Palladium-Catalyzed Vinylation of Aminals with Simple Alkenes: A New Strategy To Construct Allylamines

Abstract

A novel, highly selective palladium-catalyzed vinylation reaction for the direct synthesis of allylic amines from styrenes and aminals has been established. The utility of this method was also demonstrated by the rapid synthesis of cinnarizine from aldehydes, amines, and simple alkenes in one-pot manner. Mechanistic studies suggested that the reaction proceeds through a valuable cyclometalated Pd(II) complex generated by the oxidative addition of aminal to a Pd(0) species.

Pentacoordinated Carboxylate π‐Allyl Nickel Complexes as Key Intermediates for the Ni‐Catalyzed Direct Amination of Allylic Alcohols

“…N ‐Allylaniline ( 3 ac ):27 1 H NMR (400 MHz, CDCl 3 , 30 °C): δ =7.21–7.18 (m, 2 H, aromatic), 6.75–6.64 (m, 3 H, aromatic), 6.03–5.93 (m, 1 H, CH 2 C H CH 2 ), 5.33–5.28 (m, 1 H, CH H CHCH 2 ), 5.20–5.17 (m, 1 H, C H HCHCH 2 ), 4.17–3.47 (m, 3 H, N H and CHC H 2 N); 13 C NMR (100 MHz, CDCl 3 , 30 °C): δ =140.0, 136.5, 128.6, 128.4, 127.2, 116.5, 53.2, 51.7 ppm.…”

“…N ‐Allyl‐4‐methoxyaniline ( 3 ae ):27 1 H NMR (400 MHz, CDCl 3 , 30 °C): δ =6.82 (d, J =8.8 Hz, 2 H, aromatic), 6.63 (d, J =8.8 Hz, 2 H, aromatic), 6.00 (tdd, J =17.2, 10.3, 5.1 Hz, 1 H, CH 2 C H CH 2 ), 5.31 (d, J =17.3 Hz, 1 H, CH H CHCH 2 ), 5.19 (d, J =10.3 Hz, 1 H, C H HCHCH 2 ), 3.77 (s, 3 H, ArOC H 3 ), 3.75 (d, J =5.3 Hz, 2 H, CHC H 2 N), 3.49 ppm (br s, 1 H, NH); 13 C NMR (100 MHz, CDCl 3 , 30 °C): δ =152.3, 142.3, 135.9, 116.1, 114.9, 114.4, 55.8, 47.6 ppm.…”

“…N ‐Allyl‐4‐trifluoromethylaniline ( 3 af ):27 1 H NMR (400 MHz, CDCl 3 , 30 °C): δ =7.41 (d, J =8.4 Hz, 2 H, aromatic), 6.65 (d, 8.4 Hz, 2 H, aromatic), 5.93 (tdd, J =17.2, 10.3, 5.1 Hz, 1 H, CH 2 =C H CH 2 ), 5.29 (m, 1 H, C H HCHCH 2 ), 5.21 (m, 1 H, CH H CHCH 2 ), 4.64 (br s, 1 H, NH), 3.82 ppm (m, 2 H, CHCH 2 N); 13 C NMR (100 MHz, CDCl 3 , 30 °C): δ =150.7, 134.6, 129.2, 126.7 (q, J CF =3.7 Hz), 125.2 (q, J CF =270.0 Hz), 119.1 (q, J CF =32.5 Hz), 116.8, 112.2, 46.1 ppm; 19 F NMR (377 MHz, CDCl 3 , 30 °C): δ =60.1 ppm.…”

Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C−N Bond Cleavage

“…[5c] The one-pot three-component reaction of 1,2,4-trifluorobenzene, DABCO,a nd [1,2,4]triazolo [4,3-a]pyridine-3-thiolw as successfully realized to provide the desired drug in 55 %y ield under 180 8 8Cfor 72 h(Scheme 4). Thereaction time could be shortened to 20 hu nder microwave heating to afford the desired product in 52 %y ield.…”

“…[1,2] Crucial to the successful development of these reactions is the identification of an active species or ap rocess that can trigger subsequent multiple bond formations with several reactants.I np rinciple,C À Nb ond cleavage could simultaneously produce two active reactive species (carbon and nitrogen nucleophiles), [3,4] which might be utilized to trigger am ulticomponent reaction under appropriate reaction conditions.H owever,t he realization of such ar eaction remains ac hallenge owing to the formidable challenge of activating simple C À Nb onds.H erein, we report that cyclic tertiary amines can act as ak ey component for initiating am ulticomponent reaction enabled by facile CÀNbond cleavage,in which av aluable sulfur atom is efficiently incorporated with simple and inexpensive Na 2 Sa st he sulfur source.S uch areaction would be particularly valuable for the synthesis of piperazine-and sulfur-containing molecules,which represent ubiquitous motifs that are widely found in natural products and medicinal compounds ( Figure 1). [1,2] Crucial to the successful development of these reactions is the identification of an active species or ap rocess that can trigger subsequent multiple bond formations with several reactants.I np rinciple,C À Nb ond cleavage could simultaneously produce two active reactive species (carbon and nitrogen nucleophiles), [3,4] which might be utilized to trigger am ulticomponent reaction under appropriate reaction conditions.H owever,t he realization of such ar eaction remains ac hallenge owing to the formidable challenge of activating simple C À Nb onds.H erein, we report that cyclic tertiary amines can act as ak ey component for initiating am ulticomponent reaction enabled by facile CÀNbond cleavage,in which av aluable sulfur atom is efficiently incorporated with simple and inexpensive Na 2 Sa st he sulfur source.S uch areaction would be particularly valuable for the synthesis of piperazine-and sulfur-containing molecules,which represent ubiquitous motifs that are widely found in natural products and medicinal compounds ( Figure 1).…”