olefin metathesis is 
 a powerful method 
 for the construction of c = c bonds in a large number of synthetic 
 contexts , including target oriented synthesis , polymer chemistry , and renewable feedstock 
 derivatization . the development of asymmetric olefin metathesis 
 catalysts has enabled the synthesis of enantioenriched compounds containing 
 olefin functional groups , which are useful functional handles for 
 further transformations . generations of mo- and ru - based catalysts 
 have been developed for asymmetric ring opening cross metathesis ( arocm ) , 
 asymmetric ring closing metathesis ( arcm ) , asymmetric ring rearrangements 
 ( arr ) and asymmetric cross metathesis ( acm ) ( figure 1 ) . these methods have been applied in the synthesis of useful 
 synthetic building blocks and natural products . despite progress in catalyst design , however , significant 
 challenges remain . furthermore , arcm 
 of unhindered trienes has so far been unsuccessful , resulting in extremely 
 low enantioselectivities . the first chiral ru - based catalyst ( 1 , figure 2 ) possessed a c2-symmetric nhc ligand with chiral centers on the backbone 
 of the nhc and unsymmetrical n - aryl substituents . it was found that substitution of chloride for iodide ligands resulted 
 in higher ee but lower yield . the highest levels of enantioinduction 
 were obtained on substrates with e - trisubstituted 
 enantiotopic olefins ; z - trisubstituted or 1,1-disubstituted 
 enantiotopic olefins reacted with much lower selectivity . subsequent 
 modifications of the n - aryl substituents resulted 
 in a more selective catalyst ( 2 ) for arcm and arocm , although the latter transformation took place 
 with poor e / z selectivity . c1-symmetric nhc ligands employing 
 a geared arene substituent have also been developed by collins and blechert . for 
 example , c1-symmetric catalyst 3 was capable of performing 
 arcm to generate tetrasubstituted olefins with good enantioselectivity hoveyda has developed stereogenic - at - ru 
 complexes bearing a binaphthyl aryloxide nhc substituent . these complexes , which can be isolated as a 
 single diastereomer , were used in e - selective arocm 
 and arcm of trienes containing disubstituted enantiotopic olefins . later , a modified complex 4 containing nhc backbone chirality 
 and a biphenyl aryloxide substituent was reported to have improved 
 activity in e - selective arocm of terminal olefins , and to catalyze z - selective 
 arocm with vinyl ethers and vinyl sulfides . subsequent studies demonstrated that a higher energy diastereomer 
 ( differing in configuration at ru ) is accessible . these diastereomers 
 can interconvert either through olefin metathesis , or a nonmetathesis 
 based polytopal rearrangement ( thermal or brnsted acid catalyzed ) . substantial progress has been made in 
 the development of cyclometalated ru complexes such as ( rac)-5 , which catalyze the z - selective 
 cross metathesis of terminal olefins . we anticipated that these complexes could also be highly enantioselective 
 catalysts in asymmetric metathesis . a mechanistic proposal has been 
 developed based on the preference of these complexes to react through 
 side - bound metallacyclobutanes ( syn to the nhc ) . 
 this orientation forces all substituents in the forming metallacyclobutane 
 to point away from the nhc n - aryl group , thus favoring 
 the formation of the z - olefin product . recently , it has been shown that ( rac)-5 can be resolved to generate enantioenriched 5 . herein , we disclose 
 a full account of our synthetic and mechanistic studies involving 
 cyclometalated ru - complexes 5 and 6 in z - selective arocm . furthermore , these complexes are shown 
 to provide promising levels of enantioinduction in two previously 
 challenging transformations : arcm of trienes composed of terminal 
 olefins and acm of prochiral 1,4-dienes . the impact of x - type ligand 
 substitution on reactivity and selectivity is also analyzed leading 
 to identification of nitrate 5 as the optimal catalyst 
 for desymmetrizing transformations . resolution of ( rac)-5 was accomplished by ligand exchange of nitrate for iodide , which 
 facilitated a second exchange with enantiopure silver carboxylate 8 ( scheme 1 ) . attempted exchange with 
 several other carboxylates was unsuccessful , for example , reaction 
 with the silver salts of -methoxy--(trifluoromethyl)phenyl 
 acetic acid , n - acetyl tert - leucine , or n - acetyl phenylglycine resulted in rapid decomposition . 
