Enantioselective cyclopropanation proces

Cyclopropanation reactions involving ethyl diazoacetate and olefins proceed with high efficiency in aqueous media using Rh(II) carboxy-lates. Nishiyama s Ru(II) Py-box and Katsuki s Co(II) salen complexes that allow for highly enantioselective cyclopropanations in organic solvents can also be applied to aqueous cyclopropanations with similar results. In-situ generation of ethyl diazoacetate and cyclopropanation also proceeds efficiently (Eq. 3.33).135... 

Lo and Fu112 have reported a new type of planar-chiral ligand 203 for the enantioselective cyclopropanation of olefins. As shown in Scheme 5-62, asymmetric cyclopropanation in the presence of chiral ligand 203 proceeds smoothly, giving the cyclopropanation product with high diastereoselectivity and enantioselectivity. 

The enantioselective cyclopropanation leading to 1,2,3-snbstitnted cyclopropane derivatives proceeds with high diastereocontrol (equation 86) . It is quite interesting to observe that the same reaction, when run in the absence of the dioxaborolane ligand, led to lower diastereoselectivity. Other functionalized 1,1-diiodoaLkanes can be used as the zinc carbenoid precursor, but it should be noted that up to 2 equivalents of the reagent (4 equivalents of RCHI2) are needed in this process. This reaction has been applied in the synthesis of ambruticin. ... 

Enantioselective cyclopropanation. The reaction of dimenthyl fumarates (2) with isopropylidene(triphenyl)phosphorane proceeds in 74% de in THF at -78 — 20°. (1S,3S)-3 is obtained when the /-menthyl group is used inductor (lR,3R)-3 is obtained in the same optical yield when the unnatural //-menthyl group is used. The concentration plays an important role enantioselectivity is increased by dilution and decreased by concentration. 

On a commercial scale, cyclopropanation of isobutylene proceeds in high enantioselectivity (92% ee) using ethyl diazoacetate in the presence of ent-16, Eq. 9. The product cyclopropane 24 is an intermediate in the synthesis of Merck s cilas-tatin (14). 

From a practical point of view, it is significant that this cyclopropanation reaction proceeds well on a very large scale. The reaction of isobutylene and ethyl diazoacetate in the presence of 0.1 mol% catalyst (55c CuOTf) (Fig. 4) provides cyclopropane 24a in >99% ee and 91% yield on a 35-gram scale (34). With this catalyst loading, a 5-h addition time of diazoester at 0°C in the presence of 10 equiv of alkene is sufficient to provide high enantioselectivities and yields. Although di-... 

Tanner et al. (58) investigated the use of chelating diaziridines (85) as ligands for transition metals. The cyclopropanation of styrene using CuOTf complexes of phenyl-substituted aziridine (85a) proceeds in modest enantioselectivity and dias-tereoselectivity, but improved enantioselectivity is observed with complexes derived from benzyl-substituted bis(aziridine) (85b), Eq. 42 (59). Complexes derived... 

Kanemasa et al. (60) showed that chiral diamine-copper complexes are moderately effective catalysts for cyclopropanation. Phenylhydrazine reduction of the complex formed from Cu(OTf)2 and excess diamine afforded the active catalyst. Cyclopropanation of styrene proceeds in moderate diastereoselectivity and good enantioselectivity with these catalysts, Eq. 43. 

Stereoselectivity) is observed however, for ethylidene complexes of Fe(CO)(PR3)Cp (69) the products reflect trans selectivity. This difference in stereoselectivity has been suggested to be dependent upon which conformer is more reactive. The reaction of a chiral-at-iron cationic carbene complex (70) with styrene or vinyl acetate affords optically active cyclopropane products with high enantioselectivity (Scheme 24). h >3 intramolecular cyclopropanation, as in the case of (71), proceeds moderately well for the formation of norcarane-type ring systems however, intramolecular C-H insertion is a competing pathway when the alkene is highly... 

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