CHIRAPHOS ligands

The five-membered ring chelate ligands (CHIRAPHOS (7) and DIPAMP (9)) showed poor activity. DIOP (5) was found to be more effective than BINAP (6), while no real improvements in the levels of asymmetric induction were found by using cationic complexes [Rh(COD)(L-L)]+ instead of neutral systems. 

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... 

Asymmetric hydrocyanation has now been achieved using norbornene and norbornadiene as substrates. The reduction of either [PdCl2(+)-DIOP] or PdCl2 in presence of (+)-DIOP led to a palladium(O) species formulated simply as [Pd(+)-DIOP]. This gave, in reaction (164), an optical yield of 30% for the 2-exo-cyanonorbornane formed. Norbornadiene with the same catalyst gave 2-exo-cyanonorborn-5-ene with an optical purity of 17%. When the ligand CHIRAPHOS (51) was used, the catalytic activity was greatly diminished.608,609 In addition to the review of the early work already mentioned, two more recent reviews of hydrocyanation have appeared.610,611... 

For the bicyclic allylic acetate depicted below only moderate asymmetric induction is achievedl7. The small bidentate ligand Chiraphos gives better results than BINAP and Diop with respect to both enantio- and regioselectivity. 

In order to explain the high stereoselectivity in the deltacyclene formation in Schemes 5 and 6 a model is used (Scheme 7), which is also successful in predicting the correct product configurations in the hydrogenation of dehydroamino acids [10]. On the left side the chelate skeleton of the ligand Chiraphos is depicted, which also... 

CHIRAPHOS (86), bdpp (87), DIOP (85), deguphos (117), and related chiral diphosphines have been used as ligands in asymmetric hydroformylation of styrene and related substrates.255 347-349... 

Early work in the field of asymmetric hydroboration employed norbornene as a simple unsaturated substrate. A range of chiral-chelating phosphine ligands were probed (DIOP (5), 2,2 -bis(diphenyl-phosphino)-l,l -binaphthyl (BINAP) (6), 2,3-bis(diphenylphosphino)butane (CHIRAPHOS) (7), 2,4-bis(diphenylphosphino)pentane (BDPP) (8), and l,2-(bis(o-methoxyphenyl)(phenyl)phos-phino)ethane) (DIPAMP) (9)) in combination with [Rh(COD)Cl]2 and catecholborane at room temperature (Scheme 8).45 General observations were that enantioselectivities increased as the temperature was lowered below ambient, but that variations of solvent (THF, benzene, or toluene) had little impact. 

The catalyst system employed was the cationic rhodium solvent complex [Rh(P-P)S2]+ (P-P = BINAP, CHIRAPHOS, S = solvent). The BINAP ligand enhances the activity of the complex (Table 10), although additional studies have revealed that both the solvent and the substituents on Si influence the levels of enantioselectivity (Scheme 29).131,132... 

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

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). 

Norton and coworkers found that catalytic enantioselective hydrogenation of the C=N bond of iminium cations can be accomplished using a series of Ru complexes with chiral diphosphine ligands such as Chiraphos and Norphos [68], Even tetra-alkyl-substituted iminium cations can be hydrogenated by this method. These reactions were carried out with 2 mol.% Ru catalyst and 3.4—3.8 bar H2 at room temperature in CH2C12 solvent (Eq. (39)). 

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. 

Recently, Borner and coworkers described an efficient Rh-deguphos catalyst for the reductive amination of a-keto acids with benzyl amine. E.e.-values up to 98% were obtained for the reaction of phenyl pyruvic acid and PhCH2COCOOH (entry 4.9), albeit with often incomplete conversion and low TOFs. Similar results were also obtained for several other a-keto acids, and also with ligands such as norphos and chiraphos. An interesting variant for the preparation of a-amino acid derivatives is the one-pot preparation of aromatic a-(N-cyclohexyla-mino) amides from the corresponding aryl iodide, cyclohexylamine under a H2/ CO atmosphere catalyzed by Pd-duphos or Pd-Trost ligands [50]. Yields and ee-values were in the order of 30-50% and 90 >99%, respectively, and a catalyst loading of around 4% was necessary. 

In general, the chiral ligands are water-soluble variants of those already studied in purely organic solvents (e.g., the sulfonated chiraphos, A, cyclobutane-diop, C, BDPP, F, MeOBIPHEP-TS, Q, BIFAPS, R and the quaternary ammonium derivatives of diop, D, BDPP, E). Solubility in water could also be achieved by attaching the parent phosphine molecule to a water-soluble polymer (J, M, P). The chiral phosphinites and phosphines derived from carbohydrates (e.g., K and L) have intrinsic solubility in water. During studies of one-phase... 

Rh complexes with ChiraPhos, PyrPhos, or ferrocenyl phosphines lacking amino alkyl side chains (such as BPPFA) are much less active toward tetrasubstituted olefins. Table 6-1 shows that in asymmetric hydrogenations catalyzed by 5a-d, the coordinated Rh complex exerts high selectivity on various substrates. It is postulated that the terminal amino group in the ligand forms an ammonium carboxylate with the olefinic substrates and attracts the substrate to the coordination site of the catalyst to facilitate the hydrogenation. 

In the intermolecular reaction of tetraynes, where two 1,6-diyne moieties were directly connected, with monoalkynes, CHIRAPHOS (2,3-bis(diphenylphosphino) butane) was the choice of chiral ligand, and axial chirality was enantiomericaUy generated between the formed benzene rings (Scheme 11.17). Hexaynes with a 1,3-diyne moiety also underwent an intramolecular [2-i-2-i-2] cycloaddition, and the Ir-xylylBINAP (2,2 -bis[di(3,5-xylyl)phosphino]-l,l -binaphthyl) catalyst induced an excellent enantiomeric excess (ee) (Scheme 11.18) [24]. 

Figure 1.3. Catalytic hydrogenation of A-acylated dehydroamino esters via an unsatu-rated/dihydride mechanism the p substituents in the substrates are omitted for clarity [P-P = (i ,R)-DIPAMP, (i ,i )-CHIRAPHOS, or (R)-BINAP S = solvent or a weak ligand].

A resolution of racemic CHIRAPHOS ligand has been achieved using a chiral iridium amide complex (Scheme 8.3). The chiral iridium complex (- -)-l reacts selectively with (S.S -CHIRAPHOS to form the inactive iridium complex 2. The remaining (R,R)-CHIRAPHOS affords the catalytically active chiral rhodium complex 3. The system catalyzes asymmetric hydrogenation to give the (5)-product with 87% ee. The opposite enantiomer (—)-l gives the (R)-product with 89.5% ee, which is almost the same level of enantioselectivity obtained by using optically pure (5,5)-CHlRAPHOS. 

This NOE idea was then extended to Pd(ii) allyl complexes with bidentate phosphine auxiliaries [99-111], with the ortho P-phenyl protons acting as the reporters (see 81). Figure 1.17 shows a section of the H, H NOESY for [Pd(P-pinene allyl) (Chiraphos)](OTf) (Chiraphos = Ph2PCH(CH3)CH(CH3)PPh2), 81 [129], and reveals the numerous contacts from the chiral phenyl array to the allyl ligand. 

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