the transition - metal - catalyzed 
 amination of aryl halides has become 
 one of the most powerful methods to construct arylamines . the development of methods to couple aryl halides 
 with amines has been studied extensively in the past decade . palladium - catalyzed reactions occur with a broad scope of both coupling 
 partners , high functional group tolerance , and good selectivity for 
 monoarylation of the amine nucleophile . both the palladium metal and the 
 ligands used for this reaction are costly , and the ligand is difficult 
 to recycle . for these types of reasons , much interest has been 
 paid recently 
 to develop reactions catalyzed by first - row metal complexes that are 
 typically catalyzed by precious metals . for example , copper complexes 
 have been studied extensively for the coupling of aryl iodides , and 
 to a lesser extent aryl bromides , with nitrogen nucleophiles . yet , the scope of such coupling with electron - rich 
 bromoarenes , ortho - substituted bromoarenes , unactivated aryl chlorides , 
 and heteroaryl halides is limited . many of the first - row metals 
 are more electropositive than those 
 of the second row and form electron - rich low - valent species . indeed , 
 nickel complexes have been shown to catalyze the amination of aryl 
 chlorides and phenol derivatives ( scheme 1 ) . such nickel - catalyzed amination reactions could be more practical 
 than palladium - catalyzed amination reactions on large scale because 
 the metal is much less expensive , and much simpler ligands on the 
 nickel center are needed for the catalyst to react with aryl chlorides . 
 for example , hidai showed over 40 years ago that ni(pph3)4 adds phenyl chloride at room temperature to form ( pph3)2ni(ph)(cl ) , whereas pd(pph3)4 does not react with aryl chlorides . however , the scope of the nickel - catalyzed amination of aryl halides 
 has been limited to the coupling of secondary alkylamines and arylamines . primary alkylamines , one of the most significant classes of amines 
 for such cross coupling , have been shown to couple only with activated 
 aryl chlorides . in addition to the limitations on the scope of the coupling 
 of 
 aryl halides with amines , the mechanism of the coupling of aryl halides 
 with amines catalyzed by nickel complexes has not been studied . many 
 papers cite the potential of ni(i ) intermediates , either as part of a one - electron redox event or as part 
 of a mechanism involving ni(i ) and ni(iii ) intermediates . in contrast , 
 the mechanism for the palladium - catalyzed amination of aryl electrophiles 
 has been studied in detail , including the kinetic behavior of the 
 catalytic reaction and stoichiometric reactions of isolated intermediates . such studies have not been conducted on nickel - catalyzed couplings 
 to form c n bonds , but are particularly important if one is 
 to determine how to create catalysts of nickel that are as long - lived 
 as those of palladium and that react with similarly broad scope . here , we present the first nickel - catalyzed amination of unactivated 
 aryl chlorides with primary aliphatic amines . the reaction occurs 
 with aryl and heteroaryl chlorides and bromides catalyzed by a single - component 
 binap - ligated nickel(0 ) precursor . kinetic studies have been conducted 
 on the reaction , and studies on the relative rates of the reaction 
 with various isolated nickel complexes have been conducted . these 
 studies rule out a catalytic cycle occurring through a ni(i ) halide 
 intermediate and are consistent with a ni(0)/ni(ii ) catalytic cycle 
 for the amination of aryl chlorides and aryl bromides , which react 
 with different ni(0 ) species . we initiated our studies 
 of nickel - catalyzed amination of aryl 
 chlorides with primary aliphatic amines by studying the reaction between 
 3-chloroanisole and octylamine . we investigated nickel complexes generated 
 in situ from ni(cod)2 and various phosphine ligands as 
 catalysts . these reactions were conducted 
 with naobu as base in toluene at 50 c . reactions catalyzed by the combination of ni(cod)2 and 
 monophosphines , such as pph3 and pcy3 , afforded 
 only trace amounts of the desired amine product ( entries 14 ) . similar results ( < 5% conversion and < 2% yield ) were obtained 
 for reactions catalyzed by the combination of ni(cod)2 ( 1 
 mol % ) and dppe , dppp , or dppb ( 1 or 2 mol % ) ( entries 510 ) . however , reactions catalyzed by the combination of ni(cod)2 and dppf or binap gave significant amounts of product ( 1667% , 
 entries 1114 ) . in particular , the reaction catalyzed by the 
 single component catalyst ( binap)ni(-nc - ph ) afforded 
 the product in 92% yield ( entry 15 ) . an explanation for the high activity 
 of this catalyst will be revealed during the presentation of our mechanistic 
 studies . conditions : 3-chloroanisole 
 ( 0.400 
 mmol ) , octylamine ( 0.600 mmol ) , naobu 
 ( 0.600 mmol ) , 24 h. conversion and yield were determined by gc analysis 
 using dodecane as internal standard . [ ni ] = ( binap)ni(-nc - ph ) . with an active catalyst in hand and reliable 
 conditions identified for this ni - catalyzed amination , we studied 
 the scope of aryl chlorides that undergo these amination reactions , 
 and the results are summarized in table 2 . 
