Alternative Classes of Cyclopropanations

Shi documented the use of the simple dipeptide 119 as a stoichiometric additive for enantioselective cyclopropanation of unfunctionalized olefins. Consequently, treatment of 118 with EtjZn and CH2I2 in the presence of 119 furnished cyclopropane 120 in 83% yield and 75% ee (Equation 18) [72]. Enolsilanes were also showcased as suitable substrates, giving cyclopropanols in up to 85 % ee. 

Corey s seminal investigations of the chemistry of trimethylsulfoxonium ylide established a powerful method for the generation of cyclopropanes from enones [19, 21, 73, 74). In a typical experiment, treatment of enones such as carvone (121) with Me3S(0)I/NaH in DMSO leads to the formation of 122 in 82% yield as a single diastereomer (Equation 19) [74]. 

The echoes of Corey s seminal discovery with sulfonium and sulfoxonium ylides have found considerable resonance in modern investigations of enan-tioselective cyclopropanation reactions. Shibasaki showed that treatment of pyrrole amides such as 126 with trimethylsulfoxonium ylide was effectively promoted by the La-Li-(biphenyldiolate) catalyst 127 to give the cyclopropane adduct 128 in 98% ee (Equation 20) [78]. Key to the success of the transformation was the use of Nal as an additive. The investigators speculated that exchange of Li for Na occurs in 127 to some extent to give an active cyclopropanation catalyst that is more enantioselective. The observation underscored the versatility of such bifunctional heterobimetallic catalysts, the properties of which can be fine-tuned in a multitude of ways by variation of the ligand and the nature of the metals employed [79]. 

MacMillan has employed sulfoxonium ylides, such as 130, derived from phenacyl bromides, in enantioselective cyclopropanation of enals (Equation 21) [80]. Treatment of hexenal (129) with 130 in the presence of 20 mol % of catalyst 131 afforded adduct 134 in 95% ee, dr=30 l, and 85% yield. The fact that unsaturated aldehydes could be used as substrates in these reactions is impressive, especially given the propensity of aldehydes to otherwise undergo epoxide formation. The system owes its success to the unique ability of the substrate enals to reversibly form the corresponding iminium ions 132, which display enhanced electrophilicity towards the reagent ylide (cf 133). 

In addition to developments with ylides in asymmetric cyclopropanation reactions, there have been promising reports involving other unrelated cyclopropanation processes. Corey has documented exciting results in a study of the Kulinkovic reaction (Equation 24) [84], This reaction involves the addition of Grignard reagents to esters in the presence of Ti(Oi-Pr)4 to afford cyclopropanols [85]. Corey demonstrated that when the reaction was conducted in the presence of bis(TADDOL)Ti complex 143, enantioenriched products 144 were obtained (up to 78 % ee) [84]. This method provides an important entry point to chiral cyclopropanols, a class of products not otherwise conveniently accessible in optically active form. 

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