Stereoselective Synthesis of Cyclopropanes Based on a 1,2‐Chirality Transfer

Abstract

A stereoselective route to enantiomerically enriched bicyclic cyclopropane derivatives 13 is described which is based on a conceptually novel 1,2-chirality transfer approach. The hyperconjugative interaction of an electronically excited carbonyl group with the sigma* orbital of an adjacent C--X bond in the transition state of a hydrogen abstraction causes the preference of a certain conformation and consequently the differentiation between two diastereotopic methylene groups. The 1,2-chirality transfer is completed by a subsequent HX elimination which destroys the only stereogenic center in the reactants 12. Furthermore, it was found that contrary enthalpic and entropic influences result in the existence of an inversion temperature T 0. Upon crossing T 0 the stereoselectivity is reversed. Considering this temperature dependency, chirality transfer efficiencies of up to 83 % could be achieved. The absolute configuration of most products could be unambiguously determined by VCD spectroscopy combined with DFT calculations.

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

“…Over the past several years there has been a rapid growth in the use of VCD to determine the AC of small chiral organic molecules. A large variety of structural types have been examined, including epoxides and cyclopropanes, [55][56][57][58] bicyclic and tricyclic structures, [59][60][61][62][63][64][65][66][67] chiral structures with no chiral center (atropisomer or molecules with axial or helical chirality), [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83] sulfur or phosphorus containing compounds, 77,[84][85][86][87][88] flexible molecules, 56,[89][90][91] and other structures that do not fit into any of the above categories. [92][93][94][95][96][97] The following examples highlight the versatility of VCD as a powerful tool for the AC determinations of different types of chiral organ...…”

Copper‐Catalyzed (2+1) Annulation of Acetophenones with Maleimides: Direct Synthesis of Cyclopropanes

“…[1] Thes ynthesis of the cyclopropane moiety has evoked considerable interest and resulted in the development of different synthetic strategies.C yclopropanation of alkenes with carbenes,c arbenoids,a nd ylides is aw idely used transformation. [2] TheS immon-Smith reaction [3] and Michael-initiated ring closure [4] have found applications in the synthesis of cyclopropanes.F urthermore, methods based on the transformation of compounds with active methylene groups [5] and photochemical approaches [6] were used for the preparation of cyclopropanes.T hese methods require the application of reactive prefunctionalized reagents.T herefore,t he development of novel and practical methods for the straightforward synthesis of strained cyclopropanes using nonfunctionalized materials remains aconsiderable challenge and their elaboration is highly desired.…”

Reaction mechanisms : Part (i) Radical and radical ion reactions

“…26 Another example involving a 1,2-chirality transfer approach was reported by Muehling and Wessig. 27 However, intramolecular hydrogen abstraction can be bad, as illustrated by a recent example reported by Matsumoto and coworkers (Scheme 12). In this case, an undesirable 1,5-hydrogen atom transfer leads to chain scission in the radical polymerization of vinyl ethers.…”