Alkylation rhodium-catalyzed

A related but distinct rhodium-catalyzed methyl acetate carbonylation to acetic anhydride (134) was commercialized by Eastman in 1983. Anhydrous conditions necessary to the Eastman acetic anhydride process require important modifications (24) to the process, including introduction of hydrogen to maintain the active [Rhl2(CO)2] catalyst and addition of lithium cation to activate the alkyl methyl group of methyl acetate toward nucleophilic attack by iodide. 

Trifluoromethyl-substituted diazonium betaines [176]. Synthetic routes to trifluoromethyl-substituted diazo alkanes, such as 2,2,2-trifluorodiazoethane [ 177, 7 78, 179] and alkyl 3,3,3-trifluoro-2-diazopropionates [24], have been developed Rhodium-catalyzed decomposition of 3,3,3-tnfluoro-2-diazopropionates offers a simple preparative route to highly reactive carbene complexes, which have an enormous synthetic potential [24] [3-1-2] Cycloaddition reactions were observed on reaction with nitnles to give 5-alkoxy-4-tnfluoromethyloxazoles [750] (equation 41)... 

Rhodium catalyzed carbonylations of olefins and methanol can be operated in the absence of an alkyl iodide or hydrogen iodide if the carbonylation is operated in the presence of iodide-based ionic liquids. In this chapter, we will describe the historical development of these non-alkyl halide containing processes beginning with the carbonylation of ethylene to propionic acid in which the omission of alkyl hahde led to an improvement in the selectivity. We will further describe extension of the nonalkyl halide based carbonylation to the carbonylation of MeOH (producing acetic acid) in both a batch and continuous mode of operation. In the continuous mode, the best ionic liquids for carbonylation of MeOH were based on pyridinium and polyalkylated pyridinium iodide derivatives. Removing the highly toxic alkyl halide represents safer, potentially lower cost, process with less complex product purification. 

Historically, the rhodium catalyzed carbonylation of methanol to acetic acid required large quantities of methyl iodide co-catalyst (1) and the related hydrocarboxylation of olefins required the presence of an alkyl iodide or hydrogen iodide (2). Unfortunately, the alkyl halides pose several significant difficulties since they are highly toxic, lead to iodine contamination of the final product, are highly corrosive, and are expensive to purchase and handle. Attempts to eliminate alkyl halides or their precursors have proven futile to date (1). 

In this manuscript, we will chronicle the discoveiy and development of these non-alkyl halide containing processes for the rhodium catalyzed carbonylation of ethylene to propionic acid and methanol to acetic acid when using ionic liquids as solvent. 

Ethylene Carbonylation. The classical rhodium catalyzed carbonylation of ethylene to propionic acid (Eqn. 1) used ethyl iodide or HI as a co-catalyst (6). In the presence of excess ethylene and CO the process could proceed further to propionic anhydride (Eqn. 2). While additional products, such as ethyl propionate (EtC02Et), diethyl ketone (DEK), and ethanol were possible (See Eqns. 3-5), the only byproduct obtained when using a rhodium-alkyl iodide catalyst was small amounts (ca. 1-1.5%) of ethyl propionate. (See Eqns. 3-5.)... 

The rhodium catalyzed carbonylation of ethylene and methanol can be conducted in the absence of added alkyl halide if the reactions are conducted in iodide based ionic liquids or molten salts. In the case of ethylene carbonylation, the imidazolium iodides appeared to perform best and operating in the absence of ethyl iodide gave improved selectivities relative to processes using ethyl iodide and ionic hquids. In the case of... 

When the rhodium-catalyzed reaction is performed under a high pressure of CO in the presence of phosphite ligands, aldehyde products (159) are formed by insertion of CO into the rhodium-alkyl bond followed by reductive elimination (Eq. 31) [90]. The bimetallic catalysts were immobilized as nanoparticles, giving the same products and functional group tolerance, with the advantage that the catalyst could be recovered and reused without loss of... 

Scheme 6.57 Rhodium-catalyzed ortho-alkylation of ketimines...

