the oxidation of alkanes 
 to alcohols or ketones and the dehydrogenation 
 of alkanes to alkenes are both widely studied targets for c  h 
 bond functionalization . for example , the oxidation of cyclohexane to a mixture 
 of cyclohexanol and cyclohexanone is a large - scale commercial 
 process for the production of adipic acid .
the oxidation of propene at the allylic c  h bond to 
 form acrolein also is a well - known large - scale 
 c  h bond oxidation process , and the oxidation of 
 allylic c  h bonds to allylic esters is being studied actively 
 for applications in target - oriented synthesis .
the dehydrogenation of light alkanes is being studied as a 
 route 
 to ethylene , propene , butene , butadiene , isobutene , and isoprene , 
 with hydrogen as the single side product or with an oxidant to consume the hydrogen and make the reaction , 
 called oxidative dehydrogenation ( odh ) , favorable thermodynamically .
although alkane dehydrogenation and allylic oxidation 
 are both known reactions , the combination of these two reactions 
 in a single process is rare .
one can envision that such a process 
 could occur by initial dehydrogenation of an alkane to an alkene , 
 followed by oxidation of allylic c  h bonds in the alkene 
 product .
indeed , one form of such a reaction is the well - established 
 synthesis of maleic anhydride from butane .
however , the combination of dehydrogenation and selective 
 oxidation of the alkene to an allylic alcohol derivative directly 
 from an alkane is poorly developed .
recently , two examples of 
 copper - catalyzed oxidative dehydrogenative 
 cross - coupling reactions of an aldehyde and toluene with cyclohexane 
 to generate allylic esters have been reported .
however , the yields of these reactions were generally low and occurred 
 with limited substrate scope .
copper - catalyzed combinations of 
 alkane dehydrogenation and aziridination or epoxidation also 
 have been reported , but the epoxide and aziridine are just one component 
 of a mixture of products , and they formed with a maximum of 34 
 turnovers .
thus , a high - yield combination of dehydrogenation 
 and c  h bond oxidation of an alkane to form an allylic 
 alcohol derivative that occurs with tolerance for a wide range of 
 functional groups is not known .
herein , we report the copper - catalyzed 
 oxidative dehydrogenative 
 carboxylation ( odc ) of unactivated alkanes in the presence of 
 carboxylic acid derivatives to form the corresponding allylic ester 
 ( scheme 1 ) .
sosnovsky reaction , but the starting material is an alkane , rather than an alkene .
the 
 reactions occur by oxidative dehydrogenation of an alkane and 
 oxidation of the resulting allylic c  h bond .
detailed 
 mechanistic studies show that the tert - butoxy radical 
 abstracts a c  h bond of cyclohexane to generate a transient 
 cyclohexyl radical , and this radical is converted to cyclohexene 
 by a copper  benzoate complex .
the relative rates for 
 trapping of the radical by the ligand on copper versus conversion 
 of the radical to an alkene control the selectivity for the formation 
 of allylic vs alkyl ester products .
to 
 extend our recently published copper - catalyzed amidation 
 of cyclohexane to the acetoxylation or benzyloxylation 
 of cycloalkanes , we conducted the reaction of cyclohexane with 
 benzoic acid and tbuootbu in the 
 presence of [ ( phen)cu](2-i)2 ( phen = 
 1,10-phenanthroline ) .
we envisioned 
 that the combination of the cu(i ) and tbuootbu should generate tbuo , which could generate cyclohexyl radical , and this radical 
 could combine with [ ( phen)cu(o2cph)2 ] to form cyclohexyl benzoate . although benzoic acid did react 
 with cyclohexane and tbuootbu in the presence of 2.5 mol% of [ ( phen)cu](2-i)2 , this combination of materials yielded the allylic 
 ester cyclohex-2-en-1-yl benzoate ( 21% ) and methyl benzoate 
 ( 16% ) , not the alkyl benzoate ( scheme 2 ) .
thus , the reaction of cyclohexane 
 with benzoic acid and tbuootbu in 
 the presence of copper occurs by a combination of dehydrogenation 
 and c  h bond carboxylation.scheme 2initial studies of odc of cyclohexane to increase the yield of 
 the allylic ester from this 
 reaction , we evaluated the reactivity of benzoic acid ( 0.5 mmol ) and 
 cyclohexane ( 10 equiv ) with a series of copper salts and discrete 
 copper complexes .
simple cu(i ) and cu(ii ) halides catalyzed 
 the coupling of benzoic acid and cyclohexane to produce cyclohex-2-en-1-yl 
 benzoate in moderate to good yields ( entries 17 ) .
for example , 
 the combination of cucl ( 5 mol% ) and tbuootbu ( 3 equiv relative to benzoic acid ) gave a high yield 
 of product ( 76% ) .
reactions conducted with a higher 10 mol% loading 
 of cu occurred in a lower yield ( 54% ) than did the reaction with 5 
 mol% copper ( entry 4 ) .
a similar trend of lower yield with higher 
 loadings of catalyst was observed for the copper - catalyzed amidation 
 of cyclohexane . the lower yield 
 of product from reactions containing higher concentrations of copper 
 presumably results from quenching of the transient tert - butoxy radical by cu(i ) to form cu(ii)-otbu species .
conditions : 0.5 
 mmol of acid , 5.0 
 mmol of cyclohexane , 0.025 mmol of catalyst , 1.0 mmol of oxidant , 
 1 ml of c6h6 at 100 c for 24 h. h nmr yield with meno2 as the internal standard added after reaction .