 the mandelate - derived diastereomers 6a and 6b were chromatographically separable ( under n2 atmosphere ) , 
 to afford a 45% yield ( 90% of theoretical ) of diastereomer 6a ( > 95:5 dr ) . a more rapid , but lower 
 yielding , route was discovered wherein trituration of the mixture 
 of 6a and 6b with 1:1 et2o / pentane 
 resulted in the isolation of pure 6a ( 77% of theoretical ) 
 due to the large difference in solubility between the diastereomers . the latter procedure is a marked improvement in the speed at which 
 synthetically useful quantities of enantioenriched 5 can 
 be produced . waste is avoided by the easy recyclability of the washes 
 containing the partially enriched diastereomeric mixture . pure carboxylate 6a was then converted to the nitrate 5 by treatment with p - tsoh followed by nano3 . ( a ) nai , thf , 75% yield ; 
 ( b ) ( s)-ago2cch(ph)(ome ) ( 8) ( 2 equiv ) , thf , 23 c , 1.5 h , 97% ; ( c ) ( 1 ) 6a , ptsohh2o , thf , 5 min ; ( 2 ) nano3 , thf / meoh , 
 15 min , 43% . arocm of strained olefins is a powerful 
 method for the construction of enantioenriched cyclic and acyclic 
 dienes containing up to 5 stereocenters . the products contain two 
 differentially substituted alkenes , which are poised for subsequent 
 chemoselective transformations . we proposed that the cyclometalated 
 nhc complexes 5 and 6 , which contain stereogenic 
 carbon and ru atoms , would control the approach of the strained olefin 
 reactant to the reactive metal center leading to a highly stereoselective 
 arocm reaction . the bulky adamantyl group limits approach of the reactant 
 olefin solely toward the opposite face of the alkylidene . strong preference 
 for side - bound metallacyclic intermediates would result in higher 
 fidelity communication of the stereochemical information stored in 
 the nhc ligand . finally , the pocket capped by the n - aryl substituent of the nhc is well suited for the z - selective ring opening as it favors the formation of all - cis metallacyclobutanes , which had been previously observed 
 in the context of ring opening metathesis polymerization ( romp ) . in accord with this proposal , enantioenriched 
 cyclometalated complex 5 catalyzed the arocm of norbornenes and cyclobutenes , resulting in the first ruthenium - catalyzed z - selective 
 and enantioselective ring opening of these strained rings with simple 
 terminal olefins ( table 1 ) . 2,3-di - endo - substituted norbornenes afforded products in high z - selectivity , and 2,3-dibenzyloxy substitution resulted 
 in high enantioselectivity ( 93% , table 1 , entry 
 1 ) . substrates bearing 7-anti and 7-syn substitution ( 9c and 9d ) were well tolerated , 
 affording products in high ee ( entries 3 and 4 ) . however , the lack 
 of 2,3 disubstitution appeared to have a strong influence on the diastereoselectivity 
 of the reaction . the strongest effect arose from 7-syn substitution , which resulted in a preference for the e product . benzonorbornadiene 9e , possessing sp carbons at the 2 and 3 positions , also 
 resulted in reduced z - selectivity , although the products 
 were formed in excellent enantiomeric excess . regardless of the e / z selectivity , it was observed that in 
 cases where both geometrical isomers could be isolated , the e and z isomers were formed with identical 
 enantioenrichment ( entries 35 ) . determined 
 by chiral sfc on chromatographically purified products . determined 
 by h nmr spectroscopy . in contrast to the reactions employing 
 norbornenes , the arocm of cyclobutenes occurred with higher yield 
 and comparable levels of z - selectivity . arocm of cyclobutenes tolerated commonly used 
 oxygen protecting groups as well as free alcohols on both the cyclobutene 
 ( 9f ) and terminal olefin ( 10c ) reactants . notably , in stark contrast to the outcome for the norbornene arocm , 
 the ee s of the z and e products 
 differed considerably . this difference was observed in all 7 cases 
 where both isomers could be analyzed . the ee s of z and e products ranged from 91 and 67% ee , to 93 
 and 86% ee ( for example , table 1 , entries 69 ) . to determine the stereochemical relationship between the double 
 bond isomers , e-9e and z-9e were hydrogenated to afford 12 . both 
 reactions afforded the same major enantiomer of 12 as 
 determined by chiral sfc ( scheme 2 ) , demonstrating 
 that the absolute configurations at the stereogenic carbons of e-9e and z-9e were identical . the equal magnitude and sense of enantioenrichment 
 suggests a common intermediate in the arocm of norbornenes from which 
