Post on 24-Feb-2016
description
Reaction of pyrrole with aldehydes – a mysterious
story Daniel T. Gryko
Institute of Organic Chemistry of the Polish Academy of Sciences
Warsaw, Poland
NH
N
HN
HNA A
B
Ehrlich reagent NH
N
HN
HNA A
B
NH
+ H+
CHO
NMe2
NH
NMe2
N
NMe2
H
Variety of products NH
N
HN
HNA A
B
NH
N
NH N
HNR R
R
R
R
NH
N
HN
HNR R
N
NH
NH
N
N
N
R
R
R
RR
R
RCHO+
NNH
HNN
NNH
HNN
N
NH
N
HNR R
R
R
at least 11 distinct macrocyclic species
Complexity NH
N
HN
HNA A
B
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.
Rothemund NH
N
HN
HNA A
B
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.
N
NH N
HN
R
R
R
RRCHO NH
+neat, pyridinesealed ampule
1-9%
Adler NH
N
HN
HNA A
B
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.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+C2H5COOH
reflux, air
~20%
Zn(OAc)2 in HOAc
Zn(OAc)2 in MeOH
ClCH2COOH, benzene
H3PO4, benzene
Lindsey NH
N
HN
HNA A
B
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.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+
1. TFA or BF3.Et2O, CH2Cl2 10-40%2. DDQ or p-chloranil
1. TFA and BF3.Et2O, CH2Cl2
2. DDQ or p-chloranil~50%
Lindsey NH
N
HN
HNA A
B
J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney et al J. Org. Chem. 1987, 52, 827.
Lindsey-salts NH
N
HN
HNA A
B
F. Li, K. Yang, J. S. Tyhonas, K. A. MacCrum, J. S. Lindsey Tetrahedron 1997, 53, 12339.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+1. BF3
.Et2O, salts
6-61%
2. DDQ or p-chloranil
1. No correlation with cations.2. No correlation with desiccative power.3. Reversible or not???
Lindsey-salts NH
N
HN
HNA A
B
F. Li, K. Yang, J. S. Tyhonas, K. A. MacCrum, J. S. Lindsey Tetrahedron 1997, 53, 12339.
Lindsey-deep NH
N
HN
HNA A
B
G. R
. Gei
er II
I, J.
S. L
inds
ey O
rg. L
ett.
2000
, 2, 1
745.
Lindsey-st. hind. NH
N
HN
HNA A
B
1. TFA or BF3.Et2O, CH2Cl2
2. DDQ or p-chloranil
CHO
N
NH N
HNNH
+
0%
30%1. BF3.Et2O, CHCl3
2. DDQ or p-chloranil
0.75% ethanol
J. S. Lindsey, R. W. Wagner J. Org. Chem. 1989, 54, 828.
Trans-A2B2-porphyrins NH
N
HN
HNA A
B
J. S. Lindsey, R. W. Wagner J. Org. Chem. 1999, 64, 2864.D. T. Gryko, M. Tasior, Tetrahedron Lett. 2003, 44, 3317.
1. TFA, CH2Cl22. DDQ, toluene
N
NH N
HN
20-30%
1. BF3.Et2O, MeCN, NH4Cl, 0 C
2. DDQ or p-chloranil
NH HN
NH HN CHO
R
NH HN
R
R
+
N
CHO
+1. TFA (4 eq.), CH2Cl22. DDQ, dioxane
~10%
20-40%
Gas phase NH
N
HN
HNA A
B
C. M. Drain, X. Gong Chem. Commun. 1997, 2117.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+
1-23%
200 C, gas phase
Gas phase-2 NH
N
HN
HNA A
B
C. M. Drain, et al. J. Porphyrins Phthalocyanines. 2010, 14, 621.
N
NH N
HN
Ar
Ar
Ar
ArNH
+
10%
200 C, Zn(OAc)2
N
CHO
Oxidative Lewis Acids NH
N
HN
HNA A
B
E. F. LLama and co-workers J. Chem. Soc. Perkin 1 1995, 2611.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+
40-65%
VOCl3 or TiCl4CH2Cl2
In phenols NH
N
HN
HNA A
B
G. A. Mirafzal, H. M. Bosse, J. M. Summer Tetrahedron Lett. 1999, 40, 623.
N
N N
N
Ar
Ar
Ar
ArArCHO NH
+2,4,6-trichlorophenol
MnCl2, reflux, air
20-70%
Mn
In micelles NH
N
HN
HNA A
B
R. P. Bonar-Law J. Org. Chem 1996, 61, 3623.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+1. SDS, H2O, HCl2. p-chloranil, THF