l1 , me2nch2ch2n = ch 
 ( 2-oh - c6h4 ) ; bpi , bis(2-pyridylimino)isoindole ; 
 phth , phthalimide .
the reaction 
 also occurred when catalyzed by cu(i ) complexes containing 
 neutral bidentate nitrogen ligands , such as 4,7-dichloro-1,10-phenanthroline , 
 3,4,7,8-tetramethyl-1,10-phenanthroline , 1,10-phenanthroline , 
 4,7-dimethyl-1,10-phenanthroline , 4,5-diazafluoren-9-one , and 
 1,10-phenanthroline-5,6-dione .
the 
 reactions catalyzed by these cu(i ) complexes ligated by dative nitrogen 
 ligands formed cyclohex-2-en-1-yl benzoate ( 2364% ) in 
 modest yields .
reactions catalyzed by 
 the well - defined [ ( l1)cucl ] ( l1 = me2nch2ch2n = ch(2-o - c6h4 ) , [ ( bpi)cu(pph3)2 ] , and [ ( bpi)cucl ] 
 ( bpi = bis(2-pyridylimino)isoindole ) reproducibly produced 
 the product in 4050% yields ( entries 913 ) .
the reactions 
 catalyzed by ligated copper complexes gave larger amounts of methyl 
 benzoate than did reactions with unligated copper .
consistent with this observation , kochi reported that nitrogen - ligated 
 cu(ii ) complexes oxidize alkyl radicals to alkenes more slowly than 
 do simple cu(ii ) salts .
although these reactions 
 with ligated copper occurred in lower yield than those with simple 
 copper halides , they did give substantial amounts of product and were 
 valuable for studying the mechanism of this reaction ( vide 
 infra ) .
the scope of the odc of cyclohexane 
 with carboxylic acids to form allylic esters is presented in table 2 .
the yields of these reactions are based on carboxylic 
 acid . the mass balance consisted of unreacted carboxylic acid and 
 methyl benzoate , the origin of which
the reaction is tolerant of halogens on the benzoic acid 4-x - c6h4-co2h ( x = f ( 1a ) , cl 
 ( 2a ) , br ( 3a ) ) , forming the corresponding 
 allylic esters in 5779% yields in these cases .
the reaction 
 is also tolerant of a halide ( 1c , 2c ) , methoxy 
 ( 4c ) , and acetyl group ( 5c ) in the ortho position .
carboxylic acids containing electron - donating 
 substituents on the aromatic system , such as methyl ( 1b , d , e ) , tert - butyl ( 2b ) , methoxy ( 1f ) , 4-phenoxy ( 2f ) , and phthalimido ( l ) groups , generated the corresponding 
 allylic ester products in 5671% yields .
substrates containing 
 electron - withdrawing substituents , such as acetyl ( m ) , 
 trifluoromethyl ( j ) , cyano ( p ) , and carboalkoxy 
 ( n ) groups , also gave the corresponding products in moderate 
 to good yields ( 5276% ) .
even a thioether ( h ) 
 is tolerated , despite the oxidizing conditions of the catalytic reaction ; 
 cyclohex-2-en-1-yl 4-(methylthio)benzoate was produced in 69% 
 yield .
yields 
 were determined by h nmr spectroscopy with meno2 as internal standard , added 
 after the reaction , and reported as an average of two reactions .
the reactions with heteroaryl carboxylic acids , such as furan 
 ( q ) and thiophene ( r ) , also gave substantial 
 yields of allylic esters ; however , pyridine carboxylic acids did not 
 yield allylic oxidation products .
finally , vinyl and aliphatic 
 carboxylic acids reacted to form allylic 
 esters . specifically , the odc of cyclohexane with cyclohexanecarboxylic 
 acid ( s ) , ( e)-2-methyl-3-phenylacrylic 
 acid ( t ) , octanoic acid ( 1u ) , and phenylacetic 
 acid ( 2u ) gave cyclohex-2-en-1-yl cyclohexanecarboxylate 
 ( 62% ) , cyclohex-2-en-1-yl ( e)-2-methyl-3-phenylacrylate 
 ( 57% ) , cyclohex-2-en-1-yl octanoate ( 69% ) , and cyclohex-2-en-1-yl 
 2-phenylacetate ( 69% ) , respectively .
the reaction also 
 occurred with smaller or larger cycloalkanes 
 and , to an extent , with acyclic alkanes .
reactions of benzoic acids 
 with cyclopentane and cycloheptane in the presence of 5 mol% of cucl 
 yielded the corresponding products in good yield ( cyclopent-2-en - yl 
 benzoate ( 1v , 75% ) , cyclohept-2-en - yl benzoate ( 2v 75% ) ) , but the reaction with cyclooctane formed cyclooct-2-en - yl 
 benzoate ( 3v , 12% ) in modest yield .
in addition to reactions 
 of cyclic alkanes , reactions of linear alkanes ( i.e. , pentane ) containing 
 multiple c  h bonds were performed to assess the selectivity 
 of the catalytic odc .
the reaction of pentane and benzoic acid in 
 the presence of 2.5 mol% of 1-pph3 and tbuootbu produced two products : 
 pent - en-2-yl benzoate ( 1w , 26% ) and pent-1-en-3-yl benzoate ( 2w , 10% ) . the potential product of pen-2-en-1-yl benzoate , 
 which would be obtained from the oxidation of the pent-2-ene 
 intermediate at the primary c  h bond , was not observed .