 the e and z products are ultimately 
 generated . a possible explanation for the identical enantioenrichment 
 of the z- and e - isomers is that 
 a secondary metathesis process isomerizes some of the z product to the more thermodynamically favored e product . however , this was ruled out by the observation that the e / z ratio of arocm products was constant 
 throughout the course of the reaction and for several hours after 
 complete conversion . likewise in the cyclobutene arocm , resubmission 
 of product z-11f to the reaction conditions 
 in the presence of enantiopure catalyst 5 resulted in 
 recovery of the pure z product in identical enantioenrichment 
 and z / e ratio . these experiments 
 strongly suggest that secondary metathesis proceeds at a negligible 
 rate as compared to the productive arocm reaction . our observations 
 regarding arocm of norbornenes and cyclobutenes suggest that the structure 
 and strain energy of the cyclic olefin reactant dramatically alter 
 the catalytic pathway responsible for the mono - cross products ( scheme 3 ) . the identical enantioenrichment of the e and z products formed in the arocm of 
 norbornenes suggests that a methylidene intermediate is involved in 
 the enantiodetermining ring - opening step . the resultant alkylidene 
 then reacts with an equivalent of terminal olefin to afford the monocross 
 products . since the enantiodetermining step precedes the olefin geometry 
 determining step , the e and z products 
 must necessarily have identical enantioenrichment . in contrast , the e and z arocm products derived from cyclobutenes are formed with 
 different ee s , suggesting that the initial ring - opening step 
 occurs through the alkylidene derived from the terminal olefin . in 
 the proposed pathway for the arocm of cyclobutenes with 5 , the initial ring opening of the strained olefin with an alkylidene 
 derived from the terminal olefin is diastereo- and enantiodetermining , 
 resulting in the difference in enantioenrichment for the e and z products . the increased strain and lower steric demand of the cyclobutenes 
 result in propagation through a ru - alkylidene species , while the bulkier 
 and less strained norbornenes result in propagation through a ru - methylidene . the absolute configuration of the arocm products requires that the 
 methylidene intermediate of the cyclobutene arocm possess the opposite 
 configuration at ruthenium compared to the alkylidene in the norbornene 
 arocm . nonproductive metathesis events could potentially be responsible 
 for epimerization of the ruthenium center , providing access to the 
 necessary active species . the effect of terminal olefin equivalents 
 and concentration on stereoselectivity has previously been studied 
 for certain catalysts . in an attempt to better understand the impact of concentration and 
 stoichiometry on the arocm of norbornenes and cyclobutenes , the reactions 
 of 9b and 9c with allyl acetate were studied 
 in further detail . in the case of 2,3-di - endo substituted 
 norbornene 9b , the z / e ratio remained constant and ee was only slightly affected by concentration 
 and equivalents of olefin ( table 2 ) . a similar 
 independence of diastereoselectivity and ee were observed in the arocm 
 of cyclobutenes . full conversion achieved after 16 h. full conversion achieved after 4 h. while the ee of z-11c produced by the arocm of 9c with allyl 
 acetate was unaffected by concentration and equivalents of terminal 
 olefin , the z / e ratio was dependent 
 on both variables with higher concentration and more terminal olefin 
 favoring z-11c ( table 3 ) . thus , in the absence of chelating substituents on the strained 
 olefin component , the diastereodetermining cross metathesis with the 
 terminal olefin is dependent on the concentration of the terminal 
 olefin . a similar dependence of olefin geometry on concentration is 
 observed in romp catalyzed by homogeneous alkylidene initiators . in romp , it has been proposed that the concentration 
 dependence arises from a rate competition between first order rotation 
 of the alkylidene and second order [ 2 + 2 ] cycloaddition with the 
 incoming monomer . higher concentrations have a greater influence on 
 the second order process . in the current arocms , we propose that a 
 similar effect is occurring with the dependence on concentration and 
 the incoming reactant . this dependence suggests that cross metathesis 
 to release the mono - cross product competes with rotation of the alkylidene . determined by chiral sfc on 
