marine sponges have 
 emerged as excellent sources of structurally 
 diverse natural products that possess activities 
 against a number of important disease targets and as such serve as 
 leads in medicinal chemistry programs . our laboratories have developed interests in the imidazole - containing 
 alkaloids belonging to the oroidin or 
 the leucetta families of natural 
 products . these synthetic programs have largely centered on the discovery 
 and development of new methods and strategies for the elaboration 
 of simple imidazole derivatives rather than the de novo construction of the imidazole ring . in this manuscript , 
 we describe the application of two such methods to the syntheses of 
 three analogs of the imidazonaphthoquinone alkaloids kealiiquinone 
 ( 1 ) and 2-deoxy-2-aminokealiiquinone 
 ( 2 ) ( figure 1 ) . specifically the use of an intramolecular diels  alder 
 reaction to construct a polysubstituted dihydrobenzimidazole and oxidation of the imidazole c2-position via 
 the intermediacy of imidazolium salts . kealiiquinone ( 1 ) was isolated from 
 a leucetta 
 sp . found off the islands of guam and saipan by the scheuer 
 lab and characterized by a combination of spectroscopic methods and 
 x - ray crystallography . more recently schmitz 
 and co - workers reported the isolation and characterization of the 
 2-amino congener 2 from leucetta chagosensis collected in chuuk state ( part of the federated states of micronesia ) . in both cases , biological activity was not reported 
 by the isolation groups , although the presence of the quinone would 
 suggest that they might be good bio - michael acceptors . the biosynthetic 
 details of the leucetta alkaloids are unknown , although 
 it has been speculated that kealiiquinone ( 1 ) may be 
 derived from the kealiinines ( 35 ) through oxidation of the c - ring . an 
 alternative hypothesis has been posited involving the intermediacy 
 and subsequent cyclization of the quinone - containing naamidine f ( 6 ) . prior to our efforts , only one report of a total synthesis of kealiiquinone 
 has appeared from the ohta lab resulting in the synthesis of the 2-keto 
 tautomer of the natural product . a second total 
 synthesis of kealiiquinone ( 1 ) and the first of 2-deoxy-2-aminokealiiquinone 
 ( 2 ) have been completed by our lab using a complementary 
 bioinspired friedel  crafts - like strategy to the approach described 
 by ohta and co - workers . the synthetic version and a regioisomer were 
 evaluated in a panel of cancer cell lines and shown to possess modest 
 activity , but the activity profile suggested 
 a possible unique mechanism of action . however , this facet does not 
 appear to have been pursued further by the ohta group or anyone else . very recently , syntheses of the less oxidized kealiinines have been 
 reported independently by two groups , including ours . the cytotoxicity of 
 the kealiinines ( 35 ) , the kealiiquinones 
 ( 1 and 2 ) , and several intermediates have 
 been investigated and shown for the most part to possess modest activity 
 ( ic50 = 2095 m in mtt growth assay with 
 mcf7 breast cancer cell lines ) . we were intrigued by the opportunity 
 offered by kealiiquinone ( 1 ) to demonstrate the utility 
 of several aspects of imidazole chemistry that we have developed , as well as providing a platform to develop novel 
 chemistry along the way . our experience with diels  alder reactions 
 of 4-vinylimidazoles suggested that an intramolecular variant of this 
 chemistry would provide rapid and controlled access to polysubstituted 
 benzimidazole ( 89 , figure 2 ) . in our hands we have found the 4-isomers to be superior in the cycloaddition 
 chemistry and thus the choice of a benzyl protecting group in enyne 9 would permit the position - selective incorporation of the 
 methyl substituent later in the synthetic sequence . whereas the cycloaddition 
 chemistry would properly position substituents around the core framework , 
 a method was needed for the installation of the 2,3-dimethoxyquinone 
 moiety . while there were limited options for this transformation , 
 chemistry reported by venuti , using a 
 cyanide - catalyzed , benzoin - like condensation via elaboration at the c2-position of the imidazole via metalation 
 and electrophilic quench would then deliver either of the two kealiiquinone 
 natural products 1 and 2 from a common late - stage 
 intermediate ( figure 2 ) . overview 
 of the synthetic strategy toward kealiiquinone . as part of our exploratory efforts 
 on the intramolecular diels  alder and as a prelude to an approach 
 to kealiiquinone we had prepared dihydrobenzimidazole 14 from n - benzyl protected enyne 13 in 83% yield . c 
 and air , and while these conditions provided the required product 15 ( scheme 1 ) , it gave inconsistent 
 yields and required extended reaction times for good conversions . subsequently , we found that the aromatization could be effected efficiently 
 and reproducibly in the presence of mno2 , delivering 15 in 91% yield . since these preliminary experiments were successful , we 
 decided 
 to construct the full substrate which required the preparation of 
 the anisyl substituted propiolic acid 12 . this was prepared 
 through a sonogashira cross - coupling between p - iodoanisole 
 and propargyl alcohol ( 85% ) . oxidation 
 of the product with mno2 provided the aldehyde ( 85% ) and a subsequent pinnick oxidation produced 
 the corresponding propiolic acid 12 ( 60% ) . the acid 12 was coupled with the benzyl protected vinylimidazole 10 through a dcc - mediated condensation delivering enyne 9 ( scheme 1 ) . subjection of the thus 
 obtained enyne 9 to heating in toluene at reflux for 
 48 h resulted in the formation of the dihydrobenzimidazole 8 in excellent yield . oxidation with mno2 affords 
 the aromatized benzimidazole 16 in good yield ( scheme 1 ) . the structure of 16 was confirmed 
 through x - ray crystallography ( see si ) 
 which nicely illustrated the relative location of the two aromatic 
 substituents . of note is the slight pyramidalization 
 of the imidazole n1 (  = 353.89 ) and the deviation 
 from orthogonality around the c3c10 bond ( crystallographic 
 numbering ) . presumably both structural effects minimize nonbonded 
 interactions between the n - benzyl and anisyl moieties . 
