extracted from club 
 moss lycopodium lucidulum , 
 the lycopodium alkaloids represent a complex family of heterocyclic 
 natural products with various structural types . these alkaloids have 
 been thoroughly studied over the past 60 years , and more than 200 
 members of this family have been isolated . within the lycopodium family , there is an abundant subclass of compounds with the general 
 c30n3 framework , including dihydrolycolucine 
 ( 1 ) and structurally relevelant lycolucine ( 2 ) ( figure 1 ) . dihydrolycolucine , isolated 
 in 1979 by ayer and co - workers , represents one of the more structurally 
 elaborate members of this alkaloid family , and its structure has been 
 fully characterized by crystallographic , spectroscopic , and chemical 
 studies . embedded within its unique architecture are nine sterogenic 
 centers and a strained seven - membered ring , both of which pose a significant 
 synthetic challenge . to our knowledge , 
 there have been no biological or synthetic studies reported for dihydrolycolucine . it was envisioned that 
 key fragments 3 and 4 would converge via 
 a c  c bond forming reaction to provide alkaloid 1 . alkyl iodide 3 would be prepared in enantiopure form 
 via a chiral n - acylpyridinium salt reaction . furthermore , 
 the tetracyclic fragment 4 would originate from a pd - mediated ester enolate ring - closure with an appropiately 
 functionalized pyridine . the pyridine motif would be incorporated 
 via a suzuki cross - coupling reaction with -bromo enecarbamate 7 , furnished by starting from another chiral n - acylpyridinium salt reaction . the synthesis of the 
 ab ring fragment 3 initiated 
 with the in situ generation of the chiral n - acylpyridinium 
 salt 5 , from 4-methoxy-3-(triisopropylsilyl)pyridine 
 and ( -)-tcc chloroformate , followed by the addition of the enantiopure 
 grignard 9 , to yield dihydropyridone 10 upon acidic work up ( scheme 2 ) . standard one - pot removal of the chiral auxiliary 
 and tips group , followed by reprotection of the nitrogen as the benzyl 
 carbamate , produced enantiopure dihydropyridone 11 . the vinylgous amide carbonyl was reduced under 
 luche conditions , followed by dehydration of the resulting allylic 
 alcohol with furukawa s reagent , to smoothly furnish dihydropyridine 13 . alder 
 ( imda ) cycloaddition , followed by hydrogenation to simultaneously 
 remove the cbz group and reduce the olefin , revealing amino ester 14 . bond cleavage was induced 
 through a retro - mannich ring - opening pathway that allowed for the formation of bicyclic compound 15 . concomitant reduction of the enecarbamate and removal of the cbz 
 group were accomplished under standard hydrogenation procedures utilizing 
 palladium on carbon . the crude amine ( 88% ) was immediately acylated 
 with acetyl chloride to give an unoptimized low yield of amide 16 . completion of fragment 3 is marked by an iododecarboxylation reaction sequence mediated 
 with pb(oac)4 and iodine . a model study to the northern fragment 4 was initiated 
 with the fundamental n - acylpyridinium salt reaction , 
 albeit in a racemic fashion . nor the addition of the grignard reagent to the n - benzyloxy-4-methoxypyridinium salt , followed by mild acid 