 chromatographically purified products a considerable 
 amount of work has been performed on catalyst development and applications 
 for arcm . the products of desymmetrizing arcm are potentially useful in target - oriented 
 synthesis since two differentiated olefins are present in the final 
 enantioenriched product . arcm has been used as the key step in a 
 number of natural product total syntheses . despite much progress , arcm substrates have largely been limited 
 to cases where the unique olefin is considerably less bulky than the 
 enantiotopic olefins . only isolated examples of all - terminal trienes 
 lacking allylic quaternary substitution have proven successful . furthermore , it has been noted 
 in several reports that attempted arcm of various all - terminal trienes 
 have been unsuccessful , due either to low ee or formation of oligomers . the arcm 
 of unhindered trienes is particularly challenging due to the difficulty 
 in controlling the cyclization pathway , and the need to differentiate 
 between relatively small enantiotopic groups . the rcm of prochiral 
 trienes can , in principle , proceed through two distinct pathways ( scheme 4 ) . in pathway a , the initial alkylidene formation 
 occurs on one of the two enantiotopic olefins , followed by cyclization 
 with the unique olefin . if initial alkylidene formation is irreversible , 
 then this step is enantiodiscriminating . in pathway b , initial alkylidene 
 formation occurs with the unique olefin , and this alkylidene subsequently 
 cyclizes with one of the two enantiotopic olefins in the enantiodiscriminating 
 step . to a first approximation , an enantiodiscriminating cyclization 
 step is more likely to be highly enantioselective than alkylidene 
 formation , because of the ordered nature of a cyclic transition state . furthermore , in order to achieve high enantioselectivity , it is desirable 
 to ensure that only one pathway is operating . competing pathways will 
 lead to decreased enantioselectivity unless they are both highly enantioselective 
 for the same product enantiomer ( an unlikely scenario ) . the substitution pattern of the enantiotopic olefins can 
 also impact the relative energy of diastereomeric transition states . cavallo has performed computational studies on the origin of stereoselectivity 
 with geared nhc ru complexes . it was found 
 that the nonreacting olefin is oriented in pseudo - equatorial and pseudo - axial 
 positions in the respective diastereomeric cyclization transition 
 states . higher selectivities are therefore expected when this substituent 
 is large , leading to a large energy difference between pseudo - equatorial 
 and pseudo - axial configurations . we felt that the necessity 
 of employing highly substituted enantiotopic olefins has limited the 
 potential utility of arcm products . we have previously observed that 
 chelated complexes such as ( rac)-5 are 
 sensitive to steric bulk at the allylic position . we hypothesized that resolved complex 5 would 
 be an ideal candidate for arcm of trienes such as 13 , 
 since this catalyst would likely disfavor initial alkylidene formation 
 with the enantiotopic olefins and favor initial reaction with the 
 allyl fragment . this preference would bias the system to undergo enantiodetermining 
 ring closing metathesis , a pathway that is likely to lead to higher 
 enantioinduction . success of this strategy would improve the scope 
 of the arcm reaction by allowing the generation of cyclic products 
 lacking the cumbersome substitution on the resultant product alkenes . furthermore , we wondered whether the addition of further steric 
 bulk , through modification of the x - type ligand , could positively 
 impact enantioselectivities . complexes 6b6i ( scheme 5 ) were prepared by ligand 
 exchange from enantioenriched iodide ent-7 . this reaction proceeded to full conversion 
 based on h nmr and afforded products of sufficient purity 
 after concentration , redissolution in benzene , and filtration through 
 a short plug of celite . complexes containing achiral 
 carboxylate ligands ( 6c6e ) and enantiopure 
 carboxylates ( 6b , 6f6i ) were obtained . while the cyclometalated iodide complex ent-7 was inactive in rcm , all of the carboxylate complexes 
 were found to be competent catalysts with varying levels of enantioselectivity 
 ( table 4 ) . thus , while  ligands 
 are more active than monodentate ligands , the electronics and sterics 
 of the carboxylate ligand also impact the arcm reaction . determined by h nmr spectroscopy ; determined by chiral sfc analysis more substituted aliphatic 