 at this stage , both the unsubstituted and p - methoxy 
 systems 15 and 16 were taken through the 
 same set of reactions to construct the imidazonaphthoquinone 
 framework but in slightly different sequences as described in schemes 2 , 3 , and 4 . initially , it was decided 
 to introduce the n - methyl group on the p - anisyl - containing substrate 16 , as this can be accomplished 
 via the intermediacy of the imidazolium salt by hydrogenolysis of 
 the benzyl group ( scheme 2 ) . conversion of 16 to the imidazolium salt 17 was accomplished 
 uneventfully by treatment with methyl iodide , and subsequent catalytic 
 hydrogenation of 17 delivered the corresponding debenzylated n - methyl benzimidazole derivative 18 . in our 
 preliminary experiments we noted some variability in the yield of 
 this reaction . ultimately however it was recognized that hydrolysis 
 of the lactone occurred ; treatment of the crude hydrogenation product 
 with aqueous acid recyclized the -hydroxy acid thus providing 
 improved yields and reproducibility . this strategy for introduction 
 of the methyl group has the advantage of avoiding potential selectivity 
 issues in comparison to an approach involving direct methylation of 
 the parent benzimidazole . reduction of 
 the lactone to the corresponding diol 19 was accomplished 
 effectively with dibal , setting the stage for the installation of 
 the final ring . in order to accomplish this critical transformation , initial 
 attempts to convert diol 19 to the phthaldehyde derivative 7 with common oxidants were thwarted by the formation of the 
 lactone ; only swern conditions were partially successful . in this 
 latter case there was some batch to batch inconsistency , the cause 
 of which we were unable to track down . fortunately , this led us to 
 investigate reagents that behaved mechanistically similarly to swern 
 reagents ; among these , the best system we identified was reported 
 by mukaiyama and co - workers involving sulfinimidoyl chlorides , e.g. , 20 in the presence of dbu . this 
 reagent combination reproducibly resulted in the formation of the 
 phthaldehyde 7 in yields between 65% and 75% . with the 
 aldehyde in hand we were in position to evaluate venuti s method 
 for its conversion into the corresponding dihydroxy benzoquinone 22 . gratifyingly , we found that 
 the 2,3-dihydroxybenzoquinone 22 was 
 produced reproducibly , albeit , in a modest yield of approximately 
 40% . at this stage , all that remained to be done to complete the total 
 synthesis of kealiiquinone ( 1 ) was the conversion of 
 the hydroxyl groups to methyl ethers and oxidation at c2 . the first 
 task was accomplished by taking advantage of the fact that the oh 
 groups are part of a vinylogous acid and as such reacted efficiently 
 with tms - diazomethane , delivering dimethoxyquinone 23 . however , the introduction of functionality at c2 was significantly 
 more difficult . we and others have routinely used metalation by deprotonation 
 at c2 with a strong base ( buli or lda ) and followed that by trapping 
 with a suitable electrophile : in this context either 
 ( tmso)2 for kealiiquinone ( 1 ) or tsn3 for the amino congener 2 . multiple attempts to perform this 
 chemistry with 23 as a substrate simply failed to produce 
 the anticipated products ; indeed these reactions did not produce any 
 products that we were able to characterize . experiments to trap out 
 any metalated intermediates with d2o or methanol - d4 were similarly unsuccessful . although we have no experimental 
 evidence to support our hypothesis , we suspect that electron transfer 
 processes are intervening . as a means to circumvent these issues , 
 we briefly attempted to introduce functionality at c2 earlier in the 
 sequence by metallating with n - buli on lactones 16 or 18 ; however issues with solubility or deprotonation 
 occurring on the n - benzyl or the lactone methylene 
 compromised this strategy . alternative timings for introducing the 
 c2-functionality were rejected as these options invariably increased 
 the step count unacceptably . given 
 this late stage failure 
 to functionalize at c2 of the naphthimidazole , we began to contemplate 
 our options for moving the synthesis forward , and it occurred to us 
 that the imidazolium salts that were prepared as a means to selectively 
 methylate the benzimidazoles may be easier to functionalize given 
 the increased acidity of the proton at c2 in these systems . based on this hypothesis , we have developed 
 an extremely mild method for introducing oxygen at c2 through exposure 
 of the imidazolium ion to bleach or alternatively nitrogen can be 
 introduced through exposure to n - chlorosulfonamides 
 or n - chlorocarbamates ; this chemistry has been 
 described in more detail elsewhere . with 
 this method in hand we subjected the lactone imidazolium species 17 to bleach and found that it too underwent the oxidation 
 to provide the 2-benzimidazolone 24 in good yield ( scheme 3 ) . an x - ray structure determination on the dibal - reduction 
 product 25 unequivocally demonstrates the introduction 
 of the 2-oxo moiety and served to confirm the relative location of 
 the methyl and aryl groups . at this point we elaborated the benzimidazolone 25 in a largely analogous 
 fashion to the corresponding phthaldehyde 26 . although 
 the efficiency was lower , dialdehyde 26 was converted 
 into the dihydroxyquinone 27 and subsequently the hydroxyl 
 groups were converted into methoxy groups by treatment with tms - diazomethane 
 ( 27  28 , scheme 3 ) . all that remained to complete the revised synthesis of 
 kealiiquinone ( 1 ) was removal of the n - benzyl protecting group ; unfortunately this proved to be exceedingly 
