Photochemical Hydroacylation of Michael Acceptors Utilizing an Aldehyde as Photoinitiator Ioanna K. Sideri, Errika Voutyritsa, and Christoforos G. Kokotos* [a] Introduction Photoredox catalysis is an increasingly important tool in organ- ic synthesis, with multiple applications in novel and already- existing organic transformations. [1] In the majority of these cases, metal-based catalysts (mainly based on ruthenium or iri- dium) are used to promote these transformations. These com- plexes have the ability to present different electronic proper- ties, depending on the ligands they are coordinated with. Nev- ertheless, they can be highly toxic, difficult to remove from the final product, and also, in most cases, expensive. To solve these problems, photo-organocatalysis came into the spot- light: it is more sustainable, eco-friendly, and gradually be- comes equally effective as entirely organic catalysts are utilized for the same transformations. [2] Over the last few years, we have initiated a program with the aim to contribute to this domain by developing a photo-organocatalytic protocol, utiliz- ing common household lamps and a commercially available small organic molecule as the photocatalyst. [3] One of these ap- plications was the green photochemical C ÀH activation of al- dehydes, leading to the hydroacylation of electron-deficient olefins (Scheme 1 d). [4] There are quite a few approaches for dealing with C ÀC bond activation for this hydroacylation, such as metal catalysis (Scheme 1 a), [5] the Stetter reaction (N-hetero- cyclic carbenes ; Scheme 1 b), [6] or photochemical processes (Scheme 1 e). [7–9] In our previous work, [4] we were able to over- come existing challenges in literature regarding this transfor- mation by achieving a wider substrate scope, including aro- matic aldehydes, and tackling the most important issue of poor selectivity towards a,a-disubstituted aldehydes. When branched aldehydes were used, the acyl radical would often decarbonylate owing to the increased stability of the secon- dary alkyl radical formed, leading to undesired products (Scheme 1, middle). In our case, phenylglyoxylic acid was used as the photocatalyst and performed remarkably well, affording high selectivity. [4] Maruoka and co-workers also provided a so- lution to this matter by employing a hypervalent iodine photo- induced protocol but used a noncommercial catalyst (Scheme 1 c). [10] During our studies concerning the mechanistic aspect of the reaction as well as the selectivity, the good per- formance exhibited by benzaldehyde motivated us to further investigate the idea of an aldehyde actually promoting the hy- droacylation of alkenes. Thus, in our present work, a commer- cially available, cheap, substituted benzaldehyde was used as the promoter, and studies on the desired selectivity were con- ducted, affording unexpectedly good results with selectivity ratios exceeding 20:1 (Scheme 1 f). Results and Discussion We initially investigated a wide range of substituted aromatic aldehydes as potential photoinitiators in the reaction between diethyl maleate (1a) and octanal (2a) (Scheme 2). [11] In general, ortho-substitution on the aromatic aldehyde provided better yields than para-substitution (4f vs. 4e and 4t vs. 4b), with the exception of fluoro-substituted aldehydes (4l vs. 4u). Al- though various aromatic aldehydes were tested for their cata- lytic activity, only a few promoted the reaction. 4-Cyanobenzal- dehyde (4d) proved to be the best initiator among the 25 ben- zaldehydes tested (Scheme 2). Next, the reaction conditions were optimized by testing different solvents, catalyst loadings, and octanal equivalents (Table 1). [11] The reaction gave medio- cre results in aqueous medium (entry 1), whereas in other sol- vents the yield ranged from low to mediocre (entry 2). The re- action took place effectively in petroleum ether (40–60 8C) as the solvent even upon decreasing the catalyst loading to 10 mol % (entries 3 and 4). [11] Notably, the reaction did not pro- ceed in the absence of light (entry 5) or catalyst (entry 6). The The hydroacylation of Michael acceptors constitutes a useful tool for the formation of new C ÀC bonds. In this work, an envi- ronmentally friendly procedure was developed, utilizing 4- cyanobenzaldehyde as the photoinitiator and household bulbs as the irradiation source. A great variety of substrates was well-tolerated, leading to good yields, and mechanistic experi- ments were performed to elucidate the catalyst’s possible mechanistic pathway. Moreover, the inherent selectivity chal- lenge regarding a,a-disubstituted aldehydes (decarbonylation problem) was studied and addressed. [a] I. K. Sideri, E. Voutyritsa, Prof. Dr. C. G. Kokotos Laboratory of Organic Chemistry Department of Chemistry National and Kapodistrian University of Athens Panepistimiopolis 15771, Athens (Greece) E-mail : ckokotos@chem.uoa.gr Supporting Information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/cssc.201901725. ChemSusChem 2019, 12, 4194 – 4201  2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4194 Full Papers DOI: 10.1002/cssc.201901725