Rhodium-catalyzed asymmetric hydrogenation of β-branched enamides for the synthesis of β-stereogenic amines

Abstract

Using a rhodium complex of a bisphosphine ligand (R)-SDP, β-branched simple enamides with a (Z)-configuration were hydrogenated to β-stereogenic amines in quantitative yields and with excellent enantioselectivities (88-96% ee).

Enantioconvergent and enantiodivergent catalytic hydrogenation of isomeric olefins

“…The Zhang group developed an asymmetric hydrogenation of simple (Z)-b-branched enamides by employing a bisphosphine ligand (R)-SDP (Scheme 21). 30 When (E)-enamides were examined the desired products were obtained with comparatively lower enantioselectivities and opposite configuration.…”

Recent Developments in Transition-Metal-Catalyzed Asymmetric Hydrogenation of Enamides

“…The latter were enantioselectively hydrogenated in 95-98% yield and with ee values of 88-96% (Scheme 13). 18 Moreover, the developed protocol was successfully applied…”

Enantioselective Synthesis of β‐Methyl Amines via Iridium‐Catalyzed Asymmetric Hydrogenation of N‐Sulfonyl Allyl Amines

“…Many biologically active compounds have amines with a chiral methyl group in β‐position. Compound 2 a is already a direct precursor of potassium channel inhibitors after simple tosyl deprotection and acylation (see SI). The mesyl amine 2 m is also a key intermediate for the preparation of allosteric modulators of AMPA receptor .…”

“…Compound 2 a is already a direct precursor of potassium channel inhibitors after simple tosyl deprotection and acylation (see SI). The mesyl amine 2 m is also a key intermediate for the preparation of allosteric modulators of AMPA receptor . However, to further showcase the applicability of our methodology, and encouraged by the relevance of these chiral β‐methyl amines as fragments of biologically active compounds we envisioned easy access to LY‐404187 and (R)‐ Lorcaserin.…”

“…The mesyl amine 2 m is also a key intermediate for the preparation of allosteric modulators of AMPA receptor. [16,17] However, to further showcase the applicability of our methodology, and encouraged by the relevance of these chiral β-methyl amines as fragments of biologically active compounds we envisioned easy access to LY-404187 and (R)-Lorcaserin. To obtain the biarylpropylsulfonamide LY-404187, [4] we designed a 3-step synthetic procedure starting from N-sulfonyl aziridine 1 l. The isomerization [12] of 1 l to 2 l and the subsequent asymmetric hydrogenation to 3 l took place in excellent yields.…”