Intermolecular reactions ester substituents

Cu complexes with bis-oxazoline ligands 6 that were first reported by Masamune and co-workers [39] have incited considerable interest because of the exceptional enantiocontrol that can be achieved with their use as catalysts for cyclopropanation reactions. Concurrent investigations by Evans [40], who added 7 Masamune, who provided 8 and 9 [41] and Pfaltz [42], who investigated a similar series, established that the C2-symmetric bis-oxazoline ligands are suitable alternatives to semicorrin ligands for Cu in creating a highly enantioselective environment for intermolecular cyclopropanation. For the first time, diazoacetates with ester substituents as small as ethyl could be used to achieve enantioselectivity >90% ee in reactions with styrene (Table 5.4). 

With respect to the substrate scope, ketones are the most efficient nucleophiles although the intermolecular reaction works also well for esters, amides and Weinreb amides (Fig. 2.7). Regarding the Michael acceptor, enones are the best electrophiles with a wide range of substituents tolerated (alkyl, aryl and heteroaryl ketones). a,p-Unsaturated esters, in the case of the intermolecular cyclopropanation, and a,p-unsaturated diimides for the intramolecular reaction, extends the substrate scope of the process (Fig. 2.7). A transition state model for the intramolecular cyclopropanation reaction has been proposed as depicted in Scheme 2.38 for catalyst 65 [106d]. In this model the ammonium salt adopts a conformation that gives the Z-enolate of the nucleophile on deprotonation with the base. The intramolecular conjugate addition of the enolate then takes place through a boat-type transition state. 

As expected, increasing the size of the R group increases enantioselection, and the buttressing effect on the bis-oxazoline ring caused by the geminal disubstitution in 10 provides further enhancement of enantiocontrol. From the results in Table S.4, however, the ligand s R substituent has only a minor influence on the trans.cis of cyclopropane products. To increase product diastereoselectivity, Evans [40] increased the size of the ester substituent from ethyl to te/t-butyl and then to the bulky BHT ester, previously reported by Doyle [43] to provide exceptional diastereocontrol in catalytic cyclopropanation reactions. Applications of these catalysts to alkenes other than styrene have demonstrated the potential generality of their uses for asymmetric intermolecular cyclopropanation (Table 5.5). 

However, the decarboxylation reaction predominates when the ortho- and para-positions of the aromatic ring are blocked by alkyl substituents [62]. Recently, Inoue and coworkers have studied the photodecarboxylation of chiral aryl esters accommodated in CD and polyethylene films [63-67]. In the photolysis of 2,4,6-trimethylphenyl-2-methylbutyrate 19, two reaction pathways simultaneously open to afford alkylmesitylene 20 and 2,4,6-trimethylphenol 21, respectively (Scheme 11). The yields of 20 and 21 obtained in aqueous and y-CD solutions are much lower (0-11%) than those in organic solution, which is ascribed to the intermolecular reaction between CD and 19. The j6-CD-mediated photodecarboxylation of racemic 19 furnishes the (7 )-enantiomer of 20 in up to 14% ee, suggesting that the reaction pathway differs in the presence and absence of j6-CD and one of the enantiomers of 19 reacts faster than another in the j6-CD cavity. When the photoreaction is carried out in the presence of y-CD, only a very small amount of... 

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. 

Intermolecular radical additions are facilitated if the alkene has a hydroxyl substituent that can form an ester to boron, so that the actual addition is intramolecular. Accordingly, bis(2-bromoethyl) alkenylboronates readily cyclize under radical conditions [85]. This concept was quickly extended to a-boryl radicals [86]. One of the more favorable examples is the reaction of diisopropyl (bromomethyl)boronate with 4-methylhex-l-en-3-ol and tris(trimethylsilyl)silane in the presence of azobis(isobuty-... 

Catalytic intermolecular coupling of alkene and alkyne is quite a challenging task. Nevertheless, cyclopentadienyl rutheniumcomplexes are able to catalyze alkyne-alkene coupling (an Alder-ene type reaction) to a mixture of the re-gioisomeric products 120 and 121 (Scheme 52). The most efficient catalysts are the complexes 78 or 53. The latter is more reactive. The scope of the reaction with respect to substituents attached to the both reactants is enormous ester, hydroxy, nitrile, ether, amino, and arylhalide groups are tolerated. Both terminal and internal alkynes and alkenes can be used. Some typical examples are summarized in Table 24 [67,69]. 

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