simple enones 
 are known to undergo ni - catalyzed cycloaddition with diynes ( eq 2 ) . however , these conditions 
 fail to provide any cycloadduct product with tropone as shown in eq 3 . thus , we focused our investigation on discovering 
 an alternative ni - catalyzed cycloaddition protocol.2 diyne 1 and tropone a were used 
 as model substrates and were subjected to a catalytic amount of ni(0 ) 
 and a variety of phosphine and n - heterocyclic carbene 
 ( nhc ) ligands ( eq 4 ) . reactions run with monodentate 
 and bidentate phosphines mostly afforded dimerization of diyne along 
 with traces or low amounts of the desired cycloadduct ( table 1 , entry 110 ) . however , reactions run with 
 nhcs resulted in good to excellent yields of cycloadduct 1a , which couples the diyne with a single c further optimization 
 led to our final reaction conditions : diyne ( 1 equiv ) , tropone ( 1.1 
 equiv ) , 3 mol % of ni(cod)2 , 6 mol % of sipr , thf , 60 c , 
 and 5 h. reaction conditions : 10 mol % of ni(cod)2 , 20 mol % of 
 l , diyne ( 1 equiv , 0.1 m ) , tropone ( 1.1 equiv ) , toluene , 
 60 c , 5 h. determined 
 by gc using naphthalene as an internal standard . the model substrates afforded 
 the desired product 1a along with another isomer 1a in excellent yield and > 90% selectivity for 1a ( eq 5 ) . similarly , cycloaddition of sulfonamide diyne 2 afforded a mixture of major and minor isomers 2a and 2a respectively , which on subsequent treatment with p - bromobenzoyl chloride / net3/dmap afforded major 
 isomer 2a in 74% yield and p - bromobenzoyl 
 derivative of minor isomer ( 2b ) in 13% yield ( eq 6 ) as crystalline solids ( figure 2 ) . surprisingly , 2b ( and , therefore , 2a as well ) has [ 576 ] ring fusion compared 
 to [ 567 ] in the case of the major isomer , 2a.5 ortep diagram of 2a and 2b . with optimized reaction conditions in hand , the substrate 
 scope was explored ( table 2 ) . the cycloaddition 
 occurred smoothly with the diyne bearing a sulfone backbone to form 3a along with minor isomer 3a. notably , 
 this diyne is completely unreactive in several reported ni - catalyzed 
 cycloadditions . although ni catalysts 
 have been reported to catalyze the cycloaddition of nitriles and diynes 
 to form pyridines , diyne 4 , which 
 has a nitrile group in the backbone , selectively reacted with tropone 
 to afford the desired cycloadducts ( 4a and 4a ) in excellent yield . inspired by carreira s work , 
 we performed the cycloaddition reaction with 5 , a diyne 
 with a metabolically stable backbone , to give cycloadduct 5a in good yield along with minor 
 isomer 5a. aryl substituted internal diynes are 
 one of the most challenging substrates in ni / nhc - catalyzed cycloaddition 
 reactions . nevertheless , the reaction of 
 aryl substituted symmetrical diynes with tropone afforded 6a and 7a in good yields . interestingly , no minor cycloadduct 
 ( 6a or 7a ) was obtained 
 in these cases . to investigate the effect of electronics on the regioselectivity , 
 we subjected unsymmetrical diynes 8 and 9 to standard reaction conditions ; remarkably , exclusive formation 
 of one regioisomer was detected ( 8a and 9a ) . the use of different aryl groups ( i.e. , 3,4-dimethoxyphenyl and 
 naphthyl ) on alkyne terminals is also possible ( 10a and 11a ) . due to recent interest in indole bearing novel compounds , diynes 12 and 13 were 
 investigated . biaryl cycloadducts ( 12a , 13a ) were formed in very good yield and high regioselectivity . interestingly , the regioselectivity was higher in the case of 3-substituted 
 indole diyne than 5-substituted indole diyne ( 13a vs 12a ) . cycloaddition of phenyl  ethyl diyne 14 and phenyl  silyloxymethyl 15 afforded regioisomers 14a and 15a , where the carbonyl resides next 
 to the phenyl ring , exclusively , while a diyne with covalently bound 
 -tocopherol can also be easily clicked together with tropone 
 to afford regioselective cycloadduct 16a . an unsymmetrical 
 diyne bearing an internal gem - dimethyl group reacted 
 with tropone to afford an exclusive regioisomer 17a , 
 which suggests that regioselectivity is highly dependent on the substituents 
 on the alkyne units of a diyne rather than backbone . the cycloaddition of unsymmetrical isopropyl  methyl 
 diyne ( 18 ) afforded products 18a and 18a , where the bulkier group is next to the carbonyl 
 of tropone . cycloaddition of phenyl  isopropyl diyne 19 affords a product where the isopropyl group is away from the carbonyl 
 group ( 19a ) , suggesting that electronic factors override 
 the steric factors ( 19a ) . unfortunately , terminal diynes 
 did not afford any cycloaddition product with tropone due to their 
 high propensity to oligomerize under our reaction conditions . reaction conditions : 