 difficult . while n - benzyl groups can be removed quite 
 readily from amines under a variety of conditions , amides on the other 
 hand tend to be much more challenging substrates . indeed it was found 
 that standard reductive or oxidative conditions failed to remove the n - benzyl moiety . ultimately , 
 we determined that heating the substrates in neat triflic acid resulted 
 in debenzylation with reasonable efficiencies . unfortunately , in the case of the precursor to kealiiquinone , 
 these reaction conditions led to the selective demethylation of the 
 7-methyl and thus the formation of 7-desmethylkealiiquinone 
 ( 29 ) . in an effort to access the natural product , various 
 attempts were made to remethylate the phenolic hydroxyl group . in 
 our hands this resulted in overmethylation ( methylation of the imidazole 
 nitrogen and the hydroxyl group ) or n - methylation 
 under a variety of different conditions and with different methyl 
 sources . an 
 alternative strategy 
 was explored concurrently with the one described above in which the 
 introduction of the c2-substituent was delayed until the end of the 
 synthesis . in part this was undertaken in order to not only evaluate 
 the strategy in general but also establish whether the highly functionalized 
 quinones were viable substrates in our oxidative chemistry . thus lactone 15 was reduced to the corresponding diol 30 and 
 then converted to the phthaldehyde 31 upon treatment 
 with 20 ( scheme 4 ) . conversion 
 to the 2,3-dihydroxyquinone 32 was accomplished 
 with glyoxal 21 , followed by methylation with tms - diazomethane . methylation of the imidazole nitrogen to prepare the imidazolium salt 34 was then carried out by exposure of 33 to 
 methyl iodide in acetonitrile at reflux . initial oxidation experiments 
 of 34 with bleach resulted in the formation of the imidazolone 35 , but the yields were rather low , ca . fortunately , we had established previously that other chloronium sources 
 effect this chemistry , and so exposure of 34 to ncs and 
 aqueous potassium carbonate delivered the imidazolone 35 in 60% yield . reaction of the imidazolone 
 with tfoh at 55 c resulted in debenzylation and the formation 
 of 4-desmethoxykealiiquinone ( 36 ) . with the imidazolium salt in hand , we also took the opportunity 
 to evaluate the introduction of an imino group through exposure to 
 an n - chlorocarbamate ( scheme 4 ) ; to date only simple benzimidazolium and imidazolium salts had 
 been investigated in this chemistry . while 
 the yield turned out to be quite modest , the reaction of 34 with n - chloro tert - butylcarbamate 
 ( produced in situ from tert - butyl 
 carbamate and t - buocl ) did produce the expected product 37 ( scheme 4 ) . a preliminary attempt 
 to remove the bn- and boc - protecting groups by sequential treatment 
 with tfoh and then tfa was not successful . one further strategy was evaluated to prepare the imidazolium 
 salt 
 near the end of the synthesis with a more easily removable n - substituent , but one that was capable of activating the 
 oxidation ( scheme 5 ) . to test the feasibility 
 of such an approach given that the n3-position is relatively hindered , lactone 18 was used as a model and converted to the corresponding 
 dimethyl imidazolium salt 38 . gratifyingly , treatment 
 of the salt with bleach resulted in c2-oxidation to deliver imidazolone 39 in good yield suggesting that late stage functionalization 
 through application of our chemistry was achievable . frustratingly 
 however , . specifically , attempted introduction of a mom 
 group was unsuccessful , whereas the attempted incorporation of a sem 
 group resulted in the net protonation 
 of the imidazole and production of the imidazolium salt 41 . the significant downfield shift of 
 the c2-proton absorbance in the h nmr spectrum of the 
 product is characteristic of the formation of an imidazolium species . this was further confirmed when an x - ray crystal structure of this 
 product was obtained , which clearly indicates the protonation of the 
 nitrogen along with chloride as the counterion ( see supporting information ) . our assumption here is that the proximity 
 of the aryl group to the nitrogen atom renders it sterically hindered 
 and only small electrophiles can access it . attempts to oxidize the 
 protonated imidazolium salt 41 with bleach to the corresponding 
 imidazolone 42 were not successful . presumably , the basic 
 nature of the reaction conditions simply results in deprotonation 
 and inactivation of the imidazole . efficient 
 routes have been developed to the heterocyclic framework 
 of kealiiquinone through application of an intramolecular diels alder 
 reaction of an enyne , c2-functionalization through a novel oxidation 
 of imidazolium salts , and application of an underutilized method for 
 the formation of dihydroxy quinones from phthaldehydes . indeed , this 
 work constitutes the first application of venuti s method for 
 the de novo construction of a 2,3-dimethoxyquinone . unfortunately deprotection of an n - benzyl moiety 
 from the penultimate intermediate resulted in concomitant demethylation 
 delivering 7-desmethylkealiiquinone rather 
 than the natural product . similar chemistry has been used to obtain 
 related materials lacking the 4-methoxy group and the 2-oxo 
 group which will enable the sar investigations of this unique family 
 of natural products . nmr 
 spectra were obtained at either 500 or 300 mhz ( for h 
 nmr spectra ) or 125 or 75 mhz ( for c nmr ) in cdcl3 unless indicated otherwise . h nmr spectra were 
 referenced to residual protiosolvent unless indicated otherwise ( chcl3  = 7.26 ppm ) . for spectra recorded in other solvents , 