Arylphosphines in rhodium catalyzed hydroformylation reactions exchange an aryl group for an alkyl, principally linear alkyl, corresponding to the alkene being hydro-formylated to give an alkyldiarylphosphine [22](see Equation 2.5). 

It thus came as a surprise that in the year 2000, three groups independently reported the use of three new classes of monodentate ligands (Scheme 28.2) [12], The ligands induced remarkably high enantioselectivities, comparable to those obtained using the best bidentate phosphines, in the rhodium-catalyzed enantioselective alkene hydrogenation. All three being based on a BINOL backbone, and devoid of chirality on phosphorus, these monophosphonites [13], monophosphites [14] and monophosphoramidites [15] are very easy to prepare and are equipped with a variable alkyl, alkoxy, or amine functionality, respectively. 

In contrast to the high enantioselectivity achieved for the Z-isomeric substrates, hydrogenation of the E-isomers usually proceeds with lower rates and afford products with diminished enantioselectivities [92]. The rhodium-catalyzed hydrogenation of the - and Z-isomers, with BINAP as a ligand in THE, affords products with opposite absolute configurations [16]. Remarkably, the DuPhos-Rh system provides excellent enantioselectivity for both isomeric substrates with the same absolute configuration, irrespective of the /Z-geometry (Eqs. 1 and 2). This result is particularly important for the construction of alkyl dehydroamino acid derivatives, which are difficult to prepare in enantiomericaUy pure form. 

Chiral l,T-diphosphetanylferrocene Et-FerroTANE serves as an effective ligand for the rhodium-catalyzed hydrogenation of y9-aryl- and /9-alkyl-substituted monoamido ita-conates (Eqs. 19 and 20) [54]. The Et-DuPhos-Rh catalyst was utihzed for the asymmetric hydrogenation of the trisubstituted olefin derivative in the preparation of an important intermediate for the drug candoxatril (>99% ee) [110]. 

Two years later, Bosnich described an extensive study of asymmetric rhodium-catalyzed intramolecular hydroacylation reactions [16]. Like Sakai, Bosnich found that Rh(l)/ BINAP is an unusually effective catalyst for this process, furnishing excellent enantioselectivity for a range of substrates (Eq. 13). Bosnich also reported thaL if the R substituent is a relatively unhindered alkyl (for example. Me) or an aromatic group, lower (< 80% ee) enantioselectivity is observed. 

In 1997, Bosnich discovered that Me-DUPHOS serves as a highly effective ligand for rhodium-catalyzed hydroacylations, particularly when R is a medium or small alkyl substituent (Eq. 14) [17]. Interestingly, in contrast to BINAP (Eq. 13), Me-DUPHOS furnishes lower stereoselection when the R group is a tert-butyl or TMS group (44 and... 

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho-... 

Evans and Nelson reexamined the rhodium-catalyzed allylic substitution reaction, in which they demonstrated that a triorganophosphite-modified Wilkinson s catalyst facilitates the allylic alkylation of secondary and tertiary aUyhc carbonates with excellent regioselectivity (Eq. 2). This work provided a convenient method for the construction of ternary and quaternary allylic products [11]. Additionally, they demonstrated that the modification of Wilkinson s catalyst with triorganophosphites serves to increase the re-... 

Evans and Kennedy later combined the regioselective rhodium-catalyzed allylic alkylation, using a-substituted malonates, with ring-closing metathesis for the construction of five-, six-, and seven-membered carbocycles (Scheme 10.2) [13]. The combination of these methodologies allowed for the rapid and flexible assembly of carbocycles possessing vicinal ternary-quaternary or quaternary-quaternary stereogenic centers. 

Evans and Nelson examined the stereospecificity of the rhodium-catalyzed allylic alkylation, with the expectation that it would provide additional insight into the mechanism for this particular reaction [16]. They reasoned that the enantiomerically enriched allylic alcohol derivative i would furnish the enantioenriched product iv, provided the initial enyl intermediate ii does not isomerize to the achiral rr-organorhodium intermediate iii prior to alkylation (k2>ki Scheme 10.3). Alternatively, the product of re-... 

---