the amination of c  h bonds provides a 
 route to n - alkyl and n - aryl amine 
 derivatives that avoids typical functional group interconversions 
 and reactants containing a functional group already present at the 
 position where a c  n bond is desired .
n bonds are 
 particularly challenging to achieve , but such reactions could directly 
 modify complex molecules , create chemical feedstocks , or create functionalized 
 polymers .
methods for the oxidation of alkanes by 
 the combination of peroxides and iron complexes have been developed , but intermolecular functionalization of purely unactivated c 
h 
 bonds with reagents that form products containing common nitrogen - based 
 functionality are rare .
h bonds have been catalyzed by copper complexes 
 and occur at benzylic or allylic positions .
reactions catalyzed by dirhodium complexes are the most developed 
 for the synthesis of complex molecules .
although remarkable 
 developments and applications have been reported for intramolecular 
 reactions , intermolecular reactions are more limited .
h 
 bond of the substrate , such that the preferred sites of reactions 
 are tertiary , benzylic , and secondary c 
h bonds . when a nitrene is the reactive intermediate , the nitrogen - based 
 reagent is limited to those containing just one substituent .
we sought an alternative route to the intermolecular functionalization 
 of alkyl c  h bonds that could form n - alkyl 
 amides , carbamates , and imides , in addition to the formation of sulfonamides . 

amides , carbamates , and imides are more common synthetic intermediates 
 or final products than those generated by prior copper - catalyzed reactions 
 with alkyl c  h bonds .
we also 
 sought to conduct these transformations with readily accessible complexes 
 of first - row metals .
although copper - catalyzed reactions at allylic 
 and benzylic c  h bonds with carboxylic acids and sulfonamides 
 in the presence of peroxides is well - known ( karasch - sosnovsky reaction ) , and the mechanism of these reactions has been studied , the amidation of c 
h bonds with such reagents has been limited 
 to reactions at benzylic c  h bonds .
we report the reactions of common amides , carbamates , and 
 imides 
 with alkanes to form n - alkyl derivatives with simple 
 copper catalysts and a peroxide ( scheme 1 ) . 

the amidation of alkanes under our catalytic conditions preferentially 
 forms the products from amidation at secondary sites over tertiary 
 sites and even leads to the functionalization of primary c 
mechanistic data from the stoichiometric reactions 
 of isolated copper amidate or imidate complexes indicate that the 
 transformation of alkanes to n - alkyl products likely 
 occurs by the reactions of a alkyl radicals with copper(ii ) amidate 
 and imidate complexes .
h bonds , we evaluated the reactivity 
 of benzamide ( 0.5 mmol ) and cyclohexane ( 10 equiv ) with 2.55.0 
 mol % of various copper precatalysts and oxidants .
results for the 
 copper - catalyzed amidation of cyclohexane with benzamide are presented 
 in table 1 .
the combination of copper and tbuootbu was crucial for catalysis ; other 
 peroxide - based oxidants and redox - active 3d transition metals did 
 not yield the amidation product .
conditions : 0.5 mmol of benzamide , 
 5.0 mmol of cyclohexane , 0.0125 mmol of catalyst , 0.0125 mmol of ligand , 
 1.0 mmol of oxidant , 1 ml of phh at 100 c for 24 h. gc yield with n - dodecane 
 as the internal standard .
the reactions 
 catalyzed by cu(i ) and cu(ii ) salts without ligand 
 gave the n - cyclohexylbenzamide in low yields ( entry 
 14 , 1027% ) .
however , the reactions catalyzed by cu(i ) 
 and bipyridine ( bipy ) , gave n - cyclohexylbenzamide 
 in a measurably higher 36% yield .
reactions catalyzed by the well - defined 
 [ ( l1)cucl ] precatalyst ( entry 8) ( l1 = ( ( ( 2-(dimethylamino)ethyl)imino ) 
 methyl)phenoxide ) provided 83% of n - cyclohexylbenzamide . 
 finally , we found that the reaction of benzamide with cyclohexane 
 catalyzed by the simple combination of phenanthroline ( phen ) ( entry 
 6 ) or 4,7-dimethoxy - phenantronline ( ( meo)2phen ) ( entry 
 7 ) and cui formed n - cyclohexylbenzamide in nearly 
 quantitative yield . the scope of benzamides that undergo 
 this c  h bond amination 
 reaction is summarized in table 2 .
benzamides 
 containing electron - withdrawing groups , such as cl , br , f , and cf3 ( a  d ) , underwent the reaction to give 
 good yields of the corresponding amidation product ( 7382% ) . 