 hydrolysis , provided 18 ( scheme 3 ) . transformation of the terminal olefin to the trans ,-unsaturated ethyl ester was carried out directly 
 via a cross - metathesis reaction using excess ethyl acrylate in the 
 presence of 0.7 mol % of a second - generation grubbs catalyst , furnishing 19 in 95% yield . with 19 in hand , reduction of the c-4 carbonyl under standard luche 
 conditions gave the desired alcohol , which 
 was dehydrated with furukawa s reagent to afford dihydropyridine 20 . the triene underwent 
 our intramolecular diels  alder ( imda ) and retro - mannich ring - opening 
 reaction sequence to provide the n - phenoxycarbony intermediate 22 . through a modification 
 of overman s protocol , enecarbamate 22 was treated with molecular bromine in the presence of excess 
 1,2,2,6,6-pentamethylpiperidine ( pmp ) and 4  
 molecular sieves to provide -bromo enecarbamate 23 in 93% yield . with the synthetic routes to 
 two of the key fragments established , 
 our attention was directed toward the preparation of the pyridine 28 for an eventual suzuki coupling . initially , 2,6-dichloropyridine 
 ( 24 ) underwent two successive nucleophilic aromatic substitutions 
 to yield the disubstituted pyridine derivative 26 ( scheme 4 ) . removal of the benzyl group with catalytic hydrogenation 
 provided the pyridone 27 , which was subsequently converted 
 to mom - protected pyridine 28 in 83% yield . utilizing the mom ether as an effective ortho - director , pyridyl 
 boronic ester 29 was prepared in high yield by deprotonation 
 of 28 with n - buli , followed successive 
 treatment with trimethylborate and pinacol . after establishing practical synthetic routes 
 to -bromo 
 enecarbamate 23 and pyridine 29 , a suzuki cross - coupling reaction mediated 
 by pd(t - bu3p)2 , followed 
 by mild acid hydrolysis of the mom group of 30 with excess 
 pyridinium p - toluenesulfonate , afforded the pyridinol 31 over two steps ( scheme 5 ) . after considerable experimentation , reduction 
 of the enecarbamate olefin proceeded smoothly to furnish 32 in high yield as a single diastereomer . treatment of pyridone 32 with tf2o in the presence of tea afforded pyridyl 
 triflate 33 in 95% yield . it is worth noting that attempted 
 conversions of the pyridone 31 into either the iodo or 
 the bromo derivatives resulted in extensive decomposition . with pyridyl triflate 33 readily in hand , 
 examination 
 of the crucial seven - membered ring formation was addressed ( scheme 6 ) . because of the sensitivity and complex nature 
 of the substrate , we chose to initially explore the mild pd - catalyzed 
 arylation conditions as reported by hartwig . the silylketene acetal of 33 was prepared in situ by 
 treatment with lda and tmscl . the crude silylketene acetal was immediately 
 exposed to cross - coupling conditions mediated by pd(phcn)2cl2 . unfortunately , 
 this reaction sequence proved ineffective and only starting material 
 was isolated . variations of this reaction also resulted in recovered 
 starting material or pyridone 32 . to the best of our 
 knowledge , this is the first attempt to couple aryl triflates with 
 ester enolates . in summary , a detailed account 
 of our progress toward lycopodium 
