Zinc Trimethylsilylamide as a Mild Ammonia Equivalent and Base for the Amination of Aryl Halides and Triflates

Abstract

We report that Zn[N(SiMe 3 ) 2 ] 2 is a mild ammonia equivalent and base for the palladium-catalyzed amination of aryl halides and triflates. In contrast to LiN(SiMe 3 ) 2 , the combination of Zn[N(SiMe 3 ) 2 ] 2 and LiCl coupled with aryl halides and triflates containing base-sensitive functionality in high yields. In addition, aryl bromides coupled with aryl and alkylamines with the combination of Zn[N(SiMe 3 ) 2 ] 2 and LiCl as base. These aminations occurred without racemization of the enolizable stereocenter of an optically active ester.Palladium-catalyzed C-N bond formation has developed into a general and efficient way to prepare arylamines from aryl halides. [1][2][3][4][5] While a variety of amines and other nitrogen nucleophiles undergo this reaction in the presence of base, ammonia does not form primary arylamines. Thus, reactions have been conducted with ammonia surrogates, such as allylamine 6 or benzophenone imine. 7,8 Recently, we reported the synthesis of primary arylamines catalyzed by Pd(dba) 2 and P(t-Bu) 3 with lithium bis(trimethylsilyl)amide (LiN-(SiMe 3 ) 2 ) as an ammonia equivalent. This reagent is inexpensive, and the aryl silylamine is easily deprotected. 9 Buchwald reported a similar coupling with catalysts containing 2-phosphinobiphenyl ligands. 10 While LiN(SiMe 3 ) 2 coupled with a range of aryl halides under mild conditions with low catalyst loading, the strong basicity of the reagent prevented reactions with aryl halides bearing base-sensitive functional groups or enolizable hydrogens. 9,10 Recently, we developed conditions for the coupling of zinc enolates with aryl halides. 11 The functional group compatability of the R-arylation of carbonyl compounds with zinc enolates was greater than that with alkali metal enolates. 12 With this result in mind, we sought conditions to use zinc

Synthesis and Application of a New Fluorous‐Tagged Ammonia Equivalent

“…A range of different reagents have been used for reductive cleavage of N À O bonds, which included Li/4,4'-di-tert-butylbiphenyl (DTBB), [22,23] Na/Hg amalgam, [24,25] SmI 2 , [14,[26][27][28][29][30] TiCl 3 , [31][32][33][34] indium, [8,11] LiAlH 4 , [35,36] BH 3 , [37] [Mo(CO) 6 ], [13,24,[38][39][40][41][42][43][44][45][46][47][48][49] [Co 2 (CO) 8 ], [50] [Fe(CO) 5 ], [13,51] Zn/H +, [43,[52][53][54][55] NiB 2 , [56] Na 2 S 2 O 4 , [57] [TiA C H T U N G T R E N N U N G (iPrO) 4 ]/EtMgBr, [58] NiH 2 , [59] trimethylsilyl chloride/KI, …”

“…Indium was clearly the least efficient. Addition of a large excess of the metal, different acids (NH 4 + and AcOH), and sonication did not change the result. [Mo(CO) 6 ] and SmI 2 were both efficient, however, SmI 2 is less convenient to work with due to the high air sensitivity, so we proceeded with [Mo(CO) 6 ].…”

“…[4] More recently, Trabanco et al [5] reported the use of fluorous tert-butyl carbamate. In many cases, the ammonia surrogates are used in BuchwaldHartwig palladium-catalyzed cross-coupling reactions to prepare aniline derivatives, however, other reaction types have also utilized ammonia equivalents.…”

Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships

“…Several approaches have been followed to address functional group compatability. [72][73][74][75] By one approach, reactions between secondary amines and chloroarenes containing protic functionality have been shown to occur when using lithium bis(trimethylsilyl) amide (LiN(SiMe 3 ) 2 ) as base. 74,75 Here we show that the combination of CyPF-t-Bu as ligand and LiN(SiMe 3 ) 2 as based leads to the coupling of a variety of primary amines with heteroaryl chlorides containing protic functionality.…”

N‐Arylation of Heterocycles with Activated Chloro‐ and Fluoroarenes using Nanocrystalline Copper(II) Oxide

“…[5] Hartwig et al developed the arylation of azoles and imines with aryl bromides using the Pd(0)/DPPF catalyst [6] and later the palladium-catalyzed amination of aryl halides and triflates in the presence of zinc silylamide. [7] Buchwald [8] and Taillefer [9] reported a catalytic path for the N-arylation of heterocycles with bromoand iodoarenes using copper in the presence of bidentate ligands. Recently, Dawei Ma and his co-workers developed CuI/amino acid-catalyzed cross-coupling reactions in mild conditions [10] and the amino acids used are significantly inexpensive and readily available.…”