molecules Article New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,20-Bis(aminomethyl)-1,10-binaphthyl Yasuhiro Sato 1,2, Yuichi Kawata 1, Shungo Yasui 1, Yoshihito Kayaki 1,* and Takao Ikariya 1,† 1 Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan; [email protected] (Y.S.); [email protected] (Y.K.); [email protected] (S.Y.) 2 Hazardous Materials Laboratory, Research and Development Division, National Research Institute of Fire and Disaster, Jindaiji-higashimachi 4-35-3, Chofu, Tokyo 182-8508, Japan * Correspondence: [email protected]; Tel.: +81-3-5734-2881 † Deceased on 21 April 2017. Abstract: As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C–N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,20-bis(aminomethyl)-1,10-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimo- 5 lar amount of [IrCl2Cp*]2 (Cp* = η –C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 ◦C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C–H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided di- Citation: Sato, Y.; Kawata, Y.; Yasui, S.; astereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear Kayaki, Y.; Ikariya, T. New Bifunctional chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation Bis(azairidacycle) with Axial Chirality of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, via Double Cyclometalation of 2,20- leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%. Bis(aminomethyl)-1,10-binaphthyl. Molecules 2021, 26, 1165. https://doi. Keywords: bifunctional catalyst; metal-ligand cooperation; dinuclear complex; iridacycle; cyclometa- org/10.3390/molecules26041165 lation; asymmetric transfer hydrogenation; cyanation; 1,1-binaphthyl; axial chirality Academic Editor: Vincent Ritleng Received: 31 January 2021 1. Introduction Accepted: 18 February 2021 Published: 22 February 2021 The metal/NH bifunctional catalysis has become a pivotal concept for redox trans- formations based on hydrogen transfer between secondary alcohols and ketones [1–5]. From in-depth studies on original (η6-arene)Ru catalysts bearing chiral N-sulfonyldiamines Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in (N–N chelate complexes) developed by Noyori and Ikariya [6,7], a fundamental hydrogen published maps and institutional affil- delivery process associated with alternating back and forth between 16e amido and 18e iations. hydrido(amine) complexes has been thoroughly realized. We have systematically inves- tigated how the interconversion operates in a range of group 8 and 9 metal complexes with protic amine chelates, and we also investigated how ligand modification, by changing the chelating atom, significantly influences the catalyst performance [2,8,9]. In particular, half-sandwich (η6-arene)Ru, Cp*Ir, and Cp*Rh complexes containing a five-membered Copyright: © 2021 by the authors. bifunctional C–N chelate ring, which were synthesized by the orthometalation of protic Licensee MDPI, Basel, Switzerland. This article is an open access article benzylamine derivatives [10–13], have been applied to efficient bifunctional catalysts based distributed under the terms and on the amine/amido functionalities (Scheme1)[ 14–26]. Compared to the prototype N–N conditions of the Creative Commons chelate Ir complex, remarkable enhancement in the transfer hydrogenation of ketones in Attribution (CC BY) license (https:// 2-propanol [12] and in the aerobic oxidation of alcohols were observed [13]. The rapid creativecommons.org/licenses/by/ hydrogen transfer from alcohols to the amidoiridium and from the hydrido(amine)iridium 4.0/). to ketones also accommodates the dynamic kinetic resolution of racemic secondary alcohols Molecules 2021, 26, 1165. https://doi.org/10.3390/molecules26041165 https://www.mdpi.com/journal/molecules Molecules 2021, 26, 1165 2 of 12 Molecules 2021, 26, 1165 2 of 12 of ketones in 2-propanol [12] and in the aerobic oxidation of alcohols were observed [13]. The rapid hydrogen transfer from alcohols to the amidoiridium and from the hy- drido(amine)iridium to ketones also accommodates the dynamic kinetic resolution of ra- cemicby combination secondary with alcohols enzymatic by combination transesterification with enzymatic using Candida transesterification antarctica lipase using B Can- [21]. Thedida uniqueantarctica catalytic lipase functionB [21]. The could