 alkaloid dihydrolycolucine is reported utilizing an n - acyl-2,3-dihydropyridone as a building block . in particular , the 
 synthesis of two major fragments was accomplished , leading to the 
 examination of the tetracylic core formation . unfortunately , initial 
 attempts at closing the seven - membered d ring by way of a palladium - catalyzed 
 ester  enolate cross - coupling proved unfruitful . a solution of 15 ( 50.5 mg , 
 0.141 mmol ) in 2 ml of ethyl acetate was hydrogenated for 4 h at rt 
 under balloon pressure in the presence of 5% pd / c ( 23 mg ) . filtration 
 over celite and removal of solvent in vacuo resulted in 28.1 mg ( 88% ) 
 of the amine as a yellow oil . the crude amine was dissolved in 1 ml 
 of ch2cl2 , followed by the addition of triethylamine 
 ( 25.1 l , 0.178 mmol ) and freshly distilled acetyl chloride 
 ( 11.3 l , 0.157 mmol ) . after 30 min , distilled h2o ( 1 ml ) was added 
 to the reaction , and the biphasic solution was transferred to a separatory 
 funnel . the organic layers were collected , washed with brine , dried over mgso4 , and filtered through a thin pad of celite . the volatiles 
 were removed in vacuo , and purification by chromatography ( sio2 , 510% meoh / ch2cl2 ) afforded 
 17.3 mg ( 47% ) of pure 16 as a yellow oil . ir ( neat ) 2926 , 
 2869 , 1737 , 1644 , 1434 , 1266 , 1172 , 1035 , 874 cm ; h nmr ( 400 mhz , cdcl3 )  4.954.89 
 ( m , 1h ) , 4.494.45 ( m , 1h ) , 3.973.93 ( m , 1h ) , 3.683.66 
 ( pair of s , due to rotamers , 3h ) , 3.603.53 ( m , 1h ) , 3.143.08 
 ( m , 1h ) , 2.632.56 ( m , 1h ) , 2.422.10 ( m , 3h ) , 2.09 
 and 2.06 ( pair of s , due to rotamers , 3h ) , 1.981.14 ( m , 7h ) , 
 1.17 and 1.10 ( pair of d , j = 7.2 hz , 3h ) ; c nmr ( 100 mhz , cdcl3 )  ( rotamers ) 173.3 , 173.2 , 
 169.2 , 168.9 , 51.9 , 51.8 , 51.7 , 46.0 , 41.8 , 39.7 , 38.6 , 38.5 , 38.2 , 
 36.4 , 32.3 , 31.9 , 31.7 , 31.5 , 29.6 , 28.2 , 27.8 , 27.4 , 26.0 , 25.0 , 
 22.3 , 21.5 , 18.7 , 18.5 , 17.7 , 17.6 ; hrms ( esi ) calcd for c15h25no3 267.1834 , found 267.1840 ; [ ]d23 44.6 
 ( c 0.28 , chcl3 ) . compound 16 ( 17.3 mg , 
 0.0647 mmol ) was dissolved in 80% aqueous meoh ( 5 ml ) , followed by 
 the addition of liohh2o ( 51.9 mg , 1.23 mmol ) . after 
 stirring at rt for 16 h , distilled h2o ( 5 ml ) was added 
 to the mixture . the mixture was acidified with a solution of 10% hcl 
 and extracted with etoac ( 3  5 ml ) . after filtration 
 through celite , the volatiles were removed in vacuo , followed by purification 
 ( sio2 , 5% meoh / ch2cl2 ) to give 13.8 
 mg ( 84% ) of 17 as a tacky white oil . ir ( neat ) 3500 , 
 2926 , 2875 , 1619 , 1561 , 1401 , 1270 , 1174 , 1036 cm ; h nmr ( 400 mhz , cdcl3 )  9.008.00 
 ( bs , 1h ) , 4.954.91 ( m , 1h ) , 4.514.46 ( m , 1h ) , 3.993.96 ( m , 1h ) , 3.603.56 ( m , 1h ) , 3.163.09 ( m , 1h ) , 2.642.58 
 ( m , 1h ) , 2.422.02 ( m , 5h ) , 2.11 and 2.08 ( pair of s , due to 
 rotamers , 3h ) , 1.981.16 ( m , 5h ) , 1.11 ( appar t , due to rotamers , 
 3h ) ; c nmr ( 100 mhz , cdcl3 )  ( rotamers ) 
 177.5 , 177.1 , 169.8 , 169.4 , 52.1 , 46.3 , 41.9 , 39.5 , 38.5 , 38.4 , 38.2 , 
 36.7 , 32.3 , 31.9 , 31.5 , 31.4 , 29.7 , 28.2 , 27.8 , 27.4 , 26.0 , 25.0 , 
 22.1 , 21.3 , 18.7 , 18.5 , 17.7 , 17.6 ; hrms ( esi ) calcd for c14h23no3 ( [ m + h ] ) 254.1757 , 
