Access to P‐ and Axially Chiral Biaryl Phosphine Oxides by Enantioselective Cp^xIr^III‐Catalyzed C−H Arylations

Abstract

An enantioselective C-H arylation of phosphine oxides with o-quinone diazides catalyzed by an iridium(III) complex bearing an atropchiral cyclopentadienyl (Cp ) ligand and phthaloyl tert-leucine as co-catalyst is reported. The method allows access to a) P-chiral biaryl phosphine oxides, b) atropo-enantioselective construction of sterically demanding biaryl backbones, and also c) selective assembly of axial and P-chiral compounds in excellent yields and diastereo- and enantioselectivities. Enantiospecific reductions provide monodentate chiral phosphorus(III) compounds having structures and biaryl backbones with proven importance as ligands in asymmetric catalysis.

Quantifying Through‐Space Substituent Effects

“…Such striking through‐space electronic influences likely account for the prevalence of proximally positioned OR and NR groups in ligands widely exploited in catalysis (e.g. SPhos, SagePhos, BI‐DIME) . Interestingly, the strong electro‐enhancing influence of the 2,6‐dimethoxy groups was found to be completely switched off in compound 1‐b ( σ p(conf) =+0.03, green in Figure C).…”

Catalytic Enantioselective Methylene C(sp3)−H Amidation of 8‐Alkylquinolines Using a Cp*RhIII/Chiral Carboxylic Acid System

“…In particular, when one wishes to functionalize enantiotopic C−H bonds of prochiral substrates to generate chiral products, stereocontrol at the C−H bond cleavage step, that is, an enantioselective C−H activation, is crucial. Cramer and co‐workers, followed by Li and co‐workers, have achieved such enantioselective C−H activation/functionalization reactions by using well‐designed chiral Cp x M III catalysts (Scheme a), where a chiral carboxylic acid was sometimes employed as a secondary chiral source . Although this strategy is successful for the enantioselective functionalization of C(sp 2 )−H bonds, functionalization of less reactive enantiotopic C(sp 3 )−H bonds has not yet been achieved.…”

Efficient Oxidative Resolution of 1-Phenylphosphol-2-Ene and Diels–Alder Synthesis of Enantiopure Bicyclic and Tricyclic P-Stereogenic C-P Heterocycles

“…The most spectacular example of their utility has been the use of (S P )-PAMP {o-anisylmethylphenylphosphine} and (R P ,R P )-DIPAMP {1,2-bis(o-anisylmethylphenylphosphine)ethane} di as chiral ligands in rhodium-catalyzed asymmetric hydrogenation of enamides [5] which led to the first application of such a process in the industrial production, i.e., the Monsanto L-DOPA process [6] However, P-stereogenicity is not a natural phenomenon, and, from the very beginning [7], it had to be generated in the lab. Despite many developed asymmetric syntheses [1,[7][8][9][10][11][12][13][14][15][16][17][18], desymmetrizations [14,[19][20][21][22][23][24][25][26][27] and kinetic resolutions [28][29][30][31][32][33][34], practical preparations of optically active P-stereogenic compounds are still relying in great part on classical resolution of racemates [7,8,[35][36][37][38][39][40]. The latter has the advantage to rely on cheap and often recoverable chiral auxiliaries, uses crystallization for separation of the P-epimers and, The subsequent resolution of rac-1 started with its reduction to the corresponding phosphine 2 by treatment with PhSiH 3 at the t...…”