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43636-AC1
Platinum-Catalyzed Hydroamination in Unactivated Olefins
Platinum Catalysts for the Intramolecular Hydroamination of Alkenes. We have previously reported that a 1:2 mixture of [PtCl2(H2C=CH2)]2 and PPh3 catalyzes the intramolecular hydroamination of benzyl 4-pentenyl amines. Although platinum-catalyzed intramolecular hydroamination displayed good functional group compatibility, the procedure required reaction temperatures of 120 °C and displayed a limited substrate scope. For this reason, one of our objectives for the previous funding period was to identify more active catalyst systems for the intramolecular hydroamination of unactivated alkenes with alkyl amines. Toward this goal, we identified a pair of highly active platinum(II) complexes for the intramolecular hydroamination unactivated C=C bonds with secondary alkyl amines. In one successful approach, we identified simple platinum dichloride complexes modified with o-biphenyl ligands such as P(t-Bu)2(o-biphenyl) (1) as highly active catalysts for the hydroamination of alkenes. For example, reaction of (1-allylcyclohexylmethyl)benzylamine (2) with a catalytic 1:1 mixture of PtCl2 and 1 in diglyme at 60 °C for 10 h led to isolation of 2-benzyl-3-methyl-2-aza-spiro[4.5]decane (3) in 86% yield after Kugelrohr distillation. Both unsubstituted 4-pentyl amines, which failed to cyclize in the presence of PtCl2/PPh3, and 5-hexenylamines, which underwent hydroamination in the presence of PtCl2/PPh3 in modest yield due to competitive alkene isomerization, underwent hydroamination in the presence of PtCl2/1 in quantitative yield within 3 h at 80 °C. In a second approach, we identified cationic platinum complexes that contain bidentate ligands such as the platinum diimine complex PtCl2[ArN=C(Me)C(Me)=NAr] [Ar = 2-C6H4(4-C6H5CF3)] (4) as highly effective precatalysts for alkene hydroamination. For example, treatment of alkenyl amine 2 with a catalytic 1:1 mixture of 4 (5 mol %) and AgOTf (5 mol %) at 80 °C for 24 h led to complete consumption of 2 to form 3 in 96% yield (GC).
Room temperature hydroamination of alkenes with urea derivatives. We have previously reported that the gold phosphine complex Au(1)Cl was an effective precatalyst for the intramolecular hydroamination of N-(γ-alkenyl)carbamates and related derivatives to form functionalized nitrogen heterocycles. As an example, treatment of benzyl (2,2-diphenyl-4-pentenyl)carbamate with a catalytic 1:1 mixture of Au(1)Cl and AgOTf (5 mol%) in dioxane at 60 °C for 18 h led to isolation of benzyl 4,4-diphenyl-2-methylpyrrolidine-1-carboxylate in 97% yield. During the most recent funding period, one of our key objectives was to identify more active and more selective Au(I) catalysts for the intramolecular hydroamination of alkenes. Toward this goal, we explored the application of N-heterocyclic carbenes as supporting ligands for the gold(I)-catalyzed hydroamination of alkenes with carboxamide deriviatves. From these efforts, we identified the gold carbene complex Au(5)Cl [5 = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine] as an exceptionally active catalyst mixture for the room temperatuure intramolecular hydroamination of 4-pentenyl and 5-hexenyl ureas. For example, reaction of N-(2,2-diphenyl-4-pentenyl)-N'-phenylurea with a 1:1 mixture of Au(5)Cl and AgOTf at room temperature for 18 h led to intramolecular hydroamination and isolation of phenyl 2-methyl-4,4-diphenyl-pyrrolidine-1-carboxlamide in 96% yield. Both N'-aryl and N'-alkyl N4-pentenyl ureas underwent intramolecular hydroamination at room temperature in high yield in the presence of a catalytic amount of Au(5)Cl/AgOTf. The Au(5)Cl/AgOTf catalyst system was sufficiently active such that efficient hydroamination was realized with 1 mol % of the catalyst mixture. Furthermore, neither the rate nor the yield of hydroamination was affected by the presence of a large excess of water or air in the reaction mixture. Gold-catalyzed hydroamination of 4-pentenyl ureas monosubstituted at the C(1) or C(2) position formed substituted pyrrolidines that possessed a cis-2,5 or cis-2,4 substitution pattern, respectively, with up to 5.5:1 diastereoselectivity. Gold-catalyzed hydroamination of alkenyl ureas also tolerated substitution at the internal olefinic carbon atom and was effective for the cyclization of 4-pentenyl ureas that possessed no substitution on the alkyl chain that tethered the C=C moiety to the urea nucleophile. 5-Hexenyl ureas also underwent room temperature hydroamination in the presence of Au(5)Cl/AgOTf to form the corresponding piperidine derivative in excellent yields.
