MPPIM catalyst

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. 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

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].

Chiral dirhodium(II) carboxamidates are preferred for intramolecular cyclopropanation of allylic and homoallylic diazoacetates (Eq. 2). The catalyst of choice is Rh2(MEPY)4 when R " and R are H, but Rh2(MPPIM)4 gives the highest selectivities when these substituents are alkyl or aryl. Representative examples of the applications of these catalysts are listed in Scheme 15.1 according to the cyclopropane synthesized. Use of the catalyst with mirror image chirality produces the enantiomeric cyclopropane with the same enantiomeric excess [33]. Enantioselectivities fall off to a level of 40-70% ee when n is increased beyond 2 and up to 8 (Eq. 2) [32], and in these cases the use of the chiral bisoxazoline-copper complexes is advantageous. 

In the carboxamidate class of complexes, the MeOX catalyst (entry 10) showed more /9-elimination than the MEPY catalyst (entry 8), while the MPPIM amide analog (entry 9) showed the least /9-elimination product. We were concerned that the application of an enantiomerically pure catalyst to a racemic substrate might bias the results, so we repeated one of the cyclizations using racemic (1 1 R/S) catalyst. The resulting product ratios (entry 11) were equivalent to those observed for the enantiomerically pure catalyst. 

Desymmetrization strategy in enantioselective oxonium ylide formation/[l,2]-shift reaction has been reported by Doyle and co-workers.With dirhodium(ii) tetrakis[methyl l-(3-phenylpropanoyl)-2-oxoimidazolidine-4(3 )-carboxylate] [Rh2(43 -MPPIM)4] as the catalyst, up to 88% ee is obtained (Equation (7)). 

Match and mismatch of chiral catalyst with chiral substrate are distinctive, that is, matched combination generally brings high yield and high stereocontrol/regiocontrol. For example, treatment of (lS,2/ )-cij-2-methylcyclohexyl diazoacetate with Rh2(4/f-MPPIM)4 resulted virtually completely in the production of the all-cix bicyclic insertion product of Scheme 5.8... 

Similarly, treatment of (l/ ,2S)-cw-2-methyIcyclohexyl diazoacetate with Rh2(4.S-MPPIM)4 gave the same result, except for the opposite stereochemical sense. However, the mismatch of substrate and catalyst configurations results in a low yield overall and in a mixture of products (Scheme 5.8). 

A critical development in efforts to achieve high enantiocontrol in C-H insertion reactions was the synthesis and applications of Rh2(MPPIM)4 [89]. This catalyst provided enhanced enantiocontrol in virtually all cases examined, but especially with 3-substituted-l-propyl diazoacetates (Eq. 5.32). Results obtained with various substrates are given in Table 5.11 [126,127], which show the unique ability of Rh2(MPPIM)4 to increase enantioselectivity. Notice also that the S-configured catalyst produces the. S -configured product and that the /f-catalyst produces the R-product. 

Diazoacetamides are also exceptional substrates for dirhodium carboxamidate-catalyzed reactions, although with these substrates a mixture of /3-lactam and y-lactam products are formed [8]. The rhodium carboxamidate catalyst can have a major effect on the ratio of products formed. A good synthetic example is the Rh2(4S-MPPIM)4)-catalyzed synthesis of (-)-hcliotridanc 11 (Scheme 5) [9]. The key C-H insertion step of 9 generated the indolizidine 10 in 86 % yield and 96 % de, whereas reaction of 9 with achiral catalysts tended to favor the opposite diaster-eomer. 

With fra 5-disubstituted allylic systems, the Rh2(MEPY)4 catalysts exhibit lower levels of stereo control. However, here again ligand switching corrects the efficiency since the steric bias imposed through the application of the W-acylimida-zolidinone-ligated catalysts raises enantioselectivity with trans systems to levels >95% ee. For example, the cinnamyl alcohol-derived diazoester in Eq. (24), with Rh2(4S-MPPIM)4 as catalyst, furnishes the bicyclic product with an ee of 96%. 

Diazoacetates derived from simple primary alcohols also undergo y-lactone formation in moderate to good yield. Through the use of Rh2(4S-MPPIM)4 as catalyst, Eq. (42), excellent stereocontrol is attainable (up to 96% ee) [60,61]. 

Two syntheses of the bioactive small molecule (+)-imperanene (197), isolated from Imperata cylindrica, demonstrate that intra- and intermolecular carbenoid C-H insertion can be used as two different means to the same end. The Doyle group reported an intramolecular approach toward this natural product, with diazoester 198 as the cyclization precursor (Scheme 49, top) [140], In the key event, Rh2(4S -MPPIM)4-catalyzed carbenoid insertion led to lactone 199 in 68% yield and 93% ee. Other rhodium catalysts were found to give inferior yields and enan-tioselectivities. Elaboration of 199 to (-i-)-imperanene provided the natural product in 12 steps and approximately 16% overall yield. 

The two main families of catalysts used are the Davies/McKervey dirhodium car-boxylate catalysts (9.24a-c) and Doyle s carboxamidates, including Rh2(MEPY)4 (9.25), Rh2(MPPIM)4 (9.26) and the azetidinones such as Rh2(IBAZ)4 (9.27). ... 

Apart from 37, other carboxamidate catalysts are also efficient intramolecular cyclopropanation catalysts. Rh2(4S-MPPIM)4 38, derived from chiral imidazole, is particularly effective in the cyclopropanation of diazoacetates, which contain rans-disubstituted or n-butyl allyl alkenes, with high enantioselectivities (Scheme 25) (117). In addition, this catalyst also proved to be efficient for the substrates of A -methyl substituted A-allyldiazoacetate, with high yields (88-93%) and high percentage of ee values (>92%) of the corresponding cyclopropanes (118). Catalyst Rh2(4S-MEOX)4, based on chiral oxazoline, is another efficient... 

In this case the use of the Doyle dirhodium catalyst Rh2(S-MPPIM)4 (a complex containing the hgand methyl (4S)-2-oxo-3-(3-phenylpropa-noyl)-4-imidazohdine carboxylate) converted the diazoacetate (S)-97 into the ds-flised bicychc lactam (—)-98 in 70% yield together with some dimeric by-products (c. 18%). Elaboration of the piperidine ring entailed lactone cleavage with the anion of phenyl methyl sulfone followed by reduction... 

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