Chiraphos, addition with

The reaction of secondary phosphine boranes 211 with anisyl iodide, catalyzed by chiral Pd complex with (S,S)-Chiraphos, proceeded with retention of absolute configuration at phosphorus [135]. Addition of Pd((S,S)-Chiraphos)(o-An) to enantioenriched secondary phosphine 211 in the presence of NaOSiMc3 led to the formation of complex 212, stable at ambient temperature. This complex at +50°C in excess of diphenylacetylene allowed the formation of (/ p)-213 in yield of 70% and with enantiomeric purity of 98% ee (Scheme 68). 

Racemic diphosphines may be resolved by using transition metal complexes that contain optically active olefinic substrates (Scheme 11) (24). When racemic CHIRAPHOS is mixed with an enantiomerically pure Ir(I) complex that has two ( —)-menthyl (Z)-a-(acetam-ido)cinnamate ligands, (S,5)-CHIRAPHOS forms the Ir complex selectively and leaves the R,R enantiomer uncomplexed in solution. Addition of 0.8 equiv of [Rh(norbomadiene)2]BF4 forms a catalyst system for the enantioselective hydrogenation of methyl (Z)-a-(acetamido)cinnamate to produce the S amino ester with 87% ee. Use of the enantiomerically pure CHIRAPHOS-Rh complex produces the hydrogenation product in 90% ee. These data indicate that, in the solution containing both (S,S)-CHIRAPHOS-Ir and (/ ,/ )-CHIRAPHOS-Rh complexes, hydrogenation is catalyzed by the Rh complex only. 

Halpem and co-workers have carried out a detailed investigation of the mechanism of the asymmetric hydrogenation of methyl (MAC) and ethyl (EAC) (Z)-a-acetamidodnnamate by rhodium complexes of the ligands DIPAMP (50) and CHIRAPHOS (51).259 Coordination of alkene precedes the oxidative addition of hydrogen. For both ligands, one of the two possible diastereoisomers of the rhodium-diphosphine-alkene complex predominates in solution to a large extent. From the reaction of EAC with the S,S-CHIRAPHOS complex, this diastereoisomer has been isolated. Its structure is represented in (57).260... 

Halpern has shown that this predominant isomer exhibits negligible activity towards the oxidative addition of hydrogen. The minor isomer, which could be detected in solution for DIPAMP but not for CHIRAPHOS, reacts far more rapidly with hydrogen and is responsible for producing the major enantiomer of the hydrogenation product. The optical selectivity is thus due to this difference in reaction rates and not simply to the preferred manner of coordination of the alkene to the rhodium-diphosphine species.259,260 The precise reasons for this large difference in the rates of reaction of the two diastereoisomers with hydrogen are not yet known. The full mechanism is shown in Scheme 14. 

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... 

Since the formation of Complex 11 from 10b is a second-order process and the formation of product from Complex 11 is a first-order process, their entropies of activation will be very different. A value of AS f = -121 J mol 1deg 1 has been reported for hydrogen addition to Yaska s compound, carbonylchloro bis-triphenylphosphineiridium(I) (12). As pointed out by Halpern (II), formation of the alkyl will be favored at low temperatures and it is observed to decay rapidly above -40°C. The observation and characterization of Complex 11 proved to be both fortunate and fortuitous, since we were unsuccessful in all of our attempts to form alkyls from chiraphos or DIOP, or from DiPAMP with itaconic acid derivatives. 

Alkene Hydroarylation. The enantioselective addition of aryl iodides to norbomene has been reported using a palladium(II) complex of (5, iS )-CHIRAPHOS. The reaction of norbomadiene with 4-methoxyiodobenzene proceeded with 30% ee (eq 5). Enantioselectivities were dependent upon phosphine structure (see (+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1 ]hept-5-ene). 

Hydrogen addition to Ir(CO)(dppe)(X) leads first to the isomer with X trans to one phosphorus of dppe in a reversible reaction. This kinetic isomer then rearranges to the thermodynamic isomer that has CO trans to a phosphorus atom of dppe. For X = H or PPh3, no rearrangement of the initially formed product is observed . Addition of H2 to an iridium complex containing the optieally active diphosphine chiraphos [bis(S),(S)-2,3-(diphenylphosphino)butane] was described - . The H2 addition to analogues of... 

Ir(CO)(dppe)X occurred similarly to that for the dppe complexes, with kinetic and thermodynamic isomers formed. For both the kinetic and thermodynamic isomers, a small preference for one diastereomer was observed . Addition of H2 to Ir(chiraphos)2 gave a single stereoisomer,... 

If hydrogen adds to 7 in accord with the mechanism depicted in Scheme 12.2, then the final hydrogenation product should be /V-acctyl-(.S>phenylalaninc ethyl ester (10, Scheme 12.3). Halpem found, however, that the predominant product in the presence of CHIRAPHOS was the //-enantiomer (10", Scheme 12.3) Based on this result and other evidence, it was possible for Halpem to say that 7 and 7" form as an equilibrium mixture rapidly and reversibly from reaction of 5 and 6. Although 7 is more stable than 7", and thus is part of what Halpem termed the major manifold shown in Scheme 12.3, the less stable minor manifold isomer (7") reacts much faster during rate-determining oxidative addition of H2, eventually leading to the //-amino acid derivative. 