 residual meoh (  = 3.31 ppm ) or dmso (  = 2.50 ppm ) were 
 used as internal references . c nmr spectra were recorded 
 in cdcl3 ( unless otherwise indicated ) using residual chcl3 (  = 77.2 ppm ) as an internal reference . for spectra 
 recorded in other solvents , residual meoh (  = 39.5 ppm ) and 
 dmso (  = 49.0 ppm ) infrared 
 ( ir ) spectra were obtained on neat samples ( atr spectroscopy ) or using 
 either kbr pellets for solids or neat films on nacl plates for liquids 
 ( transmission ) . analytical thin - layer chromatography ( tlc ) was performed 
 on silica gel plates , 200 mesh with f254 indicator . visualization 
 was accomplished by uv light ( 254 nm ) and/or a 10% ethanol solution 
 of kmno4 . high resolution mass spectra ( hrms ) were recorded 
 by electrospray ionization ( esi - tof ) or atmospheric - pressure chemical 
 ionization ( apci - tof ) unless otherwise indicated . propiolic acid 12 ( 2.00 g , 11.4 mmol ) , alcohol 10 ( 2.94 g , 13.7 mmol ) , dmap ( 0.14 g , 1.2 mmol ) , and camphorsulfonic 
 acid ( 0.16 g , 0.70 mmol ) were dissolved in ch2cl2 ( 50 ml ) and cooled to 78 c under n2 . dcc 
 ( 3.50 g , 17.1 mmol ) dissolved in ch2cl2 ( 20 
 ml ) was added dropwise . the mixture was allowed to come to rt and 
 stir for 2 h. the solids were filtered through celite and washed with 
 ch2cl2 . the filtrate was reduced , and the resulting 
 brown residue was purified by column chromatography ( 8:2 etoac / hexane ) 
 to afford 9 as an off - white solid ( 2.53 g , 56% ) . mp : 
 6567 c ; h nmr :  = 7.52 ( s , 1h ) , 7.49 
 ( d , j = 2.1 hz , 2h ) , 7.367.31 ( m , 3h ) , 7.157.13 
 ( m , 2h ) , 6.86 ( m , 3h ) , 6.58 ( d , j = 15.6 hz , 1h ) , 
 6.476.38 ( dt , j = 15.5 , j = 6.2 hz , 1h ) , 5.06 ( s , 2h ) , 4.82 ( d , j = 6.6 hz , 
 2h ) , 3.81 ( s , 3h ) ; c nmr :  = 161.6 , 154.2 , 139.8 , 
 137.9 , 135.9 , 135.0 , 129.1 , 128.5 , 127.4 , 127.0 , 120.6 , 117.9 , 114.4 , 
 111.5 , 87.3 , 80.1 , 66.5 , 55.5 , 51.0 ; ir ( kbr , cm ) : 3105 , 2195 , 1899 , 1697 , 1602 , 1567 , 1541 ; hr - esims ( m / z ) : calcd for [ m + h ] c23h21n2o3 is 373.1547 , found 373.1564 . enyne 9 ( 2.54 g , 6.84 mmol ) was dissolved 
 in toluene ( 200 ml ) and purged with n2 for 15 min . the 
 solution was then heated at 130 c in a sealed tube for 48 h. 
 the solvent was removed , and the resulting solids were washed with 
 diethyl ether to afford 8 as an off - white solid ( 2.14 
 g , 84% ) . mp : 199201 c ; h nmr :  = 
 7.44 ( s , 1h ) , 7.247.10 ( m , 5h ) , 6.85 ( dd , j = 5.7 , 1.8 hz , 2h ) , 6.64 ( dd , j = 5.1 , 1.5 hz , 
 2h ) , 4.68 ( dd , j = 16.5 , 7.5 hz , 2h ) , 4.43 ( d , j = 15.6 hz , 1h ) , 4.01 ( t , j = 8.7 hz , 
 1h ) , 3.83 ( s , 3h ) , 3.673.58 ( m , 1h ) , 3.06 ( dd , j = 15.0 , 8.7 hz , 1h ) , 2.73 ( dd , j = 17.1 , 15.9 hz , 
 1h ) ; c nmr :  = 168.1 , 160.3 , 144.4 , 141.2 , 139.4 , 
 135.8 , 128.7 , 128.4 , 128.1 , 126.6 , 123.9 , 117.2 , 70.6 , 55.4 , 50.3 , 
 38.1 , 28.0 ; ir ( kbr , cm ) : 3465 , 2946 , 1737 , 1621 , 
 1512 , 1252 ; hr - esims ( m / z ) : calcd 
 for [ m + h ] c23h21n2o3 373.1547 , found 373.1571 . to 14(11 ) ( 5.5 g , 16 mmol ) 
 in ch2cl2 ( 250 ml ) was added mno2 ( 85% act . ) ( 15 g ) followed by heating at 40 c for 
 48 h. the solids were filtered through celite and washed with ch2cl2 . the filtrate was reduced to give the product 
 as a white solid ( 5.0 g , 91% ) . mp : 185186 c ; h nmr :  = 8.02 ( s , 1h ) , 7.85 ( s , 1h ) , 7.42 ( t , j = 7.5 hz , 1h ) , 7.30 ( t , j = 7.5 hz , 2h ) , 7.21 ( d , j = 7.5 hz , 1h ) , 7.187.13 ( m , 4h ) , 6.54 ( d , j = 7.5 hz , 2h ) , 5.37 ( s , 2h ) , 4.93 ( s , 2h ) ; c nmr :  = 169.8 , 148.9 , 140.5 , 135.7 , 132.3 , 129.8 , 128.8 , 
 128.6 , 128.1 , 127.9 , 127.6 , 126.2 , 118.4 , 112.6 , 68.1 , 50.3 ; ir ( cm ) : 3005 , 2923 , 1752 , 1497 , 1363 , 1251 , 1130 , 1018 ; 
 hr - esims ( m / z ) : calcd for [ m + na ] c22h16n2o2na 
 363.1104 , found 363.1114 . 8 ( 7.0 g , 19 mmol ) was dissolved 
 in ch2cl2 ( 500 ml ) , and mno2 ( 18.0 
 g , 188 mmol ) was added . then the mixture was stirred at rt for 24 
 h. the solids were filtered and washed with ch2cl2 followed by meoh . the filtrate was concentrated to give 16 as an off - white solid ( 6.24 g , 89% ) . mp : 176178 c ; h nmr :  = 8.01 ( s , 1h ) , 7.82 ( s , 1h ) , 7.217.16 
 ( m , 3h ) , 7.06 ( d , j = 8.9 hz , 2h ) , 6.83 ( d , j = 8.9 hz , 2h ) , 6.59 ( d , j = 7.5 hz , 2h ) , 
 5.35 ( s , 2h ) , 4.97 ( s , 2h ) , 3.84 ( s , 3h ) ; c nmr :  
 = 170.0 , 159.8 , 149.4 , 148.9 , 140.5 , 135.8 , 132.7 , 131.0 , 128.7 , 128.0 , 
 127.6 , 126.2 , 124.2 , 118.5 , 113.3 , 112.4 , 68.0 , 55.3 , 50.3 ; ir ( kbr , 
 cm ) : 2947 , 1739 , 1614 , 1500 , 1347 , 1253 ; hr - esims 
 ( m / z ) : calcd for [ m + na ] c23h18n2o3na 393.1210 , 
 found 393.1210 . 16 ( 0.37 g , 1.0 mmol ) 
 was dissolved in toluene ( 20 ml ) , and mei ( 0.20 ml , 3.2 mmol ) was 
 added . the mixture was heated at 120 c for 24 h during which 
 additional aliquots of methyl iodide ( 0.5 equiv ) were added until 
 no starting material could be detected by tlc . the solids were filtered 
 and washed with etoac to afford 17 as a pale yellow solid 
 ( 0.48 g , 93% ) . mp : 198200 c ; h nmr :  
 = 10.50 ( s , 1h ) , 8.03 ( s , 1h ) , 7.257.12 ( m , 5h ) , 6.946.87 
 ( m , 4h ) , 5.43 ( s , 2h ) , 5.27 ( s , 2h ) , 4.32 ( s , 3h ) , 3.86 ( s , 3h ) ; c nmr :  = 167.7 , 160.8 , 146.4 , 144.8 , 136.8 , 132.2 , 
 131.4 , 131.1 , 130.1 , 129.2 , 127.7 , 122.8 , 121.0 , 113.9 , 106.7 , 68.0 , 
 55.5 , 53.2 , 35.4 ; ir ( cm ) : 2939 , 1775 , 1612 , 1575 , 
 1501 , 1451 , 1378 , 1337 ; hr - esims ( m / z ) : calcd for [ m + h ] c24h21n2o3 385.1547 , found 385.1548 . to 
 imidazolium salt 17 ( 0.44 g , 0.86 mmol ) was added etoh 
