due to their importance 
 and ubiquity , significant efforts have 
 been made toward the construction of enantioenriched amines . hydroamination , the formal addition of a nitrogen 
 and hydrogen atom across a carbon  carbon -bond , represents 
 a particularly attractive and direct method for appending amino groups 
 onto a molecule . although significant progress has been achieved in 
 this regard using late transition metal catalysis , a number of drawbacks 
 have limited the utilization of these methodologies . in the context of intermolecular hydroamination , these 
 methods furnish products with moderate stereoselectivity and rely 
 on the use of activated alkenes , such as vinyl arenes and acrylate 
 derivatives , while unactivated alkenes typically fail to react . similarly , 
 lanthanide and early transition metal catalysts have shown promise 
 as hydroamination systems although further developments are needed 
 to address the generally limited substrate scope . the development of a general approach for regio- and enantioselective 
 hydroamination of a broad range of alkene classes remains an important 
 challenge . in 2013 , miura s and our lab disclosed 
 contemporaneous reports describing a new method of styrene hydroamination 
 that involves a copper(i ) hydride ( cuh ) catalyst and amine electrophiles 
 to generate -chiral amines in excellent yields and enantioselectivities . since then , cuh - catalyzed hydroamination has been extended to a wide 
 scope of substrate classes , including vinyl silanes , terminal alkenes , 
 internal unactivated alkenes , alkynes , and strained cyclic alkenes . a general catalytic cycle for the hydroamination of styrene 
 is 
 shown in scheme 1 . formation of the phosphine - ligated cuh catalyst ( l*cuh , 1 ) occurs from the combination of cu(oac)2 , a phosphine 
 ligand , and silane . interception of 2 by amine electrophile 3 generates chiral amine 4 and phosphine - ligated copper(i ) benzoate ( l*cuobz , 5 ) . regeneration of l*cuh 1 from l*cuobz complex 5 closes the catalytic cycle . given that this cuh - catalyzed hydroamination 
 strategy has undergone 
 rapid development in terms of substrate scope , we felt a general understanding 
 and improvement of these processes would be welcomed . in particular , 
 identification of the turnover - limiting step and resting state of 
 the copper catalyst might provide a foundation for the development 
 of a more efficient and practical protocol . herein , we report detailed 
 kinetic and spectroscopic studies of the cuh - catalyzed hydroamination 
 of styrene . these studies have provided evidence that the phosphine - ligated 
 cuobz complex 5 is the resting state of the catalyst 
 and the turnover - limiting step entails regeneration of the cuh catalyst 
 via its reaction with a silane reagent . through this mechanistic insight , 
 rational optimization of several parameters has led to short reaction 
 times ( < 30 min ) and operational simplicity ( simple copper(ii ) precatalyst 
 and open to air ) for an array of olefin and alkyne substrates . similarly , 
 a separate modified protocol is amenable to the use of low loadings 
 of the chiral ligand ( 0.10.2 mol % ) . this is important as 
 it is the most expensive component of this catalyst system . the hydroamination 
 of styrenes was chosen as the model system for 
 our detailed kinetic studies . to begin , the reaction profile for the 
 hydroamination of 4-fluorostyrene was studied . in our initial report , 
 we detailed a reaction time of 36 h to give the desired product in 
 86% yield and 97% ee . using in situ f nmr spectroscopy , the reaction , under the previously reported 
 conditions , was found to be complete in approximately 9 h. moreover , 
 the process appeared to be overall zero - order in substrate ( scheme 2 ) . same - excess experiments were 
 also conducted and displayed a similar reaction profile , indicating 
 that catalyst deactivation and product inhibition were not significant 
 in this system ( see supporting information for details ) . l = dtbm - segphos ; 1 equiv of 
 1-fluoronaphthalene added as internal standard . initial rate experiments were next performed with styrene and amine 
 electrophile 3 to gather more detailed information about 
 the catalytic cycle of this hydroamination process ( scheme 3 ) . corroborating our full kinetic 
 analysis , initial - rate kinetics demonstrated that the reaction was 
 zero - order in styrene and amine electrophile 3 across 
 a range of concentrations for each component . in addition , a clear 
