György Keglevich

P-heterocycles as ligands in homogeneous catalytic reactions.

Ligands with phosphorus donor atoms have probably been the most studied ones in transition metal catalyzed reactions. Because of the recognition of the carbon-metal bonding properties and the mechanistic understanding of the basic catalytic reactions, the application of homogeneous catalytic reactions is steadily emerging. The definition of the scope and limitations has rendered many of the transition metalphosphorus ligand catalytic systems the most efficient solution to practical problems. Most of the “textbook” homogeneous catalytic reactions, among them enantioselective reactions, apply tertiary phosphines as most conventional ligands. Among the ligands with phosphorus of sp3 hybridization, the cyclic ligands have reached an impressive maturity. In spite of this fact, in general, the chemistry of phosphorus heterocycles is much less developed than the analogous nitrogen chemistry. It is especially true in the area of coordination chemistry, even though cyclic phosphines proved to be excellent ligands for catalysis.1-5 Thus, the main objective of this review is to shed some more light into the synthesis, coordination chemistry, and catalysis of some 3-, 4-, 5-, 6-, and 7-membered Pheterocycles of unprecedented structure not reviewed before. The objective of this paper is not to present a full coVerage of P(III) deriVatiVes, since several aspects of these types of P-heterocycles such as theoretical background, synthesis, * To whom correspondence should be addressed. E-mail: kollar@ttk.pte.hu. † This paper is dedicated to the memory of Professor Pascal Le Floch. György Keglevich was born in Budapest, Hungary, in 1957. He received his M.Sc. under the supervision of Professors L. Tõke and Imre Petneházy from the Technical University of Budapest in 1981. After getting the Ph.D., he was a postdoctoral fellow with Professor L. D. Quin (at Duke University, Durham, NC). In 1994, he received his D.Sc. from the Hungarian Academy of Sciences. After different teaching positions, he was appointed full professor at the Department of Organic Chemical Technology, Budapest University of Technology and Economics, in 1996, and he was the head of this Department in the period of 1999-2006. After a fusion in 2007, he has been the head of the Department of Organic Chemistry and Technology. His research interests include organophosphorus and environmentally friendly chemistry comprising P-heterocycles, low-coordinated P-fragments, P(III)-ligands, their boraneand transition metal complexes, catalytic reactions, selective syntheses, resolution of P(IV) compounds, microwave synthesis, ionic liquids, and optimization of reactions by on-line methods. Chem. Rev. 2010, 110, 4257–4302 4257

The Kabachnik–Fields Reaction: Mechanism and Synthetic Use

The Kabachnik–Fields (phospha-Mannich) reaction involving the condensation of primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H species, especially dialkyl phosphites, represents a good choice for the synthesis of α-aminophosphonates that are of significant importance due to their biological activity. In general, these three-component reactions may take place via an imine or an α-hydroxy-phosphonate intermediate. The monitoring of a few Kabachnik–Fields reactions by in situ Fourier transform IR spectroscopy has indicated the involvement of the imine intermediate that was also justified by theoretical calculations. The Kabachnik–Fields reaction was extended to >P(O)H species, comprising cyclic phosphites, acyclic and cyclic H-phosphinates, as well as secondary phosphine oxides. On the other hand, heterocyclic amines were also used to prepare new α-amino phosphonic, phosphinic and phosphine oxide derivatives. In most cases, the synthesis under solvent-free microwave (MW) conditions is the method of choice. It was proved that, in the cases studied by us, there was no need for the use of any catalyst. Moreover, it can be said that sophisticated and environmentally unfriendly catalysts suggested are completely unnecessary under MW conditions. Finally, the double Kabachnik–Fields reaction has made available bis(phosphonomethyl)amines, bis(phosphinoxidomethyl)amines and related species. The bis(phosphinoxidomethyl)amines serve as precursors for bisphosphines that furnish ring platinum complexes on reaction with dichlorodibenzonitriloplatinum.

Enantioselective Michael reaction of 2-nitropropane with substituted chalcones catalysed by chiral azacrown ethers derived from α-D-glucose

Abstract The chiral monoaza-15-crown-5 lariat ethers anellated to methyl-4,6-O-benzylidene-α- d -glucopyranoside 1a–c showed significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to substituted chalcones. Among the catalysts bearing different side arms at the nitrogen atom, the compound with a phosphinoxidoalkyl side chain 1c proved to be the most effective (max. 78% e.e.). The type of substituent on the chalcone was found to have a very significant influence on both the chemical yield and the enantioselectivity of the reaction. The absolute configuration of the Michael adducts 3b and 3i was determined by chemical methods, while that of 3d was assigned by X-ray crystal structure determination.

