Asymmetric Hydrogenation of α‐Primary and Secondary Amino Ketones: Efficient Asymmetric Syntheses of (−)‐Arbutamine and (−)‐Denopamine

Abstract

Two beta-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of alpha-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation represents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.

Asymmetric Reduction of α‐Amino Ketones with a KBH4 Solution Catalyzed by Chiral Lewis Acids

“…Encouraged by the promising results obtained in the reduction of α‐secondary amino ketones, we subsequently switched our exploration to α‐primary amino ketones for the syntheses of N ‐unprotected 1,2‐amino alcohols. To the best of our knowledge, only few examples of direct asymmetric hydrogenation of α‐primary amino ketones hydrochlorides have been reported with limited substrate scope 1c. 13 After a general investigation on the reaction conditions, the desired products were isolated in moderate to good yields and enantioselectivities by using L3 –Sc(OTf) 3 as the catalyst 14.…”

Transition Metal‐Catalyzed Homogeneous Asymmetric Hydrogenation

“…Zhang and others ' Ru -C3 -TunePhos catalyst also showed excellent enantioselectivities ( > 99% ee) for the asymmetric hydrogenation of α -phthalimide ketones with turnover numbers up to 10,000 ( have also provided excellent enantioselectivities and reactivities in the hydrogenation of α -, β -, or γ -amino ketones. The Zhang group recently reported a highly effi cient hydrogenation of a series of unprotected α -and β -amino ketones using the electron -rich DuanPhos [266] and BINAPINE [267] . The effi cient preparation of chiral amino alcohols via asymmetric hydrogenation has been employed for the syntheses of many important chiral intermediates and drugs.…”

“…The tran sRuCl 2 [( R ) -XylBINAP][( R ) -daipen] complex has been applied as a catalyst to the enantioselective synthesis of ( R ) -denopamine, a β 1 -receptor agonist used for the treatment of congestive heart failure (Scheme 7.10 ) [265] . Zhang and others ' short synthesis afforded this compound via the hydrogenation of unprotected amino ketone precursor using the Rh -DuPhos catalyst [267] . ( R ) -arbutamine was also synthesized with reasonable enantioselectivity.…”

Synthesis of 2‐Substituted 2‐Amino Ketones by Rhodium‐Catalyzed Reaction of N‐Sulfonyl‐1,2,3‐triazoles with 2‐Alkenols

“…2‐Amino ketones are a valuable structural motif found in a number of biologically active compounds, which include commercially available drugs such as amfepramone, bupropion, and prasugrel . They also act as the key intermediate for the synthesis of chiral 2‐amino alcohols[4] and various nitrogen‐containing heterocycles [5]. Thus, the development of an efficient method to synthesize this functionality, starting from readily available compounds is highly demanded [6]…”