HO
HO
OHOOC
COOH
43%
40%
0%
18%
Rocha-Gonzalves NH
N
HN
HNA A
B
M. d’A. Rocha Gonzalves and co-workers J. Het. Chem. 1985, 22, 931.
N
NH N
HN
Alk
Alk
Alk
AlkAlkCH(OMe)2 NH
+1. TFA, CCl4, 60 C2.DDQ or p-chloranil
18%
Rocha-Gonzalves NH
N
HN
HNA A
B
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
NH N
HN
Ar
Ar
Ar
Ar
ArCHO NH
+
HOAc, nitrobenzenereflux
5-78%
1. BF3.Et2O, CHCl32.H2O2, HOAc
12-40%
propionic acid, nitrobenzene, MW 4-25%
Sharghi NH
N
HN
HNA A
B
H. Sharghi, A. H. Nejad Helv. Chim. Acta 2003, 86, 408.H. Sharghi, A. H. Nejad Tetrahedron 2004, 60, 1863.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+1. PCl5 or CF3SO2Cl
30-65%
2. O2
Krausz NH
N
HN
HNA A
B
P. Krausz et al. J. Porphyrins Pkthalocyanines 2006, 10, 937.P. Krausz et al. Tetrahedron Lett. 2008, 49, 5537.
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+1. activated charcoal
~40%
2. 1 h, 200 oC
N
NH N
HN
Ar
Ar
Ar
ArArCHO NH
+1. I2, CH2CL2, MW
30-40%
2. p-chloranil, MW
Furuta/Lotos NH
N
HN
HNA A
B
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.
N
NH
N
HN
Ar
Ar
Ar
Ar
NH
+
1. BF3.Et2O
4-7%
2. p-chloranil
CHO
CHO
HBr, t-BuOH, CH2Cl2
NH
+
4 : 7
1 : 1
Lindsey N-confused NH
N
HN
HNA A
B
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.
N
NH
N
HN
Ar
Ar
Ar
Ar
NH
+
1. CH3SO3H
40%
2. p-chloranil
CHO
CHO
1. TFA or BF3.Et2O
NH
+
2. DDQ or p-chloranil
ubiquitous product
Lindsey N-confused NH
N
HN
HNA A
B
G. R. Geier III, D. M. Haynes, J. S. Lindsey Org. Lett. 1999, 1, 1455.
Cavaleiro NH
N
HN
HNA A
B
J. A. S. Cavaleiro and coworkers Chem. Commun. 1999, 385.
NH
+
CHOF
FF
F
F AcOH, PhNO2
N
NH N
HNC6F5 C6F5
C6F5
C6F5
+NH N
HNNC6F5C6F5
R C6F5
C6F5C6F5
N
N
15% 1%
Cavaleiro NH
N
HN
HNA A
B
J. A. S. Cavaleiro and coworkers Chem. Commun. 1999, 385.
NH N
HNNC6F5C6F5
C6H5 C6F5
C6F5C6F5
N
N
HNNH
NH HNC6F5 C6F5
C6H5C6F5
C6F5 C6F5
N
N
Osuka-1 NH
N
HN
HNA A
B
J.-Y. Shin, H. Furuta, K. Yoza, S. Igarashi, A. Osuka J. Am. Chem. Soc. 2001, 123, 7190.
NH N
NH N
HNC6F5 C6F5
C6F5
C6F5
+
CHOF
FF
F
F
N
NH N
HNC6F5 C6F5
C6F5
C6F5 n = 2-9
12 + 15 + 20 + 5 + 6 + 3 = 61%
1. BF3.Et2O, CH2Cl22. DDQ
+
Osuka-2 NH
N
HN
HNA A
B
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.
Who was first? NH
N
HN
HNA A
B
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.
NH
+ 1. BF3.Et2O
2. DDQ, ?%
R
NH
N
HN
HNR R
CHONO2O2N
But
MoOC COCO
CHO
CHO
HOAc
4%
1. ??
2. ???
No catalyst… NH
N
HN
HNA A
B
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.
N
+CHO
O
NOH
Obenzene, RT, 2h
67%
NH
1.benzene, rflx, 2h2. NaIO4 N
HCHOOHC
NH
benzene, rflx, 2hNH OH
O
78%
21%
With base… NH
N
HN
HNA A
B
S. Taniguchi and co-workers Synlett 1999, 73.
NH
(CH2O) aq, K2CO3
NH OH
86%
5 C, 7dHO
Summary NH
N
HN
HNA A
B
• We utilize the reaction which we do not understand
• More accidental than rational development
• Probably still at the early stage