benzamides containing electron - donating groups , such as me , bu , and ome ( e  k ) , also underwent 
 the amidation process , but the isolated yields of the amidation products 
 were slightly lower ( 5578% ) than those of the benzamides containing 
 electron - withdrawing groups .
heteroaromatic amides , such as 2-thienylamide ( m ) and 2-pyridylamide ( l ) , also underwent the 
 oxidative coupling with cyclohexane to give the corresponding n - alkyl products .
the reaction of the 2-pyridylamide is 
 noteworthy because the 2-pyridylamide product could form a strong 
 chelating ligand that would prevent catalysis .
the position of the 
 substituent on the benzamide ( ortho , meta , or para ) did not have a 
 pronounced effect on the reaction yields .
conditions : 0.5 
 mmol of amide , 5.0 
 mmol of cyclohexane , 0.0125 mmol of cui , 0.0125 mmol of ( meo)2phen , 1.0 mmol of tbuootbu , 1 ml of phh at 100 c for 24 h. four equivalents of oxidant .
the reactions of cyclohexane with primary and secondary 
 alkyl amides , 
 carbamates and imides also occurred ( table 2 ) .
the yields of the reactions of cyclohexane with acetamide ( n ) , tert - butylcarbamate ( o ) , 
 and toluenesulfonamide ( p ) to form n - cyclohexylacetamide , tert - butyl - n - cyclohexylcarbamate , and n - cyclohexyltoluenesulfonamide 
 ( 38% , 42% , and 55% , respectively ) were lower than those that formed n - alkyl benzamides .
however , the reaction of tert - butylcarbamate , with excess tbuootbu ( 4 equiv ) gave tert - butyl - n - cyclohexylcarbamate 
 in 75% yield .
the reactions of cyclohexane with secondary nitrogen 
 sources ( n - methylbenzamide , phthalimide , pyrrolidinone , 
 and n - me - p - toluenesulfonamide ) also 
 occurred 
 to form the corresponding n - alkyl products .
the yields 
 of these reactions were variable ( 1075% ) ( q  t ) , but they do demonstrate that the mechanism can not involve a nitrene 
 intermediate .
the reaction of phthalimide was improved from 20% to 
 75% by changing the solvent from benzene to 1,2-dichlorobenzene to 
 increase the solubility of the reagent .
the selectivities for 
 amidation of various alkanes with benzamide 
 are presented in table 3 .
h bonds formed 
 products from functionalization at the secondary c  h bonds 
 ( entry 15 ) .
for example , the major products of the reactions 
 of benzamide with trans- and cis-1,4-dimethylcyclohexane ( entry 1,2 ) resulted from amidation of secondary 
 c  h bonds , while the minor products resulted from the amidation 
 of primary c 
no product was formed from amidation 
 of the tertiary c  h bond . likewise , the reaction of 3-ethylpentane 
 ( entry 5 ) occurred preferentially at secondary and primary c 
the reaction of 2,4-dimethylpentane 
 ( entry 7 ) , in which the secondary c  h bond is hindered , occurred 
 exclusively at the primary c  h bond .
this product distribution 
 contrasts that of most c  h oxidations by a radical mechanism . for reactions of cycloalkanes ranging from cyclopentane to cyclododecane
, 
 the ring size did not affect the yield of the corresponding n - alkyl products ( 6980% ) ( entry 8) .
conditions : 0.5 mmol of benzamide , 
 1 ml of alkane ( 1017 equiv ) , 0.0125 mmol cui , 0.0125 mmol 
 of ( meo)2phen , 2.0 mmol of tbuootbu , 1 ml of o - c6h4cl2 at 
 100 c for 36 h. regioselectivity determined by crude h nmr .
yield for the reaction 
 with t - butylcarbamate . to assess 
 whether copper - amidate and copper - imidate complexes with cu in the 
 oxidation state of + 1 and + 2 are intermediates in the catalytic amidation 
 reactions , we synthesized and characterized a variety of these amidate 
 and imidate complexes supported by phen and 2-(dimethylamino)ethyl)imino)methyl ) 
 phenoxide ( l1 ) ( scheme 2 ) .
salt - metathesis 
 reactions of [ ( phen)cucl]2(-cl)2 with 
 potassium phthalimide ( kphth ) or a combination of naotbu and h2nso2ph or h2ncoph in thf 
 at room temperature yielded air- and moisture - stable [ ( phen)cu(phth)2 ] ( 1-phth2 ) , [ ( phen)cu(nhso2ph)2 ] ( 2 ) , and [ ( phen)cu(nhcoph)2 ] ( 3 ) , respectively .