 first - order dependence was observed for diethoxymethylsilane ( dems ) 
 and an apparent fractional - order was 
 observed while simultaneously changing the concentration of cu(oac)2 and dtbm - segphos . hammett studies were conducted 
 to determine the impact that electronic 
 variation of the styrene and the amine electrophile components had 
 on the rate of hydroamination . in the 
 first hammett study , a series of para - substituted styrenes reacted 
 with amine electrophile 3 at similar rates ( scheme 4a ) , implying that 
 the olefin is most likely not involved in the turnover - limiting step 
 of this process . a second hammett study showed that electronic variation 
 of the amine electrophile had a significant impact on the rate of 
 styrene hydroamination ( scheme 4b ) . a linear correlation was observed with para hammett constants (  = 0.71 , r = 0.97 ) indicating more electron rich amine - o - benzoates led to increased reaction rates . each data point is the average 
 of two experiments with standard deviations included as error bars ; 
 l = dtbm - segphos . the observations described 
 above suggested that regeneration of 
 the cuh catalyst 1 from the presumed ligated cuobz complex 5 and silane is the turnover - limiting step of the cuh - catalyzed 
 hydroamination process ( scheme 1 ) . this interpretation is supported 
 by ( a ) the zero - order dependence on styrene and amine electrophile ; 
 ( b ) the first - order dependence on the silane , dems ; and ( c ) the linear 
 free energy relationship between the hammett electronic parameter 
 of the amine electrophile benzoate and the initial rate . the enhanced 
 initial rates observed with more electron - rich benzoates is consistent 
 with a faster transmetalation of phosphine - ligated cuobz complex 5 with silane . interestingly , independent initial - rate measurements 
 collected with diphenylsilane and deutero - diphenylsilane ( ph2sid2 ) of the model reaction did not show a measurable 
 kinetic isotope effect ( kie ) ( kh / kd= 1.06  0.10 ) . the fractional order dependence observed while manipulating 
 [ cu(oac)2 ] and [ dtbm - segphos ] inspired a closer examination 
 of the 
 active catalytic species . a series of studies were employed to investigate 
 the possible nature of the copper catalyst in the cuh - catalyzed hydroamination 
 of styrene . historically , cuh complexes with sterically unencumbered 
 ligands have been isolated as higher - order species and aggregates . our initial p nmr studies on the cuh catalyst solution 
 ( cu(oac)2 , ( s)-dtbm - segphos , and dems 
 in thf ) did not allow identification 
 of a distinct cuh species . however , the major new species observed 
 in the spectrum does have a similar p nmr shift and peak 
 shape attributed to phosphine - ligated cuh clusters reported in the 
 literature . when this cuh solution was 
 subjected to the model hydroamination reaction , p nmr 
 showed that a new species attributed to lcuobz 5 accounts 
 for the majority of the ligated species observed . these observations are consistent with intermediate 5 acting as the catalyst resting state prior to the turnover - limiting 
 step of the hydroamination reaction . surprisingly , approximately 50% 
 of the dtbm - segphos ligand remains unbound throughout the course of 
 the reaction . additional details and a discussion of these experiments 
 are provided in the supporting information . electrospray ionization mass spectrometric 
 ( esi - ms ) analysis of 
 aliquots taken from the purported cuh mixture gave major peaks that 
 are attributed to a monomeric dtbm - segphos - bound copper(i ) species 
 and the unbound dtbm - segphos ligand ( see supporting information for details ) . a cuh cluster or copper aggregate 
 could readily decompose on ionization and can not be ruled out with 
 these experiments . nonlinear effect studies on the enantiomeric composition 
 of the chiral ligand and amine product indicated a linear relationship 
 ( see scheme 5 ) . these 
 results are consistent with an active catalyst being of a monomeric 
 nature ; however , we can not exclude the possibility that higher order 
 species are involved . we next sought to identify the enantioselectivity - determining 
 step 
 ( eds ) of the styrene hydroamination reaction . to this end , we searched 
 for linear free energy relationships ( lfers ) between substrate hammett 
 electronic parameters and the observed enantioselectivities for a 
 variety of para - substituted styrenes . a linear relationship 
 was observed with para - substituted styrenes as enantioselectivity 
 decreased with the introduction of electron - withdrawing substituents 
