Cationic Rh catalysts

Scheme 4 syn-Diastereoselective intermolecular hydrogen-mediated aldol coupling employing cationic Rh catalysts ligated by tri-2-furylphosphine... 

NMR evidence for intermediate dihydrides of cationic Rh catalysts remained elusive for a long time, ever since the first demonstrations [33] of effective enan-tioselective catalysis, for example in the homogeneous hydrogenation of dehydroamino acid derivatives for the synthesis of L-DOPA. 

By using PHIP-NMR studies, various intermediates such as the previously elusive dihydrides of neutral and cationic hydrogenation catalysts, as well as hydrogenation product/catalyst complexes, have already been detected during the hydrogenation of styrene derivatives using cationic Rh catalysts. Information about the substituent effect on chemical shifts and kinetic constants has been obtained via time-resolved PASADENA NMR spectroscopy (DYPAS). 

A Rh catalyst with (/ ,/ )-MeDuPHOS is effective for the asymmetric hydrogenation of sterically congested functionalized olefins, a key intermediate in the synthesis of Tipranavir, an HIV protease inhibitor [32]. The cationic Rh catalyst is found to enable an highly efficient and enantioselective hydrogenation of a unique carboxylate for the 12-kg reaction scale production of candoxatril, a cardiovascular agent [33]. 

Chiral cationic Rh catalysts for the hydrogenation of prochiral C-C double bonds require the use of BARF or related anions even with potentially CO2-S0IU-ble ligands such as Et-DuPHOS (DuPHOS l,2-bis(2,5-dialkylphospholano)-benzene) [70] or a perfluoroalkyl-substituted aryl phosphonite [19]. The ligand... 

All hydrogenations performed with cationic Rh catalyst precursors [(COD)R]i-DuPHOS]OTf and with a-enamide methyl ester substrates in MeOH, unless otherwise noted. All results involving. -Cbz substrates were extracted from references 7 and 19. All results involving A-Boc substrates derive from reference 17. 

In the case of the hydroboration of perfluoroalkylolefins, the choice of Rh-complex and borane species can influence regioselectivity dramatically. For instance, while the reaction of perfluoroalkylolefins with catecholborane in the presence of a cationic Rh-catalyst produces the secondary alcohols predominantly after the oxidative work-up process, a Wilkinson s complex-catalyzed reaction with pinacolborane affords the primary alcohols (eq 66). ... 

Table 8.1 Enantioselective hydroacylation reaction using cationic Rh catalysts reported by Bosnich.

As can be seen from Table 2, there are some trends as to which type of complex is most often used for the hydrogenation of C=C, C=0 and C=N bonds. The hydrogenation of alkenes is preferentially catalyzed by cationic Rh catalysts or with Ru complexes without halogen anions. There is no discemable correlation between the substitution pattern of the C=C bond and the best catalyst type. Ketones substituted (or activated) in a- or p-position usually require the presence of a Ru... 

The cationic Rh catalyst was prepared in situ by stirring the mixture of [Rh(cod)Cl]2, AgBp4 and an appropriate chiral DP AMP (135) in THF for 2 h. The resulting cationic catalyst was characterized by P NMR. In a stainless steel autoclave, dehydroamino acid derivative 147 (0.02 mmol) was dissolved in a degassed solvent (0.4 mL). To the solution was added the prepared catalyst (0.0002 mmol). The reactor was then pressurized with hydrogen and the reaction was run under the chosen conditions. The enantiopurity of the products were determined by GC on a Chrompack Chirasil-L-Val colutnn (Agilent Technologies, Santa... 

Upon careful examination of reaction parameters, Tanaka and coworkers successfully developed a highly enantioselective lactone synthesis by reaction with both aldehydes and activated ketones as the coupling partners for the synthesis of spirocyclic benzopyranones. Cationic Rh catalysts were again found to be the most efficient. Importantly, homodimerization of the parent 2-aIkynylbenzaldehydes was not observed under the optimized conditions [92]. 

The C-H bond addition reactions across alkynes using a Rh catalyst such as RhC PPhjjj described earlier appear to proceed through oxidative addition of C-H toward a Rh species, alkyne insertion into the resulting Rh-H bond, and reductive elimination (path A in Scheme 18.82). An alternative pathway may be a sequence involving C-H metallation by an electrophilic Rh species, alkyne insertion into the resulting Rh-C bond, and protodemetallation (path B). The latter mechanism was proposed by Schipper ei al. [82] for their reaction of N-carbamoylindoles with alkynes in the presence of a cationic Rh catalyst (Scheme 18.83). 

The catalytic hydroboration reaction of fluorinated olefins also provided both Markovnikov and anti-Markovnikov products by the prudent choice of the catalyst and reagent mixture (43). Thus, catecholborane in the presence of cationic Rh catalysts affords anti-Markovnikov hydroboration whereas pinacolborane in the presence of neutral Rh catalysts provide anti-Markovnikov products (Figure 11). We have achieved up to 70% enantioselectivity for catalytic asymmetric hydroboration of fluoroolefins (39). The search for an optimal chiral ligand continues. 

A cationic Rh-catalyst was employed in the presence of silver(I) carbonate to alkenylate heteroarylphosphine oxides. Thiophene derivatives underwent alkenylaton in modest to good yields (59-72%) using ethyl and terf-butyl acrylates (eq 38). 

Scheme 13.6 Enantioselective hydrogenation of prochiral a-enamides with cationic Rh catalysts.

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