Efficient Synthesis of Allylic Amines from α-Aminoalkyl Cuprates and Enol Triflates

Abstract

Allylic amines 1 are an important class of compounds in organic synthesis as evidenced by the continuing development of numerous methods for their preparation. 2-12 A characteristic feature of these methods is the narrow range of applicability for generating a wide array of substitution patterns in both cyclic and acyclic amines. It appears that a simple, regioselective synthetic route to allylic amines of diverse substitution patterns is unavailable. We now report that R-aminoalkyl cuprates prepared from CuCN and 2 equiv of tert-butoxycarbonyl-protected R-amino organolithium reagents undergo substitution reactions with enol triflates to afford a direct and efficient synthesis of allylic amines.Organocopper reagents are a powerful tool in the arsenal of synthetic organic chemists, and innovative developments continue to emerge. 13 The reaction of enol triflates with organocuprates 14a,b has recently been extended to allylcuprate 14c reagents. Recently, we reported 15 the development of R-aminoalkyl cuprates as useful reagents for conjugate addition reactions and now report that these reagents undergo substitution reactions with enol triflates to afford allylic amines in good to excellent yields (eq 1). The enol triflates used in this study were readily prepared by established procedures. 16

Allylic Amination

“…Instead we refer to the review and some of the papers which have appeared since then. [9][10][11][12][13][14][15][16][17][18][19] One way to obtain chiral allylamines is by transformation of compounds from the chiral pool and a recent example is the degradation of R-amino acids as shown in Scheme 2. 20 Through reduction and concomitant Wittig reaction, optically active allylamines could be obtained in 48-78% yield depending on the structure of the starting amino acid.…”

“…A few examples of the indirect approaches will be mentioned here (Schemes and ), otherwise these and related methods will not be discussed any further. Instead we refer to the review and some of the papers which have appeared since then. −

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Heteroatomcuprates and α‐Heteroatomalkylcuprates in Organic Synthesis

“…Reagents prepared from copper cyanide (R 2 CuLiÁLiCN or RCuCNLi) or CuCl (RCuÁLiCl) react with alkyl, aryl, and alkenyl acid chlorides to afford a-amino ketones in good to excellent yields [166]. Substitution reactions between a-aminoalkylcuprates and acid chlorides [166], vinyl triflates [167], and vinyl iodides (Boc ¼ t-butoxycarbonyl) [168]. Substitution reactions between a-aminoalkylcuprates and acid chlorides [166], vinyl triflates [167], and vinyl iodides (Boc ¼ t-butoxycarbonyl) [168].…”

“…a-Aminoalkylcuprates prepared from CuI, CucCC 4 H 9 , CuMe, or CuPPh 2 and a-lithiocarbamates gave low to moderate yields of allylic amines on treatment with vinyl triflates prepared from cyclic ketones [167]. a-Aminoalkylcuprates prepared from CuI, CucCC 4 H 9 , CuMe, or CuPPh 2 and a-lithiocarbamates gave low to moderate yields of allylic amines on treatment with vinyl triflates prepared from cyclic ketones [167].…”

Synthesis of Allylic and Propargylic Primary Amines by Reaction of Organometallic Reagents with α-Amidoalkyl Sulfones

“…Allylic and propargylic amines play a prominent role in organic synthesis, and their importance continues to grow with time . A plethora of synthetic methods have been devised for the preparation of allylic amines, including substitution reactions with nucleophilic nitrogen, use of azallylic anions, coupling reactions, and palladium-catalyzed reactions . Similar approaches can also be used for the synthesis of propargylamines, but the most reliable and efficient method for the preparation of allylic and propargylic amines still remains the addition of an appropriate organometallic reagent to imino derivatives …”