h 
 bond is favored over oxidation of a primary allylic c  h 
 bond .
the reaction 
 of 2,2-dimethylpentane and benzoic acid produced 4,4-dimethylpent-1-en-3-yl 
 benzoate ( y , 16% ) and methyl 
 benzoate ( 80% ) as the major byproduct .
although 
 most of the catalytic reactions were performed with cucl as catalyst , 
 copper complexes ligated by the imidobipyridine ligand bpi did catalyze 
 the reaction , and the molecular complex [ ( bpi)cu(o2cph ) ] 
 ( 1-o2cph ) was amenable 
 to isolation .
the soluble , single - component cu(ii ) species 1-o2cph was prepared 
 in 80% yield as a green solid by salt metathesis between [ ( bpi)cucl ] 
 ( 1-cl ) and nao2cph in meoh at room temperature 
 for 3 h ( scheme 3 )
. elemental analysis of the 
 product was consistent with the proposed atomic composition for 1-o2cph .
we suspect that 
 the molecular structure of 1-o2cph is similar to that of the derivatives of [ ( bpi)cux ] 
 ( x = 2,6-dimethoxybenzoate and 3,4-dimethoxybenzoate ) 
 ( vide infra ) . to assign the oxidation state 
 of the copper center , we performed x - band epr measurement on 1-o2cph in toluene at 
 25 k. the x - band epr spectrum of 1-o2cph revealed an axial pattern , consistent with 
 a cu(ii ) ( s = 1/2 ) center . to isolate a discrete 
 cu(i ) complex , [ ( pph3)2cu(oac ) ]
the reaction in toluene 
 at room temperature formed [ ( bpi)cu(pph3)2 ] 
 ( 1-pph3 ) in 58% yield as an orange 
 crystalline solid ( scheme 3 ) .
compound 1-pph3 was characterized by multinuclear 
 ( h , c , p ) nmr spectroscopy , 
 ft - ir spectroscopy , and elemental analysis . with discrete cu(i ) and 
 cu(ii ) complexes in hand , we investigated the resting state of the 
 catalyst .
the resting state of the copper 
 species in the reaction between 
 cyclohexane and benzoic acid catalyzed by 1-pph3 with tbuootbu as oxidant was determined by uv  vis spectroscopy , x - band 
 epr spectroscopy , and independent synthesis of copper complexes .
a mixture of benzoic acid , cyclohexane , 
 and tbuootbu with 5 mol% 1-pph3 in benzene was allowed to react for 2 h 
 at 100 c .
the uv  vis spectrum of this reaction mixture 
 was identical to that of independently synthesized 1-o2cph recorded in benzene .
likewise , the x - band epr spectrum of the reaction 
 mixture collected at 25 k was identical to that of an authentic sample 
 of 1-o2cph . to assess the identity of this complex 
 further , a stoichiometric 
 reaction of 1-pph3 with benzoic 
 acid ( 1.5 equiv ) and tbuootbu in 
 the absence of cyclohexane was conducted at 100 c for 
 0.5 h in benzene .
this reaction afforded 1-o2cph in 64% isolated yield ( scheme 4 ) , as determined by ft - ir , x - band epr spectroscopy , 
 elemental analysis , and comparison of the material to 1-o2cph synthesized independently 
 from the salt metathesis reaction of 1-cl with nao2cph .
these data from the spectroscopic measurement of the 
 copper species in the catalytic reactions and of the species formed 
 independently from stoichiometric reactions strongly indicate that 
 a copper(ii)benzoate complex is the resting state of the catalyst . to assess the role of 1-o2cph in the catalytic reaction
the reaction of 1-o2cph with cyclohexane was conducted 
 in the presence of tbuootbu at 100 
 c for 21 h in acetonitrile ( scheme 5 ) . 

the products consisted of cyclohex-2-en-1-yl benzoate ( 44% ) 
 and methyl benzoate ( 49% ) .
these results are consistent with competitive 
 reactions of a cyclohexenyl radical and a methyl radical with 1-o2cph to produce cyclohex-2-en-1-yl 
 benzoate and methyl benzoate , respectively .
the analogous reaction 
 performed in the absence of tbuootbu gave no product from reaction of the cyclohexane .
these 
 results show that the copper  benzoate does not react directly 
 with the alkane . instead , a species generated from copper and tbuootbu reacts with the alkane .
to assess the sequence of bond - forming events in the catalytic 
 odc of cyclohexane , we conducted the reaction of cyclohexyl 
 benzoate and cyclohexene ( separately ) ( scheme 6,a ) with tbuootbu and the 
 copper catalyst .
these two reactions reveal whether formation 
 of the alkene occurs before or after formation of the c 
the reaction of cyclohexyl benzoate , benzoic acid , and tbuootbu with 2.5 mol% of 1-o2cph at 100 c for 24 h 
 did not form cyclohex-2-en-1-yl benzoate .
the detection of methyl benzoate 
 indicates that tert - butoxy radical was generated 
 from the reaction of tbuootbu with 
 copper , but that this radical reacts more slowly with the cyclohexyl 
 benzoate than it undergoes -methyl scission to generate the 
 methyl radical ( which reacts with the copper  benzoate complex 
 to form methyl benzoate ) .
in contrast to the 
 reaction of cyclohexyl benzoate , the reaction 
 of cyclohexene with benzoic acid and tbuootbu in the presence of 2.5 mol% 1-o2cph generated the allylic ester .
this 
 reaction formed cyclohex-2-en-1-yl benzoate in 58% yield and 
 methyl benzoate in 27% yield after 24 h at 100 c ( scheme 6b ) .
moreover , the reaction of cyclohexane 
 with tbuootbu in the presence of 
 1 mol% of 1-o2cph ( based on tbuootbu ) in benzene - d6 at 100 c for 20 h ( scheme 6c ) formed cyclohexene in 12% yield , with respect to 
 cyclohexane , as determined by h nmr spectroscopy . 

