The Origin of the High Enantioselectivity in Asymmetric Cyclopropanation of Unfunctionalized Olefins

Abstract

The mechanism of the asymmetric Simmons-Smith cyclopropanation for unfunctionalized olefins was investigated using density functional theory (DFT) methods. The calculated results of model reactions showed that the coordinated Lewis acidic zinc halide ZnX 2 (X = Cl, I) and/or halo-A C H T U N G T R E N N U N G methylzinc halide XZnCH 2 X in the catalyst play an important role in the enantioselectivity. The catalyst not only forms the ring with the substance in the reaction centre, but also establishes two steric repulsions that can lead to an explanation for the high enantioselectivity. Hence, these results highlight some important insights for the prerequisites of an effective catalyst and a proper substrate towards high enantioselectivity for this kind of reaction.

A novel class of tunable cyclopropanation reagents (RXZnCH2Y) and their synthetic applications

“…Compound 125 could then act as a chiral Lewis acid to activate XZnCH 2 I and form complex 127 which cyclopropanates the alkene (Scheme 44, pathway B). As indicated by the X-ray structure of 124 as well as theoretical studies, 86 the oxygen of the Boc group could also coordinate to the Zn atom in 126 and 127 as shown in Fig. 4 (126′, 127′).…”

Asymmetric Cyclopropanation Reactions

“…This second zinc atom can accelerate the reaction acting as Lewis acid. 39 Shitama and Katsuki reported a Simmons-Smith cyclopropanation by asymmetric catalysis with an aluminum complex (10 mol%, Figure 5, left) in which the aluminum atom acts as the Lewis acid site and a nitrogen atom from the ligand acts as the Lewis base site. 41 Unfortunately, good substrates are limited to trans-disubstituted allylic alcohols [92-99% isolated yield with 63-94% ee of the (S,S)-cyclopropylmethanol], while the enantioselectivity of the reaction of (Z)-cinnamyl alcohol was moderate (58% ee of the R,S-isomer).…”

Density functional theory study of the mechanism of zinc carbenoid promoted cyclopropanation of allenamides

“…The polarizable continuum model 78,80 has been commonly used in theoretical studies on organometallic reactions. 23,32,74,81 The single-point energy calculations with IEFPCM were done at the same level of theory and basis sets as those used in gas-phase optimization and based on the gasphase-optimized structures. The energetics is discussed on the basis of the potential energy.…”

“…24,27 On the basis of results from previous studies on (halomethyl)metal carbenoid-mediated cyclopropanation of olefins 28,29 and alkoxides, the asymmetric cyclopropanation reaction systems using other kinds of metal complex catalysts or modified olefins have also been explored. [30][31][32][33][34][35][36][37][38] Among these other reaction systems, a great deal of experimental and computational effort has been directed toward the cyclizations of allenes and their derivatives. 16,[39][40][41][42][43][44][45] Allenamines are useful allene-analogues in organic chemistry as they are electron-rich and can be readily activated in the presence of an electrophile.…”