 in general , a range of electron - rich ( 2a2e ) , electron - neutral ( 2h ) , and electron - deficient 
 ( 2i2l ) aryl chlorides coupled with 
 octylamine in high yields ( 7696% ) under the developed conditions 
 with 1 mol % of nickel complex 1 . for very electron - rich 
 aryl chlorides , 4 mol % of the catalyst was required to obtain modest 
 to good yields ( 2f and 2 g ) . for these two 
 reactions , aryl chlorides were not fully converted , and only trace 
 amounts ( < 5% ) of biaryl compounds were detected by gc analysis . mono - ortho - substituted aryl chlorides reacted in 
 high yields ( 2a , 2c2e , 2h , and 2j ) . however , di - ortho - substituted aryl chlorides , such as 2-chloro-1,3-dimethylbenzene , 
 did not couple with octylamine under the developed conditions . conditions : arcl ( 0.400 mmol ) , octylamine 
 ( 0.600 mmol ) , ( binap)ni(-nc - ph ) ( 4.0 mol , 
 1 mol % ) , naobu ( 0.600 mmol ) , toluene 
 ( 1 ml ) ; temperature , 50 c ; reaction time , 24 h. ( binap)ni(-nc - ph ) 
 ( 16.0 mol , 4 mol % ) . the scope of primary amines was studied by conducting the amination 
 reactions of 3-chloroanisole catalyzed by 2 mol % complex 1 . the results of this study are summarized in table 3 . in general , a variety of primary aliphatic amines underwent 
 this amination process in good to excellent isolated yields ( 7596% ) . conditions : 3-chloroanisole ( 0.400 
 mmol ) , primary amine ( 0.600 mmol ) , ( binap)ni(-nc - ph ) 
 ( 8.0 mol , 2 mol % ) , naobu ( 0.600 
 mmol ) , toluene ( 1 ml ) ; temperature , 50 c ; reaction time , 24 
 h. ( binap)ni(-nc - ph ) 
 ( 16.0 mol , 4 mol % ) . the steric bulk of the alkyl group of the primary amines significantly 
 influenced the yields of these reactions . the reactions of an amine 
 containing a primary alkyl group ( 2 m ) afforded the product 
 in higher yield than the reactions of amines containing a secondary 
 alkyl group ( 2n and 2o ) , although the primary 
 amines containing a secondary alkyl group still coupled with aryl 
 chlorides in good yield . however , the amination of 3-chloroanisole 
 with primary amines containing a tertiary alkyl group , for example , tert - butylamime and amylamine , gave only trace amounts of 
 the desired products . amines containing aryl ( 2p ) , heteroaryl 
 ( 2q and 2r ) , allyl ( 2s ) , and 
 cyano ( 2 t ) groups reacted in high yields ( 9096% ) . primary amines bearing 1,3-dioxolane ( 2u and 2v ) and morpholine ( 2w ) moieties also reacted in high 
 yields ( 8388% ) . the reaction of n - isopropylethylenediamine , 
 a substrate containing both a primary and a secondary amine , occurred 
 selectively with the primary amine , leaving the secondary amine intact 
 ( 2x ) . nitrogen - containing heterocycles containing 
 amino substituents 
 are of particular importance for pharmaceutical applications . however , 
 the c  n coupling reactions between nitrogen - containing heteroaryl 
 electrophiles and primary amines are challenging , presumably because 
 of the coordinating properties of both pyridines and primary amines . nickel catalysts have been reported for the amination of heteroaryl 
 chlorides , but the amine nucleophiles are limited to secondary amines . cross - coupling reactions between nitrogen - containing 
 heteroaryl 
 chlorides and primary amines catalyzed by 2 mol % of complex 1 are summarized in table 4 . the scope 
 of heteroaryl chlorides that underwent this amination reaction encompassed 
 a range of 2-pyridyl ( 3a3f ) , 3-pyridyl 
 ( 3g3l ) , and 4-pyridyl ( 3m3p ) chlorides containing electron - donating groups 
 ( me and ome ) and electron - withdrawing groups ( cn and cf3 ) . in general , these reactions afforded the corresponding heteroaryl 
 alkylamine in good to excellent isolated yields ( 5796% , average 
 yield : 81% ) . this amination also occurred in high yields with 2-chloroquinoline 
 ( 3q ) and 2-chloropyrazine ( 3r ) . the scope of primary amines that underwent reactions with chloropyridines 
 was similar to that of the reactions of 3- chloroanisole described 
 in table 3 . conditions : 3-chloroanisole ( 0.400 
 mmol ) , primary amine ( 0.600 mmol ) , ( binap)ni(-nc - ph ) 
 ( 8.0 mol , 2 mol % ) , naobu ( 0.600 
 mmol ) , toluene ( 1 ml ) ; temperature , 50 c ; reaction time , 24 
 h. ( binap)ni(-nc - ph ) 
 ( 16.0 mol , 4 mol % ) . compared 
 to the well - established palladium - catalyzed amination of aryl bromides , the nickel - catalyzed amination of aryl bromides has been less studied , 
 and conditions for coupling of aryl bromides with amines by nickel 
 catalysts have not been identified . only two examples of nickel - catalyzed 
 amination of aryl bromides have been published , and these two reactions occurred in poor yields ( eqs 1 and 2 ) . having identified conditions 
 for the nickel - catalyzed amination of aryl chlorides , we tested these 
 conditions for the coupling of aryl bromides with primary amines . the amination of aryl bromides catalyzed by benzonitrile complex 1 in toluene with naobu base 
 occurred in good yields in some cases , but the scope of the reaction 
 was limited . bromobenzene and 4-bromobenzotrifluoride reacted with 
 octylamine in high gc - yields ( 98% and 94% , repectively ) under conditions 
 listed in table 2 with 3 mol % of complex 1 ( eq 3 ) . however , 3-bromoanisole coupled 
 with 2-(1,3-dioxolan-2-yl)ethan-1-amine in only 55% gc - yield , whereas 