these results clearly indicate that odc of cyclohexane to cyclohex-2-en-1-yl 
 benzoate proceeds by initial conversion of the cycloalkane to the 
 cycloalkene , followed by oxidation of the cycloalkene to the 
 final allylic ester product .
the mechanism for the initial conversion 
 of cyclohexane to 
 cyclohexene likely proceeds by abstraction of a hydrogen atom 
 from cyclohexane by a tert - butoxy radical to 
 generate a cyclohexyl radical , which undergoes oxidation 
 to the alkene .
the oxidation of alkyl radicals to olefins by 
 copper  peroxide systems has been studied by kochi and walling .
their studies imply that 
 oxidation of the cyclohexyl radical formed in the current 
 system likely generates cyclohexyl cation , which undergoes deprotonation 
 to form the alkene .
the deprotonation could occur by the anionic 
 cu(i ) complex [ ( bpi)cu(o2cph ) ] ( 1-o2cph * ) ( scheme 7 ) .
the yield of allylic ester would then be a function 
 of the relative rate of oxidation of the alkyl radical versus 
 reaction of the alkyl radical with the copper carboxylate .
after formation of cyclohexene , 
 oxidation at 
 the allylic position to form cyclohex-2-en-1-yl benzoate would 
 occur through the mechanism of the kharasch  sosnovsky reaction . in this pathway ,
the allylic hydrogen is abstracted by a tert - butoxy radical , and the resulting allylic radical reacts 
 with the copper carboxylate to form the allylic ester . to detect 
 for the possible formation of 1,3-cyclohexadiene 
 or benzene from cyclohexene through a series of steps involving 
 abstraction of the allylic hydrogen , oxidation of the allyl 
 radical , and deprotonation of the allyl cation , the catalytic 
 reaction of benzoic acid , cyclohexane , and tbuootbu in the presence of 1-pph3 ( 2.5 mol% ) in d6-benzene ( or d3-mecn ) at 100 c 
 for 16 h was monitored by h nmr spectroscopy .
the result 
 of the reaction revealed only cyclohex-2-en-1-yl benzoate and 
 methyl benzoate as products in 40% and 14% yields , with respect to 
 benzoic acid .
the stoichiometric and 
 catalytic odc of benzoic acid with cyclohexane 
 forms methyl benzoate as the major side product .
the observation of 
 this product is consistent with the intermediacy of tert - butoxy radical .
-methyl scission of a tert - butoxy radical is known to produce a methyl radical , and this radical 
 would react with the resting - state 1-o2cph to give methyl benzoate . to evaluate 
 the potential generation of tert - butoxy 
 radical in the system ,
the standard catalytic reaction of benzoic 
 acid in c6d6 was performed in the absence of 
 cyclohexane ( scheme 8a ) . without a source 
 of an alkyl radical besides the one formed by -methyl scission 
 of otbu , the reaction produced 
 a quantitative yield of methyl benzoate and acetone ( based on benzoic 
 acid as limiting reagent ) .
this high - yield formation of methyl 
 benzoate from benzoic acid and tbuootbu in the presence of 1-pph3 further supports the intermediacy of a transient tert - butoxy radical in the catalytic reaction . as a final test of 
 the potential intermediacy of tert - butoxy radical 
 in the catalytic process , we conducted reactions 
 in the presence of diphenylmethanol , a known trap for tert - butoxy radical , and in the presence 
 of 9,10-dihydroanthracene , which forms anthracene via hydrogen atom 
 abstraction by alkoxy radicals . the catalytic reaction of cyclohexane , 
 benzoic acid , and diphenylmethanol in the presence of 1-o2cph produced methyl benzoate 
 ( 18% ) , benzophenone , and diphenylmethanol in a ratio of 1:10:7.3 ( scheme 8b ) . the same reaction between cyclohexane 
 and benzoic acid at 100 c for 24 h in the presence of 9,10-dihydroanthracene 
 produced anthracene as the exclusive product from the hydrocarbon 
 reactants ( scheme 8c ) .
the formation 
 of benzophenone and anthracene is consistent with h - atom abstraction 
 of the methine c  h bond of diphenylmethanol and a methylene 
 c  h bond of dihydroanthracene by tert - butoxy 
 radical to produce the organic products .
the detection of methyl benzoate 
 as an additional product , again , is consistent with -methyl 
 scission of a tert - butoxy radical under the catalytic 
 conditions . to assess the potential intermediacy of a cyclohexyl 
 radical , 
 the catalytic reaction of cyclohexane with benzoic acid was 
 performed in the presence of cbr4 .
the 
 observation of bromocyclohexane is further consistent with the 
 formation of cyclohexyl radical by abstraction of a hydrogen 
 atom from cyclohexane by a tert - butoxy radical 
 in the catalytic reaction . in this case
parallel reactions were performed with cyclohexane and cyclohexane - d12 to determine if cleavage of the c 
h 
 bond of the alkane is the turnover - limiting step of the copper - catalyzed 
 odc of cyclohexane .
