will continue working on new visible-light photoredox-catalyzed conversions involving carboxylic acids.

a

Reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol, 2.0 equiv), DMDC (0.3 mmol, 3.0 equiv), TTMSS (0.2 mmol, 2.0 equiv), fac-Ir(ppy)3 (0.002 mmol, 2 mol %), K3PO4 (0.2 mmol, 2.0 equiv), and CH3CN (2 mL) at room temperature using 5 W blue LEDs for 20−24 h. bThe reaction was carried out on a 4 mmol scale with a reaction time of 36 h.

carboxylic acids bearing either electron-donating (e.g., methyl, tert-butyl, methoxy, benzyloxy, or phenyl) or electron-withdrawing (e.g., fluoro or chloro) substituents reacted smoothly to furnish the desired ketone products in moderate yields (3ba−ha). In addition, the substituent position (ortho, meta, or para) showed little influence on the reaction efficiency (3ba, 3ia, 3ja). Moreover, when 2-furanyl-, 3-thienyl-, and 2naphthyl-substituted acids were employed, the desired products were obtained in moderate yields (3ka−ma). In addition, the intramolecular hydroacylation of 2-vinylbenzoic acid (4) could also be achieved. Under the standard conditions, 4 underwent activation and radical cyclization to afford the product, 1indone (5), in high yield. When the radical scavenger TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl) was introduced into the model reaction, the hydroacylation was completely terminated, which indicated that a SET radical process is operative. The proposed mechanistic details of our transformation are depicted in Scheme 4. In the presence of base, the mixed anhydride intermediate 6 is generated from carboxylic acid 1a and DMDC.8a The photocatalyst fac-Ir(ppy)3 leads to the formation of a longlived excited state, Ir*III, which undergoes a metal-to-ligand charge transfer process under visible-light irradiation. Then the SET process from this strongly reducing excited state species Ir*III to 6 generates acyl radical precursor 7 and IrIV. Intermediate 7 delivers acyl radical 8 along with CO2 and methanoate after fragmentation. This reactive acyl radical adds to the olefin to deliver the radical intermediate 9, which rapidly undergoes HAT from TTMSS to give the desired coupling

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b01391. Experimental procedures and characterization data (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (C.Z.). *E-mail: [email protected] (S.Y.). ORCID

Shouyun Yu: 0000-0003-4292-4714 Chengjian Zhu: 0000-0003-4465-9408 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the National Natural Science Foundation of China (21474048, 21372114, 21672099, and 21472084). 3432

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DOI: 10.1021/acs.orglett.7b01391 Org. Lett. 2017, 19, 3430−3433