 ( 50 ml ) and sat . nahco3 ( 5 ml ) , followed by 10% pd / c ( 0.10 
 g ) . the reaction mixture was heated at 80 c under h2 ( 1 atm ) for 24 h. the solids were filtered and washed with ch2cl2/meoh followed by water . the aqueous solution 
 was then acidified to ph = 5 with 3 m hcl and stirred for 2 h. the 
 resulting aqueous solution was extracted multiple times with ch2cl2 . the resulting solid was 
 recrystallized from meoh to afford 18 as a white solid 
 ( 0.19 g , 76% ) . mp : > 250 c ; h nmr ( dmso - d6 ) :  = 8.32 ( s , 1h ) , 7.69 ( s , 1h ) , 7.55 ( d , j = 9.2 hz , 2h ) , 6.98 ( d , j = 9.2 hz , 2h ) , 
 5.39 ( s , 
 2h ) , 3.89 ( s , 3h ) , 3.80 ( s , 3h ) ; c nmr ( dmso - d6 ) :  = 170.5 , 159.7 , 147.9 , 143.1 , 142.6 , 139.8 , 133.4 , 133.2 , 
 125.4 , 114.6 , 113.2 , 102.9 , 68.4 , 55.7 , 31.6 ; ir ( kbr , cm ) : 3044 , 2957 , 2835 , 1739 , 1603 , 1501 , 1453 ; hr - esims ( m / z ) : calcd for [ m + h ] c17h15n2o3 295.1077 , found 295.1092 . benzimidazole 18 ( 0.19 g , 
 0.65 mmol ) was dissolved in ch2cl2 ( 5 ml ) and 
 cooled to 78 c under n2 . dibal - h ( 1 m in 
 hexane ) ( 1.5 ml , 1.5 mmol ) was added dropwise , and the reaction mixture 
 was allowed to warm to rt and stirred for 3 h. the reaction mixture 
 was cooled to 0 c , and water was added slowly followed by meoh . the organic extract was separated , and the residual aqueous 
 solution was extracted multiple times with ch2cl2 . the resulting white solid was triturated 
 with et2o to afford 19 as a white solid ( 0.15 
 g , 79% ) . mp : 245247 c ; h nmr ( dmso - d6 ) :  = 8.02 ( s , 1h ) , 7.58 ( s , 1h ) , 7.43 ( d , j = 8.6 hz , 2h ) , 6.98 ( d , j = 8.6 hz , 2h ) , 
 5.25 ( t , j = 5.5 hz , 1h ) , 4.83 ( d , j = 5.2 hz , 2h ) , 4.79 ( t , j = 4.8 hz , 1h ) , 4.43 ( d , j = 4.5 hz , 2h ) , 3.81 ( s , 3h ) , 3.79 ( s , 3h ) ; c nmr ( dmso - d6 ) :  = 158.8 , 144.7 , 141.6 , 137.6 , 
 134.2 , 133.3 , 132.5 , 129.9 , 129.8 , 113.5 , 108.4 , 62.4 , 58.5 , 55.6 , 
 31.2 ; ir ( cm ) : 3074 , 2889 , 1608 , 1574 , 1340 , 1237 , 
 1174 , 1015 ; hr - esims ( m / z ) : calcd 
 for [ m + h ] c17h19n2o3 299.1390 , found 299.1411 . diol 19 ( 0.10 g , 0.34 mmol ) 
 was dissolved in ch2cl2 , and dbu ( 0.2 ml , 1.34 
 mmol ) was added . the solution was cooled to 78 c under 
 n2 , and n - tert - butylbenzenesulfinimidoyl 
 chloride ( 20 ) ( 0.22 g , 1.02 mmol ) dissolved in ch2cl2 ( 5 ml ) was added dropwise . the resulting residue 
 was purified by column chromatography ( the silica gel was neutralized 
 with 5% et3n prior to purification ) ( etoac to 2% meoh in 
 etoac ) to afford 7 as an off - white solid ( 0.069 g , 70% ) . h nmr :  = 10.61 ( s , 1h ) , 10.16 ( s , 1h ) , 8.09 ( s , 1h ) , 
 8.05 ( s , 1h ) , 7.49 ( d , 2h , j = 8.4 hz ) , 7.08 ( d , 
 2h , j = 8.4 hz ) , 3.97 ( s , 3h ) , 3.89 ( s , 3h ) ; c nmr :  = 193.5 , 192.9 , 160.2 , 147.7 , 145.3 , 139.8 , 
 136.7 , 133.1 , 132.7 , 129.5 , 125.1 , 114.1 , 109.7 , 55.5 , 31.7 ; ir ( kbr , 
 cm ) : 3105 , 2928 , 2881 , 1777 , 1751 , 1682 , 1663 , 
 1566 ; hr - esims ( m / z ) : calcd for 
 [ m + h ] c17h15n2o3 295.1077 , found 295.1110 . to phthaldehyde 7 ( 74 mg , 
 0.27 mmol ) in etoh ( 1.5 ml ) was added 21 ( 50 mg , 0.81 
 mmol ) followed by the simultaneous addition of kcn ( 0.021 g , 0.33 
 mmol ) in h2o ( 0.5 ml ) and et3n ( 0.040 ml , 0.27 
 mmol ) . the reaction was stirred at rt for 15 min and then quenched 
 with 10% hcl until a ph = 5 was attained . the aqueous 
 layer was reduced , and the resulting solids were filtered and washed 
 with acetone to give 22 as a red - orange solid ( 35 mg , 
 39% ) . h nmr ( dmso - d6 ) :  = 9.73 ( brs , 
 2h ) , 8.34 ( s , 1h ) , 8.18 ( s , 1h ) , 7.16 ( d , j = 8.6 
 hz , 2h ) , 6.92 ( d , j = 8.6 hz , 2h ) , 3.93 ( s , 3h ) , 
 3.78 ( s , 3h ) ; c nmr ( dmso - d6 ) :  = 181.8 , 
 181.3 , 158.9 , 148.8 , 146.8 , 141.9 , 139.4 , 137.1 , 135.8 , 131.1 , 129.9 , 
 127.5 , 121.5 , 113.4 , 109.6 , 55.6 , 31.9 ; ir ( cm ) : 2981 , 1642 , 1627 , 1608 , 1337 , 1243 , 1211 , 1021 ; hr - esims ( negative 
 mode ) ( m / z ) : calcd for [ m  h ] c19h13n2o5 349.0830 , found 349.0832 . to dihydroxyquinone 22 ( 23 
 mg , 0.066 mmol ) in thf ( 3 ml ) were added meoh ( 1 ml ) and tmschn2 ( 2.0 m in et2o ) ( 0.080 ml , 0.16 mmol ) with subsequent 
 stirring at rt for 1 h. the reaction mixture was diluted with ch2cl2 and washed with sat . the resulting 
 residue was purified by column chromatography ( 2:8 acetone / hexane 
 to 1:1 acetone / hexane ) to give 23 as an orange residue 
 ( 16 mg , 64% ) . h nmr :  = 8.24 ( s , 1h ) , 8.00 ( s , 
 1h ) , 7.28 ( d , j = 8.6 hz , 2h ) , 7.02 ( d , j = 8.6 hz , 2h ) , 4.10 ( s , 3h ) , 4.01 ( s , 3h ) , 3.95 ( s , 3h ) , 3.86 ( s , 
 3h ) ; c nmr :  = 182.3 , 182.0 , 159.1 , 148.9 , 147.4 , 
 146.5 , 136.8 , 130.6 , 130.2 , 128.8 , 128.3 , 122.8 , 114.5 , 113.8 , 108.8 , 
 61.4 , 61.3 , 55.3 , 31.7 ; ir ( cm ) : 2924 , 2852 , 1658 , 1618 , 1515 , 1456 , 1341 , 1307 , 1245 , 1215 , 1054 ; hr - apcims ( m / z ) : calcd for [ m + h ] c21h18n2o5 379.1288 , found 
 379.1296 . imidazolium salt 17 ( 1.0 g , 
 1.9 mmol ) in thf ( 40 ml ) was cooled to 0 c , and 5% naocl ( 30 
 ml ) was added dropwise . the reaction was diluted with etoac , and the aqueous 
 layer was extracted with etoac ( 2 ) . the combined organic extracts 
 were washed with h2o and then brine , dried ( anhyd . the resulting residue was 
 purified by column chromatography ( 7:3 etoac / hexane ) to give 24 as an off - white solid ( 0.58 g , 75% ) . mp : 185187 
 c ; h nmr :  = 7.127.09 ( m , 3h ) , 7.03 
 ( s , 1h ) , 6.94 ( d , j = 8.6 hz , 2h ) , 6.77 ( d , j = 8.9 hz , 2h ) , 6.586.56 ( m , 2h ) , 5.23 ( s , 2h ) , 
 4.79 ( s , 2h ) , 3.83 ( s , 3h ) , 3.57 ( s , 3h ) ; c nmr :  
