Kinetic resolution of racemic 2-substituted 1,2-dihydroquinolines via asymmetric Cu-catalyzed borylation

Abstract

A highly efficient kinetic resolution of racemic 2-substituted 1,2-dihydroquinolines via asymmetric Cu-catalyzed borylation has been realized for the first time to afford chiral 3-boryl-1,2,3,4-tetrahydroquinolines and recover 2-substituted 1,2-dihydroquinolines with excellent enantioselectivities and selectivity factors of up to 569.

Copper-Catalyzed Asymmetric Hydroboration of 2H-Chromenes Using a Chiral Diphosphine Ligand

“…Despite a higher yield achieved in 1,2-dimethoxylethane, the enantioselectivity was slightly decreased (Table , entry 10). On the basis of the pioneering work, some diphosphine ligands (Figure ) were capable of promoting the hydroboration reaction of various substrates. − These ligands including ( R )-SegPhos ( L2 ), ( R )-DM-SegPhos ( L3 ), ( R , S p )-JosiPhos-1 ( L4 ), and ( R , R )-Me-DuPhos ( L5 ), which exhibited good performance were evaluated in this transformation. However, most of them could only give poor yields or enantioselectivities (Table , entries 11–14).…”

“…Therefore, to develop efficient catalysts and approaches for enantioselective synthesis of chiral borylated chromans is highly desirable. Although highly chemo- and regioselective catalytic asymmetric hydroboration of various substrates, such as olefins and N-heterocyclic substrates including indoles, 1,2-dihydropyridines, and 1,2-dihydroquinolines, has emerged substantially for the synthesis of optically active boron-containing compounds and significant progress has also been achieved, the catalyzed enantioselective hydroboration of 2 H -chromenes still remains a challenge. This is possibly attributed to the high energy barrier encountered during the conjugation of the CC double bond with the phenyl ring, as well as the interaction of the oxygen atom with the borated reagent which may have a negative effect on the hydroboration.…”

Synthesis and Applications of β‐Aminoalkylboronic Acid Derivatives

“…Later, Hou and co‐workers expanded the scope to quinoline substrates bearing substituents at the 2‐position by using a similar sequence (Scheme 14, eq. 3) [51] . In this case, however, the Cu‐catalyzed asymmetric borylation step proceeds through a kinetic resolution, forming chiral 3‐boryl‐1,2,3,4‐tetrahydroquinolines with two stereogenic centers featuring anti diastereochemistry.…”

Organocatalytic alkylation of carbohydrate‐containing aldehydes with dihydroquinoline N,O‐acetals: Absolute configuration of 1,2‐dihydroquinolines

“…4,5 Most approaches for the preparation of chiral 2substituted dihydroquinolines in nonracemic form are able to introduce only rather simple organic frameworks making use of sophisticated metal catalysts in strictly anhydrous and/or oxygen-free reaction conditions. [6][7][8][9][10] Mannich-type reactions have recently been reported by us and other research groups using synergistic cooperative metal-organocatalysis starting from dihydroquinoline N,O-acetals as proelectrophiles [11][12][13][14] or directly from quinolines. 15 It should be noted that while there are precedents about the use of chiral aldehydes as the electrophilic acceptors in organocatalyzed reactions, 16,17 we are not aware of reactions in which chiral aldehydes, such as saccharidic aldehydes, have been used as the nucleophilic donor.…”

“…The most striking example is N ‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ), a powerful irreversible dopamine‐receptor antagonist . Most approaches for the preparation of chiral 2‐substituted dihydroquinolines in nonracemic form are able to introduce only rather simple organic frameworks making use of sophisticated metal catalysts in strictly anhydrous and/or oxygen‐free reaction conditions . Mannich‐type reactions have recently been reported by us and other research groups using synergistic cooperative metal‐organocatalysis starting from dihydroquinoline N,O‐acetals as proelectrophiles or directly from quinolines .…”