PROPHOS

In enantioselective, 1,3-dipolar cycloadditions of nitrones to methacrolein the catalysts used were (r 5-C5Me5)MR-Prophoscontaining complexes (M = Rh, Ir and (R)-Prophos = l,2-bis(diphenylphosphino)propane) (754b). 

It was not until 1995 that a synthetically useful enantioselective hydroalumination was first described.123 The early attempts to develop enantioselective hydroalumination used chiral phosphines such as prophos, chiraphos 26, and BINAP 23 as ligands. The most successful of these was BINAP with ee s of 56% being obtained (entry 1, Table 11). 

As already stated, DIOP led the way for a number of ligand systems that were built on a carbon framework containing stereogenic centers. Some of these ligands followed closely on the heels of DIOP, such as ChiraPhos (16) where the chelate ring is five-membered [82, 83]. Even one stereogenic center in the backbone, as in ProPhos (17), provides reasonable selectivity [83, 84]. The main problem with these systems is that of slow reactions. 

The enantioselective catalytic 1,3-dipolar cycloaddition of linear or cyclic nitrones to enals was accomplished using the half-sandwich rhodium(III) complex S, Rc)-[(ri -C5Me5)Rh (/ )-Prophos (H20)](SbF6)2 as catalyst precursor [33, 34]. At —25°C, quantitative conversions to the cycloadducts, with up to 95% ee, were achieved (Scheme 10). The intermediate with the dipolarophile coordinated to the rhodium has been isolated and completely characterized, including the X-ray determination of its molecular structure [33, 34]. 

The same rhodium precursor, (S Rh,/ c)-[(Tl -C5Me5)Rh (l )-Prophos (H20)] (SbFg)2, promotes the reaction between the nitrones A-benzylideneaniline A-oxide or 3,4-dihydroisoquinoline A-oxide with other enals different from methacrolein (Scheme 10). The cycloadducts were prepared with excellent regioselec-tivity, perfect endo selectivity, and enantiomeric excesses up to 94% [35]. 

The (ri -C5Me5)Ir (/ )-Prophos system is very selective for the OCR of nitrones and methacrolein with enantioselectivity up to 96% ee. A few structural features of... 

Interesting information about the catalytic systems was obtained by studying the stereochemistry of the reaction of the catalyst precursor 1 with methacrylonitrile. The water molecule of complex 1 is readUy displaced by methacrylonitrile rendering complex [(t -C5Me5)Ir (/ )-Prophos (methacrylonitrile)] (SbFg)2 (9) as a mixture of the two possible epimers at metal, namely, R iJic and 5ir,/ c, in 34% diastereomeric excess in the former (Scheme 20). In acetone, at 50°C, the R r,Rc isomer slowly epimerizes to the thermodynamically preferred epimer. From the solution, pure samples of the latter can be isolated that have been employed as stoichiometric catalysts for the DCR between methacrylonitrile and nitrones IV and V. 

Diastereomerically pure iridium complexes of the formula [(ri -C5Me5)lr (/ )-Pro-phos (activated alkene)](SbF6)2 (activated alkene = enal, methacrylonitrile) are active, and selective catalysts for the DCR between one point binding activated alkenes and nitrones. Enals coordinate to the metal in a completely diastereoselec-tive way with a restricted geometry. From the point of view of the selectivity, a key point in enal coordination is the establishment of CH/n-attractive interactions between the CHO aldehyde proton and one (f )-Prophos phenyl group. This interaction fixes the methacrolein rotamer around the M-O bonds and renders the system enantioselective. 

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