phen - ligated cu(i ) complexes containing benzamidate and 
 benzenesulfonamidate 
 ligands were isolated from the reaction of [ cu(mes)]n with phen , followed by the addition of benzenesulfonamide 
 and benzamide to produce the corresponding products [ ( phen)2cu][cu(nhso2ph)2 ] ( 4 ) and [ ( phen)2cu][cu(nhcoph)2 ] ( 5 ) . the complex 
 [ ( phen)cu(phth ) ] ( 1-phth )
salt - metathesis reactions 
 of [ ( l1)cucl ] with phthalimide 
 ( hphth ) , benzenesulfonamide , 
 and benzamide produced the corresponding cu(ii ) complexes of [ ( l1)cu(phth ) ] ( 6 ) , [ ( l1)cu(nhso2ph ) ] ( 7 ) , and [ ( l1)cunhcoph ] ( 8) ( scheme 2 ) .
previous structural 
 characterizations of phen - ligated copper(i ) 
 amidate and imidate complexes revealed that these complexes can exist 
 as mononuclear or ion - pair species .
therefore , we assessed the atomic 
 connectivity of 1-phth2 and 4 by single crystal x - ray diffraction ( xrd ) analysis .
all pertinent bond distances and angles for these 
 complexes are listed in the caption of figure 1 .
phen - ligated cu(ii ) phthalimidate 1-phth2 is mononuclear in the solid state with a square planar 
 geometry around the cu(ii ) ion ( figure 1 ) .
molecular 
 structures of [ ( phen)cu(phth)2 ] ( 1-phth2 ) , [ ( phen)2cu ] [ cu(nhso2ph)2 ] ( 4 ) , [ ( l1)cu(phth ) ] ( 6 ) , and [ ( l1)cu(nhso2ph ) ] ( 7 ) shown with 50% thermal ellipsoid . selected bond lengths (  ) 
 and angles (  ) of 1-phth2 : cu1n1 = 2.0480(14 ) ; cu1n2 = 2.0363(14 ) ; cu1n3 
 = 1.9667(14 ) ; n1cu1n3 = 170.29(5 ) ; n1cu1n2 
 = 93.45(5 ) ; n1cu1o1 = 92.5(3 ) . selected bond lengths 
 (  ) and angles ( ) of 4 : cu1n1 
 = 1.9920(15 ) ; cu1n2 = 2.1079(16 ) ; cu1n3 = 1.8553(17 ) ; 
 n1cu1n2 = 81.75(6 ) ; n3cu1n3 
 = 178.92(10 ) . selected bond lengths (  ) and angles ( ) of 6 :
cu1n1 = 1.938(7 ) ; cu1n2 = 2.045(7 ) ; 
 cu1n3 = 1.958(7 ) ; cu1o1 = 1.919(6 ) ; n1cu1n3 
 = 175.2(3 ) ; n1cu1n2 = 83.4(3 ) ; n1cu1o1 
 = 92.5(3 ) . selected bond lengths (  ) and angles ( ) of 7 : cu1n1 = 1.956(6 ) ; cu1n2 = 2.104(6 ) ; 
 cu1n3 = 1.972(6 ) ; cu1o1 = 1.993(5 ) ; n1cu1n3 
 = 170.0(2 ) ; n1cu1n2 = 83.7(2 ) ; n1cu1o1 
 = 91.2(2 ) .
in contrast , the copper(i ) 
 compounds were ion pairs in the solid 
 state .
the structure of phen - ligated benzenesulfonamidate 4 is an ion pair consisting of the cationic [ ( phen)2cu ] , in which cu(i ) is ligated by two phen ligands in a distorted 
 tetrahedral environment , and the linear anion [ cu(nhso2ph)2 ] ( figure 1 ) .
in contrast to the diverse molecular structures of phen - ligated 
 copper species , complexes 6 and 7 containing 
 the tridentate amino imine phenoxide ligands are mononuclear cu(ii ) 
 species with square - planar geometries in the solid state ( figure 1 ) .
these structures are also mononuclear in solution , 
 as evidenced by x - band epr spectroscopy recorded at 20 k in ch2cl2 indicating an axial environment . to determine whether the structures of 1-phth2 and 4 in solution 
 differ from those 
 in the solid state we measured the conductivities 
 of 1-phth2 , and 4 in dmso .
the conductivities of 1-phth2 , and 4 ( 1.0 mm in dmso , 25 c ) were compared 
 to those of a 1.0 mm ( dmso ) solution of ferrocene ( 0.2  cm mol ) and n(bu)4cl ( 11.1  cm mol ) .
the conductivity of the solutions of cu(i ) complexes 4 and 5 in dmso ( 1.0 mm ) were 33.0 and 23.1  cm mol , respectively . 

these values are similar to the reported values for related ( phen)cu(i ) 
 amidate and imidate complexes .
in contrast , 
 the conductivity of the solution of 1-phth2 was 0.0  cm mol , showing that 1-phth2 retains its neutral , mononuclear structure in dmso . 

