Intermolecular Hydroamination of Allenes with N-Unsubstituted Carbamates Catalyzed by a Gold(I) N-Heterocyclic Carbene Complex

Abstract

Reaction of 2,3-pentadienyl benzoate and benzyl carbamate with a catalytic 1:1 mixture of (NHC) AuCl and AgOTf in dioxane at 23 °C for 5 h led to isolation of (E)-4-(benzyloxycarbonylamino)-2-pentenyl benzoate in 84% yield as a single regio-and diastereomer. Gold(I)-catalyzed hydroamination was effective for a number of N-unsubstituted carbamates and a range of substituted allenes.Allylic amines are components of many naturally occurring and biologically active molecules and are versatile building blocks for the synthesis of complex nitrogen-containing molecules. As a result, considerable effort has been directed toward the development of general and selective methods for the synthesis of allylic amines. 1,2 The transition metal-catalyzed addition of the N-H bond of an amine or carboxamide derivative across the C=C bond of an allene represents an attractive and atom economical approach to the synthesis of allylic amines. 3 However, whereas general and efficient methods for the intramolecular hydroamination of allenes have been developed, 4,5 the intermolecular hydroamination of allenes remains problematic and no methods are availavble that effectively employ ammonia or ammonia equivalents as nucleophiles. 6,7 Here we describe a general, regio-and stereoselective gold(I)-catalyzed protocol for the intermolecular hydroamination of allenes that employs Nunsubstituted carbamates as ammonia surrogates.We have developed an effective protocol for the intramolecular hydroamination of N-γ-and δ-allenyl carbamates catalyzed by a mixture of the gold phosphine complex (1)AuCl [1 = PtBu 2 o-biphenyl] 5 and AgOTf and a protocol for the intermolecular hydroalkoxylation of allenes with alcohols catalyzed by a mixture of the gold (NHC) complex (2)AuCl [2 = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine] and AgOTf (Scheme 1). 8,9 We therefore targeted (1) AuCl and (2) AuCl as precatalysts for the intermolecular hydroamination of allenes with Nunsubstituted carbamates. In an initial experiment, reaction of 3-methyl-1,2-butadiene (3) and benzyl carbamate catalyzed by a 1:1 mixture of (1)AuCl and AgOTf in dioxane at 23 °C for rwidenho@chem.duke.edu. Supporting Information Available: Experimental procedures and scans of NMR spectra for N-allylic carbamates (PDF). This material is available free of charge via the Internet at

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Espinet showed that acyclic carbenes can be used as ligands for Au(I) to realize intramolecular hydrocarbamation [240], while Widenhoefer has used the commercially available 1,3-bis[(2,6-diisopropylphenyl)imidazole-2-ylidine] (IPr) NHC in combination with cationic Au(I) to realize regioselective intermolecular hydroamination of 1,1-disubstituted allenes with benzyl carbamate to access allylamines with quaternary centers adjacent to N. This same catalyst can also accommodate 1,3-disubstituted allenes and even tetrasubstituted allenes (Table 15.19) [241]. Interestingly, these products are in contrast to the preferred products accessed with related Au(I)-phosphine complexes in combination with aniline substrates (Table 15.18) [239].…”

Gold‐Catalyzed Addition of Nitrogen and Sulfur Nucleophiles to CC Multiple Bonds

“…1-Alkylallenes, 1,1-, and 1,3-disubstituted allenes also underwent gold(I)-catalyzed hydroamination with morpholine, albeit with diminished efficiency and/or regioselectivity. Widenhoefer has reported the intermolecular hydroamination of allenes with Nunsubstituted carbamates catalyzed by a gold(I) N-heterocyclic carbene complex [41]. For example, reaction of 3-methyl-1,2-butadiene 57 with benzyl carbamate catalyzed by a 1 : 1 mixture of (IPr)AuCl and AgOTf in dioxane at 23 C for 24 h formed benzyl 1,1-dimethyl-2-propenylcarbamate in 93% isolated yield as a single regioisomer resulting from attack of benzyl carbamate at the more hindered terminus of 57 (Eq.…”

Regio‐ and Enantioselective Hydroamination of Dienes by Gold(I)/Menthol Cooperative Catalysis

“…[11] Our initial studies focused on the reaction of diene 1 with catalytic amounts cationic gold(I) complexes (see the Supporting Information for a complete list). While attempts to catalyze the reaction with triphenylphosphinegold(I) did not produce appreciable amounts of pyrrolidine (Table 1, entry 1), we were pleased to find that the combination of (R)-DTBM-SEGPHOS(AuCl) 2 (5) and AgBF 4 in dichloromethane gave pyrrolidine 2 exclusively in 5 % conversion after 24 hours (entry 2). After examining a variety of protecting groups on the nitrogen atom, we found that the Mbsprotected (Mbs = p-methoxy benzenesulfonyl) amine gave a small enhancement in reactivity (entry 3).…”

“…[1,2] While significant progress has been made in the asymmetric hydroamination of allenes, enantioselective goldcatalyzed hydroamination of simple alkenes and dienes has been limited to reactions in which urea is employed as a nucleophile. [3] Furthermore, as simple Brønsted acids are also known to be effective catalysts for alkene hydroamination [4] and gold(I) triflates are often employed in olefin activation, [5] the role of gold in these reactions is unclear. In 2009, we found that, in presence of stoichiometric amounts of base, alkylgold(I) complexes could be formed by gold-promoted addition of nitrogen nucleophiles to unactivated alkenes [Eq.…”