Preparation of Vinylphosphonates from Ketones Promoted by Tf2O.

An efficient triflic anhydride promoted phosphorylation of ketone was disclosed, and vinylphosphorus compounds were prepared under solvent- and metal-free conditions. Both aryl and alkyl ketones could perform smoothly to give vinyl phosphonates in high to excellent yields. In addition, the reaction was easy to carry out and easy to scale up. Mechanistic studies suggested that this transformation might involve nucleophilic vinylic substitution or a nucleophilic addition-elimination mechanism.

The stereoselective conversion of epimerized alkoxyl phosphine-borane to P,C, axial-stereogenic tertiary phosphine via cleavage of P-O bond.

The P-O bond of epimerized alkoxyl phosphine-borane was cleaved by naphthalene-lithium, to form two diastereomers of P-anions in a ratio of 86 : 14, which was then converted to secondary phosphine-borane via acidification, and to tertiary phosphines with alkyl halides with enhanced 96 : 4 dr. The isolated tertiary phosphine containing hydroxyl (in >99 : 1 dr) was converted to multi-stereogenic tertiary phosphines via O-alkylation with alkylene dihalides.

Stereoselective preparation of P,axial-stereogenic allenyl bisphosphine oxides via chirality-transfer.

P,C-Stereogenic propargyl alcohols RC-3/SC-3' were prepared by the addition of (L)-menthyl-derived SPOs to propynals, which were converted to P,axial-stereogenic allenyl bisphosphine oxides. The chirality transfer was controlled by α-carbon via syn [2,3]-sigmatropic rearrangement. For SC-3' linking weak WDG on the alkynyl moiety, the chirality on the axis depended on stereogenic phosphorus.

Functional Phosphine Derivatives Having Stationary and Flexible Chiralities: Their Preparation and Chirality Controlling.

Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

Hydrophosphorylation of Alkynes Catalyzed by Palladium: Generality and Mechanism.

We carried out a comprehensive study on the generality, scope, limitations, and mechanism of the palladium-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds (i.e., H-phosphonates, H-phosphinates, secondary phosphine oxides, and hypophosphinic acid). For H-phosphonates, Pd/dppp was the best catalyst. Both aromatic and aliphatic alkynes, with a variety of functional groups, were applicable to produce the Markovnikov adducts in high yields with high regioselectivity. Aromatic alkynes showed higher reactivity than aliphatic alkynes. Terminal alkynes reacted faster than internal alkynes. Sterically crowded H-phosphonates disfavored the addition. For H-phosphinates and secondary phosphine oxides, Pd/dppe/Ph2P(O)OH was the catalyst of choice, which led to highly regioselective formation of the Markovnikov adducts. By using Pd(PPh3)4 as the catalyst, hypophosphinic acid added to terminal alkynes to give the corresponding Markovnikov adducts. Phosphinic acids, phosphonic acid, and its monoester were not applicable to this palladium-catalyzed hydrophosphorylation. Mechanistic studies showed that, with a terminal alkyne, (RO)2P(O)H reacted, like a Brønsted acid, to selectively generate the α-alkenylpalladium intermediate via hydropalladation. On the other hand, Ph(RO)P(O)H and Ph2P(O)H gave a mixture of α- and ß-alkenylpalladium complexes. In the presence of Ph2P(O)OH, hydropalladation with this acid took place first to selectively generate the α-alkenylpalladium intermediate. A subsequent ligand exchange with a P(O)H compound gave the phosphorylpalladium intermediate which produced the Markovnikov adduct via reductive elimination. Related intermediates in the catalytic cycle were isolated and characterized.

Nonepimerizing Alkylation of H-P Species to Stereospecifically Generate P-Stereogenic Phosphine Oxides: A Shortcut to Bidentate Tertiary Phosphine Ligands.

The secondary RP-(-)-menthyl alkylphosphine oxide was confirmed as configurationally stable toward base and was used in base-promoted alkylation, stereospecifically affording P-retained bis or functional tertiary phosphine oxides in excellent yields. The alkylated products were deoxygenated using oxalyl chloride followed by ZnCl2-NaBH4 to form P-inversed bidentate phosphine boranes in high stereoselectivities.

Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl Compounds: Stereochemistry, Mechanism, and Applications.

Nucleophilic substitutions at P centers are of high importance in biological processes and asymmetric synthesis. However, detailed studies on this topic are rare. P-Stereogenic compounds containing P-Cl, P-O, and P-S bonds were diastereoselectively prepared and then used to study the substitution of Cl, O, and S at phosphorus centers with organometallic reagents. It was proposed that with alkynyl metallic reagents an SN2-like mechanism (route A1) and a Berry pseudorotation (BPR) of pentacoordinated phosphorus intermediates (route B1) were involved and afforded P-inverted and P-retained products, respectively. The P-inverted conversion of a P-Cl functionality to a P-C functionality can be controlled by either the temperature or the order of addition of the starting materials. The introduction of a P-Cl bond using an alkyl metallic reagent proceeded through routes A2 and A2'. At higher temperatures, P-inverted products were predominantly afforded via SN2-like route A2. At lower temperatures, bis-substituted products were formed via route A2' and cleavage of the P-O bond. The P-S bonds were accompanied by the epimerization of the starting materials, triggered by the alkylthio anion, via route C. The epimerization can be suppressed by the use of a poorly soluble magnesium alkylthiolate, and the P-retained compounds will be formed as the major products via route B3 and BPR of the intermediates.