 (  = 0.50 , r = 0.98 , scheme 6 ) : 98% ee and 95% 
 ee were observed for 4-methylstyrene ( p = 0.14 ) 
 and 4-(trifluoromethyl)styrene ( p = 0.53 ) , respectively . in contrast , a linear free energy relationship was not observed 
 between the electronic nature of the amine electrophile ( varying the 
 para - substituent of the benzoate of the amine - o - benzoate ) 
 and the enantioselectivity of the product ( see supporting information for details ) . additionally , the identity 
 of the silane did not appear to affect the enantioselectivity of the 
 process . taken together , these results indicate that hydrocupration 
 is most likely the enantio - determining step . we expected hydrocupration to 
 be irreversible since it appears 
 to be the enantio - determining step and occurs before the rate - determining 
 step . to provide further support that 
 hydrocupration is enantiodetermining , styrene-,,-d3 ( 6 ) was subjected to the standard 
 hydroamination conditions using dems as the hydride source . if hydrocupration 
 is reversible due to -hydride elimination of copper(i ) alkyl 7 , then isotopic isomers 8 and 9 should be observed throughout the reaction due to potential -deuteride 
 elimination . the reaction was monitored 
 by h nmr spectroscopy and no signals attributable to olefinic 
 protons were observed throughout the course of the reaction , indicating 
 that -deuteride elimination did not occur . further , we would 
 expect to see some proportion of 10 containing only two 
 deuteria . in fact , a single isotopic product 10 was isolated 
 from the crude reaction mixture ( scheme 7 ) . in addition , these results are consistent with 
 previous reports that -hydride elimination most likely does 
 not occur during the cuh - catalyzed hydrosilylation of ketones . l = dtbm - segphos . with 
 a good understanding of the factors controlling the rate and selectivity 
 of this cuh - catalyzed hydroamination process , we next turned our attention 
 to improving the overall efficiency of the reaction . we focused our 
 efforts on the identity of the silane and amine electrophile components 
 since these appear to be directly involved in the rate - determining 
 step . importantly , we expected to be able to increase the overall 
 rate of hydroamination without significantly diminishing the enantioselectivity 
 of the reaction since the rate- and enantio - determining steps are 
 presumed to be separate processes . table 1 shows 
 the observed initial rates of hydroamination using a variety of readily 
 available silanes . most notably , with the use of dimethoxymethylsilane 
 ( dmms ) , a 3-fold initial - rate enhancement was observed relative to 
 dems ( entries 1 and 2 ) . employing other siloxanes , such as 1,1,2,2-tetramethyldisiloxane 
 and pmhs , resulted in lower reaction rates ( entries 3 and 4 ) . the 
 use of diphenylsilane provided product , whereas trialkylsilanes , such 
 as triethylsilane , were ineffective hydride sources ( entries 5 and 
 6 ) . due to safety concerns , trialkoxysilanes were not investigated . in terms of performance and practicality , as noted earlier , the electronic 
 nature of the amine electrophile 
 dramatically affected the initial rate of the hydroamination reaction , 
 which is believed to influence the regeneration of the cuh catalyst 
 from copper(i ) benzoate intermediate 5 ( scheme 4b ) . for example , use of amine 
 electrophile 11 , bearing a 4-diethylaminobenzoate group , 
 led to a 3-fold rate enhancement compared to amine 3 with 
 an unsubstituted benzoate group ( scheme 8) . this rate enhancement could be increased 
 further by using 2,4,6-trimethoxybenzoate ( 12 ) , acetate 
 ( 13 ) or pivalate ( 14 ) bearing amine electrophiles 
 ( initial - rates ( 2.52.8 )  10 we selected the pivalate - appended oxidant ( 14 ) as the 
 optimal amine electrophile due to its accessibility and long - term 
 stability . an amine electrophile featuring 
 a carbonate ( 15 ) , which could potentially decarboxylate 
 to access a copper alkoxide intermediate , was found to provide a comparable 
 rate of reaction to amine electrophile 3 . lipshutz has reported 
 that secondary ligands , such as pph3 , can be employed in 
 cuh catalysis to lower catalyst loadings and 
 improve overall reactivity for certain systems . addition of 2.2 mol % pph3 to our model system 
 did indeed result in a slight rate enhancement ( 1.2-fold increase ) , 
 but higher loadings of pph3 did not result in any further 
 increase in reaction rate . testing the addition of other achiral phosphine 
