Transcript J. Am. Chem. Soc

B
N
HN
A
A
NH HN
Reaction of pyrrole with
aldehydes – a mysterious
story
Daniel T. Gryko
Institute of Organic Chemistry of the
Polish Academy of Sciences
Warsaw, Poland
B
N
Ehrlich reagent
N
H
NMe2
H+
+
NMe2
N
H
A
NH HN
NMe2
CHO
HN
A
N
H
B
N
Variety of products
N
NH
R
N
HN
R
R
R
N
HN
R
NH
N
R
R
R
N
NH HN
HN
R
+ RCHO
N
H
R
NH N
NH N
R
R
N
R
HN
N
N
NH N
R
at least 11 distinct macrocyclic species
NH N
N
R
A
NH HN
R
R
HN
A
HN
B
Complexity
Fig. 1 A representative LD-MS spectrum from a crude
oxidized reaction mixture of pyrrole + benzaldehyde
(100 mM pyrrole + benzaldehyde, 10 mM BF3–Et2O,
CH2Cl2, room temperature, 2 min). The oligomer length
(n) is given by the number above the symbol. The yield
of TPP (UV–Vis) is noted.
N
HN
A
A
NH HN
B
N
Rothemund
RCHO
+
N
H
NH
N
R
R
N
A
NH HN
R
neat, pyridine
sealed ampule
HN
A
HN
R
1-9%
P. Rothemund J. Am. Chem. Soc. 1935, 57, 2010.
P. Rothemund J. Am. Chem. Soc. 1936, 58, 625.
P. Rothemund J. Am. Chem. Soc. 1939, 61, 2912.
P. Rothemund, A. R. Menotti J. Am. Chem. Soc. 1941, 63, 267.
B
N
Adler
ArCHO
+
N
H
A
NH HN
Ar
C2H5COOH
reflux, air
HN
A
NH
N
Ar
Ar
N
HN
Ar
~20%
Zn(OAc)2 in HOAc
Zn(OAc)2 in MeOH
ClCH2COOH, benzene
H3PO4, benzene
A. D. Adler, F. R. Longo, W. Shergalis J. Am. Chem. Soc. 1964, 86, 3145.
A. D. Adler, F. R. Longo and co-workers J. Org. Chem. 1967, 32, 476.
B
N
Lindsey
HN
A
A
NH HN
1. TFA or BF3.Et2O, CH2Cl2
10-40%
2. DDQ or p-chloranil
Ar
NH
ArCHO
+
N
Ar
Ar
N
H
N
HN
Ar
1. TFA and BF3.Et2O, CH2Cl2
2. DDQ or p-chloranil
~50%
J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney et al J. Org. Chem. 1987, 52, 827
G. R. Geier III, J. A. Riggs, J. S. Lindsey JPP 2001, 5,681.
B
Lindsey
N
HN
A
A
NH HN
J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney et al J. Org. Chem. 1987, 52, 827
B
N
Lindsey-salts
HN
A
A
NH HN
Ar
ArCHO
+
1. BF3.Et2O, salts
N
H
2. DDQ or p-chloranil
NH
N
Ar
Ar
N
HN
Ar
6-61%
1. No correlation with cations.
2. No correlation with desiccative power.
3. Reversible or not???
F. Li, K. Yang, J. S. Tyhonas, K. A. MacCrum, J. S. Lindsey Tetrahedron 1997, 53, 12339.
B
Lindsey-salts
N
HN
A
A
NH HN
F. Li, K. Yang, J. S. Tyhonas, K. A. MacCrum, J. S. Lindsey Tetrahedron 1997, 53, 12339.
G. R. Geier III, J. S. Lindsey Org. Lett.
2000, 2, 1745.
B
Lindsey-deep
A
N
NH HN
HN
A
B
N
Lindsey-st. hind.
