Dirhodium intramolecular cyclopropanation

In 2005, Doyle et al. reported an original sequence of two successive intramolecular cyclopropanations involving a bis(diazoacetates), using a sterically encumbered oxaimidazolidine carboxylate dirhodium(II) catalyst, Rh2[(45, 5)-BSPIM]4. An excellent result, depicted in Scheme 6.16, was obtained resulting from a double diastereoselection. 

R,5S)-(-)-6,6-Dimethyl-3-oxabicyclo[3.1,0]hexan-2-one. Highly tnantioselective Intramolecular Cyclopropanation Catalyzed by Dirhodium(ll) Tetrakis[methyl 2-pyrrolidone-5(R)-carboxylate],... 

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. 

Diazoacetamides undergo intramolecular cyclopropanation with similarly high enantios-electivities (Eq. 4) [33, 36, 37]. In these cases, however, competition from intramolecular dipolar cycloaddition can compHcate the reaction process. Therefore, the use of R = Me or Bu has been required to achieve good yields of reaction products. Representative examples of applications of chiral dirhodium(II) carboxamidates for enantioselective intramolecular cyclopropanation of diazoacetamides are compiled in Scheme 15.2. 

Doyle, Martin, Muller, and co-workers communicated exceptional enantiocontrol for intramolecular cyclopropanation of a series of allyl diazoacetates (Eq. 5.16) by using dirhodium(II) tetrakis(methyl 2-oxopyrrolidine-5-carboxylates), Rh2(MEPY)4, in either their R- or S-configurations [87], and they have fully elaborated these results in a subsequent report [88],... 

Once again, cis-disubstituted olefins lead to higher enantioselectivities than do trans-disubstituted olefins, but here the differences are not as great as they were with allyl diazoacetates. Both allylic and homoallylic diazoacetamides also undergo highly enantioselective intramolecular cyclopropanation (40-43) [93,94], However, with allylic a-diazopropionates enantiocontrol i s lower by 10-30% ee [95], The composite data suggest that chi ral dirhodium(II) carboxamide catalysts are superior to chiral Cu or Ru catalysts for intramolecular cyclopropanation reactions of allylic and homoallylic diazoacetates. 

Dirhodium(II) tetrakis(carboxamides), constructed with chiral 2-pyrroli-done-5-carboxylate esters so that the two nitrogen donor atoms on each rhodium are in a cis arrangement, represent a new class of chiral catalysts with broad applicability to enantioselective metal carbene transformations. Enantiomeric excesses greater than 90% have been achieved in intramolecular cyclopropanation reactions of allyl diazoacetates. In intermolecular cyclopropanation reactions with monosubsti-tuted olefins, the cis-disubstituted cyclopropane is formed with a higher enantiomeric excess than the trans isomer, and for cyclopropenation of 1-alkynes extraordinary selectivity has been achieved. Carbon-hydro-gen insertion reactions of diazoacetate esters that result in substituted y-butyrolactones occur in high yield and with enantiomeric excess as high as 90% with the use of these catalysts. Their design affords stabilization of the intermediate metal carbene and orientation of the carbene substituents for selectivity enhancement. 

A-Cu,N-Co, and P-Cu to carbenoid transformations have been limited to intermolecular reactions, for which they remain superior to chiral dirhodium(II) catalysts for intermolecular cyclopropanation reactions. Few examples other than those recently reported by Dauben and coworkers (eq 1) (35) portray the effectiveness of these chiral catalysts for enantioseleetive intramolecular cyclopropanation reactions, and these examples demonstrate their limitations. However, with Rh2(5S-MEPY)4 intramolecular cyclopropanation of 3-methyl-2-buten-1 -yl diazoacetate (eq 2) occurs in high yield and with 92% enantiomeric excess (36). 

R,5S)-(-)-6,6-DIMETH YL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. HIGHLY ENANTIOSELECTIVE INTRAMOLECULAR CYCLOPROPANATION CATALYZED BY DIRHODIUM(II) TETRAKIS[METHYL 2-PYRROLIDONE-5(R)-CARBOXYLATE]... 

This is the first detailed procedure for the synthesis of a chiral dirhodium(ll) carboxamide catalyst and its application to intramolecular cyclopropanation. The preparation of the ligand, methyl 2-pyrrolidone-5(R)-carboxylate, is adapted from the procedure of Ackermann, Matthes, and Tamm.2 The method for ligand displacement from dirhodium(ll) tetraacetate is an extension of that reported for the synthesis of dirhodium(ll) tetraacetamide.6 The title compound, (1 R,5S)-(-)-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one, is a synthetic precursor to (1 R,3S)-(+)-cis-chrysanthemic acid.5... 

Dirhodium(ll) tetrakis[methyl 2-pyrrolidone-5(R)-oarboxylate], Rh2(5R-MEPV)4, and its enantiomer, Rh2(5S-MEPY)4, which is prepared by the same procedure, are highly enantioselective catalysts for intramolecular cyclopropanation of allylic diazoacetates (65->94% ee) and homoallylic diazoacetates (71-90% ee),7 8 intermolecular carbon-hydrogen insertion reactions of 2-alkoxyethyl diazoacetates (57-91% ee)9 and N-alkyl-N-(tert-butyl)diazoacetamides (58-73% ee),10 Intermolecular cyclopropenation ot alkynes with ethyl diazoacetate (54-69% ee) or menthyl diazoacetates (77-98% diastereomeric excess, de),11 and intermolecular cyclopropanation of alkenes with menthyl diazoacetate (60-91% de for the cis isomer, 47-65% de for the trans isomer).12 Their use in <1.0 mol % in dichloromethane solvent effects complete reaction of the diazo ester and provides the carbenoid product in 43-88% yield. The same general method used for the preparation of Rh2(5R-MEPY)4 was employed for the synthesis of their isopropyl7 and neopentyl9 ester analogs. 