moreover , the results for conductivity of 6 ( 0.0  cm mol ) and 7 ( 0.1  cm mol ) also revealed that these complexes are neutral molecules 
 in solution .
unfortunately , the insolubility of 1-phth2 and 4 in benzene prevented 
 the measurement of their conductivities in a less polar solvent . to gain information on the mechanism 
 of the catalytic amidation of alkanes
, we conducted catalytic and 
 stoichiometric reactions with isolated [ ( phen)cu(phth)n ] ( n = 1 , 2 ) complexes .
these well - defined complexes 
 contain a reactive phthalimidate group bound to copper in the oxidation 
 states of + 1 and + 2 .
first , we investigated the effect of the 
 oxidation state of the metal in the copper complexes lying on the 
 catalytic reaction .
the reactions of cyclohexane with hphth catalyzed 
 by 2.5 mol % of 1-phth2 and 2.5 
 mol % of 1-phth produced n - cyclohexylphthalimide 
 ( cy - phth ) in 54% and 80% yield , respectively ( scheme 3 ) .
n - methylphthalimide ( me - phth ) was observed 
 in 13% and 20% yields in the reactions catalyzed by 1-phth2 and 1-phth , respectively . 

the observation of this side - product implies the intermediacy of a tert - butoxy radical because this radical is known to undergo 
 -me scission to generate a methyl radical .
this methyl radical can then combine with 1-phth2 to form me - phth ( scheme 3 ) .
the observation of this side 
 product suggests that the n - cyclohexylphthalimide 
 forms from a reaction between 1-phth2 and a cyclohexyl radical generated from hydrogen atom abstraction 
 of cyclohexane by a tert - butoxy radical . in the reaction catalyzed by 1-phth , the 
 orange solution 
 of 1-phth rapidly transformed to a light - blue suspension . 
 a similar light - blue suspension
was also observed in the reaction 
 catalyzed by 1-phth2 . moreover , 1-phth2 was isolated from a reaction 
 of 1-phth , tbuootbu , 
 and hphth in benzene at 100 c for 0.5 h ( scheme 4 ) .
the identity of 1-phth2 was confirmed by comparison of its ir spectrum to that of the authentic 
 sample of 1-phth2 , prepared by 
 the method in scheme 2 , and by elemental analysis . 

the isolation of 1-phth2 from 
 the reaction catalyzed by 1-phth clearly demonstrates 
 that a cu(i)-imidate or amidate is a short - lived species in the presence 
 of excess oxidant and imide or amide under catalytic conditions .
therefore , 
 under the catalytic condition , the predominant species in the system 
 is a cu(ii)-amidate or imidate complex .
second , we investigated the role of oxidant in the catalytic 
 reaction 
 by conducting a series of stoichiometric reactions with 1-phth and 1-phth2 in the presence 
 and absence of tbuootbu .
c  h 
 bond amidations of cyclohexane by copper complexes have been proposed 
 to occur by insertion of a copper - nitrene intermediate into a c  h 
 bond or by hydrogen atom abstraction . in one study ,
a copper - nitrene 
 species stabilized by sc and an isolated bridging copper - nitrene 
 complex were shown to undergo stoichiometric reactions with cyclohexane 
 to form n - cyclohexyl-4-methylbenzenesulfonamide and n - cyclohexyladamantane , respectively . in another study , an isolated , three - coordinate cu(ii)-nhad (
ad 
 = adamantane ) complex was shown to react with cyclohexane to form n - cyclohexyladamantane ; this reaction was proposed to occur 
 by abstraction of a hydrogen atom from cyclohexane and capture of 
 the cyclohexyl radical by cu(ii ) .
a mechanism 
 involving a nitrene intermediate in our system is ruled out by the 
 reaction of secondary nitrogen reagents ( i.e. , phthalimide ) with cyclohexane 
 to form the corresponding n - alkyl product , but reaction 
 of the amidate and imidate complexes with the alkane could occur .
thus , we tested the potential reactions of the copper amidate and 
 imidate complexes with cyclohexane . to do so , we performed stoichiometric 
 reactions of 1-phth and 1-phth2 with cyclohexane
. these reactions would assess whether 
 these complexes are capable of abstracting a hydrogen atom from cyclohexane . 