 additives led only to slightly increased reaction rates and variable 
 levels of enantioselectivity ( see supporting information for details ) . by employing the optimized reagents , n , n ,- dibenzyl - o - pivaloylhydroxylamine 
 ( 14 ) , dmms , and pph3 additive , the hydroamination 
 of styrene was complete in 1 h at 40 c with a high yield and 
 enantioselectivity ( eq 1 , 99% yield , 96% ee ) . for comparison , our previous report detailed 
 reaction times at 36 h at this temperature , while we found ( see above ) 
 that the reaction actually required 9 h to proceed to completion . the greatly reduced reaction time suggests that the increased reaction 
 rates observed while optimizing these reagents independently are indeed 
 additive . final optimization of the hydroamination protocol is described 
 in the following section.1 at the outset of this study , our ultimate goal was 
 to improve the 
 efficiency and practicality of our previously reported asymmetric 
 hydroamination methodologies . we specifically sought to decrease the 
 relatively long reported reaction times ( 2436 h ) , enable lower 
 catalyst loadings , and make reaction setup more robust and user - friendly . to these ends , we first prepared a precomplexed copper catalyst 
 mixture that contained cu(oac)2 , ( s)-dtbm - segphos , 
 and pph3 ( 1:1.1:1.1 ratio ) that was used throughout this 
 section ( see supporting information for 
 details of the preparation of this precatalyst ) . this air - stable free - flowing powder rapidly dissolves in 
 a variety of organic solvents and enables quick reaction setup . in 
 our previous reports , the preparation of the active cuh catalyst was 
 performed in a separate reaction flask than the one that the hydroamination 
 reaction was carried out in and required up to 30 min for activation 
 due to the slow complexation of cu(oac)2 with dtbm - segphos 
 ligand and subsequent reaction with dems . we have found that this 
 two - pot procedure is unnecessary and instead are able to perform a 
 simple one - pot operation in which the silane is added once all the 
 other reagents are in solution . traditionally , reactions that proceed 
 through copper(i ) alkyl intermediates are performed under an inert 
 atmosphere due to their incompatibility with oxygen and moisture . we wished to remove this constraint for as many 
 hydroamination reactions as possible , and the reaction setups described 
 below are carried out fully open - to - air unless otherwise noted . after optimizing temperature and concentration 
 parameters , we found 
 that the cuh - catalyzed hydroamination of styrene could be completed 
 in 10 min at 60 c while open to the atmosphere , delivering the 
 chiral amine product 4 in 90% isolated yield and 95% 
 ee ( entry 1 , table 2 ) . it is worth noting that this reaction is complete in a third of 
 the time previously required to prepare the active cuh solution and 
 only a fraction of the 36 h total reaction time originally reported . cucatmix 
 = cu(oac)2 , 
 ( s)-dtbm - segphos , pph3 ( 1:1.1:1.1 ratio , 
 precomplexed ) . reaction 
 performed under argon atmosphere . at this point in our study , all of the hydroamination reactions 
 described have involved unsubstituted styrenes , a relatively unhindered 
 and reactive class of alkene . we wanted to see whether this optimized 
 protocol would be amenable to other classes of alkenes and alkynes . trans--substituted styrenes , 
 vinylsilanes , alkynes , and terminal alkenes all underwent hydroamination 
 in high yield in short reaction times ( entries 2 , 4 , 6 , and 7 , 88%91% 
 yield , 98%99% ee , 1520 min ) . these results suggest 
 that regeneration of the cuh catalyst is likely rate limiting for 
 the hydroamination of these substrate classes . however , by performing the hydroamination of these substrates 
 under an inert atmosphere , we were able to significantly decrease 
 the previously reported reaction times of 36 h to under 4 h ( entries 
 3 and 5 ) . as a final demonstration of the improvements 
 made by the new hydroamination 
 protocol , table 3 shows 
 that high yields were obtained when using just 0.10.2 mol 
 % ( s)-dtbm - segphos ligand in the hydroamination of 
 styrene and 4-phenyl-1-butene . reactions that employ low ligand loadings 
 are more air - sensitive and require setup in an inert atmosphere glovebox 
 with longer reaction times ( 24 h ) . with 
 a good understanding of the factors controlling the rate and selectivity 
 of this cuh - catalyzed hydroamination process , we next turned our attention 
 to improving the overall efficiency of the reaction . we focused our 