 diyne ( 1 equiv , 0.1 m ) , tropone ( 1.2 equiv ) , 3 mol % of ni(cod)2 , 6 mol % of sipr , thf , 60 c , 5 h. isolated yields ( in black ) , ratio of major and 
 minor cycloadducts ( in blue ) , ratio of major and minor regioisomers 
 ( in red ) . the ratios were 
 determined by h nmr of crude reaction mixture . the lack of general methods to access troponoids prompted 
 our investigation on the ability to convert the cycloadduct to a fully 
 aromatized product . we found that compound 2a can be 
 consistently converted to tropone 20a by a three - step 
 protocol . the hydrogenation of alkene 2a led to a saturated cycloheptanone , which was then subjected 
 to dibromination . specifically , 
 we studied the catalytic cycles for [ ni(ipr)2]-catalyzed 
 cycloaddition of nona-2,7-diyne and tropone with dft calculations . homocoupling , where 
 two alkynes undergo initial oxidative coupling , and heterocoupling , where an alkyne and the tropone undergo initial 
 oxidative coupling , were both investigated . the free energy 
 changes for the homocoupling pathway are shown in figure 3 . from [ ni(ipr)2 ] complex 21 , the coordination of diyne to form intermediate 22 is 
 endergonic by 7.0 kcal / mol . subsequent intramolecular oxidative cyclization 
 via ts23 requires a 13.4 kcal / mol barrier with respect 
 to 22 , generating the metallacyclopentadiene intermediate 24 . this intermediate undergoes a facile 8 insertion 
 ( instead of 2 insertion , vide infra ) of tropone via ts25 , with a barrier of only 9.8 kcal / mol . the 8 insertion produces 
 the eight - membered ring intermediate 26 with the tropone 
 oxygen coordinated to nickel . the tropone piece of complex 26 can coordinate to nickel in four different fashions , generating 
 the complexes 26 to 29 . the four isomers have similar stabilities , and complex 29 undergoes reductive elimination via ts30 to 
 give the product - coordinated complex 31 . product extrusion 
 from 31 is exergonic by 2.8 kcal / mol to release the product 
 and regenerate the nickel  diyne complex 22 . the 
 tautomerization of intermediate complex 29 to 29-enol is endergonic by 5.8 kcal / mol , and subsequent reductive elimination 
 from 29-enol will form the 576 tricyclic 
 product ; however , the irreversible reductive elimination via ts30 suggests that the 576 tricyclic product 
 arises from ni - free tautomerization . free 
 energies ( 298 k ) with respect to 21 are shown in kcal / mol . the calculations indicate that 
 the resting state of pathway a is [ ni(ipr)2 ] complex 21 , and oxidative cyclization through ts23 is 
 the rate - limiting step of the catalytic cycle . the overall reaction 
 barrier is 20.4 kcal / mol , which is consistent with the experimental 
 conditions ( 60 c , 5 h ) . in contrast , the heterocoupling pathway 
 of [ ni(ipr)]-catalyzed cycloaddition between nona-2,7-diyne and tropone 
 displays higher free energies ( figure 4 ) . specifically , 
 from nickel  diyne complex 22 , the intermolecular 
 oxidative cyclization between alkyne and tropone can occur via ts34 , with the carbonyl group of tropone distal to the forming 
 c  c bond . this step requires a barrier of 42.5 kcal / mol with 
 respect to the [ ni(ipr)2 ] complex 21 , which 
 is much less favorable as compared to the homocoupling pathway discussed 
 above ( figure 4 ) . alternatively , the intermolecular 
 cyclization can occur with the tropone carbonyl group proximal to 
 the forming c  c bond , as in ts36 . ts36 is 31.6 kcal / mol higher in free energy than the resting state 21 , which is also less favorable than the productive homocoupling 
 pathway . therefore , unlike other ni - catalyzed couplings between alkynes 
 and carbonyls , a heterocoupling mechanism is 
 not operative in the [ ni(ipr)]-catalyzed cycloaddition between diyne 
 and tropone . free energies ( 298 k ) with respect 
 to 21 are shown in kcal / mol . next , insertion of the tropone was investigated , and two 
 probable pathways emerged : a traditional 2 insertion and a 
 distinctive 8 insertion . the transition states of 8 
 ( ts25 ) and 2 insertion ( ts37 ) of 
 tropone were both located , and their free energies and structures 
 are shown in figure 5 . interestingly , the 8 insertion is found to be more favorable 
 by 12.3 kcal / mol . optimized structures , gibbs free energies , and distortion 
 and interaction energies of transition states of 8 insertion 
 ( ts25 ) and 2 insertion ( ts37 ) of 
 tropone . the gibbs free energy changes ( 298 k ) with respect to 24 are shown in kcal / mol . we studied the origins of this preference by employing the 
 distortion / interaction model on ts25 and ts37 . the distortion energy reflects the 
 structural changes from nickel complex 24 or tropone 
