Refined routes to chlorin building blocks
A method of making chlorins comprises the steps of reacting (e.g. condensing) a dipyrrin western half intermediate with an eastern half intermediate to form a tetrahydrobilene, and then cyclizing the tetrahydrobilene to form a chlorin. Intermediates including tetrahydrobilenes useful in such reactions are also described.
1. A method of making a chlorin of Formula X:
wherein:
M is a metal selected from the group consisting of Cu, Zn, Mg, Pt, Pd, Sn and Al, or M is absent;
K 1 , K 2 and K 4 are atoms independently selected from the group consisting of N, O, S, Se, Te, and CH;
K 3 is N;
S 1 , S 2 , S 3 , S 4 S 5 , S 6 , S 7 , S 8 , S 9 , S 10 , S 11 , S 12 , S 13 , and S 14 are independently selected from the group consisting of H, aryl, phenyl, cycloalkyl, alkyl, alkenyl, alkynyl, halogen, alkoxy, alkylthio, perfluoroalkyl, perfluoroaryl, pyridyl, cyano, thiocyanato, nitro, amino, alkylamino, acyl, sulfoxyl, sulfonyl, imido, amido, and carbamoyl;
and wherein from one to four of S 1 , S 2 , S 3 , S 4 S 5 , S 6 , S 7 , S 8 , S 9 , S 10 , S 11 , S 12 , S 13 , and S 14 may optionally be independently selected linking groups Q, wherein said linking groups Q are of the formula:
wherein:
n is from 0 to 10;
R 3 may be present or absent;
R 1 , R 2 , and R 3 are each independently selected from the group consisting of ethene, ethyne, aryl, and heteroaryl groups, which aryl and heteroaryl groups may be unsubstituted or substituted one or more times with H, aryl, phenyl, cycloalkyl, alkyl, alkenyl, alkynyl, halogen, alkoxy, alkylthio, perfluoroalkyl, perfluoroaryl, pyridyl, cyano, thiocyanato, nitro, amino, alkylamino, acyl, sulfoxyl, sulfonyl, imido, amido, and carbamoyl;
Y is a protected or unprotected reactive substituent selected from the group consisting of hydroxy, thio, seleno, telluro, carboxylic acid, boronic acid, phenol, silane, sulfonic acid, phosphonic acid, alkylthiol, formyl, halo, alkenyl, alkynyl, haloalkyl, alkyl phosphonate, alkyl sulfonate, alkyl carboxylate, and alkyl boronate groups;
said method comprising oxidatively cyclizing a tetrahydrobilene of Formula XI:
wherein Z is selected from the group consisting of halo, alkoxy, and acyloxy; in an organic solvent in the presence of a base, an oxidant and a metal salt MX n , where X is an anion, and n is 2-3, to produce a compound of Formula X above; and then
optionally displacing metal M to create a free base chlorin.
2. The method according to claim 1 , wherein said organic solvent is a polar or nonpolar solvent.
3. The method according to claim 1 , wherein said organic solvent is a protic or aprotic solvent.
4. The method according to claim 1 , wherein said base is piperidine or tetramethylpiperidine.
5. The method according to claim 1 , wherein said oxidant is air.
6. The method according to claim 1 , wherein said oxidant is silver iodate.
7. The method according to claim 1 , wherein said cyclizing step is carried out in the presence of a silver salt.
8. The method according to claim 1 , wherein said cyclizing step is carried out in the presence of silver triflate.
9. The method according to claim 1 , wherein Z is Br.
10. The method according to claim 1 , wherein said step of displacing metal M is carried out with an acid.
11. The method according to claim 1 , wherein S 1 and S 5 are independently selected trans-substituted linking groups Q.
12. The method according to claim 1 , wherein S 2 and S 6 are independently selected trans-substituted linking groups Q 1 and Q 2 .
13. The method according to claim 1 , wherein K 1 , K 2 and K 4 are independently selected from the group consisting of N, O, S, and CH.
14. The method according to claim 1 , wherein K 1 , K 2 and K 4 are all N.
15. The method according to claim 1 , wherein S 1 , S 2 , S 3 , S 4 , S 5 , S 6 , S 7 , S 8 , S 9 , S 10 , S 11 , S 12 , S 13 , and S 14 are all alkyl.