Preparation of Optically Pure Tertiary Phosphine Oxides via the Addition of P-Stereogenic Secondary Phosphine Oxide to Activated Alkenes.

Functionalized P,C-stereogenic tertiary phosphine oxides were prepared by the addition of (RP)-menthyl phenylphosphine oxide to activated olefins, in high drP and drC, and were isolated in excellent yields. The reaction was readily catalyzed by Ca(OH)2 or occurred with gentle heating. A wide range of substrates, including vinyl ketones, esters, nitriles, and nitro alkenes, can be used in the reaction.

Stereospecific Preparations of P-Stereogenic Phosphonothioates and Phosphonoselenoates.

P-Stereogenic phosphonothioates and phosphonoselenoates were readily prepared utilizing RP-menthyl phenylphosphite 1 by two methods. The first method used elemental sulfur or selenium to react with 1, followed by alkylation of the intermediates with alkyl halides. The second used 1 to react with disulfide or diselenide. Both methods stereospecifically produced the title compounds in nearly quantitative yields under mild conditions. Stereospecific chalcogenation of the phosphoryl was proposed as the key step in these reactions.

Variable mechanism of nucleophilic substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents.

The variable mechanism for substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents, which depends on temperature, stoichiometry of starting materials, and the structure of the nucleophilic reagent, is assumed as either SN2-like or Berry pseudorotation of pentacoordinated phosphorus intermediates, affording inversion and retention products, respectively. The formation of the inversion product can be controlled to occur predominantly to afford (RP)-alkynylphosphinates.

Double Asymmetric Induction During the Addition of (RP)-Menthyl Phenyl Phosphine Oxide to Chiral Aldimines.

P,C-Stereogenic α-amino phosphine oxides were prepared from the addition of (RP )-menthyl phenyl phosphine oxide to chiral aldimines under neat condition at 80 °C in up to 91:9 drC and 99% yields. The diastereoselectivity was mainly induced by chiral phosphorus that showed matched or mismatched induction with (S)- or (R)-aldimines, respectively.

Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism.

Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or α-carbon.

Tandem addition of nucleophilic and electrophilic reagents to vinyl phosphinates: the stereoselective formation of organophosphorus compounds with congested tertiary carbons.

Carbon anions formed via the addition of Grignard reagents to SP-vinyl phosphinates were modified with electrophilic reagents to afford organophosphorus compounds with diverse carbon skeletons. The electrophiles included acids, aldehydes, epoxy groups, chalcogens and alkyl halides. When alkyl halides were used, bis-alkylated products were afforded. Substitution reactions or polymerization occurred when the reaction was applied to vinyl phosphine oxides.

(1-Methyl-1H-imidazol-3-ium-2-yl)(phen-yl)phosphinate monohydrate.

The title compound, C(10)H(11)N(2)O(2)P·H(2)O, contains a tetra-coordinate penta-valent P atom. The phosphinate group plays a predominant role in the cohesion of the crystal structure by forming chains along the b axis via inter-molecular C-H⋯O hydrogen bonds. These chains are connected by O-H⋯O and N-H⋯O hydrogen bonding involving the lattice water.

1,2-Diphenyl-2-[(1-phenyl-eth-yl)amino]-ethanol.

In the mol-ecule of the title compound, C(22)H(23)NO, there are two chiral atoms (R* for the C atom attached to the OH group and S* for the C atom attached to the phenyl ring). In the crystal, neighbouring mol-ecules are connected into a chain along the b axis by N-H⋯O hydrogen bonds.

(R(P))-5-Methyl-2-(propan-2-yl)cyclo-hexyl phen-yl{phen-yl[(1-phenyl-eth-yl)amino]-meth-yl}phosphinate.

In the title compound, C(31)H(40)NO(2)P, the P atom has a distorted tetra-hedral stereochemistry [bond-angle range about P = 103.33 (6)-115.24 (15)°] and has R(P) chirality, which was confirmed crystallographically. The dihedral angles between the P-bonded phenyl ring and the other two phenyl rings are 40.4 (3) and 12.2 (2)°. In the crystal, a C-H⋯O inter-action links mol-ecules into chains which extend along [100].

Direct phosphorylation of benzylic C-H bonds under transition metal-free conditions forming sp3C-P bonds.

Direct phosphorylation of benzylic C-H bonds was achieved in a biphasic system under transition metal-free conditions. A selective radical/radical sp3C-H/P(O)-H cross coupling was proposed, and various substituted toluenes were applicable. The transformation provided a promising method for constructing sp3C-P bonds.

7-Phenyl-7H-dinaphtho-[2,1-b:1',2'-d]phosphole 7-oxide.

In the title compound, C(26)H(17)OP, the naphthyl ring systems are bent away from each other [dihedral angle = 30.81 (8)°]. In the crystal, weak inter-molecular C-H⋯O inter-actions link the mol-ecules into helical chains along the 2(1) screw axis.

2-Isopropyl-5-methyl-cyclo-hexyl diphenyl-phospho-namidate.

In the title compound, C(22)H(30)NO(2)P, the P atom has an irregular tetra-hedral geometry. In the crystal, mol-ecules are connected by N-H⋯O hydrogen-bonding inter-actions, giving rise to a chain along the b axis. The phenyl ring of the anilino group is twisted by 77.40 (16)° relative to the other phenyl ring. The absolute configuration of phospho-rus is S(p).