Rhodium MEPY catalyst

Having established that pure enantiomer ( S,ZR)-77 was capable of undergoing remarkably regioselective and diastereoselective C-H activation, it followed that highly efficient enantiomeric differentiation of rac-77 could be accomplished.199 Hence, the Rh2(5Y-MEPY)4-catalyzed reaction of rac-77 effectively gave close to a 1 1 mixture of enantioenriched (lY)-78 (91% ee) and ( R)-79 (98% ee) (Equation (68)). Other equally spectacular examples of diastereo- and regiocontrol via chiral rhodium carboxamide catalysts in cyclic and acyclic diazoacetate systems have been reported.152 199 200 203-205... 

Fig. 4.20. Complexes for asymmetric cyclopropanation with acceptor-substituted diazomethanes. 1 [1372], 2 [1373], 3 [1033], Rh2(55-MEPY>4, Rh2(55-MPPIM)4 [1001,1074], For related rhodium-based catalysts, see, e.g., [997,1000,1002].

In the carboxylate series, the TPA catalyst (entry 4) was the most selective for methine over methylene insertion. Should this remarkable chemoselectivity prove to be general, this complex may add a possibility for high chemoselectivity not previously observed with rhodium(ll) catalysts. The other carboxylate catalysts show less preference for CH over CH2 insertion. We expect that the CH/CH2 ratios would be more pronounced with a less carefully balanced substrate. In the carboxamidate class, MPPIM catalyst (entry 9) was more selective than the corresponding MeOX catalyst (entry 10), with the MEPY catalyst (entry 8) being the least discriminating for CH over CH2 insertion. 

The mechanism by which selectivity is induced in rhodium mediated asymmetric cyclopropanations is not clear. What is known is that the pyrrolidinone of the MEPY catalyst is bonded to the rhodiums through the carboxamide, with the nitrogens cis to each other, as shown in Figure 6.11 [113]. This arrangement places the two carbomethoxy groups cis to each other on both sides of the catalyst. With... 

Metal catalyzed enantioselective C-H insertions of carbenes have so far not been studies in great detail. Copper catalysts are of no use for this type of reaction, rhodium(Il) catalysts, however, allow intramolecular C-H insertions, for example, in the alkyl group of diazoacetates with longer chains. The formation of five-membered rings such as y-lac-tones is favored. [Rh2(55-mepy)4] affords... 

Hodgson et al. (138) chose to investigate a system that had previously been shown to undergo an effective intramolecular addition of a tethered olehn (Scheme 4.72). In his first attempt, using Doyle s Rh2[(5/ )-MEPY]4, the yield of cycloadduct 270 obtained was comparable to that with rhodium acetate, but no asymmetric induction was observed. Changing to the Davies catalysts in dichloromethane resulted in a... 

The reaction of methyl phenyldiazoacetate with N-Boc-piperidine (36) is a good illustration of the potential of this chemistry because it leads to the direct synthesis of f/ireo-methylphenidate (37) [27]. The most efficient rhodium car-boxylate catalyst for carrying out this transformation is Rh2(S-biDOSP)2 (2), which results in the formation of a 71 29 mixture of the readily separable threo and erythro diastereomers. The threo diastereomer 37 is produced in 52% isolated yield and 86% ee [Eq. (19)]. Other catalysts have also been explored for this reaction. Rh2(R-DOSP)4 gives only moderate stereoselectivity while Rh2(R-MEPY)4 gave the best diastereoselectivity in this reaction (94% de) [29]. 

Chiral rhodium(II) carboxamides are exceptional catalysts for highly enantio-selective intermolecular cyclopropenation reactions (50). With ethyl diazoacetate and a series of alkynes, use of dirhodium(II) tetrakis[methyl 2-pyrrolidone-5-(R)-carboxylate], Rh2(5R-MEPY)4, in catalytic amounts ( 1.0 mol %) results in the formation of ethyl eyelopropene-3-earboxylates (eq 4) with enantiomeric excesses... 

Alternative rhodium(II) carboxamide catalysts derived from 4-(R)-benzyloxa-zolidinone (47 -BNOXH) and 4-(S)-isopropyloxazolidinone (4S-IPOXH) provided only a fraction of the enantioselection obtained with Rh2(MEPY)4 catalysts. Whereas cyclopropenation of 1-hexyne with ethyl diazoacetate in the presence of Rh2(5R-MEPY)4 resulted in 15 (eq 4, R = n-Bu) with 54% ee, Rh2(47 -BNOX)4 gave the same compound in 5% ee, and Rh2(4S-IPOX)4 provided only 6% ee. 