Phospholes with reduced pyramidal character from steric crowding III NMR and X-ray diffraction studies on 1-(2,4,6-tri-isopropylphenyl)-3-methylphosphole

Abstract The 2,4,6-tri-isopropylphenyl substituent was placed on the phosphorus of a phosphole to reduce the pyramidal character. That this was accomplished was revealed by single crystal X-ray diffraction analysis; with respect to the plane of C2PC5 in the phosphole ring, the ipso carbon of the benzene ring was deflected by only 58.0°, whereas the deflection is 66.9° in the uncrowded 1-benzylphosphole. This proves that the concept of reducing the pyramidal character (with the goal of increasing the electron delocalization) through steric crowding can be realized. In the crystal the two rings are in orthogonal planes, but this relation is not retained in solution; NMR studies show that the two edges of the benzene ring, as well as the 2,6-isopropyl groups, are identical.

Insights into a surprising reaction: The microwave-assisted direct esterification of phosphinic acids

It is well-known that phosphinic acids do not undergo direct esterifications with alcohols under thermal conditions. However, the esterifications take place under microwave (MW) irradiation due to the beneficial effect of MW. As a comparison, maximum 12-15% conversions were observed on traditional heating. It was proved experimentally that the MW-assisted esterifications are not reversible under the conditions applied that may be the consequence of the hydrophobic medium established by the long chain alcohol/phosphinic ester. Neither the thermodynamic, nor the kinetic data obtained by high level quantum chemical calculations justify the direct esterification of phosphinic acids under thermal conditions. The thermodynamic data show that there is no driving force for the reactions under discussion. As a consequence of the relatively high values of activation enthalpy (102-161 kJ mol(-1)), these esterifications are controlled kinetically. Comparing the energetics of the esterification of phosphinic acids and the preparative results obtained under MW conditions, one can see the potential of the MW technique in the synthesis of phosphinates. During our study, a series of new cyclic phosphinates with lipophilic alkyl groups was synthesized.

Novel Synthesis of Phosphinates by the Microwave-Assisted Esterification of Phosphinic Acids

Abstract 1-Hydroxy-3-phospholene oxides (1 and 3) and phenyl-H-phosphinic acid (6) are converted to the corresponding phosphinic esters (2, 4, and 7, respectively) by reaction with simple alcohols on microwave irradiation. Under traditional heating conditions, the esterification does not take place, as in the cases of 1 and 3, or is highly incomplete, as in the case of 6. Steric hindrance in diphenylphosphinic acid prevents efficient microwave-assisted esterification.

Enantioselective Michael addition of 2-nitropropane to chalcone analogues catalyzed by chiral azacrown ethers based on α-d-glucose and d-mannitol

Abstract The chiral monoaza-15-crown-5 type lariat ethers 1 and 2 derived from α- d -glucose and from d -mannitol, respectively, have been applied as phase transfer catalysts in the enantioselective Michael addition of 2-nitropropane to aromatic 3b–c and heteroaromatic 3d–h chalcone analogues. Among the catalysts, the glucose-based 1c with a phosphinoxidobutyl side arm proved to be the most effective, it inducing 34% e.e. for 4b, 59% e.e. for 4c, 80% e.e. for 4d, 64% e.e. for 4e, 17% e.e. for 4f. Catalyst 1a having 3-hydroxypropyl substituent resulted in 81% e.e. for compound 4g. The formation of the (+)-(S)-enantiomer of 4 was preferred using crown ethers 1a–c, while the (−)-(R)-enantiomer was in excess with catalyst 2. The absolute configuration of the Michael adduct 4d was determined by single-crystal X-ray analysis.

Diastereoselective synthesis of 1,2,3,6-tetrahydrophosphinine 1-oxides with an exocyclic P-function by a Michael type addition

The anions generated from diphenylphosphine oxide or dialkyl phosphites add easily at the α,β-double-bond of 1,2-dihydrophosphinine oxides 1 to afford a single diastereomer of 3-substituted tetrahydrophosphinine oxides 2–4 existing in a twist-boat conformation.

B(C6F5)3-catalyzed silylation versus reduction of phosphonic and phosphinic esters with hydrosilanes

Abstract HSiR3/cat-B(C6F)3 induced dealkylation or reduction of esters of phosphorus at 20°C. A specific conversion to silylesters occurred by reaction with tertiary silanes. In contrast, free phosphines were observed in the reaction with mono- or disubstituted silanes. A mechanism was proposed to rationalize these results.

Photolysis of the cycloadduct of a 1,2-dihydrophosphinine oxide with N-phenylmaleimide in the presence of protic species: new aspects on the mechanism of the fragmentation of a 2-phosphabicyclo[2.2.2]octene

Abstract Phosphabicyclo[2.2.2]octene 2 is useful in the UV light mediated phosphorylation of protic species. Experiments suggest that the fragmentation takes place according to concurrent EA and AE mechanisms.