Cleavage of PO in the Presence of P–N: Aminophosphine Oxide Reduction with In Situ Boronation of the PIII Product

In contrast to tertiary phosphine oxides, the deoxygenation of aminophosphine oxides is effectively impossible due to the need to break the immensely strong and inert P?O bond in the presence of a relatively weak and more reactive P? N bond. This long‐standing problem in organophosphorus synthesis is solved by use of oxalyl chloride, which chemoselectively cleaves the P?O bond forming a chlorophosphonium salt, leaving the P? N bond(s) intact. Subsequent reduction of the chlorophosphonium salt with sodium borohydride forms the P^III aminophosphine borane adduct. This simple one‐pot procedure was applied with good yields for a wide range of P? N‐containing phosphoryl compounds. The borane product can be easily deprotected to produce the free P^III aminophosphine. Along with no observed P? N bond cleavage, the use of sodium borohydride also permits the presence of ester functional groups in the substrate. The availability of this methodology opens up previously unavailable synthetic options in organophosphorus chemistry, two of which are exemplified.     

Access to P‐ and Axially Chiral Biaryl Phosphine Oxides by Enantioselective CpxIrIII‐Catalyzed C−H Arylations

An enantioselective C?H arylation of phosphine oxides with o‐quinone diazides catalyzed by an iridium(III) complex bearing an atropchiral cyclopentadienyl (Cp^x) 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.     

Copper-Catalyzed Dynamic Kinetic Asymmetric P−C Coupling of Secondary Phosphine Oxides and Aryl Iodides

Transition-metal-catalyzed enantioselective P−C cross-coupling of secondary phosphine oxides (SPOs) is an attractive method for synthesizing P-stereogenic phosphorus compounds, but the development of such a dynamic kinetic asymmetric process remains a considerable challenge. Here we report an unprecedented highly enantioselective dynamic kinetic intermolecular P−C coupling of SPOs and aryl iodides catalyzed by copper complexes ligated by a finely modified chiral 1,2-diamine ligand. The reaction tolerates a wide range of SPOs and aryl iodides, affording P-stereogenic tertiary phosphine oxides (TPOs) in high yields and with good enantioselectivity (average 89.2 % ee). The resulting enantioenriched TPOs were transformed into structurally diverse P-chiral scaffolds, which are highly valuable as ligands and catalysts in asymmetric synthesis.     

Rhodium-Catalyzed ortho-Olefination of Sterically Demanding Benzamides: Application to the Asymmetric Synthesis of Axially Chiral Benzamides

It has been established that an unsubstituted cyclopentadienyl rhodium(III) (CpRh^III) complex is a highly active catalyst for the aerobic oxidative ortho C−H bond olefination of sterically demanding ortho-substituted benzamides with alkenes. This catalysis was successfully applied to the diastereoselective synthesis of axially chiral N,N-dialkylbenzamides. The combination of the ruthenium(II)-catalyzed enantioselective hydrogenation and the CpRh^III-catalyzed diastereoselective ortho C−H bond olefination enabled the asymmetric synthesis of axially chiral N,N-dialkylbenzamide derivatives with high ee values.     

Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio‐ and diastereoselective construction of cyclopropanes through C?H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing‐group‐assisted C?H activation strategy was used to realize mild and redox‐neutral Rh^III‐catalyzed C?H activation and cyclopropylation of N‐phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a Rh^V nitrenoid intermediate, and Noyori‐type outer sphere concerted proton‐hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity.     

