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Scheme 4.48 Synthesis of a library of tricyclic pyrroles.
313{1} NH3 x HOAc
313{2} H2NMe 313{3} H2N 313{4} H2N 313{5} H2N 313{7} H2N H 2N
313{9} H2N 313{10} H2N 313{11} H2N 313{12} H2N 313{13} H2N HO
O
F
OMe
OH
OMe
S
NH
OH
OH
N NH
N
O
NH
N O
O
O
N
R2 R2 313{14} H2N 313{21} H2N MeO OMe
313{15} H2N 313{16} H2N O
313{17} H2N H 2N
MeO
O
F
313{19} H2N 313{20} H2N Et 3N, 1,4-dioxane,
30 mol% 292
70 °C, 20 min,
75-93%
BzN O
R1 311{1-2}
MeO2C H 2. H2 (1 atm), Pd/C, MeOH, 18h
88-99%
310{1-3}
3 : R
313{6} H2N 313{8}
R 1 :
OH
1.
F
OH
F
OCF 3
Me
F F
F
BzN O
R1 MeO2C H O
N
O R2 R2 F OMe
310{1} 310{2} 310{3}
313{18}
313{22} H2N 313{23} H2N HO
H
313{24} H2N F 3C
313{25} H2N 313{26} H2N 312{1-3,1-2}
313{27} H2N N
N
O
N
Me
Cl
SO 2Me
Me
OH
CH3 S
R 2 :
313{1-41} R 3 -NH 2
AcOH, EtOH
µW, 150W, 60-100 °C
15-30 min
0-80%
313{28} H2N Ph
313{29} H2N 313{30} H2N 313{31}
O
313{32} H2N 313{33} H2N O
N
H 2N
313{34}
Br H2N N
Me
N
N
N
O
Me
NH
Me
OH
OH
BzN
R 1
MeO2C H
OH
OMe
OMe
313{35} H2N Br
O
H
313{36} H2N 313{37} H2N 313{38} H2N H 2N
H 2N
N R3
R2 314{1-3,1-2,1-41}
O
N
311{1} 311{2}
313{39}
313{40}
313{41}
N
N
NO 2
H
N
H
N
H
N
H
N
N
H 2N HN
N
R
O
2
Using the previously discussed cyclocarbonylation protocol, α-alkylidene cyclopentenones
310{1-3} were obtained in 40-50% yield for the diastereomer shown (all reactions subsequent to
this step were performed by the staff at the UPCMLD). Next, performing six Stetter reactions in
parallel using a Radley’s carousel station, followed by reduction of the double bond afforded
122
Me
Cl
N
OMe
OH
F
CF 3