Photo‐Organocatalysis of Atom‐Transfer Radical Additions to Alkenes

Abstract

We have found that an organic molecule as simple as p-anisaldehyde efficiently catalyzes the intermolecular atomtransfer radical addition (ATRA) of a variety of haloalkanes onto olefins, one of the fundamental carbon-carbon bondforming transformations in organic chemistry. The reaction requires exceptionally mild reaction conditions to proceed, as it occurs at ambient temperature and under illumination by a readily available fluorescent light bulb. Initial investigations support a mechanism whereby the aldehydic catalyst photochemically generates the reactive radical species by sensitization of the organic halides by an energy-transfer pathway.Atom-transfer radical addition (ATRA) [1] to alkenes provides a clear demonstration of the utility of radical reactivity in organic synthesis. The chemistry, pioneered by Kharasch almost 70 years ago, [2] has evolved to become an atomeconomical and effective way to functionalize easily available olefinic substrates, mainly thanks to the contributions from the groups of Curran, [1b, 3] Oshima, [4] and Renaud. [5] The addition of an organic halide across a carbon-carbon double bond generates a new CÀC and CÀX bond (X = halogen) in a single operation. This reactivity is also at the heart of atomtransfer radical polymerization (ATRP) processes. [1a,c] ATRA proceeds through a radical chain propagation mechanism (Figure 1 a), and the formation of the radicals from alkyl halides classically requires stoichiometric amounts of initiators, such as organotin reagents, [3] triethyl borane, [4] or potentially explosive oxidants, [2] and high reaction temperatures. Recently, metal-mediated catalysis, [6] including metalbased photoredox catalysis driven by visible light, [7] has further expanded the potential of the ATRA technology.However, we still need a suitable approach for generating radical intermediates under mild reaction conditions which avoids expensive transition-metal catalysts or toxic reagents.Herein, we describe a strategy that addresses this gap in synthetic methodology. Motivated by our interest in devising metal-free photochemical processes, [8] we have found that an organic molecule as simple as p-anisaldehyde (1 a) can efficiently catalyze the intermolecular ATRA of a variety of haloalkanes (2) onto olefins (3; Figure 1 b). The chemistry requires irradiation from a household 23 W compact fluorescent light (CFL) bulb to proceed, and ambient temperature is sufficient for achieving functionalized olefins (4) with synthetically useful results. Initial investigations support a mechanism whereby the aldehydic catalyst generates the reactive radical species by energy transfer [9] to the haloalkane substrates. Although the utility of UV-absorbing organic chromophores as triplet photosensitizers has been wellestablished for decades, [10] applications of triplet sensitization induced by readily available CFL light sources have found limited use in synthetic chemistry so far. [11] Our initial explorations toward an ATRA protocol under mild reaction conditions focused on the...

Green Photo‐Organocatalytic C−H Activation of Aldehydes: Selective Hydroacylation of Electron‐Deficient Alkenes

“…[10] The mixture of phenylglyoxylic acid and diethyl maleate presenteda ll the expected signals. [10] As observed in the UV/Vis experiments, 1 Ha nd 13 CNMR spectroscopy confirm that in the case of the reaction mixture (PhCOCOOH, diethyl maleate, and heptanal in H 2 O), benzaldehyde is present, but it forms to al esser extent than when the HATd onor is absent ( Figure 2C). [10] As observed in the UV/Vis experiments, 1 Ha nd 13 CNMR spectroscopy confirm that in the case of the reaction mixture (PhCOCOOH, diethyl maleate, and heptanal in H 2 O), benzaldehyde is present, but it forms to al esser extent than when the HATd onor is absent ( Figure 2C).…”

“…The association of an electron-rich molecule with an electron acceptorc an lead to the formation of an aggregate, called an electron donor-acceptor (EDA) complex. [13] In an effort to understand the use of phenylglyoxylica cid as the photocatalyst, we performed an umber of UV/Vis andN MR studies. [13,14] An EDA complex sometimes is recognized when upon addition of the two components,ani ncrease in the UV absorbance of the mixture is observed.…”

“…Thise xciplex is probablyaradical ion pair,a sd epictedi nS cheme 5, resembling the exciplex formed between benzophenonea nd alkyl amines. The differences observed in the UV/Vis experiments,d epending on the solvente mployed, can be attributed to how easily 13 CNMR spectrum of PhCOCOOHi nC DCl 3 .B) 13 CNMR spectrum of PhCOCOOH in CDCl 3 after irradiation for 2h.C) 13 CNMR spectrum of a mixture of PhCOCOOH, diethyl maleate, and heptanali nC DCl 3 after irradiation for 2h. [15b] When aH AT donor (aldehyde)i sn ot present, photodecomposition occurs quickly,l eadingt ob enzaldehyde.…”

Benzophenone vs. Copper/Benzophenone in Light‐Promoted Atom Transfer Radical Additions (ATRAs): Highly Effective Iodoperfluoroalkylation of Alkenes/Alkynes and Mechanistic Studies

“…As highlighted and discussed by Curan and Studer in a recent review, one should be very cautious when talking about catalysis/photocatalysis in radical‐based chemical processes. Indeed, it is often difficult to assess the exact role of the catalyst in such processes, catalysts which could be mostly involved in a radical initiation step, and/or be a killer of radical traps …”

Visible Light‐Driven Atom Transfer Radical Addition to Olefins using Bi2O3 as Photocatalyst

“…[15] In a different approach, Melchiorre and coworkers have very recently reported a photochemical metalfree process to mediate the ATRA reaction. [16] Scheme 1. Catalysts for the visible light photoinduced atom transfer radical addition (ATRA) reaction.…”