 = 169.8 , 159.7 , 155.6 , 141.8 , 136.4 , 136.2 , 131.3 , 128.2 , 127.8 , 127.2 , 
 126.0 , 124.0 , 123.6 , 117.1 , 113.1 , 99.5 , 67.7 , 55.3 , 45.8 , 27.8 ; ir 
 ( cm ) : 1748 , 1705 , 1609 , 1517 , 1496 , 1352 , 1244 , 
 1028 ; hr - esims ( m / z ) : calcd for 
 [ m + na ] c24h20n2o4na 423.1315 , found 423.1316 . imidazolone 24 ( 1.4 g , 3.5 mmol ) 
 was dissolved 
 in ch2cl2 ( 25 ml ) and cooled to 78 c 
 under n2 . dibal - h ( 1 m in hexanes ) ( 9.8 ml , 9.8 mmol ) was 
 added dropwise , then allowed to come to rt , and stirred for 4 h. the 
 reaction mixture was cooled to 0 c , and water was added slowly 
 followed by meoh . the resulting solids were washed with hexane and then et2o to give 25 as an off - white solid ( 1.17 g , 83% ) . mp : 
 205206 c ; h nmr :  = 7.117.09 
 ( m , 3h ) , 7.03 ( s , 1h ) , 6.87 ( d , j = 8.6 hz , 2h ) , 
 6.70 ( d , j = 8.6 hz , 2h ) , 6.596.57 ( m , 2h ) , 
 4.81 ( s , 2h ) , 4.64 ( s , 2h ) , 4.38 ( s , 2h ) , 3.82 ( s , 3h ) , 3.46 ( s , 3h ) ; c nmr :  = 159.4 , 155.5 , 137.1 , 134.0 , 132.5 , 131.5 , 
 130.1 , 128.1 , 127.2 , 126.9 , 125.8 , 125.6 , 113.4 , 108.5 , 65.1 , 59.5 , 
 55.4 , 45.4 , 27.4 ; ir ( cm ) : 3313 , 2930 , 1669 , 1611 , 
 1515 , 1398 , 1244 , 1181 ; hr - apcims ( m / z ) : calcd for [ m + h ] c24h25n2o4 405.1809 , found 405.1826 . diol 25 ( 0.22 g , 0.54 mmol ) was 
 dissolved 
 in ch2cl2 ( 10 ml ) and cooled to 78 c 
 under n2 . dbu ( 0.32 ml , 2.2 mmol ) was added followed by 20 ( 0.38 g , 1.7 mmol ) in ch2cl2 ( 1 ml ) , 
 and the reaction was stirred at 78 c for 30 min . sat . the organic layer was separated , and the aqueous layer was 
 extracted with ch2cl2 ( 2 ) . the resulting residue was purified by column chromatography 
 ( the silica gel was neutralized with et3n prior to purification ) 
 ( 4:6 etoac / hexane ) to give 26 as an off - white solid ( 0.17 
 g , 77% ) . mp : 152155 c ; h nmr :  = 
 10.40 ( s , 1h ) , 9.67 ( s , 1h ) , 7.68 ( s , 1h ) , 7.147.08 ( m , 3h ) , 
 6.92 ( d , j = 8.6 hz , 2h ) , 6.74 ( d , j = 8.6 hz , 2h ) , 6.54 ( d , j = 6.8 hz , 2h ) , 4.74 ( s , 
 2h ) , 3.84 ( s , 3h ) , 3.59 ( s , 3h ) ; c nmr :  = 192.6 , 
 192.0 , 160.1 , 155.6 , 136.1 , 133.7 , 132.2 , 131.9 , 131.8 , 130.2 , 128.3 , 
 128.0 , 127.3 , 125.6 , 123.6 , 113.7 , 106.5 , 55.5 , 45.8 , 27.9 ; ir ( cm ) : 2934 , 1701 , 1675 , 1606 , 1513 , 1357 , 1243 , 1076 ; 
 hr - esims ( m / z ) : calcd for [ m + na ] c24h20n2o4na 
 423.1315 , found 423.1309 . to phthaldehyde 26 ( 0.10 g , 
 0.25 mmol ) in thf ( 3 ml ) was added 21 ( 42 mg , 0.75 mmol ) 
 followed by the addition of kcn ( 0.029 g , 0.44 mmol ) and k2co3 ( 0.17 g , 1.3 mmol ) in h2o ( 1 ml ) . the reaction 
 was stirred at rt for 5 min , then quenched with 6 m hcl , and diluted 
 with h2o ( 5 ml ) . the combined organic extracts were washed with h2o and then brine , dried ( anhyd . the resulting solids were filtered to give the dihydroxyquinone 27 as an orange solid ( 22 mg , 20% ) . mp : 204206 c ; h nmr ( dmso - d6 ) :  = 9.65 ( s , 1h ) , 9.60 ( s,1h ) , 
 7.80 ( s , 1h ) , 7.137.11 ( m , 3h ) , 6.79 ( d , j = 8.6 hz , 2h ) , 6.63 ( d , j = 8.6 hz , 2h ) , 6.566.54 
 ( m , 2h ) , 4.44 ( s , 2h ) , 3.71 ( s , 3h ) , 3.50 ( s , 3h ) ; c 
 nmr ( dmso - d6 ) :  = 181.6 , 181.1 , 159.1 , 155.1 , 141.0 , 
 138.4 , 137.3 , 134.0 , 131.2 , 130.5 , 128.5 , 127.7 , 127.3 , 127.0 , 125.7 , 
 125.0 , 122.6 , 113.5 , 106.0 , 55.6 , 45.5 , 28.1 ; ir ( cm ) : 3240 , 1697 , 1654 , 1597 , 1514 , 1400 , 1283 , 1243 . hrms - esi ( negative 
 mode ) ( m / z ) : calcd for c26h19n2o6 [ m  h ] 455.1249 , found 455.1243 . the dihydroxyquinone 27 prepared 
 above ( 22 mg , 0.048 mmol ) was dissolved in thf ( 3 ml ) , and meoh ( 0.5 
 ml ) was added followed by tmschn2 ( 2.0 m in et2o ) ( 0.07 ml , 0.15 mmol ) with subsequent stirring at rt for 30 min . the reaction was diluted with etoac and washed with 2 m na2co3 ( 2 ) and then brine . the 
 resulting residue was purified by column chromatography ( 1:1 etoac / hexane ) 
 to give 28 as an orange solid ( 15 mg , 65% ) . mp : 176178 
 c ; h nmr :  = 7.82 ( s , 1h ) , 7.137.11 
 ( m , 3h ) , 6.79 ( d , j = 8.9 hz , 2h ) , 6.89 ( d , j = 8.9 hz , 2h ) , 6.586.56 ( m , 2h ) , 4.60 ( s , 2h ) , 
 4.03 ( s , 3h ) , 3.92 ( s , 3h ) , 3.81 ( s , 3h ) , 3.60 ( s , 3h ) ; c nmr :  = 182.0 , 181.5 , 159.2 , 155.4 , 148.1 , 145.2 , 136.6 , 
 134.0 , 130.1 , 128.2 , 127.1 , 127.0 , 125.5 , 124.0 , 113.5 , 105.4 , 61.4 , 
 61.3 , 55.3 , 45.8 , 27.9 ; ir ( cm ) : 2950 , 1716 , 1651 , 
 1619 , 1601 , 1455 , 1241 , 1211 ; hr - esims ( m / z ) : calcd for [ m + na ] c28h24n2o6na 507.1527 , found 507.1533 . to 28 ( 30 mg , 0.062 mmol ) 
 was added tfoh ( 2.5 ml ) , and the mixture was heated at 55 c 
 in a vial for 4 h. the reaction was allowed to cool to rt and poured 
 into etoac . the resulting 
 residue was purified by column chromatography ( 8:2 etoac / hexane ) to 
 give 29 as an orange solid ( 10 mg , 56% ) . mp : > 290 
 c ; h nmr ( dmso - d6 ) :  = 10.95 ( s , 
 1h ) , 9.41 
 ( s , 1h ) , 7.63 ( s , 1h ) , 6.96 ( d , j = 8.6 hz , 2h ) , 
 6.75 ( d , j = 8.6 hz , 2h ) , 3.90 ( s , 3h ) , 3.82 ( s , 
 3h ) , 3.35 ( s , 3h ) ; c nmr ( dmso - d6 ) :  
 = 181.9 , 181.7 , 157.2 , 155.3 , 148.4 , 145.6 , 134.4 , 133.1 , 130.3 , 127.0 , 
 126.4 , 124.5 , 123.2 , 115.8 , 104.9 , 61.2 ( 2c ) , 27.3 ; ir ( cm ) = 3200 , 2921 , 2851 , 1702 , 1656 , 1609 , 1515 , 1105 , 1059 , 1033 ; hr - esims 
 ( m / z ) : calcd for [ m + na ] c20h16n2o6na 403.0901 , 
 found 403.0911 . benzimidazole 15 ( 5.0 g , 15 
 mmol ) was dissolved in ch2cl2 ( 100 ml ) and cooled 
 to 78 c under n2 . dibal - h ( 1 m in hexanes ) 
 ( 41 ml , 41 mmol ) was added dropwise , and the mixture was allowed to 
 come to rt and stirred overnight . the reaction mixture was then cooled 