 carboxylates , such as the pivalate 6e and n - acetyl amino carboxylates 6g6i , were more competent catalysts than acetate 6c , forming 
 the product in essentially full conversion ( entries 5 , 79 ) . while the steric bulk of the amino acid side chain had little bearing 
 on the enantioselectivity ( no difference was observed between alanine 
 and valine ) , the presence of an electron - withdrawing heteroatom in 
 the  position of the carboxylate afforded a more enantioselective 
 catalyst . for example , the 2-phenylbutyric acid - derived catalyst 6f generated the product in only 18% ee , while the relatively 
 isosteric o - methyl mandelate 6b provided 13 in 42% ee ( entries 6 and 2 ) . the stereochemistry of the carboxylate has little influence on the 
 stereochemical outcome of the arcm as complexes 6 g and 6h , containing either d- or l - alanine carboxylates , 
 gave identical ee ( entries 7 and 8) . we concluded that the nitrate 
 catalyst 5 ( 98% conversion , 54% ee , entry 10 ) was a significant 
 improvement to the previous generation geared catalyst 1 ( 20% conversion , 0% ee , entry 11 ) and sought to study the reaction 
 scope enabled by this advance . we next probed the influence 
 of substitution in the allylic position , nature of the heteroatom , 
 and ring size on the efficiency and enantioselectivity of arcm . prochiral 
 trienes composed of monosubstituted olefins were cyclized cleanly , 
 resulting in generally high yields ( table 5 ) . moving from a dimethyl siloxy to the bulkier diphenyl siloxy tether 
 resulted in a slower cyclization and required an increase in catalyst 
 loading to achieve good conversion ( entries 1 and 2 ) . triene 19 , which contains trisubstituted enantiotopic olefins , did 
 not undergo ring closure ( entry 3 ) . saturated nitrogen - containing 
 heterocycles were formed in high yield and moderate enantioselectivity , 
 ( entries 4 and 5 ) . reaction conditions : 
 triene ( 0.5 m ) , 5 ( 5 mol % ) , thf , 23 c , 24 h. determined by h 
 nmr using mesitylene as an internal standard . using 10 mol % catalyst . a particularly challenging substrate 23 , bearing a fully substituted carbon in the allylic position of the 
 1,4-diene moiety , completely shut down the reaction ( entry 6 ) . on 
 the other hand , the presence of a fully substituted carbon in the 
 homoallylic position , as in 25 , restored reactivity ( entry 
 7 ) . these results suggest that reducing the steric bulk of the catalyst , 
 perhaps through the use of alternative cyclometalated nhc ligands , 
 may expand the scope of the reaction to form synthetically challenging 
 tertiary ether products . triene 27 , containing 
 a homoallyl diphenyl silyl group , was synthesized in order to test 
 the efficiency of forming seven membered rings ( figure 4a ) . in contrast to triene 17 , 27 underwent ring closure under the standard conditions in good yield , 
 indicating that the additional methylene unit was sufficient to relieve 
 the steric bulk of the diphenylsilyl unit . surprisingly , the product 
 was racemic . to probe whether enantioselectivity is lost due to reversibility , 
 the reaction was performed in a sealed nmr tube and monitored by h nmr ( figure 3 ) . after 4 h , 71% conversion 
 had been achieved . however , the reaction eventually stalled at 78% 
 conversion . upon purging ethylene from the nmr tube , the reaction 
 resumed and eventually reached 92% conversion . this result suggests 
 that in a closed vessel , the rcm of 27 is reversible , 
 and equilibrium can be reached prior to full conversion . time course 
 for the arcm of 27 ( closed nmr tube ) . to remove ethylene during the course of the arcm 
 reaction , the reaction was performed in an open vial in a nitrogen 
 filled glovebox ( figure 4 ) . after 24 h , full conversion of starting material was achieved , 
 and the 7-membered product was generated in 37% ee . this result demonstrates the importance of assessing reversibility in arcm reactions and suggests that removal of ethylene limits reversibility . although reactivity was slightly diminished 
 relative to closed vial conditions , the product was generated in an 
 almost identical 58% ee , ( compared to 54% ee for closed vial ) . the reversible nature of the arcm of 27 , but not 13 , is most likely due to the increased 
 ring strain of 28 . ( a ) effect of open vial on enantioselectivity 
 in arcm of triene 27 ; ( b ) effect of open vial on enantioselectivity 
 in arcm of triene 13 . the absolute configuration of diene 14 ( figure 5 ) produced by arcm of 13 with 5 was determined by x - ray crystallographic analysis to be 
