Aminophosphines with alcohols

Mechanistic Studies. - The mechanism of the reaction of tetra-zole-activated phosphoramidites with alcohols has been studied. A series of diethyl azolyl phosphoramidites (85) was prepared from diethyl phosphorochloridite and fully characterized, and the same compounds shown to be formed from the phosphoramidite (86) and azole. The degree of formation of (85) from (86) increases with the acidity of the azole, and the proposed mechanism is a fast protonation of (86), followed by a slow, reversible formation of (85) and a fast reaction of (85) with alcohols. Another study was concerned with the influence of amine hydrochlorides on the rate of methanolysis of the phosphoramidites (87) or (88), or tris(diethylamino)phosphine.The chloride content was measured to be 10-20 mM in doubly distilled samples which explains that "uncatalysed alcoholysis is possible. Intensive purification, including treatment with butyllithium and distillation from sodium, brought the chloride content down to 0.1-1 mM. The methanolysis reaction, in methanol as the solvent, was found to be first-order in catalyst concentration. An aJb initio calculation on N- and P-protonated aminophosphine (89) gave similar proton affinities for N and P this contrasts with earlier MNDO calculations which had ff-protonated species as the most stable. The M-protonated compound had an electronic structure reminiscent of a phosphenium ion-ammonia complex. 

Tervalent phosphorus acid derivatives are normally liquids or low-melting solids which can be purified by distillation, or sometimes by recrystallization from a non-polar solvent. Most are oxidized in contact with the atmosphere, and many are easily hydrolyzed, so they must be kept under an inert atmosphere (N2 or Ar) during all manipulations. Flasks should be predried and solvents dried and deoxygenated before use. Tervalent phosphorus acid derivatives are, with few exceptions, thermally stable and can be kept indefinitely in ampoules under an inert gas (many halophosphines dissolve stopcock grease and should not be kept in stoppered flasks for prolonged periods). Inert solvents are hydrocarbons, ethers and, for most compounds, dichloromethane, ethyl acetate and tertiary amines. Aminophosphines react vigorously with tetrachloromethane and slowly with trichloromethane, and most tervalent phosphorus acid derivatives are oxidized by dimethyl sulphoxide and react with alcohols. 

In a search for tervalent phosphorus acid derivatives with better phosphitylation properties than usual aminophosphines or phosphoramidites Nifant ev et al. have prepared several new reagents. These include pyrazole derivatives, e.g. (51), 2-aminopyridine derivatives, e.g. (52), amidine derivatives, e.g. (53), and hydrazine derivatives, e.g. (54). They were prepared by standard methods and examined for their reactivity towards alcohols and, in the case of the amidine derivatives, for their tendency to isomerize by migration of the phosphorus group to the other nitrogen atom. Another type of reactive tervalent phosphorus acid derivative is phosphites derived from hydroxylamine. Several stable derivatives, e.g. (55) and (56), have been prepared and substitution reactions with alcohols studied. ... 

A cationic (S)-BINAP-Ir(I) complex combined with an aminophosphine catalyzes hydrogenation of isobutyrophenone affording an R alcohol in 84% ee... 

Other similar phosphorus ligands on solid supports and screened them in the Heck reaction.Starting from supported amino alcohols, representative members of five different families of phosphine and phosphinite ligands were synthesised /3-aminophosphines 73, A, /3-diphosphinoamines 74, a,/3-diphosphinoamines 75, /3-aminophosphi-nites 76, and A -phosphino-/3-aminophosphinites 77. Following their complexation with Pd(OAc)2, the ligands were screened in the Heck reaction and led to the identification of two lead ligands for future studies. 

Miscellaneous.- A simple method to resolve racemic l,l -binaphthalene-2,2 -diol involves reaction with menthyl phosphorodichloridite (139) and separation of the diastereomeric phosphites by crystallisation from ether. The new cyclic chlorodiaminophosphine (140), prepared in and two new cyclic triaminophosphines (141) have been used to determine the enantiomeric purity of chiral alcohols, thiols, and amines by means of Ip n.m.r. New optically pure phosphites used for Rh catalysed asymmetric hydroformylation reactions are (142), two diastereomers of (143), and (144) the diphosphinite (145) was similarly employed. Some new cyclic aminophosphines (146) were prepared for use as ligands in asymmetric Pd catalysed allylic substitution reactions. 

Recently, many research groups have focused their efforts oti the development of stereoselective routes leading to optically pure aminophosphinic acids. With this aim, Yamagishi and co-workers recently devised a practical methodology for the preparation of optically pure A-protected 1,1-diethoxyethyl(aminomethyl) phosphinates (12) [39] and their participation in diastereoselective alkylation reactions [40] which were first studied several years ago by McCleery and Tuck [41] (Scheme 4). In particular, they managed to obtain on a gram-scale and 99 % enantiomeric excess (ee) compound 11, after addition of paraformaldehyde to l,l-diethoxyethyl-//-phosphinate (10) and subsequent lipase-catalyzed resolution of the resulting racemic alcohol. Conversion of 11 to substrate 12 in four steps afforded a valuable substrate suitable for lithium bis(trimethylsilyl)amide (LHMDS)-promoted alkylation performed in a diastereoselective fashion (dr = 10 1) (Scheme 4). 

Thus the enantioselective oxidation of P-racemic tertiary phosphines and aminophosphines was successfully attained by treatment with tetrahalomethanes and an alcohol. Oxidation of iV-phosphorylated amino acids by these reactants proceeded diastereoselectively with formation of aminophosphinates 131 in 80-85% yields and with 50-98% de. The compounds were purified by crystallization and obtained in optically pure form (>99% de) (Scheme 40) [33, 39]. 

The reaction of aminophosphine borane 21 with o-iodophenethyl alcohol yields the phosphinite borane 22, with the expected inversion of configuration, although only in 24% yield. 

Interest in potentially aromatic heterocyclic systems has continued at a similar level to the previous year, with most work again relating to the chemistry of fused ring phospholes and phospholyl anions. Activity in the phosphirene area, however, has again been minimal in the past year. Streubel s group has studied the thermal reactions of 2ff-phosphirene complexes (124) with primary and secondary amine deriwitives and alcohols," leading to the formation of aminophosphine and alkoryphosphine complexes, so as to explore the boundaries between complexed phosphanide, phosphinidenoid and transient phosphinidene intermediates. 

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