Steps toward Rationalization of the Enantiomeric Excess of the Sakurai–Hosomi–Denmark Allylation Catalyzed by Biisoquinoline N,N’-Dioxides Using Computations

Allylation reactions of aldehydes are chemical transformations of fundamental interest, as they give direct access to chiral homoallylic alcohols. In this work, we focus on the full computational characterization of the catalytic activity of substituted biisoquinoline-N,N’-dioxides for the allylation of 2-naphthaldehyde. We characterized the structure of all transition states as well as identified the π stacking interactions that are responsible for their relative energies. Motivated by disagreement with the experimental results, we also performed an assessment of 34 different density functional methods, with the goal of assessing DFT as a general tool for understanding this chemistry. We found that the DFT results are generally consistent as long as functionals that correctly account for dispersion interactions are used. However, agreement with the experimental results is not always guaranteed. We suggest the need for a careful synergy between computations and experiments to correctly interpret the data and use them as a design tool for new and improved asymmetric catalysts.

New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,2′-Bis(aminomethyl)-1,1′-binaphthyl

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 2,2′-bis(aminomethyl)-1,1′-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 equimolar amount of [IrCl2Cp*]2 (Cp* = η5–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 diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.

New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,2’-Bis(aminomethyl)-1,1’-binaphthyl

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 2,2’-bis(aminomethyl)-1,1’-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 equimolar amount of [IrCl2Cp*]2 (Cp* = 5-C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium (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 diastereomers of hydrido(amine)iridium with retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to 67% ee.

1.6 Sulfur-, Selenium-, and Silicon-Centered Radicals

Sulfur-, selenium-, and silicon-centered radicals are versatile reaction intermediates in modern synthetic organic chemistry. These radicals are capable of adding to carbon–carbon multiple bonds such as alkene and arenes, thus introducing the corresponding elements into the products. These radicals can also serve as mediators of free-radical reactions, including as polarity-reversal catalysts, asymmetric catalysts, and halogen-atom abstraction agents, without these elements being incorporated into the products of the reactions. This chapter describes the utility of sulfur-, selenium-, and silicon-centered radicals in two sections. The first covers reactions involving incorporation of the corresponding elements into the products, while the second describes reactions using these radicals as catalysts or reagents to prepare products that do not contain the corresponding elements.

Asymmetric construction of tetrahedral chiral zinc with high configurational stability and catalytic activity

Chiral metal complexes show promise as asymmetric catalysts and optical materials. Chiral-at-metal complexes composed of achiral ligands have expanded the versatility and applicability of chiral metal complexes, especially for octahedral and half-sandwich complexes. However, Werner-type tetrahedral complexes with a stereogenic metal centre are rarely used as chiral-at-metal complexes because they are too labile to ensure the absolute configuration of the metal centre. Here we report the asymmetric construction of a tetrahedral chiral-at-zinc complex with high configurational stability, using an unsymmetric tridentate ligand. Coordination/substitution of a chiral auxiliary ligand on zinc followed by crystallisation yields an enantiopure chiral-only-at-zinc complex (> 99% ee). The enantiomer excess remains very high at 99% ee even after heating at 70 °C in benzene for one week. With this configurationally stable zinc complex of the tridentate ligand, the remaining one labile site on the zinc can be used for a highly selective asymmetric oxa-Diels-Alder reaction (98% yield, 87% ee) without substantial racemisation.

An Unexpected Oxidative C-O Bond Formation: 11,17a-Dihydrobenzo[4,5]oxazolo[3,2-A]dinaphtho[2,1- C:1',2'-E]azepine

Phosphoric acids bound to 3,3’-subsituted 1,1’-binaphthalene-2,2’-diol (BINOL) have found wide application as effective asymmetric catalysts. In this work, we describe our attempt to construct a new binaphthalene-based phosphoric acid <b>6</b>. We found that both the key precursor <b>2</b> and the desired product <b>6 </b>decay rapidly and quantitatively to a stable dihydrooxazole <b>3</b> via an O₂-driven oxidative C-O bond formation.

An Unexpected Oxidative C-O Bond Formation: 11,17a-Dihydrobenzo[4,5]oxazolo[3,2-A]dinaphtho[2,1- C:1',2'-E]azepine

Phosphoric acids bound to 3,3’-subsituted 1,1’-binaphthalene-2,2’-diol (BINOL) have found wide application as effective asymmetric catalysts. In this work, we describe our attempt to construct a new binaphthalene-based phosphoric acid <b>6</b>. We found that both the key precursor <b>2</b> and the desired product <b>6 </b>decay rapidly and quantitatively to a stable dihydrooxazole <b>3</b> via an O₂-driven oxidative C-O bond formation.