Dearomative Dienolate-Mediated Catalysis: A Remote Activation Strategy for Asymmetric Functionalization of Benzylic C–H Bonds of Heteroaryl Aldehydes

Abstract

A dearomative remote activation strategy for the asymmetric functionalization of benzylic C-H bonds of heteroaryl aldehydes under bifunctional Brønsted base catalysis has been developed. The in situ generated o-QDMs-type dienolate intermediates were efficiently and stereoselectively trapped by nitroolefins through an asymmetric Michael/nitro-aldol cascade reaction. Using this strategy, a wide variety of synthetically significant tetrahydrodibenzothiophene and tetrahydrodibenzofuran derivatives were synthesized in good yields with high enantioselectivities.

Cinchona Derivatives as Bifunctional H‐bonding Organocatalysts in Asymmetric Vinylogous Conjugate Addition Reactions

“…[44b] In the same year, Xu et al documented an unconventional application of quinine-derived squaramide catalyst C17a in asymmetric cascade transformation of arylogous heteroaryl aldehydes 72 (Scheme 31). [45] Brønsted basic tertiary amine group on the bifunctional catalyst C17a carried out a noncovalent and dearomative activation of aldehydes 72. The resulting orthoquinodimethane type dienolate underwent a highly enantioselective Michael-Henry cascade reaction with nitroalkenes 4 to furnish the formal [4 + 2] cycloaddition adducts, which then converted to optically active tetrahydrodibenzothiophene or tetrahydrodibenzofuran derivatives 73 after a sequential dehydration/reduction step.…”

Direct, Asymmetric Synthesis of Carbocycle‐Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach

“…1b). [13] Tricyclic products with four contiguous stereocenters were obtained as epimeric mixtures, which were subjected to carbinol reduction to yield the corresponding deoxy-derivatives. The application of this chemistry to restricted categories of reactants (e. g. trifluoromethyl ketones or aromatic aldehydes bearing additional aryl substituents at the benzylic vinylogous site) and the lack of direct procedures are major limitations of these approaches.…”

“…In 2018, Xu and colleagues developed another two‐step methodology for the asymmetric [4+2] cycloaddition between 2‐benzylbenzofuran(thiophene) carbaldehydes and nitroalkene dienophiles under bifunctional quinine‐squaramide catalysis (Scheme 1, eq. 1b) [13] . Tricyclic products with four contiguous stereocenters were obtained as epimeric mixtures, which were subjected to carbinol reduction to yield the corresponding deoxy‐derivatives.…”

Development of Nitrolactonization Mediated by Iron(III) Nitrate Nonahydrate

“…Nitro compounds are useful synthons in synthetic organic chemistry due to their availability for various transformations. The strong electron-withdrawing property of the nitro group plays an important role in C-C bond formation reactions 1,2) including the nitro-aldol reaction (Henry reaction), [3][4][5] Michael reaction, [6][7][8][9][10][11] and alkylation. 12,13) Nitrones and nitrile oxides generated from nitro compounds undergo 1,3-dipole cycloaddition reaction to give various heterocycles.…”