Dirhodium catalyst

Du Bois originally used rhodium(n) acetate and rhodium triphenylacetate (tpa) as catalysts and found that regio-and diastereocontrol was influenced by the catalysts, but neither was particularly effective when low catalyst loadings were used. Inspired by the bridged dirhodium catalysts which have been developed for carbenoid chemistry,40,273,274 a second generation catalyst Rh2(esp)2 116 (esp = a,a,a, o -tetramethyl-l,3-benzenedipropionate) was designed which was capable of much higher turnover numbers (Scheme ll).275 Furthermore, this catalyst was effective in intermolecular reactions. 

Fig. 14.3 Predictive models for asymmetric induction by (a) (R)-panto-lactone as a chiral auxiliary (b) (S)-prolinate dirhodium catalysts...

The C-H activation of allylic and benzylic C-H bonds has considerable application in organic synthesis. Studies by Muller [131] and Davies [130] on reactions with cyclohexene revealed that Rh2(S-DOSP)4 in a hydrocarbon solvent is the optimum system for high asymmetric induction (Tab. 14.13). Although this particular example gives a mixture of the C-H activation product 179 and cyclopropane 180, similar reactions with ethyl diazoacetate gave virtually no C-H activation product. Some of the other classic chiral dirhodium catalysts 181 and 182 were also effective in this chemistry, but the en-antioselectivity with these catalysts (45% ee and 55% ee) [131] was considerably lower than with Rh2(S-DOSP)4 (93% ee) [130]. 

By far the greatest advances in enantiocontrolled C-H insertion reactions have been provided by Doyle and co-workers with chiral dirhodium(II) carboxamidate catalysts [7,10]. The key development here is the creation of chiral imidazolidinone-ligated dirhodium catalysts 22 to control diastereoselectivity and enhance enantiocontrol [122]. A significant example of the power of this methodology is the insertion reactions of cycloalkyl diazoacetates. With cyclohexyl diazoacetate, for example, four products are possible via C-H insertion constituted in two pairs of diastereoisomers (Eq. 5.28). 

A bicyclic ketone was generated when 1,2-diphenylethyne was heated with CO, methanol and a dirhodium catalyst. " 2-Iodostyrene reacted at 100°C with CO and a palladium catalyst to give the bicyclic ketone l-indanone. " ° Another variation reacted a conjugated allene-alkene with 5 atm of CO and a rhodium catalyst to give a bicyclic ketone.An intermolecular version of this reaction is known... 

The use of chiral additives with a rhodium complex also leads to cyclopropanes enantioselectively. An important chiral rhodium species is Rh2(5-DOSP)4, which leads to cyclopropanes with excellent enantioselectivity in carbene cyclopro-panation reactions. Asymmetric, intramolecular cyclopropanation reactions have been reported. The copper catalyzed diazoester cyclopropanation was reported in an ionic liquid. ° It is noted that the reaction of a diazoester with a chiral dirhodium catalyst leads to p-lactones with modest enantioselectivity Phosphonate esters have been incorporated into the diazo compound... 

Figure 12.1 Dirhodium catalysts (TCPTTL, N tetrachlorophthaloyl (S) tert leucinate TCPTAD, N tetrachloro phthaloyl (S) (1 adamantyl)glycinate).

Chiral dirhodium catalysts confined in porous hosts... 

In this study chiral dirhodium catalysts (Rh2(MEPY)4) and Rh2(BNOX)4), developed by Doyle [10] (see Scheme 1) were immobilised. It can be anticipated that the spatial constraints induced by the carrier (MCM-41 or silica), and especially by the pores of MCM-41, are able to increase the influence of the chiral ligands. Earlier research [11,12] showed that enantioselective reduction catalysed by a palladium complex immobilised inside the pores of MCM-41 resulted in a threefold increase in enantioselectivity compared to the homogeneous palladium complex. In order to immobilise the homogeneous catalysts on the surface, an organic linker group was... 

The theoretical maximum loading of dirhodium catalyst on the carrier (Table 1) was calculated from the loading of the CN-tether (determined by C,H,N analysis). Actual rhodium loadings are usually around 70% of the CN-loading, but drop to 15% in some cases. 

The immobilisation of the homogeneous dirhodium catalysts on silica surfaces and inside the pores of MCM-41 affords a significant improvement in regioselectivity (cyclopropanation reaction) and enantioselectivity (Si-H insertion) of these catalysts. The improvement is attributed to the confinement resulting from immobilisation. 