a comparison of the initial rates for catalytic 
 odc of octanoic acid with cyclohexane and cyclohexane - d12 in separate vessels revealed a kie value 
 of 2.8  0.2 ( scheme 10 ) .
in addition , a comparison 
 of the rates of the catalytic reaction 
 of octanoic acid with cyclohexane and cyclohexene revealed 
 that the conversion of cyclohexene to cyclohex-2-en-1-yl 
 octanoate is faster than the conversion of cyclohexane .
after 1 h , the reaction of octanoic acid and 
 cyclohexene cleanly produced 40% of cyclohex-2-en-1-yl 
 octanoate , whereas the reaction of octanoic acid with cyclohexane 
 produced only 4% of cyclohex-2-en-1-yl octanoate and 2% of methyl 
 octanoate .
h 
 bond from cyclohexane , not from cyclohexene , is the turnover - limiting 
 step in the catalytic odc .
the roles of copper in the catalytic odc of cyclohexane are 
 closely related to those of copper in the catalytic amidation 
 of cyclohexane we reported recently .
however , the two reactions form products containing different hydrocarbyl 
 groups ( alkyl vs allylic ) , and the difference between these groups 
 likely stems from a difference in relative rates for reaction of the 
 alkyl radical with the copper  benzoate and copper 
the alkyl radical can undergo electron transfer , or it 
 can combine with a ligand at copper to form a product containing a 
 new carbon  heteroatom bond ( scheme 11 ) .
apparently , oxidation of the alkyl radical by the 
 copper  benzoate is faster than reaction of the alkyl radical 
 with the benzoate ligand , whereas oxidation of the alkyl radical 
 by the copper  amidate is slower than reaction of the alkyl 
 radical with the amidate ligand ( scheme 11 ) .
this difference in relative rates could arise from a difference 
 in redox potential of the benzoate and amidate complexes .
a cu(ii)benzoate 
 complex , presumably , is less electron - rich than a cu(ii)amidate 
 complex .
therefore , the former complex could oxidize the alkyl radical 
 to an alkyl cation faster than the latter complex .
alternatively , 
 the difference in relative rates could arise from differences in the 
 rates of reaction of alkyl radicals with the cu(ii)carboxylate 
 and cu(ii)amidate complexes . to reveal the origin of 
 the difference in formation of alkyl 
 and allyl products with amide and carboxylic acid reagents we conducted 
 a series of reactions in which a methyl radical
is generated in the 
 presence of a copper  carboxylate , amidate , or imidate complex . 

first , the reaction of a source of methyl radical ( tbuootbu ) with a combination of [ ( bpi)cu(nhc(o)[heptyl ] ) 
 ( 1-nhc(o)hept ) and [ ( bpi)cu(o2c[heptyl ] ) ] 
 ( 1-o2chept ) at 100 
 c ( scheme 12a ) was performed to assess 
 the ratio of products resulting from reactions of alkyl radicals with 
 cu(ii)amidate and cu(ii)carboxylate complexes together . 

this reaction produced only menhc(o)[heptyl ] ( 52% at 24 h ) ; meo2c[heptyl ] was not observed by gc .
thus , the rate of reaction 
 of methyl radical with 1-nhc(o)hept is faster than that 
 with 1-o2chept . 

analogous reactions of methyl radical with a combination of 1-o2cph and either [ ( bpi)cu(nhc(o)ph ) ] 
 ( 1-nhc(o)ph ) or [ ( bpi)cu(phth ) ] ( 1-phth ) 
 in the presence of tbuootbu ( 20 
 equiv ) in benzene at 100 c also showed that the reaction of 
 methyl radical with 1-nhc(o)ph and 1-phth is faster than that with 1-o2cph .
second , a competition 
 reaction was performed between unligated 
 [ cu(nhc(o)[heptyl ] ) ] and [ cu(o2c[heptyl ] ) ] in the presence 
 of tbuootbu at 100 c in benzene 
 ( scheme 12b ) to probe the effect of the bpi 
 ancillary ligand on the rate of reaction of the methyl radical with 
 the cu(ii)amidate and cu(ii)carboxylate complexes . 
 like the reactions with the ligated copper complexes , the reaction 
 of the unligated complexes with the source of me produced higher yields of menhc(o)[heptyl ] than of meo2c[heptyl ] throughout the reaction .
the result of this experiment 
 indicates that the rate of reaction of a methyl radical with a ligandless 
 copper  amidate is faster than that with a ligandless copper  carboxylate .
third , a competition reaction was performed with 1-o2chept and 1-nhc(o)hept in the presence of cyclohexane and tbuootbu at 100 c in benzene ( scheme 13 ) . unlike a methyl radical
heteroatom bond or convert to cyclohexene ; 
 carboxylation of the resulting alkene then forms an allylic 
 ester .
the reaction of the two copper complexes formed n - cyclohexyloctanamide in 92% yield and the allylic 
 ester product cyclohex-2-en-1-yl benzoate in 30% yield .
this 
 result is consistent with faster reaction of an alkyl radical with 
 a copper  amidate than with a copper  benzoate , but the 
 origin of the absence of product from reaction of the allylic radical 
 with the copper  amidate is unclear .
we also observed the odc 
 of cyclohexane to cyclohex-2-en-1-yl benzoate only after 
 an appreciable amount of 1-nhc(o)hept is consumed because 1-nhc(o)hept would react rapidly with the transient alkyl 
 radical . to investigate the effects of the nitrogen substituents 
 on the 
 reactions with alkyl radicals
, we conducted the reaction of 1-nhc(o)ph and 1-phth with tbuootbu ( 20 equiv ) in benzene at 100 c for 
 24 h. this reaction formed higher yields of the menhc(o)ph ( 70% ) than 
 of me - phth ( 53% ) ( scheme 14 ) .
the result of 
 this competition experiment indicates that the reaction of the alkyl 
 radical with 1-nhc(o)ph is faster than that with 1-phth .
this trend is consistent with faster reaction of an 
 alkyl radical with the more electron - rich anionic ligand on copper . to gain more systematic 
 data conerning the electronic effects on 
 the rates of reactions of alkyl radicals with the copper complexes , 
 we studied reactions with a series of substituted benzoate complexes . 