 the reaction of the same amine with 3-chloroanisole afforded the desired 
 product in 87% isolated yield ( eq 4 ) . this 
 limited scope for the amination of aryl bromides may stem from the 
 faster thermal decomposition of arylnickel(ii ) bromide species to 
 nickel(i)3 bromide , relative to the rate of decomposition 
 of arylnickel(ii ) chloride species . the 
 catalyst precursor employed in this study is a single - component nickel(0 ) 
 complex ( binap)ni(-nc - ph ) ( 1 ) . previously , 
 we reported the synthesis of this nickel complex by substitution of 
 the 1,5-cyclooctadiene ( cod ) in ni(cod)2 by binap , and 
 benzonitrile . to avoid using the thermally 
 labile , air- and moisture - sensitive ni(cod)2 , we developed 
 a new synthesis ( scheme 2 ) of this complex 
 starting from the air - stable nickel precursor ( dme)nicl2 . reaction of ( dme)nicl2 with 1 equiv of binap in thf 
 at 50 c afforded ( binap)nicl2 , which was then reduced 
 by zinc metal in the presence of cod . p nmr analysis 
 of this reaction indicated a clean formation of ( binap)ni(cod ) . the 
 byproduct zncl2 was removed by washing the reaction mixture 
 with degassed aqueous naoh . at this stage , the residue was 
 suspended in toluene and then allowed to react with benzonitrile . arylnickel halide complexes are important intermediates 
 in nickel - catalyzed cross - coupling reactions . in general , arylnickel 
 halides ligated by monophosphines are synthesized by oxidative addition 
 reactions of aryl halides to ni(pr3)x ( r = alkyl or aryl ) , but arylnickel 
 halides ligated by bisphosphines are prepared by ligand substitution 
 reactions between monophosphine - ligated arylnickel halide complexes 
 with bisphosphines . the direct oxidative 
 addition of aryl halides to bisphosphine - ligated ni(0 ) has rarely 
 been investigated , mainly due to the lack of bisphosphine - ligated 
 ni(0 ) precursors that can react with aryl halides at ambient temperature . recently , we reported the synthesis of binap - ligated arylnickel halide 
 complexes by reactions of aryl halides with ( binap)ni(cod ) in the 
 presence of catalytic amounts of benzonitrile , and we identified ( binap)ni(-nc - ph ) as the active ni(0 ) species . in our communication on the nickel - catalyzed asymmetric -arylation 
 of ketones , we reported the single reaction of electron - deficient 
 4-chlorobenzotrifluoride with this newly defined ni(0 ) precursor 1 and no isolation of the products . here we show the results 
 of the reactions of complex 1 with electronically varied 
 aryl chlorides . electron - neutral and electron - deficient aryl 
 chlorides reacted smoothly with ni(0 ) complex 1 in thf 
 at room temperature to afford the arylnickel(ii ) chloride complexes 47 in 7689% isolated yields ( eq 5 ) . these complexes are stable in the solid state 
 at ambient temperature for at least six months without noticeable 
 decomposition . however , upon standing in thf solution at room temperature 
 for about 48 h , they fully decomposed to [ ( binap)ni(-cl)]2 ( 8) with concomitant release of biaryls , as 
 detected by gc - ms analysis . however , the reaction 
 of electron - rich 4-chloroanisole with complex 1 in thf 
 did not form the arylnickel chloride complex resulting from simple 
 oxidative addition , as determined by p nmr spectroscopy . 
 instead , p nmr signals corresponding to two mutually trans phosphine resonances ( doublets at 24.2 and 14.4 ppm 
 with jpp = 352 hz ) were observed . 56single - crystal x - ray diffraction of the isolated 
 material ( figure 1 ) showed that this product 
 is complex 9 ( eq 7 ) . complex 9 contains a coordinated monophosphine ligand ph2p(c6h4 - 4-ome ) and a six - membered nickelacyclic 
 structure . nickelacyclic complex 9 contains a small dihedral 
 angle between the two naphthyl groups of 63 , and the nickel 
 center consists of a distorted square planar geometry . complex 9 is formed by p  c bond cleavage of the binap backbone 
 after the initial formation of binap - ligated arylnickel chloride complex 
 ( binap)nicl(c6h4 - 4-ome ) . c 
 bond cleavage of the binap backbone 
 in a binap - ligated phenylpalladium bromide complex was reported by 
 our group previously . all the ellipsoids are 
 drawn at the 50% probability and all the 
 hydrogen atoms are omitted for clarity . complex 9 was tested as a catalyst for the amination 
 of 4-chloroanisole with octylamine under the conditions described 
 in table 2 . only trace ( < 5% by gc analysis ) 
 amounts of the amination product were formed . thus , the formation 
 of catalytically inactive complex 9 by the reaction of 
 4-chloroanisole and nickel precursor 1 explained the 
 high catalyst loading required for the amination of electron - rich 
 4-chloroanisole . the oxidation state of the nickel intermediates 
 in the 
 amination of aryl halides with amines has been ambiguous , and pathways 
 involving both ni(0)/ni(ii ) and ni(i)/ni(iii ) couples have been proposed 
 for these reactions . with isolated , binap - ligated 
 ni(0 ) , ni(i ) halide , and arni(ii ) halide complexes in hand , we were 
 able to assess precisely the competence of these complexes to be intermediates 
 in the amination reactions . to do so , we conducted the reaction 
 of the isolated ( binap)nicl(c6h4 - 4-cf3 ) ( 7 ) with octylamine and naobu in the presence of 1 equiv of binap to trap a ni(0 ) product 
