Decarboxylative sp 3 C–N Couplings: Recent Progress September, 2018 ■ Outline N H X Mes I OCOR OCOR N X R R Y Y Ir Cu or Cu ■ Decarboxylative sp 3 C–N coupling under non-photonic conditions ■ Decarboxylative sp 3 C–N coupling using bicyclic tertiary acids ■ Decarboxylative sp 3 C–N coupling using new N -heterocycles ■ General considerations Initial publication: Liang, Y.; Zhang, X.; MacMillan, D. W. C. Nature 2018 , 559, 83–88
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Decarboxylative sp C–N Couplings: Recent Progress...2 equiv BTMG dioxane (3 mL), r.t., 1 h 1 equiv 2 equiv 0.1 mmol NN Me Me Me 4-Phen Me Me Cl Cl 75% NMR yield Procedure: To an
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Procedure:To an 8 mL vial equipped with a stir bar was added N-nucleophile, copper salt, ligand, and iodomesitylene dicarboxylate.Dioxane was added and the solution was degassed immediately by sparging with N2 for 3–5 minutes. If necessary, exogenous base (such as BTMG or DBU) was added under the atmosphere of N2. The reaction was stirred for 1 hour at room temperature. An internal standard (mesitylene) was added and the crude reaction mixture was analyzed by 1H NMR.
Notes:1. If the iodomesitylene dicarboxylate or the N-nucleophile is a liquid, its solution in dioxane was used instead.2. Pre-mixing the copper salt and the ligand in solution is not necessary. If a stock solution of copper catalyst is needed, the ligation step (such as stirring or sonification the solution) should be performed under the atmosphere of N2.
Procedure:To an 8 mL vial equipped with a stir bar was added photocatalyst, N-nucleophile, copper salt, ligand, and iodomesitylene dicarboxylate. Dioxane was added and then base was added to the mixture. Next, the solution was degassed by sparging with N2 for 3–5 minutes. The reaction was stirred and irradiated using 34 W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 hour. An internal standard (mesitylene) was added and the crude reaction mixture was analyzed by 1H NMR.
Notes:1. If the iodomesitylene dicarboxylate or the N-nucleophile or the ligand is a liquid, its solution in dioxane was used instead.
Procedure:To an 8 mL vial equipped with a stir bar was added N-nucleophile, copper salt, ligand, and iodomesitylene dicarboxylate.Dioxane was added and the solution was degassed immediately by sparging with N2 for 3–5 minutes. If necessary, exogenous base (such as BTMG or DBU) was added under the atmosphere of N2. The reaction was stirred for 1 hour at room temperature. An internal standard (mesitylene) was added and the crude reaction mixture was analyzed by 1H NMR.
Notes:1. If the iodomesitylene dicarboxylate or the N-nucleophile is a liquid, its solution in dioxane was used instead.2. Pre-mixing the copper salt and the ligand in solution is not necessary. If a stock solution of copper catalyst is needed, the ligation step (such as stirring or sonification the solution) should be performed under the atmosphere of N2.
■ Decarboxylative sp3 C–N coupling under non-photonic conditions
■ Decarboxylative sp3 C–N coupling using bicyclic tertiary acids
■ Decarboxylative sp3 C–N coupling using new N-heterocycles
■ General considerations
Unpublished Results
Decarboxylative sp3 C–N Couplings: New N-HeterocyclesSeptember, 2018
■ New N-heterocycles: summary of results
NMR yield
NH
X
MesI
OCOCy
OCOCy NX
RR
YY
Ir Cu
N NN
75% yield
Cl
N NN
77% yield
N NN
76% yield
N
NN
85% yield
ClN
NN
69% yield
Br
N
N N
86% yield
Cl
N
N N
54% yield
Cl
N
N N
60% yield
Cl Br
N
N
N
66% yield
BrN
N N
N
82% yield
Cl
N
N N
N
75% yield
Cl
Cl
N
N
NN
54% yield
Br
0.10 mmol1 equiv
2 equivdioxane, r.t., 1 h
single regioisomer
Decarboxylative sp3 C–N Couplings: New N-HeterocyclesSeptember, 2018
■ New N-heterocycles: summary of conditions
NMR yield
NH
X
MesI
OCOCy
OCOCyN
XR R
Y Y
0.10 mmol1 equiv
2 equiv
1 mol% photocatalyst20 mol% CuTC, 30 mol% ligand
2 equiv base
dioxane (3.0 mL), r.t., 1 h
N
N NHN
N
NHN N
H
N
N NH
NN
NH
NN
NH
NN
N NH
N
Ir(F-Meppy)2(dtbbpy)dOMe-Phen, BTMG
Ir(ppy)3BPhen, BTMG
Ir(F-Meppy)2(dtbbpy)BPhen, no base
Ir(F-Meppy)2(dtbbpy)dOMe-Phen, BTMG
Ir(F-Meppy)2(dtbbpy)dOMe-Phen, BTMG
Ir(ppy)3BPhen, BTMG
Ir(F-Meppy)2(dtbbpy)BPhen, no base
N
N
NH
N
Ir(ppy)3BPhen, BTMG
Decarboxylative sp3 C–N Couplings: New N-HeterocyclesSeptember, 2018
■ Experimental procedure: photoredox conditions
Procedure:To an 8 mL vial equipped with a stir bar was added photocatalyst, N-nucleophile, copper salt, ligand, and iodomesitylene dicarboxylate. Dioxane was added and then base was added to the mixture. Next, the solution was degassed by sparging with N2 for 3–5 minutes. The reaction was stirred and irradiated using 34 W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 hour. An internal standard (mesitylene) was added and the crude reaction mixture was analyzed by 1H NMR.
Notes:1. If the iodomesitylene dicarboxylate or the N-nucleophile is a liquid, its solution in dioxane was used instead.