reactions of a methyl radical generated from tbuootbu with a mixture of [ ( bpi)cu(o2c[c6h4 - 4-ome ] ) ( 1-ome ) and [ ( bpi)cu(o2c[c6h4 - 4-cn ] ) ( 1-cn ) were conducted 
 at 100 c in benzene ( scheme 15a ) .
the 
 result showed that methyl radical reacted faster with the electron - rich 1-ome to produce the corresponding methyl 4-methoxybenzoate 
 than with the more electron - poor 1-cn to produce methyl 
 4-cyanobenzoate .
for example , at 24 h the reaction produced 
 methyl 4-methoxybenzoate in 76% yield and methyl 4-cyanobenzoate 
 in 10% yield .
to gain analogous information on the reaction of an alkyl 
 radical 
 with copper  amidates , the analogous experiment was conducted 
 with [ ( bpi)cu(nhc(o)[c6h4 - 4-ome ] ) ( 1-nhome ) and [ ( bpi)cu(nhc(o)[c6h4 - 4-cf3 ] ) ( 1-nhcf3 ) .
the reaction of tbuootbu with these complexes at 100 c 
 in benzene ( scheme 15b ) showed that the methyl 
 radical reacts faster with the more electron - rich 1-nhome than with the more electron - poor 1-nhcf3 to produce the corresponding product of n - methyl-4-methoxybenzamide ( 53% ) at 24 h. the results of these 
 competition reactions clearly demonstrate that alkyl radicals react 
 faster with the more electron - rich copper  benzoate and amidate 
 complexes than with the more electron - deficient copper 
benzoate 
 and amidate complexes to form the corresponding n - alkyl and o - alkyl products , respectively . to elucidate the steric effect 
 of aromatic ring of the carboxylate ligand in copper 
benzoate 
 complexes on the reactivity , we performed reactions of cyclohexane 
 and tbuootbu in the presence of 
 a series of copper  benzoates containing methyl groups in the 
 ortho , meta , and para positions : [ ( bpi)cux ] , with x = 2,6-dimethylbenzoate 
 ( 2,6-me2 ) , 2,4-dimethylbenzoate 
 ( 2,4-me2 ) , and 3,4-dimethylbenzoate 
 ( 3,4-me2 ) ) .
the reaction with the combination of 2,4-me2 and 2,6-me2 formed a higher yield of cyclohex-2-en-1-yl 2,4-dimethylbenzoate 
 than cyclohex-2-en-1-yl 2,6-dimethylbenzoate ( scheme 16a ) .
the reaction with a combination 
 of 2,4-me2 and 3,4-me2 formed the corresponding cyclohex-2-en-1-yl 
 3,4-dimethylbenzoate in higher yields than it formed cyclohex-2-en-1-yl 
 2,4-dimethylbenzoate ( scheme 16b ) . 

lastly , the reaction with the combination of 3,4-me2 and 2,6-me2 produced higher yield of cyclohex-2-en-1-yl 3,4-dimethylbenzoate 
 ( 40% ) than of cyclohex-2-en-1-yl 2,6-dimethylbenzoate 
 ( 20% ) at 24 h ( scheme 16c ) .
similar 
 results were obtained from competition reactions between cyclohexane 
 and tbuootbu with a series of dimethoxybenzoate 
the difference in rates of reaction of the carboxylate 
 complexes 
 as a function of the steric properties could result from the effect 
 on the conformation of these copper  benzoate complexes 
 and overlap of the aryl  system with the carbonyl group .
the 
 molecular structures of 2,6-ome2 and 3,4-ome2 were determined 
 by x - ray diffraction ( figure 1 ) .
the aryl ring 
 of the 2,6-dimethoxybenzoate is nearly orthogonal to the carbonyl 
 group with a torsion angle of 76 , whereas the benzene 
 ring of the 3,4-dimethoxybenzoate lies nearly in plane with 
 the carbonyl group with a torsion angle of 163. thus , 
 the aryl ring of 3,4-ome2 has more orbital overlap between 
 the carbonyl and benzene -systems than does that of the 2,6-dimethoxylbenzoate . 