 ( a , scheme 3 ) . this reaction afforded n - octyl-4-(trifluoromethyl)aniline in quantitative yield 
 in less than 5 min at room temperature , as indicated by f nmr spectroscopic analysis . in addition , we conducted the amination 
 reaction of 4-chlorobenzotrifluoride with octylamine in the presence 
 of naobu catalyzed by 2 mol % of ( binap)nicl(c6h4 - 4-cf3 ) at room temperature ( b , scheme 3 ) . full conversion of 4-chlorobenzotrifluoride was 
 achieved in 2 h , and this reaction afforded n - octyl-4-(trifluoromethyl)aniline 
 in 91% isolated yield . the same reaction catalyzed by 2 mol % of [ ( binap)ni--cl]2 did not afford any amination product ( c , scheme 3 ) . these results show clearly that the binap - ligated 
 arylnickel(ii ) chloride compound is kinetically and chemically competent 
 to be an intermediate in the catalytic process and the binap - ligated 
 nickel(i ) halide is not . to identify the resting 
 state of the catalyst in this nickel - catalyzed 
 amination reaction , we monitored by p{h } 
 nmr spectroscopy the reaction of 4-chlorobenzotrifluoride with octylamine in the presence of naobu catalyzed by 2 mol % of ( binap)ni(-nc - ph ) 
 ( 1 ) at room temperature . during the first 50% conversion 
 of 4-chlorobenzotrifluoride , however , during the second 50% conversion , a new species 
 corresponding to a p{h } nmr resonance at 
  31.7 ppm gradually accumulated . this new species is ( binap)2ni , as determined by independently preparing this complex 
 by reduction of ( dme)nicl2 with zn metal in the presence 
 of 2 equiv of binap in thf and comparing the p nmr chemical 
 shift . to test the catalytic activity of ( binap)2ni for this amination process , we conducted the reaction of 4-chlorobenzotrifluoride 
 with octylamine catalyzed by 5 mol % of ( binap)2ni in the 
 presence of naobu at room temperature . this reaction did 
 not afford detectable amounts of the amination product ( a , scheme 4 ) . this result is consistent with the early report 
 that ( binap)2ni does not undergo oxidative addition with 
 aryl chlorides or bromides at ambient temperatures . the same reaction catalyzed by 5 mol % ( binap)2ni in 
 the presence of a catalytic amount of phcn ( 30 mol % ) afforded the 
 amination product in 84% yield in 20 h ( b , scheme 4 ) . for comparison , we conducted the same reaction catalyzed 
 by only 2 mol % ( binap)ni(-nc - ph ) . this reaction 
 afforded the amination product in almost quantitative yield in 2 h 
 at room temperature ( c , scheme 4 ) . thus , ( binap)ni(-nc - ph ) is a more active catalyst than the combination of 
 ( binap)2ni and phcn . to assess the origin of the 
 effect of benzonitrile on the rate 
 of the catalytic reaction , we performed the reaction of ( binap)2ni with benzonitrile and the reaction of ( binap)ni(-nc - ph ) with binap . the reaction of ( binap)2ni 
 with 10 equiv of benzonitrile did not form detectable amounts of ( binap)ni(-nc - ph ) , as determined by p nmr spectroscopy 
 ( d , scheme 4 ) . the reaction of ( binap)ni(-nc - ph ) with 1 equiv of binap afforded ( binap)2ni quantitatively at ambient temperature ( e , scheme 3 ) . based on these stoichiometric reactions and the catalytic 
 reactions in scheme 3 , we conclude that the 
 formation of ( binap)2ni is reversible in the presence of 
 benzonitrile , but the equilibrium lies largely on the side of ( binap)2ni and free nitrile . the formation of bis(amine)-ligated palladium complexes 
 was reported 
 as one possible pathway for deactivation of the catalyst in the palladium - catalyzed 
 amination of aryl halides . formation of 
 analogous bis(amine ) complexes of nickel was proposed to explain the 
 much lower reactivity of primary aliphatic amines than that of cyclic 
 secondary aliphatic amines and anilines in the nickel - catalyzed amination 
 reaction . however , these bis(amine)-ligated 
 nickel complexes have never been prepared or characterized . in the 
 nickel - catalyzed amination of aryl chlorides with primary amines catalyzed 
 by ( binap)ni(-nc - ph ) , we observed the formation 
 of ( binap)2ni . the stoichiometry of this conversion indicates 
 that there are nickel complexes lacking binap ligand in the reaction 
 mixture . thus , we studied the ligand substitution reactions between 
 primary aliphatic amines and binap - ligated ni(0 ) and binap - ligated 
 ni(ii ) complexes . the reaction of ( binap)ni(-nc - ph ) with 50 equiv of n - butylamine in toluene 
 did not form any new nickel species , and free binap was not detected 
 by p nmr spectroscopy ( a , scheme 5 ) . this result is consistent with the affinity of the electron - rich 
 ni(0 ) center for softer , -accepting ligands . however , the reaction of ( binap)nicl(c6h4 - 4-cn ) with 50 equiv of n - butylamine afforded 
 free binap and trans-(n - butylamine)2nicl(c6h4 - 4-cn ) ( 10 ) ( b , 
 scheme 5 ) . complex 10 was isolated 
 in 76% yield . with the bis(amine)-ligated complex 10 in hand , we 
 tested its potential to serve as an intermediate in the amination 
 reaction . we conducted the reaction of 10 with 2 equiv 
 of naobu in the presence or in the absence 
 of 1 equiv of binap ( c , scheme 5 ) . this result 
 indicates that the formation of bis(amine)-ligated nickel complexes 
 is one possible pathway for decomposition of the nickel catalyst . after identifying the resting state of the nickel catalyst and 
 possible paths for catalyst deactivation , we sought to identify the 