 to 0 c , and water was added slowly followed by meoh . the resulting solids 
 were washed with et2o to give 30 as a white 
 solid ( 3.2 g , 63% ) . mp : 191193 c ; h nmr : 
  = 7.81 ( s , 1h ) , 7.79 ( s , 1h ) , 7.35 ( t , j = 
 8.0 hz , 1h ) , 7.23 ( d , j = 7.4 hz , 2h ) , 7.187.12 
 ( m , 3h ) , 7.08 ( d , j = 6.9 hz , 2h ) , 6.50 ( d , j = 6.9 hz , 2h ) , 4.91 ( s , 2h ) , 4.74 ( s , 2h ) , 4.49 ( s , 2h ) ; c nmr :  = 146.0 , 143.4 , 136.5 , 135.9 , 135.1 , 134.1 , 
 131.5 , 130.4 , 128.6 , 128.1 , 128.0 , 127.7 , 127.7 , 126.0 , 121.2 , 65.4 , 
 59.6 , 49.6 ; ir ( cm ) : 3056 , 2856 , 1504 , 1441 , 1311 , 
 1175 , 1018 , 1000 ; hr - esims ( m / z ) : 
 calcd for [ m + h ] c22h21n2o2 345.1598 , found 345.1604 . diol 30 ( 3.0 g , 8.7 mmol ) 
 was dissolved in ch2cl2 ( 75 ml ) and cooled to 
 78 c under n2 . dbu ( 4.8 ml , 35 mmol ) was 
 added followed by 20 ( 4.7 g , 22 mmol ) in ch2cl2 ( 3 ml ) , and the reaction was stirred at 78 
 c for 30 min . sat . the organic layer was separated , and the 
 aqueous layer was extracted with ch2cl2 ( 2 ) . the resulting residue was purified by 
 column chromatography ( the silica gel was neutralized with et3n prior to purification ) ( 6:4 etoac / hexane ) to give 31 as a white solid ( 2.0 g , 68% ) . mp : 167169 c ; h nmr :  = 10.49 ( s , 1h ) , 9.88 ( s , 1h ) , 8.43 ( s,1h ) , 
 8.06 ( s , 1h ) , 7.44 ( t , j = 7.5 hz , 1h ) , 7.31 ( t , j = 8.0 hz , 2h ) , 7.23 ( d , j = 7.5 hz , 1h ) , 
 7.217.14 ( m , 4h ) , 6.51 ( d , j = 7.5 hz , 2h ) , 
 4.86 ( s , 2h ) ; c nmr :  = 192.8 , 192.4 , 149.7 , 146.8 , 
 135.4 , 134.0 , 132.9 , 132.4 , 132.0 , 131.4 , 130.5 , 129.2 , 128.9 , 128.4 , 
 128.2 , 125.9 , 121.8 , 50.2 ; ir ( cm ) : 3070 , 2871 , 
 1756 , 1678 , 1595 , 1488 , 1455 , 1303 , 1213 ; hr - esims ( m / z ) : calcd for [ m + na ] c22h16n2o2na 363.1104 , found 363.1108 . to phthaldehyde 31 ( 150 mg , 0.44 mmol ) in thf was added 21 ( 0.037 g , 0.66 mmol ) followed by the simultaneous addition 
 of kcn ( 29 mg , 0.44 mmol ) in h2o ( 1 ml ) and et3n ( 0.06 ml , 0.44 mmol ) . the reaction was stirred at rt for 15 min 
 and then quenched with h2o ( 5 ml ) . 1 m hcl was added until 
 ph = 5 was reached , and the aqueous layer was extracted with etoac 
 ( 2 ) . an orange - red residue was 
 recovered and recrystallized from meoh to give 32 as 
 an orange - red solid ( 74 mg , 43% ) . mp : 280 c ( decomp . ) ; h nmr ( dmso - d6 ) :  = 9.71 ( brs , 2h ) , 8.46 
 ( s , 1h ) , 8.30 ( s , 1h ) , 7.327.29 ( m , 1h ) , 7.197.16 
 ( m , 5h ) , 7.017.00 ( m , 2h ) , 6.45 ( d , j = 4.6 
 hz , 2h ) , 4.75 ( s , 2h ) ; c nmr ( dmso - d6 ) :  
 = 181.6 , 181.1 , 151.2 , 146.6 , 141.8 , 139.6 , 137.6 , 136.5 , 135.5 , 129.3 , 
 129.1 , 128.8 , 128.2 , 127.8 , 127.8 , 127.1 , 125.9 , 122.9 , 118.7 , 49.3 ; 
 ir ( cm ) : 2831 , 1662 , 1615 , 1595 , 1569 , 1343 , 1315 , 
 1206 , 1189 , 905 ; hr - apcims ( m / z ) : 
 calcd for [ m + h ] c24h17n2o4 397.1183 , found 397.1196 . dihydroxyquinone 32 ( 84 mg , 0.21 
 mmol ) was suspended in thf ( 5 ml ) , and meoh 
 ( 2.0 ml ) was added followed by tmschn2 ( 2.0 m in et2o ) ( 0.37 ml , 0.74 mmol ) with subsequent stirring at rt for 
 4 h. the reaction was diluted with etoac and washed with sat . the resulting residue was purified by column chromatography 
 ( 1:1 etoac / hexane ) to give 33 as a yellow solid ( 45 mg , 
 54% ) . mp : 189191 c ; h nmr :  = 8.65 
 ( s , 1h ) , 7.92 ( s , 1h ) , 7.37 ( t , j = 7.5 hz , 1h ) , 
 7.27 ( d , j = 8.0 hz , 2h ) , 7.237.18 ( m , 3h ) , 
 7.04 ( d , j = 7.5 hz , 2h ) , 6.57 ( d , j = 8.0 hz , 2h ) , 4.65 ( s , 2h ) , 4.07 ( s , 3h ) , 3.94 ( s , 3h ) ; c nmr :  = 182.1 , 181.9 , 149.5 , 148.7 , 147.0 , 146.4 , 136.1 , 
 135.9 , 135.8 , 129.2 , 128.8 , 128.5 , 128.3 , 128.1 , 127.9 , 127.8 , 126.1 , 
 124.0 , 120.2 , 61.4 , 61.3 , 50.0 ; ir ( cm ) : 3009 , 
 2940 , 1649 , 1596 , 1441 , 1348 , 1291 , 1027 ; hr - esims ( m / z ) : calcd for [ m + h ] c26h21n2o4 425.1496 , found 425.1490 . to quinone 33 ( 45 mg , 
 0.11 mmol ) in ch3cn ( 8 ml ) was added mei ( 0.20 ml ) followed 
 by heating at 70 c for 15 h. the reaction mixture was concentrated , 
 and the resulting residue was triturated with et2o to give 34 as a red - orange solid ( 52 mg , 86% ) . mp : 184188 
 c ; h nmr :  = 10.33 ( s , 1h ) , 8.49 ( s , 1h ) , 
 7.48 ( t , j = 7.5 hz , 1h ) , 7.39 ( t , j = 7.5 hz , 2h ) , 7.297.27 ( m , 3h ) , 7.18 ( d , j = 7.5 hz , 2h ) , 6.96 ( d , j = 7.5 hz , 2h ) , 4.93 ( s , 
 2h ) , 4.26 ( s,3h ) , 4.10 ( s , 3h ) , 3.98 ( s , 3h ) ; c nmr : 
  = 180.2 , 180.0 , 149.3 , 147.7 , 146.4 , 134.9 , 132.9 , 132.9 , 
 132.3 , 132.2 , 131.1 , 129.4 , 129.3 , 128.9 , 128.6 , 128.0 , 127.0 , 111.8 , 
 61.6 ( 2c ) , 53.0 , 34.9 ; ir ( cm ) : 3031 , 2945 , 1718 , 
 1660 , 1609 , 1452 , 1314 , 1209 , 1052 , 916 ; hr - esims ( m / z ) : calcd for [ m ] c27h23n2o4 439.1652 , found 439.1634 . to imidazolium salt 34 ( 31 
 mg , 0.055 mmol ) in thf ( 1 ml ) was added 1 m k2co3 ( 0.27 ml ) and ncs ( 8 mg , 0.06 mmol ) , followed by stirring at rt 
 for 30 min . the reaction was diluted with water ( 4 ml ) and extracted 
 with etoac ( 2  5 ml ) . the resulting residue was purified 
 by column chromatography ( 1:1 etoac / hexane ) to give 35 as a yellow solid ( 15 mg , 60% ) . mp : 160162 c ; h nmr :  = 7.84 ( s , 1h ) , 7.33 ( t , j = 7.5 hz , 1h ) , 7.17 ( t , j = 7.5 hz , 2h ) , 7.137.09 
 ( m , 3h ) , 6.89 ( d , j = 6.9 hz , 2h ) , 6.53 ( d , j = 6.3 hz , 2h ) , 4.52 ( s , 2h ) , 4.03 ( s , 3h ) , 3.91 ( s , 3h ) , 
 3.60 ( s , 3h ) ; c nmr :  = 181.9 , 181.4 , 155.4 , 148.1 , 
 145.3 , 136.5 , 135.2 , 134.0 , 131.4 , 129.0 , 128.2 , 128.1 , 127.9 , 127.5 , 
 127.1 , 125.6 , 125.5 , 123.7 , 105.5 , 61.4 , 61.3 , 45.7 , 27.9 ; ir ( cm ) : 2927 , 1709 , 1651 , 1620 , 1601 , 1452 , 1344 , 1209 , 