the reaction of 1-phth or 1-phth2 with cyclohexane ( 80 equiv ) in mecn or benzene without tbuootbu at 100 c for 2472 
 h produced no cy - phth detectable by gc ( scheme 5 , a ) .
the absence of any cy - phth product from these reactions rules 
 out a mechanism involving hydrogen atom abstraction by the cu(i ) or 
 cu(ii ) phthalimidates and combination of the resulting alkyl radical 
 with the copper complexes .
however , the stoichiometric reaction of 1-phth2 with cyclohexane and tbuootbu ( 16 equiv ) for 24 h produced cy - phth ( 70% 
 yield based 
 on copper ) , me - phth , and cy - otbu in a 70:25:35 ratio 
 ( scheme 5 , b ) . the analogous reaction of 1-phth with cyclohexane and tbuootbu ( 16 equiv ) also produced cy - phth ( 73% yield based on copper ) , 
 me - phth , and cy - otbu in a 73:21:32 ratio ( scheme 5 , c ) .
formation of the ether product has been observed 
 from cu(i)-catalyzed decomposition of tbuootbu and recombination of a cyclohexyl radical with a cu  otbu functionality .
moreover , 
 the observation of cy - otbu suggests that [ ( phen)cu(phth)(otbu ) ] is a likely intermediate in these reactions lacking 
 free phthalimide ; reaction of the cyclohexyl radical with this complex 
 would form cy - phth and cy - otbu .
the formation 
 of n - alkyl amides in the presence 
 of tbuootbu , but not in the absence 
 of tbuootbu , was observed for copper 
 complexes 1-phth2 or 1-phth .
complexes 26 also reacted with 
 cyclohexane to produce their corresponding n - alkyl 
 products in the presence of tbuootbu , but not in the absence of tbuootbu .
these studies provide further evidence 
 that tbuootbu leads to formation 
 of tert - butoxy radical , which cleaves the alkane 
 c  h bond . to investigate if the cu(ii ) complex 1-phth2 and the cu(i ) complex 1-phth react by 
 a common pathway , we measured the kinetic isotope effect of the amination 
 reactions catalyzed by these two complexes .
reactions of the combination 
 of cyclohexane and cyclohexane - d12 in 
 a single vessel containing phth , tbuootbu , and 2.5 mol % 1-phth2 occurred 
 with a primary kie of 2.7  0.1 .
the reaction of 1-phth under the same experimental conditions occurred with a primary kie 
 of 3.0  0.3 .
the similarity of these values is consistent with 
 reaction of cu(i ) and cu(ii ) complexes through the same c 
h 
 bond cleavage step . furthermore , the catalytic reaction of cyclohexane 
 and cyclohexane - d12 in the same vessel 
 with benzamide and 2.5 mol % of the phen - ligated cu(ii ) benzamidate 
 complex 5 occurred with a primary kie value of 2.8  
 0.4 .
these results imply that the same c  h bond cleavage step 
 occurs for reactions of the different copper - amidate complexes .
results from the stoichiometric and catalytic reactions of 1-phth2 and 1-phth strongly 
 suggest that a tert - butoxy radical is responsible 
 for the c  h abstraction of cyclohexane . to assess this hypothesis 
 further , we performed experiments that would trap the tert - butoxy and alkyl radicals .
first , we conducted the catalytic 
 reaction in the presence of diphenylmethanol ( 2.5 equiv ) ( scheme 6 , a ) , a common probe for tert - butoxyl 
 radical .
this alcohol can react with an alkoxy radical 
 by abstraction of the c  h hydrogen atom from cu(ii)-diphenylmethoxide 
 to form a cu(ii)-ketyl radical that is then oxidized to form benzophenone 
 to regenerate cu(i ) .
alternatively , an 
 alkoxy radical abstracts the c  h bond of diphenylmethanol to 
 form a ketyl radical .
this ketyl radical undergoes another hydrogen 
 atom abstraction at the oh group by another alkoxy radical to form 
 benzophenone .
consistent with the generation 
 of an alkoxy radical , the catalytic reaction conducted in the presence 
 of diphenylmethanol formed the n - cyclohexyl benzamide 
 product in only 47% yield , based on benzamide . instead of the n - cyclohexyl amide , a large amount of benzophenone ( 2.4:1.0 
 ratio of benzophenone to n - cyclohexyl benzamide ) 
 formed .
this reaction to form benzophenone decreases the amount of 
 available tert - butoxy radical for hydrogen atom abstraction 
 of cyclohexane and thus decreased the yield of the n - cyclohexyl benzamide product .
second , we probed 
 for the formation of tert - butoxy 
 radical by conducting the reaction in the presence of the hydrogen 
 atom donor 9,10-dihydroanthracene .
the tert - butoxy 
 radical should abstract the weak c  h bond of 9,10-dihydroanthracene 
 over the stronger c  h bonds in cyclohexane .
indeed , the catalytic 
 reaction of benzamide with cyclohexane conducted under the standard 
 conditions , except for the addition of 3 equiv of 9,10-dihydroanthracene , 
 yielded anthracene as the only organic product besides tert - butanol ( scheme 6 , b ) . finally , to 
 probe for a transient cyclohexyl radical in the reaction , 
 we performed the catalytic reaction in the presence of cbr4 ( scheme 7 , a ) , which would trap a cyclohexyl 
 radical to form bromocyclohexane .
the reaction of benzamide 
 with cyclohexane and tbuootbu at 
 100 c for 24 h did not form any product from the amidation of 
 cyclohexane . instead , bromocyclohexane formed in 90% yield , based 
 on benzamide .
this result is consistent with the intermediacy of a 
 cyclohexyl radical in the catalytic reaction .
the reaction of this alkane in the presence of cbr4 and 2.5 mol % cui/(meo)2phen in benzene at 100 
 c for 24 h ( scheme 7 , b ) formed the products 
 from bromination at the tertiary and the secondary sites : cis- and trans-1-bromo-1,4-dimethylcyclohexane 
 and cis- and trans-2-bromo-1,4-dimethylcyclohexane . 