 found 254.1756 ; [ ]d23 86.7 ( c 0.09 , chcl3 ) . an oven - dried 
 flask was charged with 17 ( 13.8 mg , 0.0545 mmol ) and 
 pb(oac)4 ( 31.4 mg , 0.071 mmol ) in anhydrous ccl4 ( 1.2 ml ) . the mixture was stirred under n2 at 
 reflux while being irradiated with a tungsten 350 w lamp . iodine ( 15.2 
 mg , 0.06 mmol ) dissolved in anhydrous ccl4 ( 0.8 ml ) was 
 added to the refluxing mixture . after heating for an additional 2 
 h , the reaction mixture was allowed to cool to rt , after which a precipitate 
 formed . the solution 
 was dried over mgso4 and filtered , and the volatiles were 
 removed under reduced pressure . purification of the crude residue 
 by chromatography ( sio2 , 05% meoh / ch2cl2 ) afforded 11 mg ( 60% ) of iodide 3 as 
 an unstable yellow oil . h nmr ( 400 mhz , cdcl3 )  4.924.85 ( m , 1h ) , 4.524.47 ( m , 1h ) , 3.943.90 
 ( m , 1h ) , 3.613.56 ( m , 1h ) , 3.173.09 ( m , 4h ) , 2.642.56 
 ( m , 1h ) , 2.11 and 2.06 ( pair of s , due to rotamers , 3h ) , 1.981.16 
 ( m , 7h ) , 1.11 ( appar t , due to rotamers , 3h ) . a solution of lithium diisopropylamide 
 ( 1.50 mmol , prepared from 0.62 ml of 2.4 m n - buli 
 and 0.218 ml of diisopropylamine ) in 5 ml of thf under n2 was cooled to 78 c ( dry ice / acetone ) . tricyclic amine 21 ( 0.113 g , 0.50 mmol ) in thf ( 4 ml ) was then added , and 
 the mixture was stirred at 78 c for 30 min . trimethylsilyl 
 chloride ( 0.223 ml , 1.76 mmol ) was added at 78 c , and 
 the mixture was warmed to rt for 15 min . this process was repeated again to finally 
 provide 0.190 g ( 103% ) of the crude bis - silyl intermediate as a yellow 
 oil . to a solution of the crude oil ( 0.60 g , 0.26 mmol ) in 5 ml of 
 dry ch2cl2 , under n2 at rt , was added 
 phenyl chloroformate ( 0.067 ml , 0.52 mmol ) . the mixture was heated 
 to reflux for 12 h and then cooled to rt . a solution of 10% hcl ( 4 
 ml ) was added , and the mixture was stirred for 1.5 h. saturated nahco3 solution ( 5 ml ) was added , followed by ether ( 20 ml ) . the 
 organic phase was washed with brine ( 5 ml ) and dried ( k2co3 ) . the solution was filtered , concentrated , and purified 
 by preparative layer chromatography ( silica gel , etoac hexanes , 
 1:5 , three elutions ) to give 0.07 g ( 86% from 21 ) of 22 as a light yellow oil . h nmr ( 300 mhz , cdcl3 ) 7.3 (m , 5h ) , 6.8 ( d , 1h ) , 4.8 ( m , 1h ) , 4.2 ( q , 2h ) , 
 3.9 ( m , 1h ) , 2.9 ( m , 1h ) , 2.9 ( m , 1h ) , 2.22.5 ( m , 2h ) , 1.12.2 
 ( m , 12h ) ; c nmr ( 75 mhz , cdcl3 ) 173.1 ( 2c ) , 
 129.2 ( 2c ) , 125.1 , 121.6 ( 2c ) , 120 , 115.8 , 105.2 , 60.8 , 53.9 , 47.2 , 
 38.6 34.5 , 34.0 , 33.6 , 24.1 , 15.6 , 14.3 ; ir ( neat ) 2920 , 1750 , 1650 , 
 1570 cm . to a solution of 22 ( 89 mg , 
 0.259 mmol ) in ch2cl2 ( 5 ml ) was added 10 mg 
 of crushed 4  molecular sieves , followed by addition of 1,2,2,6,6-pentamethylpiperidine 
 ( 141 mg , 0.906 mmol ) . the mixture was cooled to 0 c and bromine 
 ( 0.518 ml , 0.259 mmol ) as a 0.5 m solution in ch2cl2 was added over 1 h via syringe pump . following completion 
 of bromine addition , the reaction was warmed to rt and stirred for 
 1 h. the mixture was filtered through a thin pad of celite , and the 
 volatiles were removed under reduced pressure . purification by radial 
 plc ( sio2 , 05% etoac / hexanes ) afforded 101 mg ( 92% ) 
