Enantioselective Synthesis of β‐Aminotetralins via Chiral Phosphoric Acid‐catalyzed Reductive Amination of β‐Tetralones

Abstract

A new protocol for the synthesis of chiral b-aminotetralins has been developed via chiral phosphoric acid-catalyzed asymmetric reductive amination of b-tetralones using a Hantzsch ester as an organic hydride donor. Various chiral b-aminotetralins were obtained in good yields with good to high enantioselectivities. Furthermore, the utility of our new protocol was successfully demonstrated in the enantioselective synthesis of rotigotine.

An expedient copper-catalysed asymmetric synthesis of γ-lactones and γ-lactams. Application to the synthesis of lucidulactone A

“…27 The absolute configuration of 23c was determined as R following cyclisation to ( R )- 22c . Subsequent treatment with ceric ammonium nitrate generated ( R )- 24c , 28 which was converted to baclofen 4 in a previous study (Scheme 5a). 3 b Likewise, 23a (78% ee), obtained from a larger scale reduction reaction (1.71 g of ( Z )- 14a – 1.8 mol% catalyst loading), was cyclised to ( R )- 22a .…”

Chiral Phosphoric Acids as Versatile Tools for Organocatalytic Asymmetric Transfer Hydrogenations

“…[45] As the first example on the reductive amination of cyclic ketones, Cheon et al disclosed the CPA-catalyzed synthesis of β-aminotetralins (Scheme 17). [46] Various β-tetralones (41 a-f) and anilines (42 a-j) bearing EWG or EDG groups could be readily reacted and the corresponding β-aminotetralins (43 a-p) were obtained in moderate to good yields and in enantioselectivities up to 83 % ee; moreover, the synthetic utility was demonstrated by the enantioselective synthesis of the dopamine agonist drug Rotigotine (44). Using 1-hydrosilatrane (3), a novel hydrogen source was introduced for the reductive amination of ketones by Adler et al Even though high yields and up to 84 % ee could be achieved, a rather high phosphoric acid loading of 30 mol% was required.…”

“…disclosed the CPA‐catalyzed synthesis of β‐aminotetralins (Scheme 17 ). [46] Various β‐tetralones ( 41 a – f ) and anilines ( 42 a – j ) bearing EWG or EDG groups could be readily reacted and the corresponding β‐aminotetralins ( 43 a – p ) were obtained in moderate to good yields and in enantioselectivities up to 83 % ee; moreover, the synthetic utility was demonstrated by the enantioselective synthesis of the dopamine agonist drug Rotigotine ( 44 ).…”

Synthesis of Pharmaceutically Relevant 2‐Aminotetralin and 3‐Aminochroman Derivatives via Enzymatic Reductive Amination

“…[17][18][19][20][21] However, limitations are also associated with these approaches, including sensitivity to moisture and the use of expensive non-commercial chiral ligands. [22,23] Other relevant, yet less effective approaches towards the synthesis of these moieties include the asymmetric aziridination of dihydronaphthalenes, [24] the organocatalytic reductive amination of 2-tetralones, [25] and the radical cyclisation of substituted benzenes with l-serine derivatives. [26,27] Biocatalysts are increasingly highlighted as attractive tools for asymmetric synthesis due to their ability to achieve high levels of chemo-and enantioselectivity under mild conditions.…”