Semicorrinato)copper catalysts have also been used for intramolecular cyclopropanation reactions of alkenyl diazo ketones (eq 9 and eq 10). In this case the (semicorrinato)copper catalyst derived from complex (5) proved to be superior to related methylene-bis(oxazoline)copper complexes. Interestingly, analogous allyl diazoacetates react with markedly lower enantioselectivity under these conditions, in contrast to the results obtained with chiral Rh complexes which are excellent catalysts for intramolecular cyclopropanations of allyl diazoacetates but give poor enantioselectivities with alkenyl diazo ketones (see Dirhodium(II) Tetrakis(methyl 2-pyrrolidone-5(S -carboxylate ) Moderate enantioselectivities in the reactions... 

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... 

For enantioselective intramolecular cyclopropanation with chiral catalysts, tetrakis[(5)- and (7 )-5-methoxycarbonyl-2-pyrrolidonato]dirhodium 30 and related rhodium complexes such as 31 and 32 (only the S -enantiomer is shown) appear the best choices at this time. With the appropriate catalyst, impressive enantiomeric excesses have been obtained for intramolecular cyclopropanations of unsaturated diazoacetates and diazoacetamides, as is illustrated by the following examples (see also Houben-Weyl, Vol. E21c, p3234). 

A polyethylene-bound soluble recoverable dirhodium(II) tetrakis(2-oxapyrrolidine-(55 )-carb-oxylate) was also highly efficient in enantioselective intramolecular cyclopropanation of allyl diazoacetates and could be used repeatedly without significant loss of enantiocontrol. Some enantiomerically pure, secondary allylic diazoacetates showed the expected substrate-induced diastereofacial selectivity in intramolecular cyclopropanation, when they were decomposed with bis(A-n-r/-butylsalicylamidinato)copper(II). ° This selectivity could be significantly enhanced or reversed with the chiral catalyst 30 or its antipode. Furthermore, catalysts 30 and 32 allowed a highly efficient kinetic resolution of racemic secondary allylic diazoacetates. 

Asymmetric cyclopropanation. The ability to effect ligand exchange between rhodium(II) acetate and various amides has lead to a search for novel, chiral rhodium(II) catalysts for enantioselective cyclopropanation with diazo carbonyl compounds. The most promising to date are prepared from methyl (S)- or (R)-pyroglutamate (1), [dirhodium(ll) tetrakis(methyl 2-pyrrolidone-5-carboxylate)]. Thus these complexes, Rh2[(S)- or (R)-l]4, effect intramolecular cyclopropanation of allylic diazoacetates (2) to give the cyclo-propanated y-lactones 3 in 65 S 94% ee (equation 1). In general, the enantioselectivity is higher in cyclopropanation of (Z)-alkenes. 

Addition to a carbon-carbon triple bond is even more facile than addition to a carbon-carbon double bond, and there are now several reports of intermolec-ular [71] and intramolecular reactions [72-74] that produce stable cyclopropene products with moderate to high enantioselectivities. One of the most revealing examples is that shown in Scheme 9 [72] where the allylic cyclopropanation product (30) is formed by the less reactive Rh2(MEPY)4 catalyst, but macrocy-clization is favored by the more reactive Rh2(TBSP)4 and Rh2(IBAZ)4 catalysts and, as expected, the highest enantioselectivities are derived from the use of chiral dirhodium(II) carboxamidate catalysts. 

In contrast to the intermolecular cyclopropanation, the dirhodium tetraprolinates give modest enantioselectivities for the corresponding intramolecular reactions with the do-nor/acceptor carbenoids [68]. For example, the Rh2(S-DOSP)4-catalyzed reaction with al-lyl vinyldiazoacetate 32 gives the fused cyclopropane 33 in 72% yield with 72% enantiomeric excess (Eq. 4) [68]. The level of asymmetric induction is dependent upon the substitution pattern of the alkene cis-alkenes and internally substituted alkenes afford the highest asymmetric induction. Other rhodium and copper catalysts have been evaluated for reactions with vinyldiazoacetates, but very few have found broad utility [42]. 

The precursor to the Rh-carbene complex is a dirhodium system that typically has four bidentate ligands attached. One example of the dirhodium complex is shown as structure 63, which was discovered by Doyle and co-workers and is abbreviated Rh2(5.S -MEPY)4,76 Here the 5.S-MEPY ligand is chiral carboxami-date, which is derived from the amino acid L-proline. The use of 63 and similar complexes makes it possible to induce chirality into the cyclopropane product. Equation 10.51 is an example of an intramolecular chiral cyclopropanation... 

A dirhodium tetracarboxylate complex coordinated by two bromocalix[4]arene macrocycles exhibited two toluene molecules coordinated to the rhodium centers and inserted in the clefts, which are formed by the vicinal -bromophenyl rings of the two calixarene units (Figure 29). This complex has been found to be an efficient catalyst for two carbene transfer reactions, alkene cyclopropanation, and intramolecular C-H insertion, in terms of stereo- and regioselectivity. 

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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