 of pure 23 as a clear oil . ir ( neat ) 3434 , 2933 , 2861 , 
 1726 , 1660 , 1493 , 1202 cm ; h nmr ( 300 
 mhz , cdcl3 )  7.397.09 ( m , 6h ) , 4.214.09 
 ( m , 3h ) , 2.492.24 ( m , 7h ) , 1.811.72 ( m , 2h ) , 1.531.42 
 ( m , 3h ) , 1.25 ( t , j = 6.9 hz , 3h ) ; c 
 nmr ( 75 mhz cdcl3 )  172.4 and 173.3 ( due to rotamers ) , 
 151.3 and 151.0 ( due to rotamers ) , 150.5 , 129.6 , 126.0 , and 125.9 
 ( due to rotamers ) , 124.6 and 124.3 ( due to rotamers ) , 121.8 , 102.1 , 
 and 101.8 ( due to rotamers ) , 60.7 , 54.0 , 53.2 , 38.5 , 36.8 , and 36.7 
 ( due to rotamers ) , 36.4 and 36.1 ( due to rotamers ) , 26.0 , 25.4 , 24.5 , 
 and 24.3 ( due to rotamers ) , 14.4 ; hrms ( esi ) calcd for c20h24brno4 421.0888 , found 421.0905 . anhydrous isopropanol ( 0.31 ml , 4.05 
 mmol ) was added to a solution of kot - bu ( 417 mg , 
 3.72 mmol ) in thf ( 3 ml ) at rt . after 30 min , 2,6-dichloropyridine 
 ( 500 mg , 3.38 mmol ) was added to the milky solution . the mixture was 
 warmed to 65 c and stirred for 12 h. the solvent was removed 
 by evaporation , water ( 5 ml ) was added , and the mixture was extracted 
 with methylene chloride . the crude 
 product was purified by radial plc ( silica gel , 2% etoac / hexanes ) 
 to afford 510 mg ( 91% yield ) of 25 as a clear oil . ir 
 ( neat ) 2980 , 2936 , 1592 , 1559 , 1441 , 1302 , 1159 , 1109 , 963 , 788 cm ; h nmr ( 400 mhz , cdcl3 )  
 7.46 ( dd , j = 6.8 hz , j = 8.0 hz , 
 1h ) , 6.82 ( d , j = 6.8 hz , 1h ) , 6.56 ( d , j = 8.0 hz , 1h ) , 5.325.20 ( m , 1h ) , 1.32 ( d , j = 104 hz , 6h ) ; c nmr ( 100 mhz , cdcl3 )  
 163.3 , 148.4 , 140.6 , 115.9 , 109.8 , 69.1 , 22.0 . benzyl alcohol ( 0.37 ml , 3.54 mmol ) was 
 added to a solution of kot - bu ( 397 mg , 3.54 mmol ) 
 in thf ( 5 ml ) at rt . after 30 min , 
 2-chloro-6-isopropoxypyridine ( 506 mg , 2.95 mmol ) was added , and the 
 mixture was stirred at 65 c for 12 h. the reaction was allowed 
 to cool to rt , the solvent was removed by concentration , and the residue 
 was extracted with methylene chloride . the combined organic layers 
 were dried over k2co3 , filtered , and concentrated . the crude product was purified by radial plc ( silica gel , 5% etoac / hexanes ) 
 to afford 629 mg ( 87% ) of 26 as a clear oil . ir ( neat ) 
 3088 , 1064 , 3033 , 2977 , 2936 , 2876 , 1596 , 1579 , 1444 , 1371 , 1312 , 
 1237 , 1140 , 1115 , 1041 , 989 , 788 cm ; h nmr ( 400 mhz , cdcl3 )  7.507.25 ( m , 5h ) , 
 6.35 ( d , j = 7.6 hz , 1h ) , 6.27 ( d , j = 7.6 hz , 1h ) , 5.36 ( s , 2h ) , 5.285.18 ( m , 1h ) , 1.34 ( d , j = 7.6 hz , 6h ) ; c nmr ( 100 mhz , cdcl3 )  162.5 , 162,4 , 141.2 , 137.9 , 128.6 , 127.9 , 102.4 101.5 , 
 68.3 , 67.6 , 22.3 ( 2c ) ; hrms ( esi ) calcd for c15h17no2 ( [ m ] ) 243.1259 , found 243.1263 . a solution of 2-benzyloxy-6-isopropoxypyridine ( 2.11 g , 
 8.65 mmol ) in meoh ( 50 ml ) was hydrogenated ( balloon pressure ) over 
 10% pd / c ( 461 mg ) at rt for 12 h. the mixture was filtered through 
 celite , and the solids were rinsed with methylene chloride . the crude 
 product was purified by radial plc ( silica gel , 50% etoac / hexanes ) 
 to afford 1.28 g ( 96% ) of 27 as a white solid , mp 106107 
 c ; ir ( neat ) 35002500 , 1648 , 1599 , 1453 , 1372 , 1273 , 
