Nickel-Catalyzed Enantioselective Alkylation of Primary Phosphines.

Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis.

Nickel-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphanyl Hydrazine Building Blocks.

Catalytic asymmetric methods for the synthesis of synthetically versatile P-stereogenic building blocks offer an efficient and practical approach for the diversity-oriented preparation of P-chiral phosphorus compounds. Herein, we report the first nickel-catalyzed synthesis of P-stereogenic secondary aminophosphine-boranes by the asymmetric addition of primary phosphines to azo compounds. We further demonstrate that the P-H and P-N bonds on these phosphanyl hydrazine building blocks can be reacted sequentially and stereospecifically to access various P-stereogenic compounds with structural diversity.

Copper-catalyzed asymmetric C(sp)-H arylation for the synthesis of P- and axially chiral phosphorus compounds.

Transition metal-catalyzed C-H bond functionalization is an important method in organic synthesis, but the development of methods that are lower cost and have a less environmental impact is desirable. Here, a Cu-catalyzed asymmetric C(sp)-H arylation is reported. With diaryliodonium salts as arylating reagents, a range of ortho-arylated P-chiral phosphonic diamides were obtained in moderate to excellent yields with high enantioselectivities (up to 92% ee).

Photoinduced Copper-Catalyzed C(sp)-P Bond Formation by Coupling of Secondary Phosphines with N-(Acyloxy)phthalimides and N-Fluorocarboxamides.

A photoinduced copper-catalyzed C(sp)-P bond formation has been developed by using N-(acyloxy)phthalimides as radical precursors and secondary phosphine boranes as coupling partners. A variety of alkyl carboxylic acid derivatives can be readily transformed into the corresponding phosphines with high reaction efficiency and structural diversity. Besides, utilizing the 1,5-HAT of the N-centered radical process, the δ C(sp)-H bond can be coupled with secondary phosphines, which provides a novel method for the regioselective formation of C(sp)-P bonds.

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(sp )-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.

Secondary Phosphine Sulfide-Enabled Iridium-Catalyzed Asymmetric Allylic Substitution.

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity.

Cobalt-Catalysed Asymmetric Addition and Alkylation of Secondary Phosphine Oxides for the Synthesis of P-Stereogenic Compounds.

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.

Asymmetric Synthesis of P-Stereogenic Secondary Phosphine-Boranes by an Unsymmetric Bisphosphine Pincer-Nickel Complex.

The first highly enantioselective catalytic synthesis of P-stereogenic secondary phosphine-boranes was realized by the asymmetric addition of primary phosphine to electron-deficient alkenes with a newly developed unsymmetric bisphosphine (PCP') pincer-nickel complex. Various P-stereogenic secondary phosphine-boranes were obtained in 57-92% yields with up to 99% ee and >20:1 dr. The follow-up alkylation upon P-C bond formation with alkyl halides provided a practical way to access P-chiral compounds with diverse functional groups.

Asymmetric construction of quaternary α-nitro amides by palladium-catalyzed C(sp)-H arylation.

Pd-Catalyzed enantioselective C(sp3)-H arylation of N-(o-Br-aryl) anilides has been disclosed, and quaternary α-nitro amides were constructed with up to 98% ee. The presence of the nitro group on the substrate enables the progress of the reaction and the ready transformation of the product to optically active quaternary amino acid derivatives.

Syntheses of Benzofuranoquinolines and Analogues via Photoinduced Acceptorless Dehydrogenative Annulation of -Phenylfuranylpyridines.

A strategy for the syntheses of benzofuranoquinolines and its analogues via the irradiation of -phenylfuranyl/thienylpyridines/pyrimidines in DCM with UV light at rt under an argon atmosphere is described. The mechanism of this reaction through the process of 6π-electrocyclization, [1,5]-hydrogen shift, and 1,3-eneamine tautomerism leading to H evolution was elucidated. Notably, the syntheses of -8b-methyl-8b,13a-dihydrobenzo[]benzofuro[3,2-]quinolone via the photoinduced rearrangement of 2-(3-methylbenzofuran-2-yl)-3-phenylpyridine relevant to the mechanism of this reaction highlights the importance of the developed methodology.

Site-Tunable C-H Bonds Functionalization by Visible-Light-Induced Radical Translocation of -Alkoxyphthalimides.

Site-tunable functionalization of C(sp)-H bonds has been accomplished through radical translocation and cross-coupling. Upon irradiation with visible light, copper-based photocatalyst [Cu(Xantphos)(dmp)]BF enabled cross-coupling of -alkoxyphthalimides with amino acid esters or amino acids to provide δ-C(sp)-H alkylated alcohols (31 examples, up to 92% yield) with additive BNDHP or α-C(sp)-H alkylated alcohols (18 examples, up to 86% yield) with additive DABCO in a highly regioselective fashion.

Palladium-Catalyzed C-H Alkenylation of Arenes with Alkynes: Stereoselective Synthesis of Vinyl Chlorides via a 1,4-Chlorine Migration.