Enantiodivergent synthesis of P-chirogenic phosphines

Several approaches for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines are described, using ephedrine methodology and phosphine borane chemistry. Firstly, both enantiomers of a tertiary phosphine can be obtained starting from the same oxazaphospholidine borane complex, prepared from (+)-ephedrine, when changing the order of addition of the organolithium reagents during the synthetic pathway. The second approach is based on the chlorophosphine boranes, which react with an organolithium reagent, to afford the corresponding phosphines with inversion of configuration. In the case where the chlorophosphine borane reacts with the t-butyl lithium reagent, a metal-halogen exchange occurs to afford the corresponding phosphide borane with retention of the configuration. The reaction of the phosphide borane with an alkyl halide leads to the same phosphine, but with the opposite configuration. Another approach depends on the diastereoselective preparation of the starting oxazaphospholidine borane complex from (?)-ephedrine, which leads according the case, to either one or the other enantiomer of a phosphine. Finally, the synthesis of (R,R)- and (S,S)-1,2-bis(methylphenylphosphino)ethane is also demonstrated using both enantiomers of the P-chirogenic diphosphinite diborane, which simultaneously allows the introduction of alkyl- or aryl substituents on the phosphorus atoms. In summary, these approaches show the great efficiency of the “ephedrine methodology” for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines, and bearing alkyl or aryl substituents.     

Phosphathiahelicenes: Synthesis and Uses in Enantioselective Gold Catalysis

Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl‐olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine–Au^I complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N‐tethered enynes (up to 96 % ee).     

Total Synthesis of (+)‐Gracilamine Based on an Oxidative Phenolic Coupling Reaction and Determination of Its Absolute Configuration

The enantioselective total synthesis of (+)‐gracilamine ( 1 ) is described. The strategy features a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza‐Michael reaction to construct the ABCE ring system. The configuration at C3a in 1 was controlled by the stereocenter at C9a, which was selectively generated (91 % ee) by an organocatalytic enantioselective aza‐Friedel–Crafts reaction developed by our research group. This synthesis revealed that the absolute configuration of (+)‐gracilamine is 3aR, 4S, 5S, 6R, 7aS, 8R, 9aS.     

Computational studies on azaphosphiridines, or how to effect ring-opening processes through selective bond activation

The relative energies of azaphosphiridine and its isomers, the ring stability towards valence isomerization, and the ring strain, as well as the kinetics and thermodynamics of possible ring‐opening reactions of P^III derivatives ( 1 – 5 ) and P^V chalcogenides ( 6 – 9 ; O to Te), were studied at high levels of theory (up to CCSD(T)). The barrier to inversion at the nitrogen atom in the trimethyl‐substituted P^III derivative 5 increases from 12.11 to 15.25 kcal mol^?1 in the P‐oxide derivative 6 (P^V); the relatively high barrier to inversion at the phosphorus in 5 (75.38 kcal mol^?1) points to a configurationally stable center (MP2/def2‐TZVPP//BP86/def2‐TZVP). The ring strain for azaphosphiridine 5 (av. 22.6 kcal mol^?1) was found to increase upon P‐oxidation ( 6 ) (30.8 kcal mol^?1; same level of theory). Various ring‐bond‐activation processes were studied: N‐protonation of P^III ( 5 ) and P^V ( 6 , 7 ) derivatives leads to highly activated species that readily undergo P? N bond cleavage. In contrast, metal chlorides such as LiCl, CuCl, CuCl₂, BeCl₂, BCl₃, AlCl₃, TiCl₃, and TiCl₄ show little P? N bond activation in 5 and 7 . Remarkably, TiCl₃ selectively activates the C? N bond, and induces stronger bond activation for P^V ( 6, 7 ) than for P^III azaphosphiridines ( 5 ). The ring‐expanding rearrangement of P^V azaphosphiridines 6 – 9 to yield P^III 1,3,2‐chalcogena‐azaphosphetidines 32 a – d is predicted to be preferred for the heavier chalcogenides 7 – 9 , but not for the P‐oxide 6 . The first comparative analysis of three bond strength parameters is presented: 1) the electron density at bond critical points, 2) Wiberg’s bond index, and 3) the relaxed force constant. This reveals the usefulness of these parameters in assessing the degree of ring bond activation.     

