Phosphinyl imines

Two technical applications of C = N-X substrates have been reported. Noyori s Ru-PP-NN catalyst system was successfully applied in a feasibility study by Dow Chirotech for the hydrogenation of a sulfonyl amidine [77], while Avecia showed the commercial viability of its CATHy catalyst based on a pentamethyl cyclopentadienyl Rh complex for the reduction of phosphinyl imines [78] (Fig. 34.11). 

Rhodium diphosphine catalysts can be easily prepared from [Rh(nbd)Cl]2 and a chiral diphosphine, and are suitable for the hydrogenation of imines and N-acyl hydrazones. However, with most imine substrates they exhibit lower activities than the analogous Ir catalysts. The most selective diphosphine ligand is bdppsuif, which is not easily available. Rh-duphos is very selective for the hydrogenation of N-acyl hydrazones and with TOFs up to 1000 h-1 would be active enough for a technical application. Rh-josiphos complexes are the catalysts of choice for the hydrogenation of phosphinyl imines. Recently developed (penta-methylcyclopentyl) Rh-tosylated diamine or amino alcohol complexes are active for the transfer hydrogenation for a variety of C = N functions, and can be an attractive alternative for specific applications. 

Asymmetric reductions. The reagent can effect asymmetric reduction of alkyl aryl ketones and unhindered dialkyl ketones in high optical yield.1 It is the most useful reagent known to date for asymmetric reduction of even hindered a-keto esters to (S)-a-hydroxy esters in >90% ee.2 It is also effective for asymmetric reduction of phosphinyl imines of dialkyl ketones, RlR2C=NP(0)(C6H5)2 (50-84% ee).3... 

The attachment of the strongly electronegative phosphinyl (P—O) group to an imine, usually via reaction of an oxime with a chlorophosphine, also gives highly electrophilic imines which are reduced by NaBFWTHF and various modified borohydride and LAH derivatives " under mild conditions. The product A-phosphinylamines are protected forms of primary amines since removal of the phosphorus substituent is accomplished under mild acidic conditions. Entries 12 and 13 (Table 16) present representative reductions and illustrate (entry 13) that highly diastereoselective reductions of cyclic systems to axial amine derivatives are accomplished with LiBHBu s. Enantioselective reductions of A-diphenylphosphinyl imines to optically active amine derivatives have also been reported (Chapter 1,7, this volume). ... 

An alternative method for the synthesis of tran -alkenyl /f-phosphinates involved AIBN initiated radical addition of ethyl phosphinate to alkenes and alkynes. The method was applied to the preparation of GABA analogues. A new route to chiral phospholanes has been presented. Enantiomerically pure P-chiral dicyclohexyl-ammonium 2-(phosphinyl)acrylates (236) have been obtained by an asymmetric Michael reaction with imine, which opens a new general route to the enantioselective synthesis of a-methylene-6-valerolactones (237) (Scheme 97). ... 

A soln. of abs. ethanol in dry toluene added during 2-2.5 hrs. at ca. —10° with vigorous stirring to a soln. of dichlorisocyanatophosphine oxide in the same solvent, warmed slowly to room temp., stirred for another hr., coned, to ca. half its volume in a flash evaporator at a bath temp, of ca. 40°, added during 2-2.5 hrs. at 0° with vigorous stirring to a soln. of 2 moles of ethylen-imine and 2 moles of triethylamine in toluene, warmed slowly to room temp., and stirred for another hr. ethyl [bis-(l-aziridinyl)phosphinyl] carbamate. Y 70.2%. F. e. s. Z. B. Papanastassiou and T. J. Bardos, J. Med. Pharm. Chem. 5, 1000 (1962). 

The aza Henry reaction of N-phosphinyl aldimines with nitroalkanes was promoted by (9) to give P-nitroamines with good enantioselectivity (Scheme 2.37) [88]. The thiourea activated the nitro group, thereby facilitating the formation of the nucleophilic nitronate anion. They subsequently found that the use of N-Boc imine improved the enantioselectivity with reversal of the facial selectivity (Scheme 2.38) [89]. 

Phosphinylation of imines in the presence of a chiral magnesium BINOL phosphate allowed the synthesis of enantioenriched a-aminophosphine... 

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