Organocatalysis with a Fluorous Tag:  Asymmetric Reduction of Imines with Trichlorosilane Catalyzed by Amino Acid-Derived Formamides

Abstract

Asymmetric reduction of ketimines 1 with trichlorosilane can be catalyzed by N-methylvaline-derived Lewis-basic formamides 3a-d with high enantioselectivity (< or =95% ee) and low catalyst loading (1-5 mol %) at room temperature in toluene. Appending a fluorous tag, as in 5a-c, simplifies the isolation procedure, while preserving high enantioselectivity (< or =92% ee).

Asymmetric Substitutions of 2‐Lithiated N‐Boc‐piperidine and N‐Boc‐azepine by Dynamic Resolution

“…The known amino-acid derivative 19 was prepared in two steps from valine according to the literature. [14] This was converted to the Weinreb amide 20 which was treated with phenyl magnesium chloride to give the ketone 21. Reduction of the ketone with simultaneous reduction of the N-Boc group gave the amino-alcohol 22.…”

Soluble Polymer‐Supported Organocatalysts: Asymmetric Reduction of Imines with Trichlorosilane Catalyzed by an Amino Acid Derived Formamide Anchored to a Soluble Polymer

“…[1] Asymmetric reduction of prochiral imines 1 is one of the key reactions in synthetic organic chemistry (Scheme 1). [2] Its organocatalytic version [3] is characterized by two fundamentally different approaches: 1) hydrosilylation with Cl 3 SiH, catalyzed by chiral Lewis-bases, [4][5][6][7][8][9] and 2) reduction with Hantzsch dihydropyridine, catalyzed by chiral Brønsted acids. [10] In the past few years, we have developed the amino acidbased formamides 3-5 (Scheme 1) as chiral Lewis-basic organocatalysts for the reduction of imines 1 ( 97 % ee; 1-5 mol % loading).…”

“…[10] In the past few years, we have developed the amino acidbased formamides 3-5 (Scheme 1) as chiral Lewis-basic organocatalysts for the reduction of imines 1 ( 97 % ee; 1-5 mol % loading). [4] The practicality was then improved by tagging the catalyst to a fluorous ponytail (7) [5] and by its anchoring to a polymer support (8). [6,11] Catalyst 7, working in a homogeneous solution, mirrored the enantioselectivities of 3-5 and the products were separated from the catalyst by filtration through a pad of fluorous silica.…”

“…[6,11] Catalyst 7, working in a homogeneous solution, mirrored the enantioselectivities of 3-5 and the products were separated from the catalyst by filtration through a pad of fluorous silica. [5] The solid-supported catalysts 8 were separated even more easily via mechanical filtration. [6] However, the latter reactions were heterogeneous and that had a negative impact on the enantioselectivities, which reached 82 % ee, that is, about 10-15 % ee below those of the homogeneous system.…”

“…Reduction of imine 1 a in toluene (an optimized solvent for homogeneous conditions [4,5] ), catalyzed by 9 a, afforded amine (S)-2 a in 85 % ee (Table 1, entry 3). Catalyst 9 b, with the higher content of the active component, turned out to be an optimum in terms of its preparation and performance, since high conversions and enantioselectivities were attained (86-88 % ee; entries 4-6) even with gradually decreasing catalyst loading (from 7 to 1 mol %).…”