1. TFA or BF3.Et2O, CH2Cl2
2. DDQ or p-chloranil
CHO
+
N
H
N
0.75% ethanol
N
1. BF3.Et2O, CHCl3
2. DDQ or p-chloranil
J. S. Lindsey, R. W. Wagner J. Org. Chem. 1989, 54, 828.
A
NH HN
0%
NH
HN
A
HN
30%
B
Trans-A2B2-porphyrins
J. S. Lindsey, R. W. Wagner J. Org. Chem. 1999, 64, 2864.
D. T. Gryko, M. Tasior, Tetrahedron Lett. 2003, 44, 3317.
N
HN
A
A
NH HN
B
N
Gas phase
ArCHO
+
N
H
NH
N
Ar
Ar
N
HN
Ar
1-23%
C. M. Drain, X. Gong Chem. Commun. 1997, 2117.
A
NH HN
Ar
200 C, gas phase
HN
A
B
Gas phase-2
C. M. Drain, et al. J. Porphyrins Phthalocyanines. 2010, 14, 621.
N
HN
A
A
NH HN
B
Oxidative Lewis Acids
Ar
ArCHO
+
VOCl3 or TiCl4
N
H
CH2Cl2
NH
N
Ar
Ar
N
HN
Ar
40-65%
E. F. LLama and co-workers J. Chem. Soc. Perkin 1 1995, 2611.
N
HN
A
A
NH HN
B
N
In phenols
ArCHO
+
N
H
A
NH HN
Ar
2,4,6-trichlorophenol
MnCl2, reflux, air
HN
A
N
N
Mn
Ar
Ar
N
N
Ar
20-70%
G. A. Mirafzal, H. M. Bosse, J. M. Summer Tetrahedron Lett. 1999, 40, 623.
B
N
In micelles
43%
HO
Ar
HOOC
ArCHO
+
1. SDS, H2O, HCl
N
H
2. p-chloranil, THF
40%
O
N
Ar
Ar
N
HN
0%
Ar
COOH
18%
R. P. Bonar-Law J. Org. Chem 1996, 61, 3623.
A
NH HN
HO
NH
HN
A
B
N
Rocha-Gonzalves
AlkCH(OMe)2 +
N
H
2.DDQ or p-chloranil
NH
N
Alk
Alk
N
A
NH HN
Alk
1. TFA, CCl4, 60 C
HN
A
HN
Alk
18%
M. d’A. Rocha Gonzalves and co-workers J. Het. Chem. 1985, 22, 931.
B
Rocha-Gonzalves
M. d’A. Rocha Gonzalves and co-workers Heterocycles 1996, 43, 1423.
M. d’A. Rocha Gonzalves and co-workers JPP, 2007, 11, 77-84.
N
HN
A
A
NH HN
B
N
Sharghi
ArCHO
+
N
H
2. O2
A
NH HN
Ar
1. PCl5 or CF3SO2Cl
HN
A
NH
N
Ar
Ar
N
HN
Ar
30-65%
H. Sharghi, A. H. Nejad Helv. Chim. Acta 2003, 86, 408.
H. Sharghi, A. H. Nejad Tetrahedron 2004, 60, 1863.
B
Krausz
P. Krausz et al. J. Porphyrins Pkthalocyanines 2006, 10, 937.
P. Krausz et al. Tetrahedron Lett. 2008, 49, 5537.
N
HN
A
A
NH HN
B
N
Furuta/Lotos
1
:
HBr, t-BuOH, CH2Cl2
N
NH
Ar
Ar
N
CHO
+
4
Ar
N
H
1
:
HN
1. BF3.Et2O
N
H
7
2. p-chloranil
A
NH HN
CHO
+
HN
A
Ar
4-7%
L. Latos-Grażyński and co-workers Angew. Chem. Int. Ed.. 1994, 33, 779.
H. Furuta, H. Osano, T. Ogawa J. Am. Chem. Soc. 1994, 116, 767.
B
N
Lindsey N-confused
CHO
HN
A
A
NH HN
ubiquitous product
.