More recently, a rran.y-chelating asymmetric ferrocenyl phosphine (abbreviated as TRAP) has been developed [63]. The rhodium complex of TRAP catalyzes asymmetric Michael additions of a-cyanocarboxylates in high enantioselectivity (72-89 % ee) (eq (18)) [64]. Because these Michael reactions proceed via a A -bound enolato complex [65], the reaction center on the enolato ligand is far from the metal center. Thus, a CLv-chelating phosphine cannot control the direction of electrophilic attack. The reaction with c/.y-chelating phosphines gives only a poor enantiomeric excess (BINAP, 17 % ee DIOP, 12 % ee CHIRAPHOS, 3 % ee). 

Bosnich and coworkers analyzed asymmetric hydrogenation using molecular graphics with MODEL-MMX (30). Dihydrogen addition to both major and minor diastereomers was analyzed for the [(5,5-CHIRAPHOS)Rh(EAC)] complex. (EAC is ethyl-A-acetyl-a-aminocinnamate.) As with the Brown approach... 

Since enantioselectivity in this reaction is a result of the energy difference between the diastereomeric transition states after H2 is added, Landis modeled the addition of Hj to the diastereomers of the CHIRAPHOS and DIPAMP complexes with MAC as the substrate. Landis posed a simple question Is there a significant barrier to hydrogen attack at the Rh center that can be modeled by molecular mechanics In the first study Landis found that all possible attack trajectories allowed almost strain-free attack of dihydrogen (molecular mechanics barriers were less than 3 kcal/mol) (32). In a subsequent study, a better picture of the reaction coordinate was generated using DFT and quantum mechanical models, which are outside the scope of this chapter. 

A qualitative approach will possibly be more fruitful. Fig. 12 illustrates how the dihydrogen addition step (late with respect to heavy atom locations, early with respect to dihydrogen) might appear for the two diastereomeric pathways of the 16-electron route, with CHIRAPHOS as the ligand. In the alternative 14-electron route, dissociation of the alkene is assumed to occur, followed by irreversible H2 addition. The process in then consummated by reformation of the alkene-rhodium bond, or by a sigma bond metathesis which bypasses the dihydride state. 

More recently, RajanBabu has reported that in the presence of appropriate chiral Ni-based catalysts, enantioselective addition of Grignard reagents to acyclic allylic ethers maybe effected (Scheme 12) [31]. Within this context, a systematic study of the effect of reaction solvent, leaving groups, chiral Hgands and nucleophiles was undertaken. As shown in Scheme 12, treatment of allylic ether 32 with EtMgBr in the presence of 5 mol % of (S,S)-chiraphos-Ni complex [formed upon treatment of Ni(cod)2 with (S,S)-chiraphos 33] results in the formation of (R)-34 in 79% ee and 78% yield. 

Based on the finding that ruthenium complexes catalyzed the Michael addition of cyanoesters, Ito developed a system of RhH(CO)(PPh3)3 and chiral bi-dentated phosphine, (S,S)-(P,P)-TRAP. The catalyst promoted the asymmetric addition of 66 to 7 giving R)-67 [64, 65, 66]. In the case of a reactive acceptor, acrolein, even 0.1 mol % of the complex effectively catalyzed the reaction. An enantiomeric excess of up to 93% was attained with the diisopropylmethyl ester. Since BINAP, DIOP, CHIRAPHOS, etc., did not induce such high stereoselectivities, the frans-coordinated structure constructed by the TRAP was considered to be critical. The structure of the ruthenium complex obtained by X-ray analysis indicated the interaction of the metal with the nitrile nitrogen atom. The frans-coordinated ligand might be required to affect the remote reaction site. 

Thus, the combination of 2-sulfonylmethyl-2-propenyl carbonate with an unsaturated ester or ketone, catalyzed by chiral ferrocenylphosphane palladium(O) complexes, forms a mixture of cis- and /ra/w-products. The ratio of the products as well as their corresponding ee is dependent on the precise nature of the ferroceny]-based phosphane. The use of the ligand incorporating an additional 1,2-diol functionality leads to the best results with ee values of 75 % and 78 % from the unsaturated ketone, as determined by chiral shift reagent NMR [Eu(hfc),]. For comparison, the use of (S.S)-Chiraphos or (+)-BINAP as phosphane leads to ee values in the range 4 46%. 

Scheme 7.15. Possible orientations for oxidative addition of dihydrogen to the major (left) and minor (right) diastereomers of the catalyst-substrate complex (for simplicity, the linkages connecting the atoms bonded to the metal are indicated with a curved line). The boxed structures are the only octahedral structures that are not encumbered by severe non-bonded interactions they are redrawn at the bottom with the bisphosphine to the rear and in the horizontal plane. The topicity illustrated is for ligands having the structure of Figure 7.8, such as R,R DIP AMP, R.R-DIOP, or R,R CHIRAPHOS (see Figure 7.8).

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