 rate - limiting step for this nickel - catalyzed amination process . to 
 do so , we measured the dependence of the initial rates of the amination 
 reaction on the concentrations of each reagent under conditions in 
 which the other reagents were present in large excess . we chose 
 the reaction of 4-chlorobenzotrifluoride with octylamine in the presence 
 of naobu for the kinetic studies because 
 this reaction occurred at ambient temperature , and we were able to 
 monitor the reaction conveniently by both p and f nmr spectroscopy . furthermore , no background nucleophilic 
 aromatic substitution reaction was observed for this aryl chloride 
 and octylamine in the presence of naobu . for the initial rates to be a valid method for kinetic 
 analysis 
 of this reaction , all reagents must be soluble in the reaction medium , 
 and no induction period can be present . the single - component catalyst 
 precursor 1 is only marginally soluble in the reaction 
 medium . thus , we used ( binap)nicl(c6h4 - 4-cf3 ) ( 7 ) as the source of nickel for our kinetic 
 experiments because it dissolves in seconds once mixed with other 
 reagents . benzonitrile was added to the reaction mixture to trap the 
 binap - ligated ni(0 ) species to form ( binap)ni(-nc - ph ) , 
 which had been identified as the catalyst resting state . in the absence 
 of benzonitrile , the irreversible formation of ( binap)2ni occurs quickly . benzonitrile ( 10 equiv relative to complex 7 ) was added so that catalyst decomposition was not observed 
 by p nmr spectroscopy over the time of the reaction . the kinetic behavior was assessed for the coupling of 4-chlorobenzotrifluoride 
 with octylamine catalyzed by the combination of complex 7 in the presence of phcn and naobu at 
 room temperature ( eq 8) . the initial rates were 
 measured by f nmr spectroscopy using 4-ocf3-anisole as the internal standard . the rate of the amination reaction 
 was determined by measuring the formation of n - octyl-4-(trifluoromethyl)aniline 
 with respect to time . the plots of concentrations of n - octyl-4-(trifluoromethyl)aniline vs time at various concentrations 
 of each reagent are shown in figures s1s5 in the supporting information . the plots of the initial 
 rates of the reaction vs the concentrations of the catalyst , aryl 
 chloride , and benzonitrile are shown in figure 2.8 the kinetic analysis showed that this nickel - catalyzed 
 amination reaction of aryl chlorides is first order in the nickel 
 catalyst , first order in aryl chloride , and inverse first order in 
 phcn . the remaining reagents , naobu and 
 amine , did not affect the initial rate of the reaction . these data 
 indicate that oxidative addition of the aryl chloride to ( binap)ni(0 ) , 
 formed by reversible dissociation of phcn from the catalyst resting 
 state ( binap)ni(-nc - ph ) , is the turnover - limiting 
 step in the amination reaction . plots of initial rates vs concentration 
 of catalyst , aryl chloride , 
 and benzonitrile for the amination of 4-chlorobenzotrifluoride ( 0.101.0 
 m ) with n - octylamine ( 0.30 m ) catalyzed by ( binap)nicl(c6h4 - 4-cf3 ) ( 0.00600.018 m ) in 
 the presence of benzonitrile ( 0.0900.180 m ) and naobu ( 0.30 m ) at room temperature . the mechanism of palladium - catalyzed cross - coupling reactions with 
 aryl halides as electrophiles has been extensively studied . these 
 studies reveal that the halide identity has a dramatic effect on the 
 mechanism for the oxidative addition of aryl halides to pd(0 ) species . the additions of the less reactive aryl chlorides occurs through lower - coordinated 
 pd(0 ) intermediate than the additions of more reactive aryl iodides . however , such mechanistic data has not been 
 gained for the nickel - catalyzed amination of aryl halides . for the 
 nickel - catalyzed enantioselective -arylation of ketones , we 
 found that aryl chlorides react in much higher yields and with much 
 higher enantioselectivities than aryl bromides , and we attributed 
 this dramatic effect of halide on the reaction yield and enantioselectivity 
 to the faster decomposition of the arylnickel(ii ) bromide intermediate 
 relative to the arylnickel(ii ) chloride intermediate to their corresponding 
 ni(i ) halide complexes . because 
 the ni(0 ) complex 1 ligated by binap and phcn catalyzes 
 the amination of both aryl chlorides and aryl bromides , we can compare 
 directly the kinetics and mechanism of the amination reactions of 
 aryl chlorides and aryl bromides catalyzed by this nickel system . to do so , we conducted kinetic experiments on the amination of aryl 
 bromides that were similar to those we conducted on the amination 
 of aryl chlorides . we monitored by p nmr spectroscopy 
 the reaction of 
 4-bromobenzotrifluoride with octylamine catalyzed by ( binap)ni(-nc - ph ) in the presence of naobu at room temperature . as was the case in the reactions of chloroarenes , 
 ( binap)ni(-nc - ph ) was identified as the resting 
 state of the catalyst in the reaction of 4-bromobenzotrifluoride with 
 octylamine . kinetic studies were conducted on the reaction of 
 4-bromobenzotrifluoride 
 with octylamine catalyzed by ( binap)nibr(c6h4 - 4-cf3 ) ( 11 ) in the presence of added phcn 
 ( eq 8) . the initial rates were measured for 
 various concentrations of each reagent while keeping the other reagents 
 in excess . the plots of concentrations of n - octyl-4-(trifluoromethyl)aniline 
