Carboxamide Derivatives as Nucleophiles

Widenhoefer and Han have reported an effective protocol for the intramolecular hydroamination of unactivated C=C bonds with carbamates [52]. As an example of this protocol, treatment of the N-y-alkenyl carbamate 76 with a catalytic 1 1 mixture of [P(f-Bu)2(o-biphenyl)]AuCl and AgOTf (5 mol%) in dioxane at 60 C for 22 h formed pyrrolidine 77 in 91% isolated yield as a 3.6 1 mixture of diastereomers (Eq. (11.43)). The protocol tolerated substitution at the internal olefinic carbon atom and along the alkyl backbone and the method was applied to the synthesis of both heterobicyclic compounds and piperidine derivatives. This protocol was subsequently expanded to include the intramolecular hydroamination of N-alkenyl carboxamides including 2-allyl aniline derivatives (Eq. (11.44)) [53]. 

Bender and Widenhoefer have reported the room temperature intramolecular hydroamination of unactivated alkenes with N,N -disubstituted ureas catalyzed by a gold(I) N-heterocyclic carbene complex [54], For example, treatment of 2-isopropyl-4-pentenyl urea 78 with a catalytic 1 1 mixture of (IPr)AuCl and AgOTf at room temperature for 22 h led to isolation of pyrroldine 79 in 98% yield as a 5.5 1 mixture of diastereomers (Eq. (11.45)). Gold(I) atalyzed hydroamination of N-4-pentenyl ureas tolerated substitution at the Cl or C4 carbon atoms and was effective for the cycHzation of unsubstituted 4-pentenyl ureas and 5-hexenyl ureas. Conversely, the method did not tolerate substitution at the terminal alkenyl carbon atom. 

In contrast to the hydroamination of alkenes with sulfonamides, the potential of an acid-catalyzed reaction pathway in the hydroamination of alkenes with carboxamide derivatives appears less likely. Hartwig found that the intramolecular hydroamination of alkenes with N-arylcarboxamides was only realized in the presence of stoichiometric amounts of triflic add [50]. In contrast, He reported that triflic add catalyzes the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate in toluene at 85 °C [55]. However, in the corresponding gold(I)-catalyzed transformation, the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate was markedly slower than was the intramolecular hydroamination of an N-4-pentenyl carbamate [52], which is inconsistent with the antidpated behavior of an acid-catalyzed pathway. Furthermore, control experiments firmly ruled out the presence of an acid-catalyzed reaction pathway in the gold(I)-catalyzed intramolecular hydroamination of alkenes with carboxamide derivates and ureas [53, 54]. 

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