this distortion from planarity of the 2,6-disubstituted benzoate makes 
 it less nucleophilic ( scheme 17 ) .
this reduced nucleophilicity is then responsible 
 for the difference in the reactivity of copper  benzoate with 
 the allylic radical to generate allylic benzoate products .
molecular structures 
 of [ ( bpi)cu(3,4-ome2-c6h4 ) ] ( 3,4-ome2 ) ( top ) 
 and [ ( bpi)cu(2,6-ome2-c6h4 ) ] ( 2,6-ome2 ) ( bottom ) are shown with 
 50% thermal ellipsoid .
selected 
 bond lengths (  ) and angles (  ) for 3,4-ome2 : cu1n1 = 2.019(2 ) ; cu1n3 
 = 1.892(2 ) ; cu1o1 = 1.9443(18 ) ; n1cu1n3 = 
 90.55(9 ) ; n3cu1o1 = 168.23(9 ) .
selected bond lengths 
 (  ) and angles (  ) for 2,6-ome2 : cu1n1 = 20074(17 ) ; cu1n3 
 = 1.9017(17 ) ; cu1o1 = 1.9721(14 ) ; n1cu1n3 
 = 90.94(7 ) ; n3cu1o1 = 167.63(7 ) . the step that distinguishes 
 the reactivity of copper - catalyzed odc of cyclohexane and copper - catalyzed 
 amidation of cyclohexane is the reaction of the transient 
 cyclohexyl radical with a copper  benzoate 
 versus a copper  amidate or copper  imidate 
 intermediate .
moreover , more electron - rich copper  amidate and benzoate 
 complexes react faster with alkyl radicals than more electron - deficient 
 copper  amidate and benzoate complexes .
benzoate 
 allows electron transfer to occur faster than ligand transfer , unless 
 the alkyl radical is not able to form an alkene ( i.e. , a methyl radical ) . 

when the alkyl radical can not form an alkene , ligand transfer occurs 
 to form an o - alkyl product . based on these hypotheses , 
 we investigated copper - catalyzed oxidative dehydrogenative amination 
 ( oda ) of cyclohexane with electron - deficient amides .
more electron - deficient 
 copper  amidate and imidate complexes would undergo slower reactions 
 with an alkyl radical and faster electron transfer . to this end
, we conducted catalytic reactions of phthalimide 
 and 
 cyclohexane ( 10 equiv ) in the presence of 2.5 mol% of [ ( phen)cu(phth ) ] , 1-pph3 , and [ cu(phth ) ] ( scheme 18 ) .
the reactions in 
 the presence of 1-pph3 and [ cu(phth ) ] 
 produced 1825% of cyclohex-2-en-1-yl pthalimidate and 
 roughly 70% of n - cyclohexylphthalimide . 

the reactions conducted with 1-pph3 and [ cu(phth ) ] apparently occur by competitive ligand transfer 
 and electron transfer to form a mixture of n - cyclohexylphthalimide 
 and cyclohex-2-en-1-yl pthalimidate , respectively .
conversely , 
 the reaction catalyzed by [ ( phen)cu(phth ) ] formed n - cyclohexylphthalimide ( 63% ) and n - methylphthalimide ( 19% ) , and no cyclohex-2-en-1-yl 
 pthalimidate , as determined by gas chromatography , mass spectrometry , 
 and h nmr spectroscopy .
the catalytic reaction in 
 the presence of [ ( phen)cu(phth ) ] exclusively 
 produced n - cyclohexylphthalimide 
 and n - methylphthalimide , presumably from 
 reaction of the methyl and cyclohexyl radicals with the resting - state 
 species [ ( phen)cu(phth)2 ] .
the preference of [ ( phen)cu(phth)2 ] to react with cyclohexyl 
 radical by ligand - transfer is presumably because [ ( phen)cu(phth)2 ] is more electron - rich than the complexes 1-phth and [ cu(phth)2]n ; thus , reaction 
 of the alkyl radical with [ ( phen)cu(phth)2 ] occurs faster 
 than electron transfer .
previously , we reported the copper - catalyzed 
 oxidative coupling 
 of p - toluenesulfonamide with cyclohexane 
 to generate the corresponding n - cyclohexyl - p - toluenesulfonamide . to achieve oda of cyclohexane , we reasoned that replacing p - toluenesulfonamide with the more electron - deficient 
 4-cf3-benzenesulfonamide should decrease the 
 rate of reaction of the alkyl radical with the ligand and increase 
 the rate of oxidation of the alkyl radical .
the reaction of 
 4-cf3-benzenesulfonamide with cyclohexane 
 and tbuootbu in the presence of 
 2.5 mol% of 1-pph3 in acetonitrile 
 produced n - cyclohexyl-4-cf3-benzenesulfonamide 
 ( 50% ) and n-(cyclohex-2-en-1-yl)-4-cf3-benzenesulfonamide ( 38% ) ( scheme 19 ) .
this result demonstrates that electron - deficient sulfonamides 
 can form substantial amount of product from oda of cyclohexane 
 by the electron - transfer pathway .
the selectivity of the reaction 
 of cyclohexane with cf3 - 4-benzenesulfonamide 
 in the presence of 1-pph3 depended 
 on solvent and supporting 
 ligand ( scheme 19 ) .
the reaction in acetonitrile 
 formed the mixture of alkyl and allylic amides just described , but 
 the reaction in benzene generated exclusively cyclohexyl-4-cf3-benzenesulfonamide ( 57% ) .
the distribution of 
 products from the reaction of cf3 - 4-benzenesulfonamide 
 and cyclohexane in the presence of  ligandless  
 copper generated from [ cu(mes ) ] also depended on solvent , but with 
 the opposite trend .
the products of oda were observed in benzene , 
 but not in acetonitrile ( scheme 19 ) . like the 
 reactions of phthalimide , the reactions of cf3 - 4-benzenesulfonamide 
 with cyclohexane in the presence of phen - ligated copper provided 
 only the n - alkyl product ( scheme 19 ) .
this result again highlights the effect of the electronic 
 properties of the supporting ligand on the relative rates to form n - alkyl and n - allyl products .