 vs time at various concentrations of each reagent are shown in figures s7s11 . the plots of the initial 
 rates of the reaction vs the concentrations of the catalyst , aryl 
 chloride , and benzonitrile are shown in figure 3 . plots of initial rates 
 vs concentration of catalyst , aryl bromide , 
 and benzonitrile for the amination of 4-bromobenzotrifluoride ( 0.100.80 
 m ) with n - octylamine ( 0.30 m ) catalyzed by ( binap)nicl(c6h4 - 4-cf3 ) ( 0.00600.018 m ) in 
 the presence of benzonitrile ( 0.0900.180 m ) and naobu ( 0.30 m ) at room temperature . like the amination of 4-chlorobenzotrifluoride , the amination 
 of 
 4-bromobenzotrifluoride with octylamine is first order in the nickel 
 catalyst , first order in aryl halide , zero order in naobu , and zero order in amine . in contrast to the reaction 
 of 4-chlorobenzotrifluoride , which is inverse first order in phcn , 
 the amination of 4-bromobenzotrifluoride is zero order in phcn . this 
 order in phcn , in combination with the first order in aryl bromide , 
 indicates that the bromoarene reacts directly with ( binap)ni(-nc - ph ) during the turnover - limiting step of the amination 
 of the bromoarene without dissociation of phcn . the different reactivities 
 of aryl halides with binap - ligated nickel complexes of different coordination 
 numbers parallels a trend in oxidative addition to pd(0 ) complexes 
 noted in the introduction to this section . based on the stoichiometric reactions of 
 the isolated binap - ligated arylnickel halides with primary amines 
 in the presence of base and the conducted kinetic studies , we propose 
 a catalytic cycle depicted in scheme 6 for 
 the nickel - catalyzed amination of aryl chlorides and aryl bromides 
 reported in this paper . the observed first order rate - dependence on 
 the concentrations of both the catalyst and aryl halides indicates 
 that the oxidative addition of aryl halides to binap - ligated ni(0 ) 
 species to form ( binap)niar(x ) ( x = cl or br ) is the turnover - limiting 
 step for both amination processes . this binap - ligated arylnickel(ii ) 
 halide complex subsequently reacts with primary amine and naobu to form an arylnickel amido complex , followed 
 by reductive elimination of the n - alkyl aniline product 
 in the presence of phcn to regenerate ( binap)ni(-nc - ph ) , which was confirmed as the catalyst resting state . interestingly , different rate - dependences on the concentration 
 of phcn were observed for this nickel - catalyzed amination of aryl 
 chlorides and aryl bromides . the reaction of aryl chlorides is inverse 
 first order in phcn , whereas the reaction of aryl bromides is zero 
 order in phcn . these reaction orders indicate that aryl chlorides 
 and aryl bromides react with different nickel(0 ) species . the aryl 
 chlorides react after reversible dissociation of phcn from ( binap)ni(-nc - ph ) to form the lower - coordinate nickel(0 ) species ( binap)ni(0 ) 
 and ultimately the binap - ligated arylnickel(ii ) chloride complex . however , the aryl bromides react directly with ( binap)ni(-nc - ph ) to form binap - ligated arylnickel(ii ) bromide complex 
 and the nitrile dissociates during or immediately after the oxidative 
 addition process . one could imagine the zero - order dependence on added 
 phcn could indicate that dissociation of this ligand is rate limiting , 
 but the first - order dependence of the reaction on the aryl bromide 
 is inconsistent with this proposal . in addition to the steps 
 within the catalytic cycle that form the 
 arylamine product , there are several pathways that generate catalytically 
 inactive nickel species . first , the reaction of ( binap)niar(cl ) with 
 amine rnh2 forms the catalytically inactive ( rnh2)2niar(cl ) and free binap . the released free binap in 
 the reaction mixture traps the ( binap)ni(0 ) fragment generated by 
 dissociation of phcn from ( binap)ni(-nc - ph ) or 
 reductive elimination of n - alkyl aniline from the 
 binap - ligated arylnickel(ii ) amido complex to form ( binap)2ni . ( binap)2ni does not undergo oxidative addition of 
 the aryl halide and does not catalyze the amination reaction . second , thermal decomposition of ( binap)niar(x ) 
 ( ar = electron - neutral and electron - rich aryl groups ) affords the 
 catalytically inactive [ ( binap)ni(-x)]2 with concomitant 
 formation of biaryl . c bond cleavage of the binap backbone is a potential 
 pathway for the deactivation of the nickel catalyst . indeed , this 
 complex was observed to accumulate ( approximately 6.4 mm of the 16 
 mm concentration of initial catalyst ) during the reaction of 4-chloroanisole 
 with octylamine . to gain 
 information on the 
 relative rates of the amination of aryl chlorides and aryl bromides 
 and the effect of temperature and concentration of phcn on the selectivity 
 of the amination reaction for an aryl chloride versus an aryl bromide , 
 we conducted a series of reactions with an aryl halide containing 
 both chloride and bromide and a mixture of aryl halides in the presence 
 of various amounts of phcn at room temperature or 50 c . the amination of 1-bromo-4-chlorobenzene with 
 octylamine catalyzed 
 by 3 mol % of ( binap)ni(-nc - ph ) at 50 c occurred 
 selectively at the c  br bond , and the product of the reaction 
 at the c  cl bond was not detected by gc - ms analysis . ( a , scheme 7 ) . however , side - by - side reactions of chlorobenzene 
