Enantioselective Synthesis of Vinylcyclopropanes and Vinylepoxides Mediated by Camphor-Derived Sulfur Ylides:  Rationale of Enantioselectivity, Scope, and Limitation

Abstract

By a sidearm approach, camphor-derived sulfur ylides 1 were designed and synthesized for the cyclopropanation of electron-deficient alkenes and epoxidation of aldehydes. Under the optimal conditions, the exo-type sulfonium salts 4a and 4b reacted with beta-aryl-alpha,beta-unsaturated esters, amides, ketones, and nitriles to give 1,3-disubstituted-2-vinylcyclopropanes with high diastereoselectivities and enantioselectivities. When the endo-type sulfonium salts 5a and 5b were used, the diastereoselectivities were not changed, whereas the absolute configurations of the products became the opposite to those of the reactions of 4a and 4b. An ylide cyclopropanation of chalcone derivatives with phenylvinyl bromide in the presence of catalytic amount of chiral sulfonium salts 4b and 5b has been developed. The sidearmed hydroxyl group was found to play a key role in the control of enantioselectivity and diastereoselectivity. The origins of the high diastereoselectivity and enantioselectivity were also studied by density functional theory calculations, which reveal the importance of the hydrogen-bonding between the sidearmed hydroxyl group and the substrate in determining the diastereoselectivity and enantioselectivity. The ylides 1 were also successfully applied for the epoxidation of aromatic aldehydes.

One-Pot Catalytic Enantio- and Diastereoselective Syntheses ofanti-,syn-cis-Disubstituted, andsyn-Vinyl Cyclopropyl Alcohols

“…Accessing enantioenriched vinylcyclopropanes is often challenging 20,77,78. Davies' pioneering route involved the catalytic asymmetric cyclopropanation of alkenes with vinyldiazoacetates.…”

Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

“…146 Of particular interest is the access of both enantiomer of the product through the use of endo or exo camphor based sulfides.…”

Copper(I)‐Catalyzed Interrupted Click Reaction: Synthesis of Diverse 5‐Hetero‐Functionalized Triazoles

“…Previously,S -methyl benzenesulfonothioate 3a was used successfully by Dai and Tang to introduce as ulfenyl group into d-camphor,b uilding ac hiral sulfide. [12] Compound 3a might be an excellent electrophilic sulfenylating reagent, because the cleaved benzenesulphinate is ag ood leaving group,w ith the pK a of phenylsulfinic acid being 2.76. To validate this concept, the phenylacetylene 1a and the benzylazide 2a were selected as model substrates with which to optimize the reaction conditions (Table 1; see the Supplementary Information for details).…”