Stereoselective Synthesis Axially Chiral Arylnitriles through Base-Induced Chirality-Relay β-Carbon Elimination of α-Hydroxyl Ketoxime Esters

Abstract

We report herein a point-to-axial chirality transfer reaction of α-hydroxyl oxime esters for the synthesis of axially chiral arylnitriles. The reaction proceeds smoothly through a base-promoted retro-benzoin condensation reaction of α-hydroxyl oxime esters, where the axial chirality is created via the C–C bond cleavage based on a proper distorted conformation of the biaryl structure induced by its stereogenic carbon center.

A Chiral Relay Race: Stereoselective Synthesis of Axially Chiral Biaryl Diketones through Ring-Opening of Optical Dihydrophenan-threne-9,10-diols

“…Tetrahydrofuran was distilled over sodium in the presence of benzophenone under an atmosphere of nitrogen. All the optical alcohols were known compounds and were prepared according to the procedure developed in our laboratory [ 36 , 37 ].…”

“…This chirality relay is based on the fact that one of the aryl rings would approach the Pd atom, ultimately resulting in the construction of axial chirality. In contrast to the 8H-indeno [1,2-c]thiophen-8-ols, the stereogenic carbon center of α-hydroxy ketone induces the configuration of the biaryl structure ( Scheme 1 c) [ 36 , 37 ]. For example, when the R -configuration carbon center is involved, the biaryl skeleton favors the S a configuration, which then leads to the construction of S -axially chiral carboxylic acids and nitriles from the corresponding α-hydroxy ketone and oxime ester, respectively.…”

Organocatalytic Michael Addition of Unactivated α-Branched Nitroalkanes to Afford Optically Active Tertiary Nitrocompounds

“…Subsequent acetylation of 8 in the presence of triethylamine was accompanied by spontaneous fragmentation giving rise to nitrile 9 in 85% isolated yield. 21 In this process, the diaryl ketone byproduct was, again, recovered in 80% yield. The absolute configuration of compound 9 was determined by single crystal X-ray analysis which served to establish that of the remaining adducts.…”

“…Thus, condensation of 3Lc with hydroxylamine in hot ethanol produced oxime 8 in 71% yield. Subsequent acetylation of 8 in the presence of triethylamine was accompanied by spontaneous fragmentation giving rise to nitrile 9 in 85% isolated yield . In this process, the diaryl ketone byproduct was, again, recovered in 80% yield.…”