Activation of Small Molecules by Phosphorus Biradicaloids

The reactivity of biradicaloid [P(μ‐NTer)]₂ was employed to activate small molecules bearing single, double, and triple bonds. Addition of chalcogens (O₂, S₈, Se_x and Te_x) led to the formation of dichalcogen‐bridged P₂N₂ heterocycles, except from the reaction with molecular oxygen, which gave a P₂N₂ ring featuring a dicoordinated P^III and a four‐coordinated P^V center. In formal [2πe+2πe] addition reactions, small unsaturated compounds such as ethylene, acetylene, acetone, acetonitrile, tolane, diphenylcarbodiimide, and bis(trimethylsilyl)sulfurdiimide are readily added to the P₂N₂ heterocycle of the biradicaloid [P(μ‐NTer)]₂, yielding novel heteroatom cage compounds. The synthesis, reactivity, and bonding of the biradicaloid [P(μ‐NTer)]₂ were studied in detail as well as the synthesis, properties, and structural features of all addition products.     

Enantioselective Total Synthesis of (+)‐Plumisclerin A

The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.0^1,5]decane and trans‐fused dihyrdopyran moiety. Scalable enantioselective La^III‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI₂‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.     

Synthesis,Structure, Spectroscopic,and Electrochemical Properties of Highly Fluorescent Phosphorus(V)–meso‐Triarylcorroles

The synthesis, spectroscopic, and electrochemical properties of seven new P^V–meso‐triarylcorroles ( 1 – 7 ) are reported. Compounds 1 – 7 were prepared by heating the corresponding free‐base corroles with POCl₃ at reflux in pyridine. Hexacoordinate P^V complexes of meso‐triarylcorroles were isolated that contained two axial hydroxy groups, unlike the P^V complex of 8,12‐diethyl‐2,3,7,13,17,18‐hexamethylcorrole, which was pentacoordinate, or the P^V complex of meso‐tetraphenylporphyrin, which was hexacoordinate with two axial chloro groups. ¹H and ³¹P NMR spectroscopy in CDCl₃ indicated that the hexacoordinated P^V–meso‐triarylcorroles were prone to axial‐ligand dissociation to form pentacoordinated P^V–meso‐triarylcorroles. However, in the presence of strongly coordinating solvents, such as CH₃OH, THF, and DMSO, the P^V–meso‐triarylcorroles preferred to exist in a hexacoordinated geometry in which the corresponding solvent molecules acted as axial ligands. X‐ray diffraction of two complexes confirmed the hexacoordination environment for P^V–meso‐triarylcorroles. Their absorption spectra in two coordinating solvents revealed that P^V–meso‐triarylcorroles showed a strong band at about 600 nm together with other bands, in contrast to P^V–porphyrins, which showed weak bands in the visible region. These compounds were easier to oxidize and more difficult to reduce compared to P^V–porphyrins. These compounds were brightly fluorescent, unlike the weakly fluorescent P^V–porphyrins, and the quantum yields for selected P^V–corroles were as high as Al^III and Ga^III corroles, which are the best known fluorescent compounds among oligopyrrolic macrocycles.     

Modulation of Multifunctional N,O,P Ligands for Enantioselective Copper‐Catalyzed Conjugate Addition of Diethylzinc and Trapping of the Zinc Enolate

In this work, we have successfully synthesized a new family of chiral Schiff base–phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp³‐central chirality from axial BINOL and sp³‐central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper‐catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer‐like bimetallic multinuclear Cu? Zn complex constructed in situ was found to be substrate‐selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C₂‐axial binaphthol and sp³‐central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)‐ L1 ‐ and (R,S)‐ L4 ‐based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C=20 000, turnover number (TON)=17 600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper‐ L4 ‐complex‐catalyzed conjugate addition, which resulted in the high‐yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4 , and the corresponding mechanistic study of the copper catalyst system were investigated by ³¹P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.     