unique be enhanced catalytic byfunc thetion high could basicity be enhanced of the amido by the moiety high basicityas well asof strongthe amido nucleophilicity moiety as well of theas strong hydrido nucleophilicity ligand with theof the aid hydrido of the pronounced ligand with theσ-donor aid of nature the pronounced of the coordinating σ-donor nature carbon of atom. the coordinating carbon atom. Scheme 1. Transfer hydrogenationhydrogenation between between alcohols alcohols and an ketonesd ketones based based on the on metal/NH the metal/NH bifunctionality bifunc- . tionality. The asymmetric versions of amidoiridium have been synthesized by the orthometa- lationThe of 1-phenyl-1-aminoalkanesasymmetric versions of withamidoiridium a chiral center have at thebeen benzylic synthesized position by and the have or- providedthometalation reasonable of 1-phenyl-1-aminoalkanes enantioselectivities in thewith asymmetric a chiral center transfer at hydrogenationthe benzylic position of ace- andtophenone have provided [25]. The reasonable structural enantioselectivi studies on theties isolable in the catalytic asymmetric intermediates transfer hydrogena- suggested tionthat theof acetophenone effective asymmetric [25]. The induction structural is intimately studies on bound the isolable up with catalytic decent diastereomeric intermediates suggestedcontrol in thethat formation the effective of hydrido(amine)iridium asymmetric induction possessingis intimately central bound chirality up with at decent the metal di- astereomericby a one-sided control approach in the of formation the hydrogen of hydrido(amine)iridium donor, 2-propanol, to possessing amidoiridium. central Related chiral- itycationic at the Ru, metal Rh, by and a one-sided Ir complexes approach bearing of cyclometalatedthe hydrogen donor, C–N chelates2-propanol, were to intensivelyamidoirid- ium.investigated Related bycationic Pfeffer Ru, and Rh, coworkers and Ir complexes [14–20] bearing from screening cyclometalated experiments C–N chelates using a were vari- intensivelyety of chiral investigated benzylic amine by Pfeffer ligands, and but cowo catalyticallyrkers [14–20] active from amido screening and hydrido(amine)experiments us- ingcomplexes a variety have of notchiral been benzylic characterized. amine ligands, but catalytically active amido and hy- drido(amine)Separately, complexes it has been have reported not been that characterized. dinuclear complexes, in which the mononuclear structureSeparately, is extended it has bybeen bridging reported ligands, that dinu exhibitclear characteristic complexes, in properties which the and mononuclear favorable structurecatalytic performance is extended by compared bridging to ligands, the parent exhibit mononuclear characteristic complexes properties [27– 34and]. Thanksfavorable to catalyticthe cooperative performance effect, incompared which the to reaction the parent sites mononuclear on multiple metals complexes play different[27–34]. Thanks roles, and to the uniquecooperative electronic effect, structure in which of the the reaction conjugated sites bridging on multiple ligands, metals the catalyticplay different activity roles, and andenantioselectivity the unique electronic can be improvedstructure of by the multinuclear conjugated assembly.bridging ligands, In particular, the catalytic as beneficial activ- ityapplications and enantioselectivity of optically active can be dinuclear improved transition by multinuclear metal complexes assembly. with In axialparticular, chirality as beneficialintroduced applications into the bridging of optically moiety, active Toste dinuclear et al. have transition demonstrated metal complexes the gold-catalyzed with axial chiralitydynamic introduced kinetic resolution into the of bridging propargylic moiety, esters Toste [32] andet al. Sasai have et demonstrated al. have demonstrated the gold- catalyzedthe vanadium-catalyzed dynamic kinetic asymmetric resolution oxidative of prop couplingargylic esters of aromatic [32] and compounds Sasai et [al.33 ,34have]. demonstratedEncouraged the by vanadium-catalyzed these works, we focused asymme ourtric interest oxidative on a dimetallic coupling compoundof aromatic with com- a poundschiral diamido [33,34]. linkage formed by the double orthometalation of benzylic diamine shown in SchemeEncouraged2. It is