 and bromobenzene under the same conditions occurred in the same gc 
 yield ( 98% ) ( b , scheme 7 ) . the amination 
 of equal amounts of 1-bromo-4-butylbenzene and 4-chlorotoluene 
 with octylamine catalyzed by 3 mol % of ( binap)ni(-nc - ph ) was conducted at both room temperature and 50 c ( c , 
 scheme 7 ) . at both temperatures , these reactions 
 occurred in similar yields , but with different selectivity . at room 
 temperature , 1-bromo-4-butylbenzene was converted selectively over 
 4-chlorotoluene , and a product ratio of 3:1 was obtained . however , 
 at 50 c , 1-bromo-4-butylbenzene and 4-chlorotoluene converted 
 equally . br 
 bond in 1-bromo-4-chlorobenzene ( a , scheme 7 ) , the decreased selectivity for amination of the c  br bond 
 over the c  cl bond in different haloarenes might stem from 
 irreversible or nearly irreversible binding of the haloarene to ni(0 ) 
 to form an arene -complex prior to cleavage of the carbon  halogen 
 bond . this preferential intramolecular oxidative addition has recently 
 been observed for the ni - catalyzed kumada cross - coupling reactions 
 that are part of chain - growth polymerizations . to evaluate the effect of phcn on the selectivity 
 between the amination 
 of an aryl chloride and an aryl bromide , we conducted the amination 
 of equal amounts of 1-bromo-4-butylbenzene and 4-chlorotoluene with 
 octylamine catalyzed by 3 mol % of ( binap)ni(-nc - ph ) 
 in the presence of 0.9 equiv of phcn ( relative to octylamine ) ( d , 
 scheme 6 ) . because our kinetic studies revealed 
 different dependences of the reaction rate on phcn for this nickel - catalyzed 
 amination ( inverse first order and zero order on phcn for the reaction 
 of aryl chloride and aryl bromide , respectively ) , we considered that 
 an increased selectivity for the conversion of aryl bromide over aryl 
 chloride would be observed for reactions conducted with higher concentrations 
 of phcn than for reactions conducted with lower concentrations of 
 phcn . consistent with this prediction , the selectivity was higher 
 ( 30:1 
 for the reaction at room temperature and 9:1 for the reaction at 50 
 c ) for the amination of 1-bromo-4-butylbenzene versus the amination 
 of 4-chlorotoluene for reactions run with higher concentrations ( from 
 0.004 to 0.18 m ) of benzonitrile at both room temperature and 50 c 
 for 24 h. these data show that the difference in ni(0 ) species that 
 adds the different aryl halides can be used to beneficially affect 
 selectivity . several first - row metal complexes catalyze cross 
 coupling reactions , 
 and many catalyze the coupling of certain classes of chloroarenes . however , no first row metal complex has been shown to catalyze the 
 coupling of primary alkylamines with unactivated chloroarenes . copper 
 complexes couple bromoarenes and iodoarenes with primary amines , but 
 they do not catalyze the coupling of chloroarenes with primary amines . previously , the combination of ni(cod)2 and dppf was 
 shown to couple an electron - poor chloroarene with a primary amine , 
 but this catalyst did not couple unactivated chloroarenes with primary 
 amines . a set of preliminary studies 
 we conducted have shown that the complexes ( dppf)ni(cod ) or ( dppf)2ni generated in situ by the reaction of ni(cod)2 and dppf do not add aryl chlorides at ambient temperature , and the 
 reaction of chloroarenes with ( dppf)ni(cod ) or ( dppf)2ni 
 at elevated temperatures forms ( dppf)ni(i)cl and biaryl . this 
 formation of ( dppf)2ni(0 ) and ( dppf)ni(i)cl at 
 the elevated temperatures required for oxidative addition of chloroarene 
 to occur , likely prevented productive coupling reactions with unactivated 
 chloroarenes . these observations further illustrate the importance 
 of the nitrile - ligated precursor with the general formula l2ni(-nc - ph ) . nickel complexes of n - heterocyclic carbenes have 
 been shown to couple aryl chlorides and sulfonates with secondary 
 amines and with arylamines , but not primary alkylamines . mechanistic 
 studies on the reactions of secondary amines catalyzed by the complexes 
 of n - heterocyclic carbenes are too limited to determine 
 the origin of their lack of reactivity with primary amines , but recent 
 studies have shown that the arylnickel halide complexes containing 
 hindered n - heterocyclic carbenes are not formed by 
 the reaction of ( imes)2ni(0 ) with chlorobenzene , bromobenzene , 
 and iodobenzene . instead , ni(i ) species 
 are formed , and this formation of ni(i ) complexes could either constitute 
 the pathway for catalyst decomposition or a mechanism for reaction 
 with this catalyst involving odd - electron nickel intermediates . we have shown that nickel complexes containing 
 common aryl bisphosphine 
 ligands can catalyze the coupling of aryl chlorides and bromides with 
 primary amines . in particular , we have shown that the mixed ni(0 ) 
 species ( binap)ni(-nc - ph ) containing one bisphosphine 
 and one side - bound nitrile is a particularly active catalyst for the 
 coupling of chloroarenes with primary amines and is more active than 
 the related ( binap)2ni catalyst . a range of electronically 
 varied aryl halides and nitrogen - containing heteroaryl chlorides , 
 including pyridine , quinoline , and isoquinoline derivatives , couple 
 with a variety of aliphatic primary amines in high isolated yields . 
