Ligands PROPHOS

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. 

Efficient asymmetric hydrogenation of alkenes other than the amino acid and dipeptide precursors described above has met with only limited success. This appears to be at least in part due to the inability of many alkenes to function as bidentate chelates. Ethyl 2-acetoxyacrylate was hydrogenated with an enantiomer excess of 89% using [Rh(cod)(R,R-DIPAMP)]+, giving the S-enantiomer (equation 53). The ligands CHIRAPHOS, PROPHOS, DIOP, BPPM and CAMP were less effective.266... 

Figure 7 shows the preferred conformations of S,S-chiraphos and R-prophos. According to our hypothesis, catalysts formed by these two ligands should give similar optical yields but of opposite chirality. This is because we assert that the chiral array of phenyl groups determines the optical induction and hence whether the ring conformations... 

Presented herein are the results of a P-31 NMR study of the solid states and liquid solution states of the following rhodium catalysts and their constituent diphosphine ligands (Rh(COD)diphos)+ C104 , I (Rh(COD)DiPAMP)+ ClOr, II (Rh(COD)BPPM)+ ClOr, III (Rh(NBD)chiraphos)+ ClOr and (Rh(COD)chiraphos)+ ClOr, IVa and IVb and (Rh(NBD)prophos)+ C104 , V. (COD = cyclooctadiene NBD = norbornadiene diphos = l,2-ethanediylbis(diphenylphos-phine) DiPAMP = (R,R)-l,2-ethanediylbis(o-methoxyphenyl-... 

Preparation of the Ligands. S,S-chiraphos and R-prophos were prepared via methods given in the literature (6, 7). Diphos was obtained from Strem Chemicals. BPPM was generously supplied by K. Achiwa and R,R-DiPAMP also was generously supplied by W. Knowles. 

The solution and solid P-31 NMR spectra of the prophos ligand are presented in Figure 10. As seen from this figure, the expected nonequivalence of the phosphorus atoms was observed in both spectra. The signals in the solid-state spectrum showed increased shielding relative to the solution spectrum. The solution spectrum also revealed a P-P coupling (/P P = 20.5 Hz). 

The asymmetric synthesis step is actually a case of homogeneous asymmetric hydrogenation of a C=C bond with a chiral catalyst it represents an example of enantio-differentiation. Two rhodium(I) catalysts incorporating as ligand either l(5, S )-chiraphos = (S, S )-(2,3)-bis[diphenylphosphino]butane, 158, or R)-prophos = (/ )- ,2-bis[diphenylphosphino]propane, 159, were used. 

While indeed a clean photoreduction of COa to CO in the complex (prophos)Cu (C03)Cu (prophos) was observed the concomitant oxidation did not yield oxygen or hydrogen peroxide but phosphine oxide (30). In order to prevent this dead end, phosphines have to be replaced by ligands that do not act as oxygen atom acceptors. For this purpose we selected the tridentate ligand hydrotris (3,5-dimethyl-l-pyrazolyl)borate (Tp ) as a suitable ligand (40). Various Cu(I) and Cu(II) complexes of Tp or other Tp derivatives have been prepared and characterized (41-45). Unfortunately, we were not able to obtain simple carbonate complexes of the Cu Tp moiety (Structure 1). In the presence of COs, Cu Tp underwent a decomposition. 

The stereoselectivity obtained with the PPFA ligand is generally higher than that obtained with (2,3-0-Isopropylidene)-2,3-dihydroxy-l,4-bis(diphenylphosphino)buta ne (DIOP) (7-16% ee), l,2-bis(diphenylphosphino)propane (prophos) (0% ee), and 2,2 -bis(diphenylphosphinomethyl)-1,1 -binaphthyl (NAPHOS) (11% ee). 

In addition, a Rh-(R,R)-NORPHOS catalyst has been used to promote enantioselective transfer hydrogenation of the C=C double bond in (Z)-a-(acetylamino)cinnamic acid and in (Z)-a- and ( )-a-(benzoylamino)-2-butenoate by using 80% aqueous formic acid as the source of H2. Optical yields were improved by the addition of sodium formate representative results are presented in Table 2. Comparable, but generally somewhat lower, optical yields were obtained by using other Rh-(biphosphine ligand) catalysts, e.g., biphosphine ligand = (R,S)-(+)-BPPFA (2), (R)-(+)-PROPHOS(3), ot(R,R)-... 

Ruthenium(II) complexes may also be used to oxidize N-Boc hydroxylamine in the presence of tert-butylhydroperoxide (TBHP) to the corresponding nitroso dieno-phile, which is subsequently trapped by cyclohexa-1,3-diene to give the hetero Diels-Alder adduct (Entry 1, Scheme 10.26) [51]. A triphenylphosphine oxide-stabilized ruthenium(IV) oxo-complex was found to be the catalytically active species. Use of a chiral bidentate bis-phosphine-derived ruthenium ligand (BINAP or PROPHOS) result in very low asymmetric induction (8 and 11%) (Entry 2, Scheme 10.26). The low level of asymmetric induction is explained by the reaction conditions (in-situ oxidation) that failed to produce discrete, stable diastereomerically pure mthenium complexes. It is shown that ruthenium(II) salen complexes also catalyze the oxidation of N-Boc-hydroxylamine in the presence of TBHP, to give the N-Boc-nitroso compound which can be efficiently trapped with a range of dienes from cyclohepta-1,3-diene (1 h, r.t., CH2CI2, 71%) to 9,10-dimethylanthracene (96 h, r.t., CH2CI2,... 

In the 1970s and early 1980s the development of new catalysts was mainly based on new optically active chelating phosphines used in Wilkinson-type catalysts. This era of design and synthesis of optically active bidentate phosphines started in 1971 with Kagan s tartaric acid derived ligand DIOP [59, 60]. Successful and well-known examples followed, namely DIPAMP [62], prophos [63], chiraphos [64], BPPM [65], BPPFA [66], norphos [67], and BINAP [68]. A selection is depicted in Figure 3. 

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