Ba3V2S4O3: A Mott Insulating Frustrated Quasi‐One‐Dimensional S=1 Magnet

Through a solid‐state reaction, a practically phase pure powder of Ba₃V₂S₄O₃ was obtained. The crystal structure was confirmed by X‐ray single‐crystal and synchrotron X‐ray powder diffraction (P6₃, a=10.1620(2), c=5.93212(1) Å). X‐ray absorption spectroscopy, in conjunction with multiplet calculations, clearly describes the vanadium in charge‐disproportionated V^IIIS₆ and V^VSO₃ coordinations. The compound is shown to be a strongly correlated Mott insulator, which contradicts previous predictions. Magnetic and specific heat measurements suggest dominant antiferromagnetic spin interactions concomitant with a weak residual ferromagnetic component, and that intrinsic geometric frustration prevents long‐range order from evolving.     

Defluorinative C(sp3)−P Bond Construction for the Synthesis of Phosphorylation gem‐Difluoroalkenes under Catalyst‐ and Oxidant‐Free Conditions

Defluorinative C(sp³)?P bond formation of α‐trifluoromethyl alkenes with phosphine oxides or phosphonates have been achieved under catalyst‐ and oxidant‐free conditions, giving phosphorylation gem‐difluoroalkenes as products. α‐Trifluoromethyl alkenes bearing various of aryl substituents such as halogen, cyano, ester and heterocyclic groups are available in this transformation. The results of control experiments demonstrated that the mechanism of dehydrogenative/defluorinative cross‐coupling reactions was not a radical route, but might be an S_N2′ process involving phosphine oxide anion.     

Atroposelective PIII/PV=O Redox Catalysis for the Isoquinoline-Forming Staudinger–aza-Wittig Reaction

Herein, we describe the feasibility of atroposelective P^III/P^V=O redox organocatalysis by the Staudinger–aza-Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.     

Rhodium(III)-Catalyzed Enantio- and Diastereoselective C−H Cyclopropylation of N-Phenoxylsulfonamides: Combined Experimental and Computational Studies

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio- and diastereoselective construction of cyclopropanes through C−H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing-group-assisted C−H activation strategy was used to realize mild and redox-neutral Rh^III-catalyzed C−H activation and cyclopropylation of N-phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a Rh^V nitrenoid intermediate, and Noyori-type outer sphere concerted proton-hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity.     

Solid‐State 17O NMR Spectroscopy of Paramagnetic Coordination Compounds

High‐quality solid‐state ¹⁷O (I=5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing V^III (S=1), Cu^II (S=1/2), and Mn^III (S=2) metal centers, the ¹⁷O isotropic paramagnetic shifts were found to span a range of more than 10 000 ppm. In several cases, high‐resolution ¹⁷O NMR spectra were recorded under very fast magic‐angle spinning (MAS) conditions at 21.1 T. Quantum‐chemical computations using density functional theory (DFT) qualitatively reproduced the experimental ¹⁷O hyperfine shift tensors.     

Synthesis of P-Stereogenic Phosphine Oxides via Nickel-Catalyzed Asymmetric Cross-Coupling of Secondary Phosphine Oxides with Alkenyl and Aryl Bromides

A general and mild nickel-catalyzed enantioselective C(sp²)−P cross-coupling for synthesizing P-stereogenic phosphine oxides has been developed. The asymmetric alkenylation/arylation of racemic secondary phosphine oxides with alkenyl/aryl bromides generated P-stereogenic phosphine oxides with high yields and enantioselectivities. Various functional groups were tolerated, and the applications of this method were demonstrated through late-stage functionalization and product transformations.     

Total synthesis of 3,4-dihydroxyprolines, -threo- -norvaline and (2S,3R,4R)-2-amino-3,4-dihydroxytetrahydrofuran-2-carboxylic acid methyl ester

The Henry reaction between -glyceraldehyde and ethyl nitroacetate allowed the practical development of a diastereoselective synthesis of 3,4,5-trihydroxy-2-nitropentanoic acid esters, which were reduced to polyoxamic acids, which were used in a new diastereoselective synthesis of 3,4-dihydroxyprolines and new enantioselective syntheses of -threo- -norvaline and (2S,3R,4R)-2-amino-3,4-dihydroxytetrahydrofuran-2-carboxylic acid methyl ester.