 efforts on the identity of the silane and amine electrophile components 
 since these appear to be directly involved in the rate - determining 
 step . importantly , we expected to be able to increase the overall 
 rate of hydroamination without significantly diminishing the enantioselectivity 
 of the reaction since the rate- and enantio - determining steps are 
 presumed to be separate processes . table 1 shows 
 the observed initial rates of hydroamination using a variety of readily 
 available silanes . most notably , with the use of dimethoxymethylsilane 
 ( dmms ) , a 3-fold initial - rate enhancement was observed relative to 
 dems ( entries 1 and 2 ) . employing other siloxanes , such as 1,1,2,2-tetramethyldisiloxane 
 and the 
 use of diphenylsilane provided product , whereas trialkylsilanes , such 
 as triethylsilane , were ineffective hydride sources ( entries 5 and 
 6 ) . due to safety concerns , as noted earlier , the electronic 
 nature of the amine electrophile 
 dramatically affected the initial rate of the hydroamination reaction , 
 which is believed to influence the regeneration of the cuh catalyst 
 from copper(i ) benzoate intermediate 5 ( scheme 4b ) . for example , use of amine 
 electrophile 11 , bearing a 4-diethylaminobenzoate group , 
 led to a 3-fold rate enhancement compared to amine 3 with 
 an unsubstituted benzoate group ( scheme 8) . this rate enhancement could be increased 
 further by using 2,4,6-trimethoxybenzoate ( 12 ) , acetate 
 ( 13 ) or pivalate ( 14 ) bearing amine electrophiles 
 ( initial - rates ( 2.52.8 )  10 m / min ) . we selected the pivalate - appended oxidant ( 14 ) as the 
 optimal amine electrophile due to its accessibility and long - term 
 stability . an amine electrophile featuring 
 a carbonate ( 15 ) , which could potentially decarboxylate 
 to access a copper alkoxide intermediate , was found to provide a comparable 
 rate of reaction to amine electrophile 3 . lipshutz has reported 
 that secondary ligands , such as pph3 , can be employed in 
 cuh catalysis to lower catalyst loadings and 
 improve overall reactivity for certain systems . addition of 2.2 mol % pph3 to our model system 
 did indeed result in a slight rate enhancement ( 1.2-fold increase ) , 
 but higher loadings of pph3 did not result in any further 
 increase in reaction rate . testing the addition of other achiral phosphine 
 additives led only to slightly increased reaction rates and variable 
 levels of enantioselectivity ( see supporting information for details ) . by employing the optimized reagents , n , n ,- dibenzyl - o - pivaloylhydroxylamine 
 ( 14 ) , dmms , and pph3 additive , the hydroamination 
 of styrene was complete in 1 h at 40 c with a high yield and 
 enantioselectivity ( eq 1 , 99% yield , 96% ee ) . for comparison , our previous report detailed 
 reaction times at 36 h at this temperature , while we found ( see above ) 
 that the reaction actually required 9 h to proceed to completion . the greatly reduced reaction time suggests that the increased reaction 
 rates observed while optimizing these reagents independently are indeed 
 additive . at the outset of this study , our ultimate goal was 
 to improve the 
 efficiency and practicality of our previously reported asymmetric 
 hydroamination methodologies . we specifically sought to decrease the 
 relatively long reported reaction times ( 2436 h ) , enable lower 
 catalyst loadings , and make reaction setup more robust and user - friendly . to these ends , we first prepared a precomplexed copper catalyst 
 mixture that contained cu(oac)2 , ( s)-dtbm - segphos , 
 and pph3 ( 1:1.1:1.1 ratio ) that was used throughout this 
 section ( see supporting information for 
 details of the preparation of this precatalyst ) . this air - stable free - flowing powder rapidly dissolves in 
 a variety of organic solvents and enables quick reaction setup . in 
 our previous reports , the preparation of the active cuh catalyst was 
 performed in a separate reaction flask than the one that the hydroamination 
 reaction was carried out in and required up to 30 min for activation 
 due to the slow complexation of cu(oac)2 with dtbm - segphos 
 ligand and subsequent reaction with dems . we have found that this 
 two - pot procedure is unnecessary and instead are able to perform a 
 simple one - pot operation in which the silane is added once all the 
 other reagents are in solution . traditionally , reactions that proceed 
 through copper(i ) alkyl intermediates are performed under an inert 