 several aspects of the current system lead to the ability of this 
 first - row metal system to catalyze this class of amination reaction . 
 in general , we attribute the high yields for these amination reactions 
 to the facile oxidative addition of aryl chlorides and heteroaryl 
 chlorides to the ( binap)ni(-nc - ph ) precatalyst 
 at ambient temperatures . detailed studies on the mechanism of 
 the amination reaction the following conclusions about the mechanism of this 
 coupling process have been drawn from these studies : ( 1 ) the 
 oxidative addition of aryl chlorides to ( binap)ni(-nc - ph ) , together with the stoichiometric reactions of ( binap)niar(cl ) 
 with primary aliphatic amines in the presence of base , support a reaction 
 pathway involving a ni(0)/ni(ii ) couple in the catalytic cycle . ( 2 ) the oxidative addition of aryl chlorides and heteroaryl chlorides 
 to the single - component nickel precursor ( binap)ni(-nc - ph ) at ambient temperatures prevents the formation of inactive 
 ni species . ( 3 ) ni(i ) intermediates , which have been observed 
 in oxidative 
 addition studies to phosphine - ligated ni(0 ) complexes , appear to result 
 from decomposition of the ni(ii ) product of oxidative addition as 
 opposed to forming from one - electron pathways for oxidative addition 
 to ni(0 ) . ( 4 ) the reaction of ( binap)ni(-nc - ph ) with electron - rich 
 aryl chlorides , such as 4-chloroanisole , leads to the p  c bond 
 cleavage of the backbone of binap and forms the nickel complex 9 containing two monophosphine ligands . the formation of the 
 catalytically inactive complex 9 explains the high catalyst 
 loading required for the amination of electron - rich aryl chlorides . ( 5 ) mechanistic and kinetic studies revealed that the turnover - limiting 
 step of these nickel - catalyzed amination reactions of aryl chlorides 
 is oxidative addition of the aryl chloride to ( binap)ni(0 ) , which 
 is formed by dissociation of phcn from the catalyst resting state 
 ( binap)ni(-nc - ph ) . ( 6 ) mechanistic and kinetic 
 studies imply that the turnover - limiting 
 step of the reactions of aryl bromides is also oxidative addition , 
 but that aryl bromides react with a different nickel species , of composition 
 ( binap)ni(-nc - ph ) containing a bound nitrile . ( 7 ) the formation of catalytically inactive bis(amine)-ligated 
 ni(ii ) species ( rnh2)2niar(cl ) , ni(i ) species 
 [ ( binap)ni(-cl)]2 , and bis - binap - ligated ni(0 ) species 
 ( binap)2ni are the major pathways for catalyst inactivation . further studies to improve the lifetime of the ni - bisphosphine 
 catalysts , to determine the mechanism by which the phosphine - ligated 
 ni(i ) species form as a means to prevent this detrimental path , and 
 to determine if ni(i ) complexes are generated during oxidative addition 
 of haloarenes will be the subject of future work .
first - row metal complexes 
 often undergo undesirable one - electron 
 redox processes during two - electron steps of catalytic cycles . 
 we 
 report the amination of aryl chlorides and bromides with primary aliphatic 
 amines catalyzed by a well - defined , single - component nickel precursor 
 ( binap)ni(2-nc - ph ) ( binap = 2,2-bis(biphenylphosphino)-1,1-binaphthalene ) 
 that minimizes the formation of ni(i ) species and ( binap)2ni . 
 the scope of the reaction encompasses electronically varied aryl 
 chlorides and nitrogen - containing heteroaryl chlorides , including 
 pyridine , quinoline , and isoquinoline derivatives . 
 mechanistic studies 
 support the catalytic cycle involving a ni(0)/ni(ii ) couple for this 
 nickel - catalyzed amination and are inconsistent with a ni(i ) halide 
 intermediate . monitoring the reaction mixture by 31p nmr 
 spectroscopy identified ( binap)ni(2-nc - ph ) as the 
 resting state of the catalyst in the amination of both aryl chlorides 
 and bromides . 
 kinetic studies showed that the amination of aryl chlorides 
 and bromides is first order in both catalyst and aryl halide and zero 
 order in base and amine . 
 the reaction of a representative aryl chloride 
 is inverse first order in phcn , but the reaction of a representative 
 aryl bromide is zero order in phcn . 
 this difference in the order of 
 the reaction in phcn indicates that the aryl chloride reacts with 
 ( binap)ni(0 ) , formed by dissociation phcn from ( binap)ni(2-nc - ph ) , but the aryl bromide directly reacts with ( binap)ni(2-nc - ph ) . 
 the overall kinetic behavior is consistent with turnover - limiting 
 oxidative addition of the aryl halide to ni(0 ) . 
 several pathways for 
 catalyst decomposition were identified , such as the formation of the 
 catalytically inactive bis(amine)-ligated arylnickel(ii ) chloride , 
 ( binap)2ni(0 ) , and the ni(i ) species [ ( binap)ni(-cl)]2 . by using a well - defined nickel complex as catalyst , the 
 formation of ( binap)2ni(0 ) is avoided and the formation 
 of the ni(i ) species [ ( binap)ni(-cl)]2 is minimized .