+
N
H
1. TFA or BF3 Et2O
2. DDQ or p-chloranil
Ar
N
NH
Ar
Ar
N
CHO
+
HN
1. CH3SO3H
N
H
2. p-chloranil
Ar
40%
G. R. Geier III, J. S. Lindsey J. Org. Chem. 1999, 64, 1596.
J. S. Lindsey, K. A. MacCrum, J. S. Tyhonas, Y.-Y. Chuang J. Org. Chem. 1994, 59,579.
G. R. Geier III, D. M. Haynes, J. S. Lindsey Org. Lett. 1999, 1, 1455.
B
Lindsey N-confused
G. R. Geier III, D. M. Haynes, J. S. Lindsey Org. Lett. 1999, 1, 1455.
N
HN
A
A
NH HN
B
N
Cavaleiro
F
+
N
H
F
F
AcOH, PhNO2
NH
C 6 F5
N
C6 F5
N
HN
N
+
C 6 F5
N
NH
C 6 F5
A
NH HN
C6F5
CHO
F
HN
A
C6F5
C 6F 5
HN
N
F
C 6 F5
15%
J. A. S. Cavaleiro and coworkers Chem. Commun. 1999, 385.
R
N
1%
C6F5
B
N
Cavaleiro
C6F5
N
C6F5
C6F5
N
C6H5
N
N
C6F5
NH
HN
HN
NH
HN
C6F5
C6F5
C6F5
A
NH HN
C6F5
N
NH
HN
A
C6F5
C6F5
N
J. A. S. Cavaleiro and coworkers Chem. Commun. 1999, 385.
C6H5
B
N
Osuka-1
F
+
N
H
F
F
1. BF3.Et2O, CH2Cl2
2. DDQ
NH
C 6F5
NH
N
C 6 F5
C 6 F5
N
HN
A
NH HN
C 6F5
CHO
F
HN
A
+
N
C 6 F5
C 6 F5
N
HN
F
C 6 F5
C6 F5
n = 2-9
12 + 15 + 20 + 5 + 6 + 3 = 61%
J.-Y. Shin, H. Furuta, K. Yoza, S. Igarashi, A. Osuka J. Am. Chem. Soc. 2001, 123, 7190.
B
Osuka-2
N
HN
A
A
NH HN
J.-Y. Shin, H. Furuta, K. Yoza, S. Igarashi, A. Osuka J. Am. Chem. Soc. 2001, 123, 7190.
S. Shimizu, J.-H. Shin, H. Furuta, R. Ismael, A. Osuka Angew. Chem. Int. Ed.. 2003, 42, 78
B
N
Who was first?
CHO
OC
+
O 2N
Mo
CO
CO
CHO
NO2
4%
R
2. DDQ, ?%
N
H
A
NH HN
HOAc
1. BF3.Et2O
HN
A
N
HN
R
R
NH HN
But
CHO
1. ??
2. ???
N. M. Loim and co-workers Izv. Akad. Nauk. Ser. Khim. 1994, 5, 925.
E. Rose and co-workers J. Am. Chem. Soc. 1996, 118, 1567.
L. Latos-Grażyński and co-workers New J. Chem. 1997, 21, 691.
B
No catalyst…
N
benzene, rflx, 2h
N
H
OH
78%
O
CHO
+
N
H
1.benzene, rflx, 2h
2. NaIO4
OHC
N
H
CHO
21%
O
benzene, RT, 2h
N
A
NH HN
O
N
H
HN
A
N
OH
67%
G. I. Zhungietu, F. N. Chukhrii Zh. Vses. Khim. Obshchest. 1970, 15, 586.
T. Severin, I. Ipach Chem. Ber. 1975, 108, 1768.
S. P. Ivonin, A. V. Lapandin, A. A. Anishchenko Synth. Comm. 2004, 34, 451.
B
With base…
N
5 C, 7d
HO
N
H
86%
S. Taniguchi and co-workers Synlett 1999, 73.
A
NH HN
(CH2O) aq, K2CO3
N
H
HN
A
OH
B
Summary
• We utilize the reaction which we do not
understand
• More accidental than rational
development
• Probably still at the early stage
N
HN
A
A
NH HN