Gold(I)‐Catalyzed Stereoconvergent, Intermolecular Enantioselective Hydroamination of Allenes

Abstract

Gold und Silber: Eine 1:2‐Mischung von [{(S)‐1}(AuCl)2] und AgBF4 katalysiert die enantioselektive Hydroaminierung von chiralen racemischen 1,3‐disubstituierten Allenen mit N‐unsubstituierten Carbamaten, wobei N‐Allylcarbamate in guter Ausbeute, mit hoher Regio‐ und Diastereoselektivität und bis zu 92 % ee gebildet werden (siehe Schema; Cbz=Benzyloxycarbonyl).

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Recent exciting developments include the application of such substrates in intermolecular variants of this reaction. For example, the intermolecular enantioselective hydrocarbamation of allenes has also been achieved and impressively, racemic mixtures of 1,3-disubstituted allenes can be used as substrates to give chiral allylamines as products with good to excellent enantiomeric excesses (60-92% ee) (Scheme 15.84) [301]. Allene racemization under catalytic reaction conditions is rapid and there is evidence for the protected allylamine product affecting the nature of the catalytically active species as the reaction progresses, such that enantiomeric excesses are somewhat eroded by the completion of the reaction [301].…”

“…For example, the intermolecular enantioselective hydrocarbamation of allenes has also been achieved and impressively, racemic mixtures of 1,3-disubstituted allenes can be used as substrates to give chiral allylamines as products with good to excellent enantiomeric excesses (60-92% ee) (Scheme 15.84) [301]. Allene racemization under catalytic reaction conditions is rapid and there is evidence for the protected allylamine product affecting the nature of the catalytically active species as the reaction progresses, such that enantiomeric excesses are somewhat eroded by the completion of the reaction [301]. To address more challenging alkene substrates, Widenhoefer [127] showed in 2009 that cyclic ureas could be used as specialized substrates for the hydroureation of completely unactivated alkenes, including ethylene (as mentioned in Section 15.3.2), propylene, terminal alkenes, and the strained internal alkene of norbornene.…”

Enantioselective Rhodium‐Catalyzed Synthesis of Branched Allylic Amines by Intermolecular Hydroamination of Terminal Allenes

“…[5] Although the enantioselective intermolecular hydroamination of allenes would be an efficient method for the synthesis of a-chiral allylic amines, [6,7] only one example has been reported, which requires internal allenes, has a limited scope, and provides only moderate levels of enantioselectivity (Scheme 1 a). [8,9] To date, the enantioselective intermolecular hydroamination of mono-substituted allenes has not been reported, owing to the propensity of many hydroamination catalysts to form achiral products (either imines or linear allylic amines) from such substrates (Scheme 1 b). [10] Herein, we report the first example of the enantioselective intermolecular hydroamination of monosubstituted allenes, producing versatile branched allylic amines with perfect regioselectivity, high yield and good enantioselectivity (Scheme 1 c).…”

Synthesis of Chiral Aliphatic Amines through Asymmetric Hydrogenation

“…The preparation of a series of chiral amines that contain only aliphatic groups proved to be difficult. It is highly desired to develop simple and efficient synthetic strategies for the preparation of simple chiral aliphatic amine building blocks, such as those listed in Scheme 1 (1-8).Recently, Widenhoefer and co-workers [4] reported a new approach to synthesize chiral allylic amines through a goldcatalyzed intermolecular hydroamination of allenes with moderate yields and enantioselectivities. [2] In comparison with the known methods to generate chiral aromatic amines, less attention was devoted to the synthesis of chiral aliphatic amines.…”

“…Among the different types of chiral amines, chiral aliphatic amines are of particular interest, and they were found as key intermediates (1)(2)(3)(4)(5)(6)(7)(8) in drugs and drug candidates such as chloroquine, a corticotropin releasing factor (CRF) drug candidate, suvorexant, dolutegravir, atreleuron, and other biologically active molecules (9)(10)(11)(12)(13)(14)(15)(16)Scheme 1). It is highly desired to develop simple and efficient synthetic strategies for the preparation of simple chiral aliphatic amine building blocks, such as those listed in Scheme 1 (1)(2)(3)(4)(5)(6)(7)(8). Functionalized aliphatic amines are important chiral amines; aliphatic amines are exemplified by allylic amine, which can be converted to simple aliphatic amines.…”