 to the corresponding geometries in the transition states , and the 
 interaction energy is the energy of interactions between the distorted 
 fragments , computed as the difference between the activation energy 
 and the total distortion energy . the difference between the distortion 
 energies of ts25 and ts37 is the major reason 
 for the preference for 8 insertion . the distortion energy is 
 17.8 kcal / mol energy for 24 and 13.7 kcal / mol energy 
 for tropone to achieve the distorted geometries in ts25 , while it requires much larger distortions ( 24.3 kcal / mol for 24 and 16.6 kcal / mol for tropone ) in ts37 . stronger 
 steric repulsions are generated between the nickelacyclopentadiene 
 moiety and tropone in ts37 as compared to those in ts25 . this difference between the steric repulsions eventually 
 leads to the preference of the unconventional 8 insertion , 
 and this is the highest order of poly- insertion so far . the transition 
 states for the 8 insertion of tropone with unsymmetrical diynes 
 were also studied . for the isopropyl  methyl diyne ( figure 6 ) , the transition state ts38-c1 that 
 contains the bulky isopropyl group on the diyne next to tropone is 
 more stable than ts38-c2 by 0.7 kcal / mol to avoid steric 
 repulsions between the isopropyl group and ipr ligand . for phenyl methyl 
 diyne , the transition state ts39-c1 is 4.7 kcal / mol more 
 stable than ts39-c2 mainly due to the steric repulsions 
 between the phenyl group and the bulky nhc ligand in ts39-c1 . also , for phenyl isopropyl diyne , the phenyl group is more 
 sterically demanding , and a 4.0 kcal / mol preference to the ts40-c1 is found . overall , our data suggest that ni - catalyzed cycloaddition 
 occurs via the mechanism shown in figure 7 . 
 the homo - oxidative coupling of diyne on ni(0 ) forms ni(ii)cyclopentadiene 
 intermediate i that undergoes 8 insertion of tropone 
 to afford seven - membered ring complex ii . intermediate ii isomerizes from oxygen coordination to -coordination resulting in intermediate iii , which can 
 subsequently isomerize to an -coordinated - ni(ii ) 
 complex v through intermediates iv . finally 
 intermediate v reductively eliminates to give vi , which releases the tricyclic product , vii , and regenerates 
 the ni(0 ) catalyst . at this point , compound vii can preferentially 
 aromatize via sigmatropic shifts to afford major product viii . however , a minor pathway involves tautomerization of vii to cycloheptatrienol ix , which undergoes further 6 
 electrocyclization to afford an interesting bis(divinyl)cyclopropane 
 intermediate , x. intermediate x can either 
 revert to ix or irreversibly rearrange to [ 576 ] 
 fused intermediate xi , which undergoes further sigmatropic 
 shifts to yield the observed minor product , xii . this 
 sigmatropic shift could be catalyzed by a trace amount of water through 
 the bridge of one or multiple molecules of water . due to the uncertainty of the catalyst , we did not perform 
 computational studies on the isomerization of the tricyclic product vii . proposed mechanism for the ni - catalyzed cycloaddition 
 of diynes and tropone . in conclusion , we have discovered a nickel catalyst that 
 can effectively and selectively incorporate a single c  c -bond 
 of tropone in the cycloaddition with diynes . the mechanism of 
 this novel cycloaddition reaction has been investigated using dft 
 calculations . it involves a unique 8 insertion of tropone to 
 form the observed major and minor products . the mechanistic studies 
 to further understand this unique reactivity of tropone and application 
 of this chemistry are underway in our laboratories .
a ni / n - heterocyclic 
 carbene catalyst couples diynes to the c()c( ) 
 double bond of tropone , a type of reaction that is unprecedented for 
 metal - catalyzed cycloadditions with aromatic tropone . 
 many different 
 diynes were efficiently coupled to afford [ 567 ] fused 
 tricyclic products , while [ 576 ] fused tricyclic compounds 
 were obtained as minor byproducts in a few cases . 
 the reaction has 
 broad substrate scope and tolerates a wide range of functional groups , 
 and excellent regioselectivity is found with unsymmetrical diynes . 
 theoretical calculations show that the apparent enone cycloaddition 
 occurs through a distinctive 8 insertion of tropone . 
 the initial 
 intramolecular oxidative cyclization of diyne produces the nickelacyclopentadiene 
 intermediate . 
 this intermediate undergoes an 8 insertion of 
 tropone , and subsequent reductive elimination generates the [ 567 ] 
 fused tricyclic product . 
 this initial product undergoes two competing 
 isomerizations , leading to the observed [ 567 ] and 
 [ 576 ] fused tricyclic products .