Fissure coupling of the fluoranthene adduct (7,12-diphenyl)benzo[k]fluoranthene (3) using AlCl3/NaCl, CoF3/TFA, or Tl(OCOCF3) gave the new polyaromatic hydrocarbon dibenzo{[f,f’]-4,4’,7,7’-tetraphenyl}diindeno[1,2,3-cd:1‘,2‘,3‘-lm]perylene (4). Crystal data for 4:  triclinic space group P1̄, a = 10.569(2) Å, b = 11.565(4) Å, c = 13.001(3) Å, α = 95.05(2)°, β = 111.24(1)°, γ = 100.53(1)°, Z = 1, R F = 0.075%. Compounds 3 and 4 are both highly fluorescent in solution and display relative fluorescence quantum yields of φF = 1.0 and 0.85, respectively. The electrochemistry and electrogenerated chemiluminescence (ECL) of each compound has been investigated. The cyclic voltammogram of 3 in benzene−acetonitrile (9:1) shows that the compound undergoes a reversible reduction and an irreversible oxidation, whereas the cyclic voltammogram of 4 displays the reversible formation of both singly and doubly charged cations and anions. Compounds 3 and 4 undergo ECL to yield blue and orange-red light, respectively, with an ECL efficiency of ∼2% for 4. Emission from 4 is observed in the ECL of unstirred solutions of 3. This indicates that 4 is produced at the electrode during the ECL experiment, presumably via an electrochemical oxidative coupling process during the anodic potential steps.

Suzuki coupling of 7 to 8 gave the biphenyl derivative 9. Reaction of 9 with ethyl vinyl ether/bromine/base gave 10, which on treatment with CsF/DMF at 130 degrees C resulted in the cross-conjugated 2,5-cyclohexadienone 6. Acid hydrolysis of 6 gave 11, which was reductively aminated to give (+/-)-narwedine 2. Since 2 has been converted into (-)-galanthamine 1 in two steps, this synthesis proceeds in eight steps with an overall yield of 63%. Also treatment of the cross-conjugated cyclohexadienone 6 with nitromethane/base gave 12, which was reduced to provide 13. Reduction of the nitro group in 13 to an amine, followed by reductive amination under acidic conditions, arrives at the codeine skeleton 15. Elaboration of 15 into (+/-)-codeine proceeds via the previously unknown alpha-epoxide derivative 18. This is the shortest synthesis of codeine (13 steps, 20% overall yield) and, for the first time, allows access to codeine without having to reduce codeinone.

Upon oxidation at a platinum electrode, (7,12-diphenyl)benzo[k]fluoranthene (1) undergoes intermolecular dehydrogenative coupling to form bis-4,4'-(7,12-diphenyl)benzo[k]fluoranthene (2). Further oxidation of this product results in a much slower intramolecular coupling reaction that yields dibenzo{[f,f']-4,4',7,7'-tetraphenyl}diindeno[1,2,3-cd:1',2',3'-lm]perylene (3). 2 can be synthesized via bulk electrolysis of 1 and also by the chemical coupling of 4-bromo-7,12-diphenylbenzo[k]fluoranthene (4) with a nickel catalyst. Compounds 1-3 are capable of electrogenerated chemiluminescence (ECL), and their coupling reactions have been detected and followed using this technique. Cyclic voltammograms of 1 have been digitally simulated to provide mechanistic and kinetic insight into the initial intermolecular oxidative coupling reaction. Evidence supports an EC(2)()EE mechanism, in which the coupling of radical cations of 1 is the rate-limiting step. A second-order rate constant of k = 7500 M(-)(1) s(-)(1) has been determined for the dimerization process by fitting experimental data to theoretical working curves.

The tetracyclic amine 9 was converted through several steps into secondary amine 13 and acetylated with (phenylthio)acetic acid activated by bis(2-oxo-3-oxazolidinyl)phosphinic acid to give amide 15. Treatment of 15 with sodium hydride in tetrahydrofuran at 25 °C resulted in rapid conversion into a single diastereomer, 16. This same conjugate addition has been conducted at the sulfoxide oxidation level and also with a chiral sulfoxide to provide optically active compounds (Scheme VI). Conversion of sulfoxide 19 into dione 27 followed by ketalization and reduction gave tertiary amine 34. Deprotection and oxidation with mercuric acetate gave the core strychnine skeleton 36. The /8-aminoacrylate double bond in 36 was reduced to give 39 followed by epimerization to give 40. Ester 40 was protected as the sulfonamide derivative 44, and the ester was reduced to give 45. Alcohol 45 undergoes normal acid hydrolysis to give hemiketal 47 (Scheme X). The Wieland-Gumlich aldehyde 48 was converted into the relay compound by the route shown in Scheme XI, thus providing a convenient correlation and short route to 47. Hemiketal 47 was converted into ketone 52 and treated with (EtO)2P(G)CH2CN/KN(SiMe3)2/THF at 25 °C to give the two geometrical isomers 53 (E) and 54 (Z) (overall 72%) in a ratio of 3:2. The incorrect stereoisomer could be recycled by irradiation in benzene to give a mixture of 53 and 54. Reduction of 53 gave the required allylic alcohol 55. Desilylation of 55 gave did 56. The synthesis of strychnine and the Wieland-Gumlich aldehyde was completed by selective silylation of the allylic hydroxyl group in 56 and oxidation to give the unstable aldehyde 58. Desilylation of 58 gave the protected Wieland-Gumlich aldehyde 49, which was deprotected by treatment with sodium anthracenide to give 48. The conversion of 48 into strychnine was reported by Robinson in 1953.

No abstract