A directing group-free, ligand-promoted palladium-catalyzed C-H arylation of internal alkynes with simple arenes was developed. Alkenyl chlorides resulting from a 1,4-chlorine migration or trisubstituted alkenes were produced in moderate to good yields depending on the type of alkyne.

Palladium-Catalyzed Asymmetric Arylation of C(sp(3))-H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids.

Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

Palladium-catalyzed enantioselective C-H arylation for the synthesis of P-stereogenic compounds.

A palladium-catalyzed enantioselective C-H arylation of N-(o-bromoaryl)-diarylphosphinic amides is described for the synthesis of phosphorus compounds bearing a P-stereogenic center. The method provides good enantioselectivities and high yields. The products were readily transformed into P-chiral biphenyl monophosphine ligands.

2-Hydroxy-1,10-phenanthroline vs 1,10-phenanthroline: significant ligand acceleration effects in the palladium-catalyzed oxidative Heck reaction of arenes.

A series of bidentate monoanionic nitrogen ligands were designed and applied in the Pd-catalyzed oxidative Heck reaction of arenes with alkenes. Significant ligand-accelerated effects were observed, and direct C-H functionalized products were formed in high yields with meta-selectivity.

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to α,β,γ,δ-unsaturated sulfonic esters: controlling regioselectivity by rational selection of electron-withdrawing groups.

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to electron-deficient dienes was developed through rational selection of electron-withdrawing groups on the dienes. Various chiral allylic phosphine derivatives were synthesized in good yields with high enantioselectivity (up to 96% ee).

Silver-mediated oxidative C-H/P-H functionalization: an efficient route for the synthesis of benzo[b]phosphole oxides.

A Ag-mediated C-H/P-H functionalization reaction of arylphosphine oxides with internal alkynes was described for the direct preparation of benzo[b]phosphole oxides with a high yield. An unusual aryl migration on the P-atom derived from a C-P bond cleavage and a new C-P bond formation was also observed and demonstrated to proceed via the radical process.

Palladium-catalyzed asymmetric addition of diarylphosphines to α,β-unsaturated sulfonic esters for the synthesis of chiral phosphine sulfonate compounds.

Highly stereoselective addition of diarylphosphines to α,β-unsaturated sulfonic esters catalyzed through a PCP pincer-Pd complex is developed to synthesize chiral phosphine sulfonic esters with excellent enantioselectivity (up to 99.5% ee). The transformation of the chiral adduct into a useful palladium phosphine sulfonate complex is also demonstrated.

Palladium-catalyzed asymmetric addition of diarylphosphines to N-tosylimines.

Bis(phosphine) pincer-Pd complex-catalyzed asymmetric addition of diarylphosphines to N-tosylimines was developed for the synthesis of chiral phosphine sulfides with high stereoselectivities (up to 96% ee) under mild conditions.

Palladium-catalyzed 1,4-addition of diarylphosphines to α,β-unsaturated aldehydes.

A highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated aldehydes catalyzed by a bis(phosphine) pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 98% ee) under mild conditions. The application of the current method to the synthesis of enantiopure bisphosphine and its pincer-Pd complex has also been demonstrated.

Palladium-catalyzed 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles.

Highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles catalyzed by a PCP pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (91-99% ee) under mild conditions. The products obtained can be further converted into chiral phosphine-oxazoline ligands.

Palladium-catalyzed asymmetric addition of diarylphosphines to enones toward the synthesis of chiral phosphines.

An asymmetric addition of diarylphosphines to beta-substituted enones under mild conditions using a chiral pincer-palladium catalyst has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 99% ee).

Organo[2-(hydroxymethyl)phenyl]dimethylsilanes as mild and reproducible agents for rhodium-catalyzed 1,4-addition reactions.

Stable and reusable tetraorganosilicon reagents, alkenyl-, aryl-, and silyl[2-(hydroxymethyl)phenyl]dimethylsilanes, undergo 1,4-addition reactions to alpha,beta-unsaturated carbonyl acceptors under mild rhodium-catalysis. The reaction tolerates a diverse range of functional groups and is applicable to gram-scale synthesis. Use of a chiral diene ligand allows the achievement of the corresponding enantioselective transformations using the tetraorganosilicon reagents, providing the silicon-based approach to optically active ketones and substituted piperidones that serve as synthetic intermediates of pharmaceuticals.

Chiral phosphine-olefin ligands in the rhodium-catalyzed asymmetric 1,4-addition reactions.

A full overview on the use of chiral phosphine-olefin ligands 1 in the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated carbonyl compounds is described. Effective chiral environment of a Rh/1 complex was shown to resemble that of a Rh/(R,R)-Ph-bod* complex by comparing the experimental results as well as the X-ray crystal structures. High catalytic activity of a Rh/1 complex was disclosed and the catalytic cycle involving a trimer-monomer equilibrium was established through mechanistic studies using a reaction calorimeter and (31)P NMR spectroscopy.