Gold(I)‐Catalyzed Enantioselective Intramolecular Dehydrative Amination of Allylic Alcohols with Carbamates

Abstract

The transition-metal-catalyzed enantioselective amination of allylic esters and carbonates represents one of the most wellestablished routes to chiral, nonracemic allylic amines. [1] With the potential to condense synthetic sequences and reduce waste streams, the dehydrative amination of allylic alcohols as a route to enantiomerically enriched allylic amines has gained considerable interest. However, while the stereospecific amination of chiral secondary allylic alcohols has been demonstrated, [2][3][4] the enantioselective amination of allylic alcohols remains problematic. [5] Carreira et al. have reported the Ir I -catalyzed enantioselective amination of 1-cyclohexylprop-2-enol with sulfamic acid in 70 % ee. [6] Hartwig et al. have reported the Ir I /BPh 3 -catalyzed enantioselective intermolecular amination of primary allylic alcohols with aromatic amines with up to 94 % ee, but this method was restricted to cinnamyl alcohols in the absence of a stoichiometric Lewis acid promoter. [7] The groups of Yamamoto [8] and Kitamura [9] have independently reported the enantioselective intramolecular amination of allylic alcohols catalyzed by Hg II and Ru II complexes, respectively. However, these methods were restricted to sulfonamide nucleophiles and high enantioselectivity was realized only for the formation of arene-fused nitrogen heterocycles. Herein we report a gold-catalyzed protocol for the intramolecular enantioselective amination of allylic alcohols with carbamates to form five-and sixmembered aliphatic nitrogen heterocycles with up to 95 % ee.We recently reported the intramolecular dehydrative amination of allylic alcohols with alkylamines catalyzed by an achiral gold(I) phosphine complex. [4,10] Encouraged by the high efficiency and stereospecificity of this transformation and guided by both our previous work in the area of gold(I)catalyzed enantioselective allene hydroamination [11,12] and Bandinis recent demonstration of gold(I)-catalyzed enantioselective arylation [13] and alkoxylation [14] of allylic alcohols, [15] we targeted axially chiral bis(gold) complexes as catalysts for the intramolecular enantioselective amination of the ebenzylamino allylic alcohol (E)-1 a (Table 1). Unfortunately, optimization within this framework [16] proved largely unsuccessful: treatment of (E)-1 a with a catalytic 1:2 mixture of [(S)-2](AuCl) 2 and AgSbF 6 in dioxane at 25 8C for 5 h led to quantitative conversion to 2-vinylpyrrolidine 3 a, but with only 29 % ee (Table 1, entry 1). [17] We then focused our attention on the manipulation of the nitrogen nucleophile as a means to amplify stereoinduction (Table 1). These experiments proved fruitful and gold(I)-catalyzed cyclization of Fmoc-protected e-amino allylic alcohol (E)-1 g employing an optimized catalyst system comprised of [(S)-2](AuCl) 2 (2.5 mol %) and AgClO 4 (5 mol %) in dioxane at room temperature for 48 h led to the isolation of (S)-3 g in 95 % yield with 91 % ee (Table 1, entry 7). [16,18]

The Regio‐ and Stereospecific Intermolecular Dehydrative Alkoxylation of Allylic Alcohols Catalyzed by a Gold(I) N‐Heterocyclic Carbene Complex

“…Efficient 1,3-chirality transfer from chiral, non-racemic secondary allylic alcohols has been previously observed in the gold(I)-catalyzed inter- [23] and intramolecular [27] dehydrative amination and intramolecular dehydrative alkoxylation of allylic alcohols [13,14] We therefore sought to evaluate the extent of 1,3-chirality transfer in the gold-catalyzed intermolecular dehydrative alkoxylation of allylic alcohols. These experiments were conducted so that sufficient quantities of both the γ- and α-regioisomeric allylic ethers were isolated so that the stereoselectivity of both the primary and secondary reaction pathways could be evaluated.…”

Gold‐Catalyzed Allylation of Aryl Boronic Acids: Accessing Cross‐Coupling Reactivity with Gold

“…Because alternatives to the oxidative addition/reductive elimination process almost invariably necessitate distinct pathways to cross-and homocoupled products, examination of potential homocoupling processes can be used to discern between possible mechanistic scenarios (Scheme 7 A). [19] Of the likely mechanisms, radical clock experiments (Scheme 7 B) argue against the implication of radicals, while the stability of 9 to high temperatures argues against reductive homocoupling processes (cf. Table 1, entry 12).…”

Merging Synthesis and Enantioselective Functionalization of Indoles by a Gold‐Catalyzed Asymmetric Cascade Reaction

“…Interestingly, almost complete inversion of stereoinduction in the presence of the same enantiomer of the chiral ligand (−65 % ee , entry 10) was recorded, providing a clear insight into the S N 2′‐type mechanism of the final allylic alkylation ring closure 7f. 17 Last but not least, a range of acid–base additives and water scavengers were tested without any significant improvements in terms of both chemical as well as optical reaction outcome (see the Supporting Information for a complete list of results).…”