this effect 
 of ligand ( i.e. , bpi vs phen ) on this selectivity reflects an opportunity 
 to design ligands that favor oda of unactivated alkanes .
a proposed mechanism for 
 the catalytic odc of cyclohexane 
 to cyclohex-2-en-1-yl benzoate is presented in scheme 20 . in this pathway
, catalysis is initiated by the 
 decomposition of tbuootbu by 1-pph3 to produce a tert - butoxy radical and [ ( bpi)cuotbu ] , which rapidly 
 reacts with benzoic acid to form 1-o2cph and tbuoh .
the tert - butoxy radical can undergo reversible , secondary internal return 
 to regenerate tbuootbu or abstract 
 a hydrogen atom from cyclohexane to generate a cyclohexyl 
 radical . to form the unsaturated product ,
1-o2cph would oxidize the alkyl radical by 
 one electron to form a carbocation , and the carbocation 
 would undergo deprotonation by an anionic cu(i ) species [ ( bpi)cu(o2cph ) ] to give cyclohexene and benzoic 
 acid .
the resulting cyclohexene would then undergo a second 
 c  h abstraction by a tert - butoxy radical to 
 give an allylic radical that reacts with 1-o2cph to release the allylic ester product 
 and regenerate a ( bpi)cu(i ) species to complete the catalytic cycle . 
 in a side reaction
, the tert - butoxy radical would 
 decompose to a methyl radical and acetone .
the methyl radical would 
 then combine with 1-o2cph to produce methyl benzoate and a ( bpi)cu(i ) species . the catalytic 
 cycle for oda of cyclohexane to form n - allyl 
 products is presumably analogous to that of the catalytic odc .
this 
 catalytic cycle would contain a copper  amidate resting state , 
 based on mechanistic investigations of a related copper - catalyzed 
 amidation of unactivated alkanes .
in summary , we have described a copper - catalyzed oxidative dehydrogenative 
 carboxylation ( odc ) of unactivated alkanes with a variety of 
 benzoic acids to produce the corresponding allylic ester products . 

a measurement of kinetic isotope effects showed that the turnover - limiting 
 step is c  h bond cleavage , and experiments to trap radical 
 intermediates revealed that a transient tert - butoxy 
 radical cleaves the c  h bond of the alkane to generate an alkyl 
 radical .
reactions of alkyl radicals with a combination of cu(ii)amidates 
 and cu(ii)benzoates revealed that the alkyl radical reacts 
 faster with a cu(ii)amidate than with a cu(ii)benzoate 
 to form n - alkyl products .
additional mechanistic 
 investigations indicated that the electronic properties of the cu(ii)x 
 ( x = amidate , benzoate ) resting state contributes to the partitioning 
 of the alkyl radical between ligand transfer to form the alkyl 
heteroatom 
 bond and electron transfer to oxidize the alkyl radical to an olefin , 
 followed by oxidative carboxylation to produce an allylic ester . 

the reaction of the alkyl radical with a cu(ii)amidate versus 
 a cu(ii)benzoate is the step that distinguishes copper - catalyzed 
 amidation and copper - catalyzed odc of the alkane .
this 
 insight into the mechanism of odc of cyclohexane led 
 to preliminary observations of copper - catalyzed oxidative dehydrogenative 
 amination of cyclohexane with electron - deficient nitrogen 
 sources ( i.e. , phthalimide and an electron - deficient sulfonamide ) 
 to form n - allyl products .
current efforts are underway 
 to discover reaction conditions to suppress ligand transfer and favor 
 electron transfer to achieve high selectivity for a copper - catalyzed 
 oda of unactivated alkanes .
 we 
 report copper - catalyzed oxidative dehydrogenative carboxylation 
 ( odc ) of unactivated alkanes with various substituted benzoic acids 
 to produce the corresponding allylic esters . 
 spectroscopic studies 
 ( epr , uv  vis ) revealed that the resting state of the catalyst 
 is [ ( bpi)cu(o2cph ) ] ( 1-o2cph ) , formed from [ ( bpi)cu(pph3)2 ] , oxidant , and benzoic acid 
 . catalytic and stoichiometric 
 reactions of 1-o2cph with alkyl radicals and radical probes imply that c  
 h bond 
 cleavage occurs by a tert - butoxy radical . 
 in addition , 
 the deuterium kinetic isotope effect from reactions of cyclohexane 
 and d12-cyclohexane in separate 
 vessels showed that the turnover - limiting step for the odc of cyclohexane 
 is c  h bond cleavage . 
 to understand the origin of the difference 
 in products formed from copper - catalyzed amidation and copper - catalyzed 
 odc , reactions of an alkyl radical with a series of copper  carboxylate , 
 copper  amidate , and copper  imidate complexes were performed . 
 
 the results of competition experiments revealed that the relative 
 rate of reaction of alkyl radicals with the copper complexes follows 
 the trend cu(ii)amidate > cu(ii)imidate > cu(ii)benzoate . 
 
 consistent with this trend , cu(ii)amidates and cu(ii)benzoates 
 containing more electron - rich aryl groups on the benzamidate and benzoate 
 react faster with the alkyl radical than do those with more electron - poor 
 aryl groups on these ligands to produce the corresponding products . 
 these data on the odc of cyclohexane led to preliminary investigation 
 of copper - catalyzed oxidative dehydrogenative amination of cyclohexane 
 to generate a mixture of n - alkyl and n - allylic products . 
Introduction
Results and Discussion
Summary and Conclusions