Asymmetric Catalytic Vinylogous Addition Reactions Initiated by Meinwald Rearrangement of Vinyl Epoxides

Abstract

The first catalytic asymmetric multiple vinylogous addition reactions initiated by Meinwald rearrangement of vinyl epoxides were realized by employing chiral N,N′‐dioxide/ScIII complex catalysts. The vinyl epoxides, as masked β,γ‐unsaturated aldehydes, via direct vinylogous additions with isatins, 2‐alkenoylpyridines or methyleneindolinones, provided a facile and efficient way for the synthesis of chiral 3‐hydroxy‐3‐substituted oxindoles, α,β‐unsaturated aldehydes and spiro‐cyclohexene indolinones, respectively with high efficiency and stereoselectivity. The control experiments and kinetic studies revealed that the Lewis acid acted as dual‐tasking catalyst, controlling the initial rearrangement to match subsequent enantioselective vinylogous addition reactions. A catalytic cycle with a possible transition model was proposed to illustrate the reaction mechanism.

Regio‐ and Enantioselective γ‐Allylic Alkylation of In Situ‐Generated Free Dienolates via Scandium/Iridium Dual Catalysis

“…The iridium complex A , given by coordination of iridium catalyst to allylic alcohol 1 a , undergoes oxidative addition promoted by Sc(OTf) 3 to furnish π‐allyl‐iridium(III) intermediate B . Concurrently, according to previous reports [13a, 14] and our density functional theory (DFT) calculation results (more details were shown in Supporting Information), the Lewis acid Sc(OTf) 3 triggers the ring opening of vinyloxirane 2 a to furnish the scandium‐bound zwitterionic species C , which undergoes a 1,2‐hydride shift and tautomerization sequence affording the active scandium dienolate E . Nevertheless, in our opinion, another possible pathway for the generation of scandium dienolate species E through iridium‐catalyzed oxidative addition of the vinyloxirane 2 a and further rapid β‐elimination could not be ruled out (more details were shown in Supporting Information) [7b,c, 20] .…”

“…We performed the reaction without 1 a under the standard conditions (Scheme 4a) and 2 a was completely consumed, generating 76 % yield of α,β‐unsaturated aldehyde 13 . Meanwhile, β,γ‐unsaturated aldehyde and the dienolate intermediate were not detected by 1 H NMR analysis in the reaction mixture, probably due to the instability and high reactivity [13a, 14] . Besides, the target allylation reaction could not be re‐established by adding 1 a to the mixture.…”

“…Brønsted acids (trifluoroacetic acid, 4-chlorobenzoic acid) were evaluated as well, but failed to afford the target product 3 a (Table S2 in Supporting Information). Further screening of different solvents (entries [14][15][16][17][18] uncovered that tetrahydrofuran (THF) was optimal for the generation of the product 3 a in good yield (76 %) with excellent enantiopurity (97 % ee). Lowering the reaction temperature to 25 °C or 0 °C (entries 19 and 20) led to a slight decrease of the yields and did not affect the enantioselectivities.…”

“…Encouragingly, the desired dienolates could be generated from vinyloxiranes [11] via Lewis acid (LA)-mediated Meinwald rearrangement [12] in an efficient and atom-economic way, and several advancing transformations were reported by the Lautens, Feng groups and others (Scheme 2a). [13,14] Hence, we set out to introduce vinyloxiranes as dienolate precursors in asymmetric allylic alkylation enabled by LA/Ir dual catalysis. This Meinwald rearrangement/allylation cascade reaction could provide a series of meaningful chiral γ-allylic crotonaldehydes (Scheme 2b).…”

Nickel-catalyzed cross-coupling of epoxides with aryltriflates: rapid and regioselective construction of aryl ketones

“…8 In the case of terminal epoxides, corresponding aldehydes are formed as the major product. 9 Various Lewis acid reagents have been addressed for the isomerization such as InCl 3 , BF 3 ·Et 2 O, lithium salts, MgBr 2 , and Pd(OAc) 2 in the presence of phosphine ligand with frequent use in stoichiometric amounts. Some of these reagents are toxic, corrosive, and air or moisture sensitive.…”