Functionalization of the indole N−H bond for enantioselective synthesis of biologically important pyrroloquinoline derivatives has been reported under oxidative N-heterocyclic carbene catalysis conditions. The interception of catalytically generated chiral α,β-unsaturated acylazoliums with the indole derivatives proceeds in an aza-Michael/Michael/ lactonization sequence to deliver the pyrroloquinoline derivatives in good yields, diastereoselectivities, and enantioselectivities. The simultaneous enhancement of reactivity and selectivity observed in polar aprotic solvents is noteworthy.
The [3 + 3] annulation of α,β-unsaturated
aldehydes
with 2-substituted 1,4-naphthoquinones allowing the facile synthesis
of functionalized dihydrocoumarins catalyzed by N-heterocyclic carbene
(NHC) is reported. The initially formed NHC-homoenolates underwent
an efficient Michael–isomerization–lactonization cascade
to furnish the products. Preliminary studies on mechanism shed light
on the homoenolate pathway over the intermediacy of the α,β-unsaturated
acylazolium intermediates. Moreover, using chiral NHCs, the desired
products were formed in up to 49% yield and 99:1 er.
Although the construction of axially chiral C−C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well‐known, the related synthesis of compounds bearing axially chiral C−N bonds are relatively rare. Described herein is the N‐heterocyclic carbene‐catalyzed atroposelective synthesis of N‐aryl succinimides having an axially chiral C−N bond via the desymmetrization of N‐aryl maleimides. The NHC involved intermolecular Stetter‐aldol cascade of dialdehydes with prochiral N‐aryl maleimides followed by oxidation afforded N‐aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C−N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.
N-Heterocyclic carbene catalyzed enantioselective functionalization of 3-aminobenzofurans at the C2-position was realized using 2-bromoenals as the coupling partner. The reaction proceeds via generation of chiral α,β-unsaturated acylazoliums and follows an aza-Claisen rearrangement. The initially formed dihydropyridinone undergoes ring-opening catalyzed by Mg to afford the δ-amino acid derivatives. The reaction worked with 3aminobenzothiophenes as well, and the C2-alkylated products were formed in moderate to high yields and selectivity.
Supporting Information 1. General Information S2 2. General Procedure for the Optimization of the Reaction Conditions S3 3. General Procedure for the Enantioselective Synthesis of Tricyclic β-lactones S5 4. X-ray data of 3a S6 5. Synthesis and Characterization of Cyclopentane-1,3-dione Derivatives S8 6. Synthesis and Characterization of Tricyclic β-lactone Derivatives S11 7. Functionalization of Tricyclic β-lactones S28 8. 1 H and 13 C NMR Spectra of Cyclopentane-1,3-dione Derivatives S31 9. 1 H and 13 C NMR Spectra of Tricyclic β-lactone Derivatives S36 10. HPLC data of Tricyclic β-lactone Derivatives S65 1 (a) Allen, C.
Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C−C bonds is wellknown, the synthesis of axially chiral C−N bond-containing compounds is relatively less explored, and the construction of axially chiral N−N bonds has received only scant attention. Demonstrated herein is the N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to the atroposelective synthesis of N−N axially chiral 3-amino quinazolinones. The NHC-catalyzed reaction of quinazolinones containing a free N−H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished the atropisomeric quinazolinone derivatives under mild conditions and broad scope. Preliminary studies on experimental and density functional theory-based N−N rotational barrier determination are also presented.
Although the construction of axially chiral C−C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well‐known, the related synthesis of compounds bearing axially chiral C−N bonds are relatively rare. Described herein is the N‐heterocyclic carbene‐catalyzed atroposelective synthesis of N‐aryl succinimides having an axially chiral C−N bond via the desymmetrization of N‐aryl maleimides. The NHC involved intermolecular Stetter‐aldol cascade of dialdehydes with prochiral N‐aryl maleimides followed by oxidation afforded N‐aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C−N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.
The core-structure motivated design has allowed the enantioselective synthesis of 5,6-dihydroindolizines via Nheterocyclic carbene (NHC) catalysis. The NHC-catalyzed reaction of α,β-unsaturated aldehydes with the suitably substituted pyrrole derivatives proceed via the initial generation of α,βunsaturated acylazoliums from enals, and enolates from pyrroles and the reaction culminated in an efficient cascade process involving the Michael−aldol−lactonization−decarboxylation sequence to afford the products in reasonable yields and high selectivities. The method is further extended to the construction of spirocyclic 5,6-dihydroindolizines.
* sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.1c01761. Details on experimental procedure, characterization data and HPLC data of all 5,6-dihydroindolizine derivatives and X-ray data of 3g (PDF)Accession CodesCCDC 2057485 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk
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