 1109 cm ; h nmr ( 400 mhz , cdcl3 )  7.35 ( dd , j = 8.8 , 7.6 hz , 1h ) , 
 6.15 ( d , j = 8.8 hz , 1h ) , 5.62 ( d , j = 7.6 hz , 1h ) , 4.664.60 ( m , 1h ) , 1.31 ( d , j = 6.4 hz , 6h ) ; c nmr ( 100 mhz , cdcl3 )  
 165.2 , 157.7 , 142.9 , 108.6 , 89.4 , 71.8 , 21.8 ; hrms ( esi ) calcd for 
 c8h11no2 ( [ m + h ] ) 154.0868 , found 154.0869 . a solution of 27 ( 75 mg , 0.489 
 mmol ) in dmf 
 ( 1 ml ) was added to a solution of kot - bu ( 60 mg , 
 0.538 mmol ) in dmf ( 2 ml ) at 0 c . after 20 min at 0 c , 
 the mixture was warmed to rt and stirred for 2 h. the mixture was 
 then cooled back down to 0 c , and momcl ( 0.04 ml , 0.59 mmol ) 
 was added dropwise . after 5 min at 0 c , the mixture was warmed 
 to rt and stirred overnight ( 15 h ) . the reaction was quenched with 
 water , and the mixture was extracted with methylene chloride . the crude product was purified by radial 
 plc ( silica gel , 5% etoac / hexanes ) to afford 80 mg ( 83% yield ) of 28 as a clear oil . ir ( neat ) 2978 , 2936 , 1600 , 1580 , 1447 , 
 1312 , 1236 , 1158 , 1141 , 1114 , 1009 , 970 cm ; h nmr ( 300 mhz , cdcl3 )  7.47 ( t , j = 7.9 hz , 1h ) , 6.346.27 ( m , 2h ) , 5.45 ( s , 2h ) , 
 5.19 ( septet , j = 6.0 hz , 1h ) , 3.50 ( s , 3h ) , 1.32 
 ( d , j = 6.0 hz , 6h ) ; c nmr ( 100 mhz , 
 cdcl3 )  162.4 , 161.4 , 141.4 , 103.7 , 101.4 , 68.3 , 
 57.0 , 22.2 ; hrms ( esi ) calcd for c10h15no3 ( [ m + h ] ) 198.1130 , found 198.1127 . to a solution of pyridine 28 ( 355 mg , 1.80 mmol ) in freshly distilled thf ( 10 ml ) was added n - buli at 42 c ( 2.36 m in hexanes , 1.21 ml , 
 2.85 mmol ) , and the mixture was stirred for 30 min at 42 c . the solution was slowly warmed to rt and stirred for an additional 
 30 min . after cooling to 78 c , neat trimethylborate 
 ( 0.41 ml , 3.60 mmol ) was quickly added , and after 15 min , the solution 
 was warmed to rt . stirring was continued at rt for 1 h , and then pinacol 
 ( 490 mg , 4.14 mmol ) was added in one portion . after 2 h , the reaction 
 mixture was filtered through a thin pad of celite with a diethyl ether 
 ( 10 ml ) wash . purification by radial plc ( sio2 , 2% et3n/1020% etoac / hexanes ) gave 517 mg ( 83% ) 
 of boronic ester 29 as a pale yellow oil . ir ( neat ) 2978 , 
 1595 , 1566 , 1370 , 1111 , 963 cm ; h 
 nmr ( 300 mhz , cdcl3 )  7.88 ( d , j = 8.1 hz , 1h ) , 6.28 ( d , j = 8.1 hz , 1h ) , 5.54 ( s , 
 2h ) , 5.20 ( m , 1h ) , 3.53 ( s , 3h ) , 1.32 ( s , 18h ) ; c nmr 
 ( 75 mhz , cdcl3 )  203.7 , 165.6 , 164.6 , 149.1 , 103.7 , 
 91.5 , 83.5 , 68.7 , 56.8 , 25.0 , 22.2 ; hrms ( esi ) [ ( m + na ) ] calcd for c16h26bno5 346.1796 , 
 found 346.1803 . in a 15 ml round - bottom 
 flask containing boronate ester 29 ( 44 mg , 0.137 mmol ) 
 was added 1 ml of degassed dme : etoh ( 20:0.5 ) . the boronate ester solution 
 was added to a 15 ml flask containing vinyl bromide 23 ( 34 mg , 0.081 mmol ) , followed by the addition of 1 ml of dme : etoh 
 ( 20:1 ) . to the combined solution was added aqueous 2.0 m na2co3 ( 0.081 ml , 0.161 mmol ) . with good stirring , the solution 
 was degassed for 10 min and then pd(t - bu3p)2 ( 2.1 mg , 0.004 mmol ) was added in one portion . the flask was quickly fitted with a reflux condenser and purged with 