 atmosphere due to their incompatibility with oxygen and moisture . we wished to remove this constraint for as many 
 hydroamination reactions as possible , and the reaction setups described 
 below are carried out fully open - to - air unless otherwise noted . after optimizing temperature and concentration 
 parameters , we found 
 that the cuh - catalyzed hydroamination of styrene could be completed 
 in 10 min at 60 c while open to the atmosphere , delivering the 
 chiral amine product 4 in 90% isolated yield and 95% 
 ee ( entry 1 , table 2 ) . it is worth noting that this reaction is complete in a third of 
 the time previously required to prepare the active cuh solution and 
 only a fraction of the 36 h total reaction time originally reported . cucatmix 
 = cu(oac)2 , 
 ( s)-dtbm - segphos , pph3 ( 1:1.1:1.1 ratio , 
 precomplexed ) . reaction 
 performed under argon atmosphere . at this point in our study , all of the hydroamination reactions 
 described have involved unsubstituted styrenes , a relatively unhindered 
 and reactive class of alkene . we wanted to see whether this optimized 
 protocol would be amenable to other classes of alkenes and alkynes . trans--substituted styrenes , 
 vinylsilanes , alkynes , and terminal alkenes all underwent hydroamination 
 in high yield in short reaction times ( entries 2 , 4 , 6 , and 7 , 88%91% 
 yield , 98%99% ee , 1520 min ) . these results suggest 
 that regeneration of the cuh catalyst is likely rate limiting for 
 the hydroamination of these substrate classes . however , by performing the hydroamination of these substrates 
 under an inert atmosphere , we were able to significantly decrease 
 the previously reported reaction times of 36 h to under 4 h ( entries 
 3 and 5 ) . as a final demonstration of the improvements 
 made by the new hydroamination 
 protocol , table 3 shows 
 that high yields were obtained when using just 0.10.2 mol 
 % ( s)-dtbm - segphos ligand in the hydroamination of 
 styrene and 4-phenyl-1-butene . reactions that employ low ligand loadings 
 are more air - sensitive and require setup in an inert atmosphere glovebox 
 with longer reaction times ( 24 h ) . spectroscopic studies 
 suggest a phosphine - ligated cuh cluster 16 is formed 
 when cu(oac)2 is treated with silane and dtbm - segphos ( l ) , although our current view is that the active catalyst 
 is of a monomeric nature . linear free energy relationship studies 
 indicate that hydrocupration to form aliphatic copper(i ) species 2 is the enantio - determining step in this catalytic cycle , 
 and deuterium - labeling studies show that this step is likely irreversible . 
 interception of this species with amine electrophile 17 produces chiral amine 4 and phosphine - ligated copper(i ) 
 carboxylate 18 , which is the resting state of the catalyst , 
 as shown through esi - ms and p nmr studies . the turnover - limiting 
 step is regeneration of the cuh catalyst 1 from the phosphine - bound 
 cuor 18 . rate enhancement is 
 observed with judicious choice of silane , amine 
 electrophile , and secondary phosphine ligand additive . we have developed 
 an efficient and optimized protocol for the hydroamination of a variety 
 of olefins and alkynes that is insensitive to air and uses a simple 
 copper precatalyst that incorporates dtbm - segphos , pph3 , and cu(oac)2 . further mechanistic work , in particular 
 stoichiometric studies and computational investigations for the mechanism 
 of the c last , new avenues for asymmetric olefin functionalization 
 through cuh catalysis are also under development .
enantioselective 
 copper(i ) hydride ( cuh)-catalyzed hydroamination 
 has undergone significant development over the past several years . 
 to gain a general understanding of the factors governing these reactions , 
 kinetic and spectroscopic studies were performed on the cuh - catalyzed 
 hydroamination of styrene . 
 reaction profile analysis , rate order assessment , 
 and hammett studies indicate that the turnover - limiting step is regeneration 
 of the cuh catalyst by reaction with a silane , with a phosphine - ligated 
 copper(i ) benzoate as the catalyst resting state . 
 spectroscopic , electrospray 
 ionization mass spectrometry , and nonlinear effect studies are consistent 
 with a monomeric active catalyst . with this insight , 
 targeted reagent 
 optimization led to the development of an optimized protocol with 
 an operationally simple setup ( ligated copper(ii ) precatalyst , open 
 to air ) and short reaction times ( < 30 min ) . 
 this improved protocol 
 is amenable to a diverse range of alkene and alkyne substrate classes .