Vinylcarbene insertion into the nitrogen–hydrogen
(N–H)
bond of amines allows direct access to α,β-unsaturated
γ-amino acid derivatives, meeting a marked challenge in the
control of regio- and enantioselectivities. Here, we report a highly
γ-selective and enantioselective insertion into N–H bonds
of aliphatic or aromatic secondary amines with vinyl substituted α-diazo
pyrazoleamides using a high-spin chiral N,N′-dioxide/cobalt(II) complex catalyst. The method affords a wide variety
of valuable optically active Z- and E-type vinyl γ-amino amides. Calculation reveals a spin state
change from the quartet cobalt(II) complex to a doublet Co(II)-carbene
species for facile Z-selective and enantioselective
nucleophilic addition.
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.
Compared to γ‐addition, the α‐addition of α‐branched β,γ‐unsaturated aldehydes faces larger steric hindrance and disrupts the π–π conjugation, which might be why very few examples are reported. In this article, a highly diastereo‐ and enantioselective α‐regioselective Mannich reaction of isatin‐derived ketimines with α‐, β‐ or γ‐branched β,γ‐unsaturated aldehydes, generated in situ from Meinwald rearrangement of vinyl epoxides, is realized by using chiral N,N′‐dioxide/ScIII catalysts. A series of chiral α‐quaternary allyl aldehydes and homoallylic alcohols with vicinal multisubstituted stereocenters are constructed in excellent yields, good d.r. and excellent ee values. Experimental studies and DFT (density functional theory) calculations reveal that the large steric hindrance of the ligand and the Boc (tButyloxy carbonyl) protecting group of imines are critical factors for the α‐regioselectivity.
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.
Compared to γ‐addition, the α‐addition of α‐branched β,γ‐unsaturated aldehydes faces larger steric hindrance and disrupts the π–π conjugation, which might be why very few examples are reported. In this article, a highly diastereo‐ and enantioselective α‐regioselective Mannich reaction of isatin‐derived ketimines with α‐, β‐ or γ‐branched β,γ‐unsaturated aldehydes, generated in situ from Meinwald rearrangement of vinyl epoxides, is realized by using chiral N,N′‐dioxide/ScIII catalysts. A series of chiral α‐quaternary allyl aldehydes and homoallylic alcohols with vicinal multisubstituted stereocenters are constructed in excellent yields, good d.r. and excellent ee values. Experimental studies and DFT (density functional theory) calculations reveal that the large steric hindrance of the ligand and the Boc (tButyloxy carbonyl) protecting group of imines are critical factors for the α‐regioselectivity.
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