Research Article pubs.acs.org/acscatalysis
Brønsted Acid Cocatalysis in Copper(I)-Photocatalyzed α‑Amino C−H Bond Functionalization Thomas P. Nicholls, Grace E. Constable, Johnathon C. Robertson, Michael G. Gardiner, and Alex C. Bissember* School of Physical Sciences-Chemistry, University of Tasmania, Hobart, Tasmania 7001, Australia S Supporting Information *
ABSTRACT: We have exploited a bis(1,10-phenanthroline)copper(I) visible light photocatalyst (VLP), [Cu(dap)2]+, to effect the direct α-C−H functionalization of amines. To our knowledge, this represents the first example of the oxidation of amines that are ultimately incorporated into synthetic targets by a copper(I) VLP. We have utilized this approach to rapidly prepare unprecedented octahydroisoquinolino[2,1-a]pyrrolo[3,4-c]quinoline frameworks and exploited this process to synthesize a novel aglycone analogue of the natural product incargranine B. Most significantly, our studies suggest that the presence of trifluoroacetic acid (TFA) is crucial in mediating the aerobic oxidative quenching of a putative photoexcited copper(I) species involved in the catalytic cycle. KEYWORDS: photocatalysis, [Cu(dap)2]Cl, trifluoroacetic acid, aerobic oxidation, visible light
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(2) (Figure 1).5 Interestingly, despite the particularly strong reducing properties of this class of VLPs,6 the synthetic applications of these systems in photocatalysis are conspicuously rare in the scientific literature. In fact, since Sauvage’s work in 1987,5 to our knowledge, there have only been a relatively small number of reports using [Cu(dap)2]+, or its analogues, as a VLP in organic synthesis, and all have appeared since 2012.7 The dearth of synthetic processes utilizing these copper-based VLPs may, in part, derive from intrinsic (unfavorable) properties that are traditionally associated with [Cu(dap)2]+ and this class of complexes. Specifically, their typically lower stability in the presence of nucleophiles and coordinating solvents relative to germane ruthenium and iridium complexes3a−c derives, in part, from the pronounced structural changes that accompany oxidation of the Cu(I) center upon photoexcitation.3 These characteristics often lead to complexes featuring lower quantum yields and shorter excited-state lifetimes relative to other systems.8,9 In addition, unlike [Ru(bpy)3]2+, [Cu(dap)2]+ cannot mediate photocatalyzed reactions via a reductive quenching cycle.3d While this last feature may be regarded as a limitation, this property of [Cu(dap)2]+ can potentially facilitate more tractable mechanistic investigations of VLP-mediated transformations, as the involvement of a reductive quenching cycle can be eliminated. As part of nascent research programs in our laboratory that are concerned with expanding the scope and applications of Cu(I) VLPs in organic synthesis, we sought to investigate whether [Cu(dap)2]+ could promote the direct α-
INTRODUCTION A particular focus of catalysis and organic synthesis, more generally, involves the identification and investigation of new methods for the direct synthesis of complex molecules. One area that has recently received significant (and renewed) interest features the development of new chemical reactions by employing metal-based visible light photocatalysts (VLPs).1 The prototypical complex [Ru(bpy)3]2+ (1) (Figure 1), first
Figure 1. [Ru(bpy)3]2+ (1) and [Cu(dap)2]+ (2).
reported over 75 years ago,2 is arguably the most well-known and most widely used metal-based photoredox catalyst in synthetic organic chemistry. This structural motif has served as a template for the design of an array of structurally related transition-metal-based VLPs which typically rely on the reactivity of precious second- and third-row transition metals.1 However, examples of viable VLPs in organic synthesis that utilize cheap, abundant base metals, such as copper, are far less common.3 In 1977, McMillin reported the preparation of a class of photoactive, bis(2,9-disubstituted-1,10-phenanthroline)copper(I) complexes featuring distorted-tetrahedral geometries.3,4 Ten years later, Sauvage disclosed the first synthesis of [Cu(dap)2]+ © XXXX American Chemical Society
Received: September 11, 2015 Revised: November 30, 2015
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DOI: 10.1021/acscatal.5b02014 ACS Catal. 2016, 6, 451−457
Research Article
ACS Catalysis C−H bond functionalization of amines. It is established that these processes can be facilitated by traditional second- and third-row transition-metal-based VLPs such as [Ru(bpy)3]2+.1c−e,i In this report, we describe the use of [Cu(dap)2]Cl to effect annulation reactions of N,N-dialkylanilines and N-aryltetrahydroisoquinolines with electron-deficient alkenes in order to rapidly furnish a range of annulated tetrahydroquinolines and tetrahydroisoquinolines at room temperature (Scheme 1). To our knowledge, this is the first
that this species could be reduced by N,N-dimethylaniline to regenerate [Cu(dap)2]+ and ultimately form an α-amino radical leading to the tetrahydroquinoline product. Although our aforementioned hypothesis required some nuance, it ultimately led to the development of a successful process. Hence, after examining a range of reaction parameters, we were pleased to find that [Cu(dap)2]Cl enables the reaction of N-phenylmaleimide with N,N-dimethylaniline to directly provide a tetrahydroquinoline in good yield (Table 1, entry 1).
Scheme 1. Standard Conditions for the Synthesis of Annulated Heterocycles
Table 1. Copper-Catalyzed Reaction of N-Phenylmaleimide with N,N-Dimethylaniline: Influence of Reaction Parameters
example of the direct functionalization of α-amino C−H bonds (that are ultimately incorporated into synthetic targets) mediated by a copper-based VLP. Furthermore, during the course of this study, the unforeseen and profoundly important role performed by trifluoroacetic acid (TFA) in this process was identified and investigated.
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RESULTS AND DISCUSSION In 2012, Bian and co-workers reported the synthesis of various annulated tetrahydroquinolines by the reaction of N,Nalkylanilines and a number of N-substituted maleimides in the presence of [Ru(bpy)3]2+ (1) or iridium-based VLPs in low to high yields.10,11 This process represents a powerful transformation in which two C−H bonds are cleaved (including an “unactivated” aryl C−H bond), two new C−C bonds are formed, and up to three contiguous stereocenters can be created in a single step. It is proposed that the aforementioned reaction exploits the reductive quenching cycle of [Ru(bpy)3]2+.10a Because the analogous pathway is not viable for photocatalysis employing [Cu(dap)2]+, we were interested in investigating whether this transformation could also be effected by exploiting the oxidative quenching cycle of [Cu(dap)2]+.3d Indeed, we anticipated that upon irradiation with visible light at ambient temperature, in the presence of air, the ensuing [Cu*(dap)2]+ complex could undergo aerobic oxidation to provide [Cu(dap)2]2+ (Figure 2).12 We believed
entry
variation from the “standard” conditions
yield (%)a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
none no [Cu(dap)2]Cl no hν no [Cu(dap)2]Cl and no hν no TFA 0.1 equiv TFA 1% [Cu(dap)2]Cl 10% dap, instead of 5% [Cu(dap)2]Cl 5% CuCl2, instead of 5% [Cu(dap)2Cl 5% CuCl, instead of 5% [Cu(dap)2]Cl 5% Cu(OTf)2, instead of 5% [Cu(dap)2]Cl CH3CN, instead of DMF 1.2 equiv N,N-dimethylaniline 23 W CFL, instead of green LED 10 equiv H2O under N2, instead of air
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