 n2 for 2 min . the reaction was heated to 100 c for 
 4 h or until disappearance of starting material by tlc . once complete , 
 the reaction vessel was cooled to rt , and the contents were filtered 
 through celite with a ch2cl2 wash . purification by flash chromatography 
 ( florisil , 05% etoac / hexanes , 2% et3n ) afforded 
 36 mg ( 80% ) of pure 30 as a clear oil . ir ( neat ) 3403 , 
 2359 , 2329 , 2090 , 1642 , 1460 , 1308 , 1202 cm ; h nmr ( 300 mhz , cdcl3 )  7.487.12 
 ( m , 7h ) , 6.346.28 ( m , 1h ) , 5.595.52 ( m , 2h ) , 5.205.11 
 ( m , 1h ) , 4.314.10 ( m , 3h ) , 3.543.51 ( m , 3h ) , 2.512.32 
 ( m , 6h ) , 1.871.50 ( m , 6h ) , 1.371.23 ( m , 9h ) ; c nmr ( 100 mhz , cdcl3 )  172.7 , 160.5 , 157.6 , 
 151.4 , and 151.3 ( due to rotamers ) , 140.2 , 129.6 , 125.8 , 122.9 , 122.6 , 
 121.8 , 113.5 , and 113.1 ( due to rotamers ) , 103.2 , 92.2 , and 92.0 ( due 
 to rotamers ) , 68.6 , 60.6 , 57.4 , 54.4 , 53.7 , 38.8 , 37.1 , and 36.9 ( due 
 to rotamers ) , 35.1 and 34.8 ( due to rotamers ) , 29.9 , 26.2 , 24.6 , and 
 24.5 ( due to rotamers ) , 22.2 , 21.9 , and 21.7 ( due to rotamers ) , 14.5 ; 
 hrms ( esi ) calcd for c30h38n2o7 538.2679 , found 538.2670 . to a stirred solution 
 of 30 ( 45 mg , 0.083 mmol ) in meoh ( 5 ml ) cooled to 0 
 c was added solid pyridinium para - toluenesulfonate 
 ( 1.42 mmol , 357 mg ) in portions . after stirring for 15 min at 0 c , 
 the temperature was raised to rt , and the mixture was stirred for 
 48 h or until complete by tlc analysis . the meoh was removed under 
 reduced pressure , and the residue was redissolved in ch2cl2 ( 5 ml ) , followed by the addition of deionized h2o ( 5 ml ) . the mixture was transferred to a separatory funnel 
 and extracted with ch2cl2 ( 3  10 ml ) . combined organic layers were washed with saturated aqueous nahco3 , dried over mgso4 , and filtered through celite . the volatiles were removed in vacuo , and purification by flash chromatography 
 ( florisil , 10% etoac / hexanes to 50% etoac / meoh ) afforded 35 mg ( 87% ) 
 of pure 31 as a clear oil . 1716 , 1630 , 1605 , 1402 , 1356 , 1274 , 1201 , 1111 cm ; h nmr ( 300 mhz , cdcl3 )  8.07 and 
 7.66 ( bs , 1h ) , 7.39 ( m , 6h ) , 5.56 ( d , j = 8.40 hz , 
 1h ) , 4.56 ( m , 1h ) , 4.25 ( m , 1h ) , 4.12 ( q , j = 7.2 
 hz , 2h ) , 2.321.49 ( m , 11h ) , 1.311.22 ( m , 11h ) ; c nmr ( 75 mhz , cdcl3 )  172.9 and 172.7 
 ( due to rotamers ) , 162.3 , 154.9 , and 154.5 ( due to rotamers ) , 151.7 
 and 151.5 ( due to rotamers ) , 138.5 and 137.0 ( due to rotamers ) , 129.4 , 
 125.6 , 122.6 , 122.1 , 121.8 , 114.2 , and 112.8 ( due to rotamers ) , 87.7 
 and 87.3 ( due to rotamers ) , 72.4 , 60.6 , 54.4 , 53.7 , 38.9 , 37.0 , 35.2 , 
 and 34.8 ( due to rotamers ) , 29.9 , 26.1 , and 25.6 ( due to rotamers ) , 
 24.6 and 24.4 ( due to rotamers ) , 21.8 , 21.0 , 14.5 ; hrms ( esi ) [ ( m 
 + na ) ] calcd for c28h34n2o6 517.2315 , found 517.2313 . a 15 ml round - bottom 
 flask was charged with pyridinol 31 ( 21 mg , 0.042 mmol ) , 
 a mixture of acetic acid : meoh : ch2cl2 ( 1:2:2 , 
 3 ml ) , and 10 mg of pd(oh)2 . the flask was fitted with 
 a balloon containing hydrogen gas . using an aspirator , the heterogeneous mixture was stirred for 3 
 h or until the disappearance of starting material by tlc . once complete , 