the two sets of constitutional isomers formed in a ratio of 1.7:1 
 and a combined 86% yield based on cbr4 .
the 1-bromo-1,4-dimethylcyclohexane 
 diastereomers were obtained as a 1.2:1 mixture , indicating that the 
 transient tertiary radical formed under this condition undergoes facile 
 racemization . to investigate whether 
 an alkyl radical would react with the copper imidates to form an n - alkyl product , we conducted reactions of the phthalimidate 
 complex 1-phth2 with precursors 
 to alkyl radicals .
we chose to use peroxides as the precursors to 
 alkyl radicals , and we performed these reactions with 1-phth2 instead of 1-phth because 
 our data indicate that 1-phth2 is the predominant complex under catalytic conditions .
the reaction 
 of 1-phth2 with tbuootbu and ( ph(me)2co)2 at 
 100 c for 18 h generated me - phth in 64% and 81% yield based 
 on copper , respectively ( scheme 8) .
the rate 
 of -me scission of the cumyloxide radical is faster than that 
 of the tert - butoxy radical .
thus , the higher yield 
 of n - alkyl product from the reaction of dicumyl peroxide 
 than from the reaction of tbuootbu is consistent with the rate of generation of the methyl radical .
these results with radical probes and alkyl radicals provide 
 strong 
 evidence that an alkoxy radical generates an alkyl radical by hydrogen 
 atom abstraction and that the alkyl radical combines with a copper(ii)-amidate 
 and -imidate species to produce the amidation and imidation products . 

the formation of products from halogenation at the tertiary c  h 
 bond of the dimethylcyclohexane indicates that the absence of the 
 products from amination at the tertiary c 
n bond ( vide infra ) . reactions in acetonitrile provide evidence against a carbocationic 
 intermediate that could form by oxidation of the radical and combination 
 of the cation with the copper amide or imidates .
the amidation 
 of cyclohexane with hphth in wet acetonitrile ( scheme 3 ) produced me - phth ( 80% ) , and this result argues against a 
 transient carbocation in our system .
additional measurements of kie values 
 were conducted to determine the turnover - limiting step ( tls ) of the 
 catalytic reaction .
the kie determined from independent measurements 
 of the rates of amidation of cyclohexane and cyclohexane - d12 catalyzed by 10 mol % of 3 was 2.9  
 0.1 .
this primary kie indicates that 
 hydrogen atom abstraction of cyclohexane by a tert - butoxy radical is the turnover - limiting step in the catalytic process . to identify the tls and to explain the observed primary kie
we obtained 
 the kinetic data by measuring the concentration of cyclohexylbenzamide 
 and n - methylbenzamide versus time by the method of 
 initial rates with varied concentrations of oxidant , cyclohexane , 
 and benzamide . at copper concentrations 
 of 23 mm ,
the reaction was found to be first - order in oxidant , first - order 
 in cyclohexane , and zero - order in benzamide .
the reaction order of 
 oxidant and cyclohexane is consistent with turnover - limiting c 
the dependence of the reaction rate on the concentration of oxidant 
 and cyclohexane was lower for reactions conducted with higher concentrations 
 of these two reagents . when the concentration of oxidant and cyclohexane 
 exceeded 1.0 m
, there was little dependence of the rate of cyclohexane 
 amidation on the concentration of these two species .
the order of cu is complex ; our data indicates that 
 the reaction 
 rate is positively dependent on the concentration of cu .
however , 
 the order of the reaction in the concentration of copper varied between 
 first - order and essentially zeroth - order . a similar dependence of reaction rate on the concentration of copper 
 was reported for copper - catalyzed allylic oxidation of cyclohexene 
 by tert - butyl perbenzoate in benzene . at low concentration of copper ,
the rate of 
 allylic oxidation increased with increasing concentration of copper ; 
 however , the rate of this reaction was less dependent on the concentration 
 at higher concentrations of copper .
in addition 
 to the difference in dependence of the rate on the 
 concentration of copper , we observed a difference in yield of the 
 amination products as a function of the concentration of copper .