 ( 2s ) . on the basis of the absolute configuration 
 of 14 , we propose that enantioinduction arises from the 
 favorable conformational effect of placing the unreacted vinyl group 
 of the 1,4-diene fragment in a pseudo - equatorial , as opposed to pseudo - axial , 
 orientation ( figure 6 ) . cross metathesis of prochiral 
 1,4 , 1,5 , or 1,6 dienes to afford desymmetrized metathesis products 
 has remained an elusive method for the construction of allylic and 
 homoallylic stereocenters . the lack of success is likely due to three 
 factors : ( 1 ) difficulty in controlling the nature of the propagating 
 species ; ( 2 ) limiting secondary metathesis events resulting in symmetrical 
 products ; and ( 3 ) designing a chiral environment capable of high levels 
 of enantioinduction . however , a previous example of acm suggested 
 that enantiopure ru - based metathesis catalysts are capable of desymmetrizing 
 cross metathesis , although in modest yields ( 1754% ) and ee s 
 ( 452% ) . after optimization 
 of reaction conditions , we have observed that cyclometalated complex 5 catalyzes the acm of 1,4 diene 29 with cis-1,4-diacetoxy-2-butene in 35% yield and with a promising 
 ee of 50% ( eq 1 ) . in contrast to the previous 
 report of e - selective acm with c2-symmetric catalysts , this method provides the z - isomer . while these results are preliminary , 
 they suggest that further optimization of the ligand set and choice 
 of the proper substitution on the pro - stereogenic carbon atom of the 
 diene reactant may result in highly enantioenriched 1,4-diene products , 
 which will be useful chiral building blocks in complex molecule synthesis.1 cyclometalated ruthenium complexes , which 
 are resolved by treatment with an enantiopure carboxylate and readily 
 diversified by ligand exchange , have demonstrated high levels of enantioinduction 
 in the reaction manifolds comprising enantioselective olefin metathesis . arocm of cyclobutenes and norbornenes with 5 afforded , 
 in many cases , highly z and enantioenriched 1,4- 
 and 1,6-dienes , respectively . in comparison to previous generations 
 of c2 symmetric ruthenium alkylidenes , 
 complexes 5 and 6 are capable of desymmetrizing 
 prochiral trienes composed solely of monosubstituted olefins . preliminary 
 results suggest that 5 is capable of acm with a level 
 of enantioselectivity on par with the state of the art , and complementary 
 in its ability to afford z products . study 
 of these reactions has led us to conclude that control of the active 
 catalytic species through the manipulation of several experimental 
 variables can greatly influence the outcome of the enantioselective 
 olefin metathesis reactions . the influence of ring strain and steric 
 bulk of the strained olefin on the mechanism of arocm has led to a 
 hypothesis for the active catalyst species in reactions catalyzed 
 by 5 . the efficiency and enantioselectivity of arcm reactions 
 catalyzed by cyclometalated catalysts is a function of both the x - type 
 ligand and substitution pattern on the prochiral triene reactant . 
 in cases where a medium - sized ring is formed , efficient removal of 
 ethylene is required to prevent reversibility , which would otherwise 
 erode enantioselectivity . the insights gained in this study will facilitate 
 further developments in the field of asymmetric metathesis and will 
 contribute more broadly to the development of new metathesis catalysts .
the 
 success of enantioselective olefin metathesis relies on the design 
 of enantioenriched alkylidene complexes capable of transferring stereochemical 
 information from the catalyst structure to the reactants . 
 cyclometalation 
 of the nhc ligand has proven to be a successful strategy to incorporate 
 stereogenic atoms into the catalyst structure . 
 enantioenriched complexes 
 incorporating this design element catalyze highly z- and enantioselective asymmetric ring opening / cross metathesis ( arocm ) 
 of norbornenes and cyclobutenes , and the difference in ring strain 
 between these two substrates leads to different propagating species 
 in the catalytic cycle . asymmetric ring closing metathesis ( arcm ) 
 of a challenging class of prochiral trienes has also been achieved . 
 the extent of reversibility and effect of reaction setup was also 
 explored . 
 finally , promising levels of enantioselectivity in an unprecedented z - selective asymmetric cross metathesis ( acm ) of a prochiral 
 1,4-diene was demonstrated .