Nickel-Catalyzed Electrophilic Amination of Organozinc Halides

Abstract

The nickel-catalyzed electrophilic amination of organozinc halides with O-benzoyl N,N-dialkyl hydroxylamines allows for the preparation of a variety of aryl and alkyl tertiary amines in good yield. The reaction is noteworthy for the mild reaction conditions employed (room temperature) and the ease of product purification (acid/base extractive work up).The dichotomous behavior of diorganozinc and organozinc halide reagents is common in the application of these compounds in organic synthesis. 1 The divergence is manifested, sometimes dramatically, in different activity of nominally similar compounds. We recently had occasion to note significant disparities in reaction efficiency of R¢ZnX and R¢ 2 Zn reagents in the context of copper-catalyzed electrophilic aminations, with the latter providing results far superior to the former. 2 In this paper we document our efforts to bridge this gap through the discovery that nickel complexes successfully catalyze the electrophilic amination of organozinc halides (Equation 1). Equation 1This study was initiated as part of a broader effort to develop new methods for C-N bond formation. 3 Of the modern methods currently available, the BuchwaldHartwig cross coupling reaction has gained prominence as a general protocol for the preparation of aryl amines, representing the state of the art in metal-catalyzed nucleophilic amination. 4,5 While typically performed under palladium catalysis, other transition metals have proven to be competent catalysts as well. Of particular interest are reports by Buchwald and others on nickel-catalyzed nucleophilic amination. [6][7][8] Electrophilic amination of nonstabilized carbanions represents an alternative approach to amine synthesis, and is noteworthy for its use of the umpolung strategy for C-N bond construction. [9][10][11] Early examples have focused on the amination of highly reactive carbon donors (R¢Li and R¢MgX), and have generally been hampered by modest yields and/or harsh reaction conditions. Reports by Erdik and Narasaka on the metal-catalyzed amination of nonstabilized carbanions employing O-sulfonyl oximes as H 2 N(+) synthons represent an improvement on previous methodology, but have as yet been limited to the preparation of non-functionalized aniline derivatives. 12,13 Rieke's observation that organozinc halide reagents undergo amination with azodicarboxylates is also germane to the present investigation. 14 In the course of our initial screen of potential catalysts and reagents for the union of weak organic nucleophiles with R 2 N(+) synthons, nickel arose as a candidate metal for the reaction of R¢ZnX with O-benzoyl hydroxylamines. 2

Development of an Air-Stable Nickel Precatalyst for the Amination of Aryl Chlorides, Sulfamates, Mesylates, and Triflates

“…The development of a general, robust, and operationally simple catalyst system for Ni-catalyzed C–N cross-coupling reactions has remained a significant challenge despite 16 years of extensive catalyst development. After our first report, many groups have expanded Ni-catalyzed C–N cross-coupling to include new electrophiles such as aryl tosylates, carbamates, sulfamates, methyl ethers, phosphates, pivalates, and nitriles. − However, many of these systems rely on air- and moisture-sensitive Ni(COD) 2 as a catalyst precursor. , While other catalyst systems have utilized air-stable Ni(II) sources, many of these systems required the use of an external reductant to generate the catalytically active Ni species. , Additionally, the overall substrate scope of all Ni-catalyst systems reported to date has remained relatively limited, with only a few successful examples of substrates containing base-sensitive functional groups. − To address these challenges we sought to develop an air-stable, highly active Ni(II) precatalyst for C–N cross-coupling reactions.…”

Cross-Coupling of Heteroatomic Electrophiles

“…289 In addition to using copper to activate N−O bonds, Johnson concurrently reported a nickel-catalyzed variant of the C−N cross-coupling reaction of O-benzoylhydroxylamines with arylzinc halides (Figure 54). 290 In the previous coppercatalyzed method, arylzinc halides (234) were not well tolerated, however, this complementary method uses aryl-or alkylzinc halides that are generated in situ from transmetalation of the corresponding Grignard reagent. The reaction also takes advantage of the commercially available and air stable bis(triphenylphosphine)-nickel(II) dichloride as the catalyst.…”

Transition‐Metal Free Electrophilic Aminations of PolyfunctionalO‐2,4,6‐Trimethylbenzoyl Hydroxylamines with Zinc and Magnesium Organometallics

“…Pioneering work of Erdik [3] and Narasaka [4] was extended by transition-metal catalyzed electrophilic aminations reported by Johnson [5] and Wang [6] using Ni-or Cu-catalysts. [7] A Co-catalyzed [8] variant has also been demonstrated. However, the main drawback of such reactions is the requirement of using instable or difficult to prepare electrophilic reagents of the type XÀ NR 2 (2: X = Cl, OSO 2 Ar, OSO 2 Me) [9] as well as the need of expensive and toxic transition metal catalysts.…”