Pd-Catalyzed Alkene Diamination Reactions of Nitrogen Electrophiles: Synthesis of Cyclic Guanidines and Ureas Bearing Dialkylaminomethyl Groups

Abstract

The Pd-catalyzed coupling of N-allylguanidines or N-allylureas with O-benzoylhydroxylamine derivatives affords cyclic guanidines or cyclic ureas bearing dialkylaminomethyl groups. The desired products are obtained in good yield, and substrates bearing substituents at the allylic position are transformed with moderate diastereoselectivity. The mechanism of these reactions appears to involve anti-aminopalladation of the alkene, followed by a rare spC-spN bond-forming reductive elimination from an alkylpalladium complex that contains β-hydrogen atoms.

Pd-Catalyzed Alkene Difunctionalization Reactions of Enolates for the Synthesis of Substituted Bicyclic Cyclopentanes

“…However, use of the wide-bite-angle ligand Dpe-Phos afforded the desired product in 65% yield when LiHMDS was employed as the base. We then examined Pd­(acac) 2 as a precatalyst, as we previously observed increased efficiency in other transformations when this precatalyst was used . The combination of Pd­(acac) 2 with SPhos provided the best results, affording 7p in 79% yield with >20:1 dr.…”

“…We then examined Pd(acac) 2 as a precatalyst, as we previously observed increased efficiency in other transformations when this precatalyst was used. 13 The Scheme 2. Reactions of Aryl Triflates with Malonates a,b,c a Conditions: 1.0 equiv of 5, 1.2 equiv of diethyl malonate, 1.4 equiv of LiO t Bu, 4 mol % Pd(OAc) 2 , 6 mol % BrettPhos, toluene (0.1 M), 95 °C, 16 h. Reactions were conducted on a 0.1−0.25 mmol scale.…”

“…All of the reagents, palladium precatalysts, and ligands were purchased from commercial sources and used without further purification unless otherwise noted. Substrates 1a – e , 1f , 1g , 5a , 5c , 5d , 8 , 10 , 16 , (BrettPhos)­Pd­(allyl)­(Cl), N -(2-pyridyl)­triflimide, 4- tert -butyl-2-allylphenol, and allyl 1-methyl-2-oxocyclohexane-1-carboxylate were prepared by previously published methods. Alkenyl triflate starting materials were stored in a freezer under nitrogen.…”

“…1 H NMR (500 MHz, CDCl 3 ): δ 7.32−7.25 (m, 2H), 7.19−7.14 (m, 1H), 5.98−5.87 (m, 1H), 5.18−5.09 (m, 2H), 3.47 (d, J = 6.6 Hz, 2H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl 3 ): δ 151. 5, 145.7, 134.9, 131.9, 128.3, 125.1, 120.7, 118.5 (q, J C−F = 321 Hz) 117.2,77.2,34.7,34.3,31.2…”

Synthesis of Five-Membered Cyclic Guanidines via Cascade [3 + 2] Cycloaddition of α-Haloamides with Organo-cyanamides

“…These classical methods for guanidine synthesis often have drawbacks such as limited availability of starting materials, low yields, harsh conditions, and generation of undesired byproducts. Recently, transition-metal-promoted intramolecular C–N bond formation via hydroamination, carboamination, diamination, and haloamination of N -propargylguanidines or N -allylguanidines have become powerful synthetic strategies to construct cyclic guanidines (Scheme A, eq 1). Besides, cycloguanidination of alkenes has emerged as an efficient route for the synthesis of five-membered cyclic guanidines (Scheme A, eq 2) .…”