Siegel and Schmalz [79] reported a new approach to optically active ferrocenes with planar chiraHty, based on a Cu-catalyzed C-H insertion (Scheme 17). Both a five- and a six-membered ring could be formed in this way. Using a copper-bisoxazoline catalyst, good yields and ees in the range of 60-80% could be obtained, whereas chiral dirhodium catalysts proved to be ineffective in this case. 

Fig. 3 Chiral dirhodium catalysts discussed in this chapter...

Although the dirhodium catalysts are the most commonly used today, other metals are still being explored for carbenoid C-H insertion [35], These include copper [36-45], silver [46, 47], iron [48-50], gold [40], and magnesium [51, 52], and most will be discussed in context, particularly in Sect. 3.1. 

Examples of more basic, but enantioselective intramolecular carbenoid C-H insertion reactions were displayed in two very similar total syntheses of the phosphodiesterase type IV inhibitor i -(-)-rolipram (179, Scheme 44) [125, 126], In 1999, Hashimoto and coworkers utilized acceptor/acceptor diazo compound 180, with the nitrogen atom protected with a p-nitrophenyl moiety, as the carbenoid precursor. After screening a number of phthalimide-based dirhodium catalysts, Rh2(5 -BPTTL)4 (30) was found to give the optimal results, providing the cyclized product in 74% yield and 88% ee. 

The dinuclear mechanism of Scheme 25 allows the hydrogenation of alkenes and alkynes under very mild conditions, and has been shown to be favored over the mononuclear pathway of Scheme 26. [77] This is in contrast to the situation found for the dirhodium catalysts precursor [Rh(fi-H)(P Pr2(CH2)j, Pr,P)]2, in which the hydrogenation of styrene catalyzed by mononuclear fragments was shown to be favored over a possible dinuclear mechanism.[12d]... 

In an approach to the gastrin receptor antagonist (+)-AG-041, the Iwabuchi group has prepared the nitrogen-substituted spirocycle 153 by means of an oxidative intermolecular aza-spiro-annulation (Scheme 38) [82], Accordingly, indole 151 was treated with dirhodium catalyst 152 in the presence of PHl(OAc)2 and MgO to afford spirocycle 153 in 70% yield and 96% ee. The deuterium labeling was necessary for successful implementation of the spirocyclization. 

Apart from the extensively documented dirhodium catalysts, several ehiral Ir complexes have lately also been shown to be catalytically efficient in the asymmetric C—H bond insertion reactions of metal carbenoids and they offer eom-plementary reaetivity profiles. In general, 1,4-cyclohexadienes and THF are two commonly used model substrates. Several groups, including Katsuki, " Che, and Musaev, Davies, and Blakey, have realized the intermoleeular C—H bond insertion reaetion of 1,4-cyclohexadienes and THF by diverse ehiral Ir complexes (Figure 1.5). 

In an extension of this work, Hashimoto and co-workers tested several chiral dirhodium catalysts for the intramolecular amidation reactions in 2006. Under the catalysis of Rh2(S-TFPTTL)4 as the optimal catalyst,... 

A theoretical approach to understanding the nature of intramolecular allylic C-H amination versus alkene aziridination reaction pathways was presented, where the reaction of 4-pentenylsulfamate 192 was investigated using three different dirhodium catalysts (14JOC9799). The 1/A ratios of products for the three catalysts range from 1 4 to 1 1 to >20 1 and the theoretical observations presented are consistent with experimental results. 

Hydroformylation in Water/Acetone Formation of a Monocationic Dirhodium Catalyst... 

Although we initially proposed that the water was inhibiting the phosphine ligand dissociation and bimetallic fragmentatiOTi from generating inactive 12r and 13rr [44], the actual situation is quite different. The dicationic dihydride catalyst llr/llr can easily deprotonate to form a new monocationic monohydride dirhodium catalyst. This is supported by in situ FT-IR, NMR, the acidity of the catalyst solution, and DPT computational studies. A 1 mM catalyst solution in 30% water/acetone after exposure to H2/CO has a pH of 3.1, while a 10 mM solution has a pH of 2.2 - consistent with a strong monoprotic acidic species. 

The DFT calculated energetics for the main hydroformylation reaction steps based on 15r starting with the 15r-alkene complex are shown in Fig. 14. The two largest activation barriers are for the initial alkene-hydride migratory insertion step (16.8 kcal/mol) and for the final reductive elimination of the acyl and hydride (21.6 kcal/mol). The computational prediction, therefore, is that the final aldehyde reductive elimination is the rate determining step for the monocationic catalyst 15r. The largest activation barrier for the dicationic dirhodium catalyst (Fig. 8) is only 13 kcal/mol, indicating that the monocationic dirhodium catalyst should be less active on a per molecule basis, which is completely consistent with the impact of... 

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