 1059 ; hr - esims ( m / z ) : calcd for 
 [ m + na ] c27h22n2o5na 477.1421 , found 477.1438 . to imidazolone 35 ( 25 mg , 
 0.055 mmol ) was added tfoh ( 2 ml ) followed by heating at 55 c 
 for 4 h. the reaction was quenched with water and neutralized with 
 sat . the aqueous layer was extracted with etoac 
 ( 2 ) , and the combined organic extracts were washed with brine , 
 dried , and concentrated . the resulting residue was purified by column 
 chromatography ( 6:4 etoac / hexane ) to give 36 as a yellow 
 waxy solid ( 10 mg , 67% ) . h nmr :  = 8.11 ( brs , 1h ) , 
 7.74 ( s , 1h ) , 7.497.43 ( m , 3h ) , 7.227.21 ( m , 2h ) , 
 4.07 ( s , 3h ) , 3.97 ( s , 3h ) , 3.47 ( s , 3h ) ; c nmr :  
 = 181.9 , 181.5 , 154.2 , 147.6 , 146.0 , 135.3 , 134.1 , 131.6 , 129.1 , 128.3 , 
 128.1 , 127.8 , 124.3 , 123.0 , 105.5 , 61.5 , 61.4 , 27.4 ; ir ( cm ) : 2919 , 1708 , 1648 , 1623 , 1443 , 1332 , 1245 , 1194 , 1056 , 1026 ; hr - apcims 
 ( m / z ) : calcd for [ m + h ] c20h17n2o5 365.1132 , 
 found 365.1144 . to tert - butyl carbamate 
 ( 19 mg , 0.16 mmol ) in ch2cl2 ( 2 ml ) was added t - buocl ( 0.02 ml , 0.17 mmol ) , followed by stirring at rt 
 for 20 min . the reaction mixture was cooled to 0 c , and dbu 
 ( 0.033 ml , 0.22 mmol ) was added followed by 34 in ch2cl2 ( 3 ml ) . the reaction was stirred at rt for 
 30 min and then diluted with water . the aqueous layer was extracted 
 with ch2cl2 ( 2 ) , and the combined organic 
 extracts were washed with brine , dried ( anhyd . the crude residue was purified by column 
 chromatography ( 1:1 etoac / hexane ) to give 37 as a yellow - orange 
 residue ( 10 mg , 30% ) . h nmr :  = 7.98 ( s , 1h ) , 7.35 
 ( t , j = 7.5 hz , 1h ) , 7.18 ( t , j = 
 7.5 hz , 2h ) , 7.127.07 ( m , 3h ) , 6.84 ( d , j = 6.9 hz , 2h ) , 6.44 ( d , j = 6.9 hz , 2h ) , 4.70 ( s , 
 2h ) , 4.03 ( s , 3h ) , 3.90 ( s,3h ) , 3.68 ( s,3h ) , 1.46 ( s,9h ) ; c nmr :  = 181.6 , 181.1 , 158.3 , 153.9 , 148.3 , 145.5 , 135.8 , 
 135.4 , 134.6 , 132.3 , 128.9 , 128.2 , 128.2 , 128.1 , 128.0 , 127.1 , 127.1 , 
 125.4 , 124.5 , 106.6 , 78.9 , 61.4 , 61.3 , 47.3 , 31.8 , 28.3 ; ir ( cm ) : 2929 , 1655 , 1581 , 1443 , 1308 , 1207 , 1147 , 1047 , 
 1026 ; hr - esims ( m / z ) : calcd for 
 [ m + h ] c32h32n3o6 is 554.2286 , found 554.2290 . to benzimidazole 18 ( 25 mg , 0.085 mmol ) in toluene ( 10 ml ) was added mei ( 0.030 ml , 
 0.42 mmol ) , followed by heating to 140 c for 20 h. the solvent 
 was reduced to give 38 ( 25 mg , 68% ) as an off - white solid . mp : 253256 c ; h nmr ( cd3od ) : 
  = 8.13 ( s , 1h ) , 7.37 ( d , j = 8.6 hz , 2h ) , 
 7.08 ( d , j = 8.6 hz , 2h ) , 5.51 ( s , 2h ) , 4.18 ( s , 
 3h ) , 3.88 ( s , 3h ) , 3.54 ( s , 3h ) ; c nmr ( cd3od ) :  = 168.9 , 160.9 , 145.2 , 136.7 , 131.1 , 130.8 , 130.5 , 121.8 , 
 113.3 , 106.3 , 68.4 , 54.6 , 36.2 , 32.9 ; ir ( cm ) : 
 2960 , 1772 , 1612 , 1577 , 1378 , 1241 , 1065 , 1018 , 823 ; hr - esims ( m / z ) : calcd for [ m ] c18h17n2o3 309.1234 , found 309.1229 . imidazolium salt 38 ( 10 mg , 
 0.023 mmol ) in thf was cooled to 0 c , and 5% naocl ( 0.3 ml ) 
 was added followed by stirring for 10 min . the resulting solids were purified by ptlc ( etoac ) to give 39 as a white solid ( 6 mg , 73% ) . mp : 239240 c ; h nmr :  = 7.26 ( d , j = 8.6 hz , 2h ) , 6.98 
 ( d , j = 8.6 hz , 2h ) , 6.98 ( s , 1h ) , 5.25 ( s , 2h ) , 
 3.87 ( s , 3h ) , 3.49 ( s , 3h ) , 2.92 ( s , 3h ) ; c nmr :  
 = 170.0 , 159.9 , 155.4 , 141.5 , 135.8 , 131.3 , 128.9 , 124.1 , 123.4 , 116.8 , 
 113.3 , 99.3 , 67.9 , 55.3 , 30.3 , 27.7 ; ir ( cm ) : 
 2930 , 2838 , 1761 , 1700 , 1609 , 1520 , 1482 , 1357 , 1287 , 1248 , 1196 , 
 1179 , 1139 , 1078 ; hr - apcims ( m / z ) : calcd for [ m + h ] c18h17n2o4 325.1183 , found 325.1191 . to 18 ( 72 mg , 0.24 
 mmol ) in acetonitrile ( 10 ml ) was added semcl ( 50 mg , 0.30 mmol ) followed 
 by stirring at 60 c for 1 h. the reaction mixture was cooled 
 to 0 c , and the precipitated solids were filtered and washed 
 with et2o to give 41 as a white solid ( 51 
 mg , 63% ) . mp : 255258 c ; h nmr ( cd3od ) :  = 9.56 ( d , j = 4.6 hz , 1h ) , 8.06 ( s , 
 1h ) , 7.51 ( d , j = 8.6 hz , 2h ) , 7.12 ( d , j = 8.6 hz , 2h ) , 5.52 ( s , 2h ) , 4.19 ( s , 3h ) , 3.89 ( s , 3h ) ; c nmr ( cd3od ) :  = 169.3 , 161.1 , 145.7 , 145.1 , 136.4 , 
 131.3 , 130.5 , 122.0 , 119.9 , 113.8 , 105.2 , 68.5 , 54.6 , 32.7 ; ir ( cm ) : 3155 , 2942 , 1728 , 1623 , 1506 , 1392 , 1243 , 1142 , 
 1110 , 1012 ; hr - esims ( m / z ) : calcd 
 for [ m + na ] c17h14n2o3na 317.0897 , found 317.0903 .
synthetic 
 approaches to the imidazonaphthoquinone core 
 of kealiiquinone and related leucetta - derived alkaloids 
 are described . 
 the polysubstituted benzimidazole framework can be 
 constructed through intramolecular diels 
 alder reactions of 
 propiolate - derived enynes followed by oxidation . 
 adjustment of the 
 oxidation state of the thus formed lactone allows introduction of 
 the 2,3-dihydroxybenzoquinone moiety through a presumed 
 benzoin - like condensation between a phthaldehyde derivative and a 
 masked glyoxal equivalent catalyzed by a cyanide ion . 
 oxidation of 
 the c2-position can be accomplished through application of an operationally 
 simple treatment of an imidazolium salt with bleach , thus producing 
 the corresponding 2-imidazolone . 
 debenzylation of a late stage intermediate 
 en route to kealiiquinone was compromised by concomitant o - demethylation upon treatment with triflic acid resulting in the 
 formation of non - natural 7-desmethylkealiiquinone . 
 other endgame strategies were evaluated ; however , these efforts did 
 not lead to completion of a synthesis of kealiiquinone but did provide 
 access to other closely related analogues .