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Insights into Alkene Activation by Gold: Nucleophile Activation with Base as a Trigger for Generation of Lewis Acidic Gold Yuyang Zhu, Wentong Zhou, Ellen M. Petryna, Brock R. Rogers, Cynthia S Day, and Amanda C Jones ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01674 • Publication Date (Web): 15 Sep 2016 Downloaded from http://pubs.acs.org on September 15, 2016
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ACS Catalysis
Insights into Alkene Activation by Gold: Nucleophile Activation with Base as a Trigger for Generation of Lewis Acidic Gold Yuyang Zhu,† Wentong Zhou, Ellen M. Petryna, Brock R. Rogers, Cynthia S. Day and Amanda C. Jones* Department of Chemistry, Wake Forest University, Salem Hall, Box 7486, Winston-Salem, North Carolina 27109, United States.
Supporting Information Placeholder ABSTRACT: Previously, the generation of alkyl gold intermediates (B) from nucleophilic addition to inactivated alkenes was limited by the use of trigold oxo complexes (A) with arylphosphine ligands, [(Ar3PAu)3O]BF4, in the presence of amine base. In this mechanism study we have found that the basicity of the gold complex is key to favoring alkyl gold complex formation. Kinetic and substrate studies have shown that the strongly Brønsted basic IPrAuOH also mediates alkyl gold complex formation. The observation of an intermediate gold amide complex suggests these processes are initiated by deprotonation of the nucleophile. Trigold oxo reactions in the absence of base reveal that the byproduct from the reaction of substrate with A is digold hydroxide complex, [(LAu)2OH]BF4 (C). This complex is catalytically active for urea hydroamination at room temperature to form pyrrolidine D, however, it does not catalyze the hydroalkoxylation of the alcohol substrate. Importantly, catalysis to D occurs faster than can be accounted for by alkyl gold protodeauration, and the alkyl gold does not react significantly on the catalyzed timescales observed. Pre-formed gold triethylamine complexes are not reactive towards alkenyl alcohols, however when alkenyl urea was treated with gold triethylamine complex [Ph3PAu(NEt3)]SbF6, a similar case was observed, of alkyl gold formation triggering the initiation of a pathway to form D. These results show that Brønsted basic conditions highly favor the formation of alkyl gold intermediates by a process that incorporates both nucleophile and π-activation. Additional experiments support the conclusion that the alkyl gold intermediates are not productive structures en route to pyrrolidine D. Work by Nolan et al. suggests that C is not simply a Brønsted Acid, but rather a source of cationic gold and gold hydroxide (L-Au-OH). Alkene gold activation modes that do not involve protodeauration of discrete alkyl gold intermediates must be considered more carefully in future studies. Keywords: gold catalysis, alkene hydroamination, alkyl gold, mechanisms, homogeneous catalysis.
1. INTRODUCTION The activation of π-bonds is ubiquitous in cationic gold(I) catalyzed reactions. In a landmark 2008 report, Hammond and et al. isolated a vinyl gold intermediate from an intramolecular allenoate cyclization, providing the first proof of the metal’s activating ability.1 Since then, a number of additional vinyl gold intermediates have been isolated and their preparation has become routine for examining gold-catalyzed additions to alkynes and allenes.2 In contrast, for control experiments requiring validation of alkyl gold intermediates,3 there is only one method.4 In Toste’s pioneering report, treatment of alkenyl amines, ureas (e.g. 1), and carbamates with [(Ph3PAu)3O]BF4 in the presence of triethylamine re-
sulted in facile aminoauration to generate β-N substituted alkyl gold complexes (Scheme 1). An important observation during this study was the facile reversion of 2a upon treatment with acid to regenerate starting alkene 1, which was followed by slow hydroamination to form the corresponding pyrrolidine. As many early alkene addition reactions were already suggested to be catalyzed solely by Brønsted acid,5 the lack of clear evidence for protodeauration has led to alternative proposals for activation, including some that require gold cooperation. For example, Toste and co-workers also reported a Brønsted acid catalyzed diene hydroamination, whereby they proposed that the operative catalyst was alcohol acidified by coordination to gold.6 Nevertheless, a number of mechanistic facets of gold-based alkene activation
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remain to be clarified, and the general gold-catalyzed mechanism shown in Scheme 1, where protodeauration of a Au3 C(sp ) bond follows nucleophilic addition to a gold coordinated alkene, continues to hold sway in the literature. In light of the importance of alkene activation in organic synthesis and in particular, the continuing development of asymmetric methods for gold catalyzed hydroamination,7 we sought to further explore the details of this process.
Scheme 1. Alkyl gold control experiments reported by Toste et al.4 and typically proposed catalytic cycle for gold(I) alkene hydroamination. O O NHt-Bu N
Ph
H
Ph
[(PPh3Au)3O]BF4 (3a) 2.0 equiv Et3N CDCl3, RT
NHt-Bu N Ph Ph
Au
TsOH
PPh3
1
2a R
H Ph
R
H
N
N
Ph
Ph
Ph L
Au
LAu
Ph Ph
R
H
R
N
N CH3
Protodeauration?
Ph Ph
Figure 1. Plots for the formation of alkyl gold complexes 2a and 5a from urea 1 and alcohol 4. Conditions are substrate (0.04 M) with 0.33 equivalents of trigold oxo 3a, 2 equivalents of triethylamine in CDCl3 at room temperature. Although it is not yet clear why decomposition is more significant with the alcohol substrate, a serendipitous set of experiments provided revealing hints about the mechanistic processes involved (Scheme 2). These experiments suggested + that the inherent basicity of (LAu)3O is key to successful alkyl gold complex formation. Observations are as follows: a)
As also shown by Maier,9 triethylamine does not displace an equivalent of gold cation from [(Ph3PAu)3O]BF4 (3a) and independently prepared triethylamine complex [Ph3PAuNEt3]SbF6 (9a)mediates the cyclization of alcohol 4 only minimally (ca 7% formation after 13.5 h).10
b)
When 4 was treated with trigold oxo complex 3b (L=JohnPhos) in the absence of base, 5b was generated in combination with digold hydroxide complex 6b 1 (a tell-tale triplet appeared at −0.36 ppm in the H 9 NMR spectrum). For the same reaction with L=PPh3, a small amount of 5a was formed (