reactions 
 conducted with a higher mol % of the cu catalyst formed the n - alkyl amide product in lower yields than the reactions 
 conducted with a lower loading of the cu catalyst . specifically , reactions 
 of cyclohexane conducted with 2.8417.0 mm 5 yielded 
 9499% of the n - cyclohexy benzamide product , 
 while those conducted with 34.045.5 mm 5 gave 
 the n - cyclohexyl benzamide product in 76% yield , 
 along with menhcoph ( 10% ) and unreacted benzamide .
perhaps , at higher 
 loading of cu(i ) , faster decomposition of peroxide leads to a higher 
 concentration of tert - butoxy radical , relative to 
 the concentration of copper complex , and the tert - butoxy radical undergoes processes that do not lead to the n - alkyl amide product . the tert - butoxy 
 radical
is known to undergo multiple 
 nonproductive pathways : ( 1 ) -me scission for the methylation 
 of the bound cu(ii)-amidate ; ( 2 ) coupling of methyl radicals ; and ( 3 ) reaction of tert - butoxy 
 radical with cu(i ) to form cu(ii)-otbu .
the quenching of the tert - butoxy radical at high 
 concentration of copper offers one possible explanation for the lower 
 yield of product at high loading of cu(i ) compared to low loading 
 of cu(i ) and the lower order in copper .
regardless of the origin 
 of the effect of the concentration of 
 copper on yield , a copper complex does not directly participate in 
 the c  h bond cleavage of cyclohexane .
several pieces of data 
 provide evidence that copper is not required for c  h cleavage 
 of cyclohexane .
for example , in the absence of copper , the reaction 
 of adamantane with tbuootbu and 
 cbr4 at 100 c for 24 h produced a mixture of 1-bromoadamantane 
 and 2-bromoadamantane in a ratio of 2.6:1 , respectively . the same reaction conducted in the presence 
 of copper , formed a mixture of products containing 1-bromoadamantane 
 and 2-bromoadamantane in a 2:1 ratio .
the similarity of the ratio 
 of products in the presence and absence of copper suggest that copper 
 is not directly involved in the c  h cleavage step .
first , copper 
 catalyzes the decomposition of tbuootbu to generate tert - butoxy radical , which is the 
 species that cleaves the c  h bond of the alkanes .
specifically , 
 reaction of 1-phth with tbuootbu and hphth in the absence of a hydrogen atom donor ( i.e. , 
 cyclohexane ) leads to rapid oxidation of 1-phth to 1-phth2 and exclusive formation of 
 me - phth , in which the methyl radical is derived from tert - butoxy radical by -me scission .
additional evidence for copper - catalyzed formation of tert - butoxy radical is the observation of benzophenone from diphenylmethanol 
 under catalytic conditions .
second , copper 
 participates in the events after the turnover - limiting step of c  h 
 activation by tert - butoxy radical to form the n - alkyl product .
this proposal is corroborated by the reaction 
 of methyl radicals , derived from the tertiary alkoxy radical precursors 
 ro - or ( r = tbu , ph(me)2c ) , with 1-phth2 to generate 
 the me - phth product .
our proposed mechanism for c  h amidation 
 of cyclohexane 
 by 1-phth is summarized in scheme 9 .
our proposed mechanism begins with the decomposition of tbuootbu initiated by 1-phth to produce a tert - butoxy radical and a potential 
 intermediate containing an alkoxide and a phthalimidate ligand [ ( phen)cu(phth)(otbu ) ] .
the tert - butoxy radical can regenerate tbuootbu by secondary geminate recombination 
 or can abstract a hydrogen atom from an alkane to form an alkyl radical . in this case , the turnover - limiting step is 
 abstraction of a hydrogen atom from cyclohexane by a tert - butoxy radical to produce a cyclohexyl radical , which recombines 
 with 1-phth2 to expel cy - phth 
 and regenerate 1-phth to close the cycle .
this species could be a transient cu(iii ) 
 intermediate ligated by a cyclohexyl and amidate ligand .
such a species 
 could undergo rapid reductive elimination to release the n - alkyl product and to regenerate cu(i ) .
prior mechanistic and dft investigations of the kharasch - sosnovsky 
 reaction have led to the conclusion that these oxidative reactions 
 occur by formation of a cu(iii ) species , which forms the c  o 
 bond by reductive elimination .
conversely , dft calculations on the combination of a cyclohexyl 
 radical with the three - coordinate [ ( nacnac)cu(ii)-otbu ] ( nacnac = [ arnc(me)]2ch ; ar = 2,6-cl2c6h3 ) to form cy - otbu suggest that capture of the alkyl radical at the oxygen atom of 
 the otbu ligand is thermodynamically favorable ( g = 13.4 kcal / mol ) , whereas combination of the alkyl 
 radical at cu(ii ) to form the square planar complex [ ( nacnac)cu(iii)(cy)(otbu ) ] is thermodynamically disfavored ( g = + 14.9 kcal / mol ) .
