DOI: 10.1002/ejoc.201800544 Full Paper Selective Reduction Lewis Base Catalyzed Intramolecular Reduction of Salicylaldehydes by Pinacol-Derived Chlorohydrosilane Benedicta Assoah,* [a] João R. Vale, [a,b] Elina Kalenius, [c] Luis F. Veiros, [d] and Nuno R. Candeias* [a] Abstract: A newly developed stable chlorohydrosilane derived from pinacol is herein described. This was successfully used in the reduction of salicylaldehydes in reasonable to excellent yields (51–97 %). The ability of the hydrosilane to react as a reducing agent is increased upon the in situ formation of a trialkoxyhydrosilane and activation with a Lewis base, as further indicated by density functional theory studies. 1,3-Dimethyl- 3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) was identified to Introduction The reduction of carbon-heteroatom unsaturated organic com- pounds remains one of the most essential transformations in synthetic organic chemistry for both academic and industrial applications. An array of catalytic protocols such as hydrogen- ation reactions, electron transfer and hydride transfer reduc- tions have been explored extensively with carbon-heteroatom multiple bond reductions. [1] In recent years, catalytic hydrosilylation has made significant progress and is being used as a major tool in the reduction of organic substrates, serving as a convenient alternative to the use of hydrogenation and metal hydrides. [2] Since the electronic and steric properties of hydrosilanes can be tuned by interac- tion with unreactive functional groups in the substrate or with external chemical agents, these reagents have found their way in the reduction toolbox of synthetic chemists, as they can be used to perform a large variety of chemoselective reductions under mild conditions. [3] Specifically, their reducing properties towards carbonyl can be controlled by the silicon substituents [a] Laboratory of Chemistry and Bioengineering, Tampere University of Technology, Korkeakoulunkatu 8, 33101 Tampere, Finland E-mail: benedicta.assoah@tut.fi nuno.rafaelcandeias@tut.fi http://www.tut.fi/syn [b] Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal [c] University of Jyväskylä, Department of Chemistry, Nanoscience Center, Jyväskylä, Finland [d] Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais No. 1, 1049-001 Lisboa, Portugal Supporting information and ORCID(s) from the author(s) for this article are available on the WWW under https://doi.org/10.1002/ejoc.201800544. Eur. J. Org. Chem. 0000, 0–0 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1 be a suitable catalyst for this metal-free reduction, promoting the regio- and chemoselective reduction of aldehydes in ortho- position to phenols, despite the presence of vicinal ketones. The performance of pinacol-derived chlorohydrosilane in the reduction of salicylaldehydes was further observed to be supe- rior to that of well-established commercially available chloro- hydrosilanes. along with catalysts [2a,4] such as Lewis acids, [5] Lewis bases [6] or transition metal complexes. [7] Despite the notable progresses made in transition metal catalyzed hydrosilylations, [3c,8] the metal-free version of such reductions has received tremendous importance in recent research endeavors; [3a] as they benefit from the absence of costly and often toxic metal catalysts and the need to remove any metal impurities particularly relevant for pharmaceutical products. [9] Mild reductions of carbonyl groups to the corresponding al- cohol functionality by metal-free hydrosilylation methods have been largely accomplished through use of acid and bases as catalysts. [2a,6b] Despite the rather low Si–H bond energy of hydrosilanes when compared with C–H bond, employing hydro- silanes in metal-free carbonyl reduction requires either carbonyl activation by complexation with Brønsted or Lewis acids or acti- vation of the hydrosilane, in which B(C 6 F 5 ) 3 has been exten- sively explored. [10] Both alcohols or hydrocarbons [5,11] can be obtained, depending on the reaction conditions and the hydro- silane used. One of the approaches explored in the activation of hydrosilanes has been the expansion of tetrahedral silicon to a pentavalent anion intermediate upon complexation with nucleophilic species. [12] Silicon valence expansion leads to a re- distribution of the electronic density, polarizing the covalent bonds around silicon, decreasing silicon electron density and increasing the electron density of the silicon substituents. Over- all, these results in a higher hydride donating ability of the pentavalent complex when compared with its tetracoordinate counterpart. [13] Mitsuo and co-workers reported an in situ for- mation of pentacoordinate bis(diolato)hydridosilicates from tri- chlorosilane and catechol or 2,2′-dihydroxybiphenyl for the reduction of carbonyl compounds. However, pentacoordinate hydridosilicates from aliphatic diols such as 1,2-ethanediol and pinacol proved to be less effective as reducing agents. [14] Cs 2 CO 3 [3a,15] TBAF, [16] tBuOK, [17] CsF, and KF [6a] have been re-