Letter pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Photochemically-Mediated, Nickel-Catalyzed Synthesis of N‑(Hetero)aryl Sulfamate Esters J. Miles Blackburn, Anastasia L. Gant Kanegusuku, Georgia E. Scott, and Jennifer L. Roizen* Department of Chemistry, Duke University, Box 90346, Durham, North Carolina 27708-0354, United States
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S Supporting Information *
ABSTRACT: A general method is described for the coupling of (hetero)aryl bromides with O-alkyl sulfamate esters. The protocol relies on catalytic amounts of nickel and photoexcitable iridium complexes and proceeds under visible light irradiation at ambient temperature. This technology engages a broad range of simple and complex O-alkyl sulfamate ester substrates under mild conditions. Furthermore, it is possible to avoid undesirable N-alkylation, which was found to plague palladium-based protocols for N-arylation of O-alkyl sulfamate esters. These investigations represent the first use of sulfamate esters as nucleophiles in transition metal-catalyzed C−N coupling processes. Scheme 1. Access to N-(Hetero)aryl Sulfamate Esters Remains Limited Despite Recent Strategic Innovations
N
itrogen-containing small molecules, including arylamines, are valuable given their importance as bioactive agents.1 While a variety of methods exist to access many Nalkyl, N-aryl, N-acyl, and N-sulfonyl aniline derivatives, examples of N-aryl sulfamate esters remain limited, as userf riendly and ef f icient preparations of N-aryl sulfamate esters have only recently emerged (Scheme 1).2 Unfortunately, these strategies often engage multistep reaction sequences and use highly reactive reagents, which may detract from their utility. Furthermore, using these approaches, preparations of sulfamate esters featuring Lewis basic N-heteroaromatic substituents are exceedingly rare, despite the importance of heteroaryl motifs in medicinally relevant small molecules.3 Because of these limitations, a transition metal-catalyzed protocol capable of coupling easily prepared primary sulfamate esters with widely available (hetero)aryl halide electrophiles would expand the accessibility of elusive N-(hetero)aryl sulfamate esters.4 Transition metal-catalyzed C(sp2)−N bond-forming reactions have revolutionized access to arylamines and are among the most practiced synthetic manipulations in both academic and industrial settings.5 The majority of transformations developed to convert (hetero)aryl halide substrates to valuable aniline derivatives feature palladium-based catalysts.6 In addition to traditional aliphatic amines, advances in the Buchwald−Hartwig reaction have enabled the efficient coupling of a variety of less nucleophilic substrates, including amides, carbamates, sulfonamides, and sulfamides.7 While sulfamate esters are employed as electrophilic components in a variety of transition metal-mediated cross-coupling manifolds,8 © XXXX American Chemical Society
sulfamate esters have not been described as viable nucleophiles within these transformations. Because of their low nucleophilicity, even examples of their use as substrates in SNAr reactions are rare.2g Received: July 25, 2019
A
DOI: 10.1021/acs.orglett.9b02621 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
(Scheme 2). Despite the remarkable potential offered by this dual-catalytic approach, the range of nitrogen-based nucleophiles has been limited to those previously known to efficiently engage in palladium-catalyzed processes. To date, only amines, sulfonamides, amides, and carbamates, which are substrates tolerated in analogous palladium-mediated processes, have been employed in these light-enabled, nickel-catalyzed reactions.11 Herein disclosed is the first general N-(hetero)arylation reaction featuring sulfamate esters as nucleophilic components. It provides broad access to O-alkyl sulfamate esters bearing both N-aryl and N-heteroaryl substituents. This protocol employs readily available substrates and reagents and proceeds under mild conditions. This process highlights the chemically distinct reactivity afforded by the dual-catalyzed reaction manifold and provides access to N-(hetero)aryl sulfamate esters, which have traditionally been underexplored, presumably because of their challenging preparation. Initial investigations to develop this N-(hetero)arylation process employed 1a as a model substrate and 4-(trifluoromethyl)bromobenzene as an electrophile (Table 1). Utilizing previously reported conditions,11d,e 1.5 equiv of sulfamate 1a was treated with 1.0 equiv of bromoarene, photoactive [Ir(ppy)2(dtbbpy)]PF6 (1 mol %), NiBr2·glyme (5 mol %), and tetramethylguanidine (TMG) as a base and furnished the desired N-arylated product 2a in 18% yield (entry 1). Importantly, the formation of the undesired N-alkylated byproducts 3a and 3b was suppressed, as unreacted 1a primarily accounted for the remaining mass balance using this dual-catalytic manifold. When 3.0 equiv of DBU was employed, full conversion to the desired N-aryl sulfamate 2a was observed (entry 4).12 Either the sulfamate ester or aryl bromide could be used as the limiting substrate (entries 4 and 6), which may be an important consideration depending on the relative accessibilities of the requisite starting materials. Equimolar amounts of the two substrates could be employed, albeit with a slight decrease in the reaction yield (entry 7).
Given that similarly nucleophilic sulfonamide and sulfamide substrates have previously been disclosed as effective components in palladium-catalyzed C(sp2)−N coupling reactions,7 we questioned whether sulfamate esters would serve as capable nucleophiles under Buchwald−Hartwig amination conditions. Unfortunately, when these established protocols were used, the N-arylation of pentyl sulfamate (1a) was found to proceed in poor yield (Scheme 2). Furthermore, Scheme 2. When Applied to Sulfamate Esters, PalladiumCatalyzed N-Arylation Protocols Generate Undesired Byproducts
N-alkylated byproducts 3a and 3b were observed to form via a competitive decomposition pathway, indicating a potential barrier to the elucidation of an efficient palladium-catalyzed protocol. Compared with palladium-mediated C(sp2)−N bondforming methods, fewer technologies rely on nickel catalysis.9 Such transformations often require a challenging reductive elimination step from Ni(II)−amido complexes, which can demonstrate increased thermal stability.10 Recently, photochemically-driven, nickel-catalyzed strategies have emerged as an approach to facilitate C(sp2)−N bond formation under mild conditions at ambient temperature.11 We hypothesized that the mild conditions offered by such a reaction manifold might bypass the deleterious sulfamate ester N-alkylation processes observed when palladium catalysts were employed Table 1. Optimization of Sulfamate Ester Arylation
entrya
photocatalyst
equiv of 1a
equiv of aryl halide
base [equiv]
yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13
[Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 [Ir(ppy)2(dtbbpy)]PF6 fac-Ir(ppy)3 [Ir(ppy)2(bpy)]PF6 [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 [Ru(bpy)3](PF6)2 4-CzIPN none
1.5 1.5 1.5 1.5 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0 1.0 1.5 1.5 1.0 1.5 1.5 1.5 1.5 1.5 1.5
TMG [1.5] DBU [1.5] DBU [2.0] DBU [3.0] DBU [2.0] DBU [3.0] DBU [3.0] DBU [3.0] DBU [3.0] DBU [3.0] DBU [3.0] DBU [3.0] DBU [3.0]
18 67 80 96 72 >98 84 20 >98 9 48 70