 the mixture was filtered through celite and concentrated under reduced 
 pressure . purification by radial plc ( 3050% etoac / hexanes ) 
 gave 18 mg ( 85% ) of 32 as a clear oil . ir ( neat ) 3855 , 
 3423 , 1626 , 1524 , 1025 , 696 , 460 cm ; h nmr ( 400 mhz , cdcl3 )  7.377.09 ( m , 7h ) , 
 5.575.54 ( m , 1h ) , 4.60 ( sep , j = 5.6 hz , 
 1h ) , 4.324.08 ( m , 4h ) , 3.25 ( t , j 12.4 hz , 
 1h ) , 2.902.83 ( m , 1h ) , 2.301.46 ( m , 12h ) , 1.34 ( d , j = 6.0 hz , 6h ) , 1.24 ( t , j = 9.6 hz , 3h ) ; c nmr ( 100 mhz , cdcl3 )  173.0 , 162.9 , 155.7 , 
 154.0 , 151.8 , 139.8 , and 139.6 ( due to rotamers ) , 129.3 , 125.2 , 122.6 , 
 122.0 , 88.0 , and 87.8 ( due to rotamers ) , 72.2 , 60.5 , 54.5 , and 53.7 
 ( due to rotamers ) , 43.7 and 42.9 ( due to rotamers ) , 39.6 , 39.1 , and 
 38.8 ( due to rotamers ) , 38.3 and 38.0 ( due to rotamers ) , 37.7 and 
 37.5 ( due to rotamers ) , 26.5 , 25.0 , 24.3 , 23.7 , and 23.4 ( due to rotamers ) , 
 21.9 , 14.4 ; hrms ( esi ) calcd for c28h36n2o6 496.2578 , found 496.2576 . to a solution 
 of pyridone 32 ( 10 mg , 0.02 mmol ) in ch2cl2 ( 1 ml ) was added triethylamine ( 0.026 mmol ) from a 1 m stock 
 solution in ch2cl2 . the solution was cooled 
 to 78 c , and to it was added tf2o ( 0.022 
 mmol ) as a 0.5 m stock solution in ch2cl2 . once 
 the addition was complete , the temperature was slowly raised to rt . 
 after 30 min , saturated aqueous nahco3 ( 3 ml ) was added , 
 and the biphasic solution was transferred to a separatory funnel . 
 the aqueous layer was extracted with ch2cl2 ( 3 
  5 ml ) , and the organics were collected , dried over mgso4 , and filtered through a thin pad of celite . the volatiles 
 were removed in vacuo , and purification by radial plc ( sio2 , 1030% etoac / hexanes ) afforded 11.3 mg ( 90% ) of pure 33 as a clear oil . ir ( neat ) 3436 , 3054 , 2985 , 2935 , 2306 , 
 1710 , 1625 , 1421 , 1265 , 705 cm ; h 
 nmr ( 400 mhz , cdcl3 )  7.62 ( m , 1h ) , 7.407.09 
 ( m , 5h ) , 6.74 ( m , 1h ) , 5.16 ( sep , j = 6.0 hz , 1h ) , 
 4.374.12 ( m , 4h ) , 3.12.93 ( m , 2h ) , 2.241.48 
 ( m , 12h ) , 1.33 ( d , j = 6.0 hz , 6h ) , 1.25 ( t , 7.2 
 hz , 3h ) ; c nmr ( 100 mhz , cdcl3 )  172.0 , 
 161.2 , 153.6 , 151.6 , 141.2 , and 140.8 ( due to rotamers ) , 129.5 , 125.5 , 
 122.0 , 119.3 , 112.1 , 70.3 , 60.6 , 54.2 , and 53.3 ( due to rotamers ) , 
 44.4 and 43.4 ( due to rotamers ) , 39.2 and 38.8 ( due to rotamers ) , 
 37.3 , 32.1 , 29.8 , 26.4 , 25.5 , 24.8 , 24.1 , 23.3 , 22.9 , 21.8 , 14.4 ; 
 hrms ( esi ) calcd for c29h35f3n2o8s ( [ m + h ] ) 629.2139 , 
 found 629.2140 .
a strategy 
 for the synthesis of the lycopodium alkaloid dihydrolycolucine 
 ( 1 ) has been investigated . 
 synthetic routes were developed 
 based on n - acylpyridinium salt chemistry to prepare 
 target fragments 3 and 4 that could ultimately 
 converge to the natural product . 
 key reactions include imda cycloadditions 
 and retro - mannich ring - openings to form both the ab and the ef ring 
 fragments . 
 the ring c precursor was prepared using pyridine substitution 
 and directed lithiation chemistry . 
 a suzuki cross - coupling of rings 
 c and ef led to the cef ring fragment . 
 initial attempts at closure 
 of the seven - membered d ring were unsuccessful .