In rhodium(II)-catalyzed intermolecular cyclopropanation reactions, chiral dirhodium(II) carb-oximidates provide only limited enantiocontrol. " Tetrakis(5-methoxycarbonyl-2-pyrrolidonato)dirhodium [18, Rh2(MEPY)J, in both enantiomeric forms of the carboxamide ligands, produces the highest enantioselectivities. As can be seen for the cyclopropanation of styrene with diazoacetates, a high level of double diastereoselectivity results from the combination of this chiral catalyst with /- or d-menthyl diazoacetate, but not with diazoacetates bearing other chiral residues.In terms of trans/cis selectivity and enantioselectivity for styrene giving 19 this catalyst is comparable to the Aratani catalysts, but they cannot match the high enantiocontrol of the chiral copper catalysts developed by Pfaltz, Masamune, and Evans vide supra). 

Doyle s chiral rhodium (II) carboxamidates have proved to be exceptionally successful for asymmetric C-H insertion reactions of diazoacetates and some diazoacetamides leading to lactones and lactams, respectively. With 2-alkoxyethyl diazoacetates and the Rh2(5S- and 5R-MEPY)4 catalysts, for example, highly enantioselective intramolecular C-H insertion reactions occur, the 5S-catalyst, Eq. (40), and 5R-catalyst furnishing the S- and R-lactone, respectively [58]. A polymer-bound version of Rh2(5S-MEPY)4 has also been applied to the cycliza-tion in Eq. (40) to yield the lactone with 69% ee (R=Me) the catalyst could be recovered by filtration and reused several times, but with decreasing enantiose-lection [59]. 

The introduction of carboxamides instead of carboxylates as bridging ligands is achieved by an exchange reaction between [Rh2(OAc)4] and the appropriate amides. In this way [Rh2(5S-mepy)4] is prepared from methyl (-)-(5)-pyrrolidone-5 -carboxylate. Similarly, [Rh2(5R-mepy)4] is accessible from methyl (-i-)-(R)-pyrrolidone-5-carboxylate so that the catalysts are available in both configurations (5S and 5R). In [Rh2(55-mepy)4] each rhodium atom is in a square-planar environment in which two O atoms and two N atoms are arranged cis to each other (Fig. 2). 

As mentioned before, enantioselective cyclopropanation has been known for a long time and there are other efficient catalysts for this reaction apart from dimeric rhodium(II) complexes. This is different to the cyclopropanation of alkynes with diazo compounds. Copper catalysts do not only result in lower enantiomeric excesses but also poor yields, since the high temperatures required for the reaction favor side and consecutive reactions such as the ring opening of the primary products. The improvements brought about by the use of [Rh2(55-mepy)4] (with regard to yield... 

Since then the field of enantioselective catalysis with rhodium(II) complexes containing mepy and mepy-like ligands has been extended appreciably, in particular by the group of M. P. Doyle. Thus, the recent references in this field can be found by searching for the name of the main author M. P. Doyle. The catalysts [Rh2(55-mepy)4] and [Rh2(5R-mepy)4] have been commercialized (REGIS Chemical Company, Morton Grove, IL 60053, USA). 

On this basis, in a joint effort with Martin and Muller (1991a), Doyle developed a series of dinuclear rhodium 2-pyrrolidone-5-carboxylate complexes that might give better enantiomeric ratios in cyclopropanations (see also Muller and Polleux, 1994). This was indeed the case for a series of intramolecular cyclopropanations of allyl diazoacetates with the complex Rh2((55)-MEPY)4 obtained with chiral methyl 2-pyrrolidone-5-carboxylate (MEPY = 8.178) an ee between 65 and 94 o was found. Doyle et al. (1993 a) continued that work with additional inter- and intramolecular cyclopropanations as well as with intramolecular CH insertions. Doyle and his coworkers again obtained good-to-excellent enantioselectivity with the same catalyst. Examples are given in Schemes 8-75 to 8-77. 

MEPY)4] and another dinuclear rhodium catalyst that showed lower enantioselec-tivity (Doyle et al., 1993 a). Those structures allowed an understanding of yield and selectivity results on the basis of the effects described above. 

Rhodium(II)-MEPY and rhodium(II)-MACIM (methyl 1-acetylimidazolidin-2-one-4-carboxylate) complexes are efficient chiral catalysts for intramolecular carbon-hydrogen insertion reactions of diazoacetates (224) and metal carbene transformations (225). Dirhodium(II) carboxylates of similar structure (eg, piperidinonate complexes of the Rh2(ligand)4 type) have been found efficient catalysts for asymmetric cyclopropanation of olefins (226). 

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