thus , it is possible 
 that the alkyl radical reacts directly with the imidate or amidate 
 ligands to form the n - alkyl imide and amide products .
the selectivity of secondary ( 2 ) and primary sites ( 1 ) 
 over tertiary ( 3 ) sites for the amidation of alkanes by this 
 copper system is different from the selectivity of 3 > 2 
 > 1 for hydrogen abstraction by a tert - butoxy 
 radical .
this selectivity for secondary 
 over primary and tertiary sites has been observed in the copper - catalyzed 
 amidation of benzylic c  h bonds , and the rationale for such 
 selectivity was based on steric effects .
h bonds results from the recombination of alkyl 
 radicals with phen - ligated cu(ii ) amidate and imidate complexes ; we 
 propose that the tertiary radical is too hindered to recombine with 
 phen - ligated cu(ii ) amidate and imidate complexes and the alkyl radical 
 undergoes decomposition . to address this proposal , we determined 
 the mass balance of the 
 reaction .
this information would provide insight into the fate of 
 all the alkyl radicals that could form .
the amidation of adamantane 
 afforded a ratio of 1.6 n-(adamantan-1-yl)benzamide 
 to 1.0 n-(adamantan-2-yl)benzamide and 1-phenyladamantane . 

the 1-phenyladamantane product likely results from the direct reaction 
 of 1-adamantyl radical with benzene .
the 
 observation of 1-phenyladamantane reveals another pathway by which 
 tertiary alkyl radicals decompose in the reaction .
the alkene likely forms from the decomposition 
 of the tertiary radical , and this decomposition likely occurs because 
 the combination of the tertiary radical with the phen copper amidate 
 or imidate is sterically disfavored .
in summary , we have described a copper - catalyzed amidation of unactivated 
 alkanes by benzamide , sulfonamide , carbamate , phthalimide , and their 
 derivatives .
the amidation of alkanes under our catalytic conditions 
 preferentially forms the products from amidation at secondary sites 
 over tertiary sites .
h bonds to 
 form n - alkyl products is observed when the secondary 
 c  h bonds are hindered .
potential cu(ii)-amidate and -imidate 
 intermediates were isolated , characterized , and demonstrated to be 
 intermediates for c  h amidation of cyclohexane .
our mechanistic 
 data imply that the tert - butoxy radical , not a copper - nitrene 
 or copper - aminyl species , leads to the activation of aliphatic c 
 we 
 report a set of rare copper - catalyzed reactions of alkanes with 
 simple amides , sulfonamides , and imides ( i.e. , benzamides , tosylamides , 
 carbamates , and phthalimide ) to form the corresponding n - alkyl products . 
 the reactions lead to functionalization at secondary 
 c  h bonds over tertiary c  
 h bonds and even occur at 
 primary c  h bonds . [ ( phen)cu(phth ) ] ( 1-phth ) and 
 [ ( phen)cu(phth)2 ] ( 1-phth2 ) , which are potential intermediates in the reaction , have 
 been isolated and fully characterized . 
 the stoichiometric reactions 
 of 1-phth and 1-phth2 with alkanes , alkyl radicals , and radical probes were investigated 
 to elucidate the mechanism of the amidation . 
 the catalytic and stoichiometric 
 reactions require both copper and tbuootbu for the generation of n - alkyl product . 
 neither 1-phth nor 1-phth2 reacted 
 with excess cyclohexane at 100 c without tbuootbu . 
 however , the reactions of 1-phth and 1-phth2 with tbuootbu afforded n - cyclohexylphthalimide ( cy - phth ) , n - methylphthalimide , and tert - butoxycyclohexane 
 ( cy - otbu ) in approximate ratios of 70:20:30 , respectively . 
 reactions with radical traps support the intermediacy of a tert - butoxy radical , which forms an alkyl radical intermediate . 
 
 the intermediacy of an alkyl radical was evidenced by the catalytic 
 reaction of cyclohexane with benzamide in the presence of cbr4 , which formed exclusively bromocyclohexane . 
 furthermore , 
 stoichiometric reactions of [ ( phen)cu(phth)2 ] with tbuootbu and ( ph(me)2co)2 at 100 c without cyclohexane afforded n - methylphthalimide ( me - phth ) from -me scission of the alkoxy 
 radicals to form a methyl radical . 
 separate reactions of cyclohexane 
 and d12-cyclohexane with benzamide showed 
 that the turnover - limiting step in the catalytic reaction is the c  
 h 
 cleavage of cyclohexane by a tert - butoxy radical . 
 
 these mechanistic data imply that the tert - butoxy 
 radical reacts with the c  h bonds of alkanes , and the subsequent 
 alkyl radical combines with 1-phth2 to form the corresponding n - alkyl imide product . 