Octahedral Chiral‐at‐Metal Iridium Catalysts: Versatile Chiral Lewis Acids for Asymmetric Conjugate Additions

Abstract

Octahedral iridium(III) complexes containing two bidentate cyclometalating 5-tert-butyl-2-phenylbenzoxazole (IrO) or 5-tert-butyl-2-phenylbenzothiazole (IrS) ligands in addition to two labile acetonitrile ligands are demonstrated to constitute a highly versatile class of asymmetric Lewis acid catalysts. These complexes feature the metal center as the exclusive source of chirality and serve as effective asymmetric catalysts (0.5-5.0 mol % catalyst loading) for a variety of reactions with α,β-unsaturated carbonyl compounds, namely Friedel-Crafts alkylations (94-99% ee), Michael additions with CH-acidic compounds (81-97% ee), and a variety of cycloadditions (92-99% ee with high d.r.). Mechanistic investigations and crystal structures of an iridium-coordinated substrates and iridium-coordinated products are consistent with a mechanistic picture in which the α,β-unsaturated carbonyl compounds are activated by two-point binding (bidentate coordination) to the chiral Lewis acid.

Suzuki Cross‐Coupling for Post‐Complexation Derivatization of Non‐Racemic Bis‐Cyclometalated Iridium(III) Complexes

“…In the context of our previous studies with cyclometalated iridium(III) complexes, we have recognized significant differences in the reactivity of benzothiazole and benzoxazole complexes . Hence, benzothiazole PhbtBr complexes Λ‐( S )‐3 d and Δ‐( S )‐3 d were applied to the cross‐coupling procedure.…”

Acyl‐Imidazoles: A Privileged Ester Surrogate for Enantioselective Synthesis

“…The adducts are flexible building blocks for easy transformation into β′‐hydroxy‐β‐amino acid derivatives 21 . One similar transformation was reported in 2015 by Meggers and co‐workers using chiral Ir(III) complex (see section 3) …”

“…They exhibited excellent reactivity towards Diels‐Alder (DA) reaction in the presence of metal‐transition/ligands catalytic system or several biohybrid catalytic systems. In the field of chiral transition‐metal catalysis, bis‐cyclometallated chiral Λ‐ IrO1 complex displayed excellent diastereo‐ and enantioselectivities in DA and hetero‐Diels‐Alder (HDA) reactions (Scheme a) . Switching to Λ‐ RhO1 complex, the synthesis of several hydrocarbazoles 64 through DA reaction between N ‐Boc‐protected 3‐vinylindole 63 and β‐carboxylic ester‐substituted α,β‐unsaturated acyl‐imidazoles 1 d was reported (Scheme b) .…”

“…One similar transformation was reported in 2015 by Meggers and co-workers using chiral Ir (III) complex (see section 3). [16] Trost developed a Pd-catalyzed vinyl-substituted trimethylenemethane (TMM) asymmetric [3 + 2] cycloaddition with 1. [17] The transformation relied on the use of unprecedented bisdiamidophosphite ligand L5 and engendered tetrasubstituted cyclopentanes 23 in high yields with good regio-, diastereo-and enantioselectivities (Scheme 11).…”

DNA‐Based Asymmetric Inverse Electron‐Demand Hetero‐Diels–Alder

“…Finally, a NOESY experiment established a correlation between H 4 and H 7a consistent with an endo ‐selective cycloaddition. As for the absolute configuration, the latter was ascertained by comparing the specific optical rotation value of the endo product 3 j (3a R , 4 R , 7a S ), which was obtained in quasi‐quantitative yield on a 105 mg scale, with the one reported in the literature, while all other products were assigned by analogy. Compound 3 l was also engaged in a hydrogenation reaction to further support our assignment (Table ).…”