The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity?
Abstract
:1. Introduction
2. Results and Discussion
2.1. Experimental
2.2. Computational
2.2.1. Global DFT Reactivity Indices
2.2.2. Local DFT Reactivity Indices
2.2.3. Transition States and Energetic Analysis
3. Materials and Methods
3.1. Cycloaddition Between Allene 1b and 4-Substituted-Phenyl Azides 3b,c
3.2. Reaction Between Allene 1b and 4-Methoxyphenylazide 3b in Carbon Tetrachloride
3.3. Reaction Between Allene 1b and 4-Methoxyphenylazide 3b in CDCl3
3.4. Computational Methods
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Entry | Reaction | Overall Yield | Product Ratio | |
---|---|---|---|---|
(%) | 4:5 | 8:9 | ||
1 | 1a+3a | 67 | 90:10 | - |
2 | 1b+3b | 71 | 100:0 | - |
3 | 1b+3c | 69 a | - | - |
4 | 2a+3a | 29 b | - | - |
5 | 2b+3a | 28 | - | 90:10 |
B3LYP/6-31G(d,p) | M08-HX/pcseg-3 //M08-HX/pcseg-2 | ωB97X-D/pcseg-3 //ωB97X-D/pcseg-2 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
µ | S | ω | Na | µ | S | ω | N | µ | S | ω | N | |||
2a | −2.55 | 0.137 | 0.44 | 2.91 | −3.73 | 0.098 | 0.68 | 3.14 | −3.42 | 0.098 | 0.57 | 3.13 | ||
2b | −4.18 | 0.136 | 1.19 | 1.27 | −5.02 | 0.079 | 1.00 | 0.66 | −4.62 | 0.080 | 0.85 | 0.77 | ||
1a | −4.13 | 0.163 | 1.39 | 1.92 | −4.91 | 0.091 | 1.10 | 1.59 | −4.65 | 0.093 | 1.00 | 1.60 | ||
1b | −4.08 | 0.199 | 1.66 | 2.54 | −4.77 | 0.116 | 1.32 | 2.90 | −4.53 | 0.116 | 1.19 | 2.78 | ||
3a | −3.63 | 0.193 | 1.27 | 2.92 | −3.89 | 0.103 | 0.78 | 3.23 | −3.66 | 0.103 | 0.69 | 3.13 | ||
3b | −3.29 | 0.210 | 1.13 | 3.46 | −3.66 | 0.112 | 0.75 | 3.85 | −3.46 | 0.113 | 0.68 | 3.76 | ||
3c | −4.82 | 0.229 | 2.66 | 2.12 | −5.24 | 0.119 | 1.64 | 2.54 | −5.03 | 0.121 | 1.53 | 2.47 |
Compound | Atom | 1000 s (eV−1) |
---|---|---|
2a | C2 | 23.1 (s–) |
2b | C2 | 50.5 (s+) |
1a | C1 | 20.9 (s+) |
1b | C2 | 5.3 (s+) |
1b | C3 | 1.3 (s–) |
3a | N3 | 20.9 (s+) |
3a | N3 | 24.4 (s–) |
3b | N1 | 23.1 (s–) |
3c | N3 | 20.2 (s+) |
ΔΩ (kJ/mol) | ||||
---|---|---|---|---|
Reaction | N1C2-N3C1 | N1C2-N3C1 | N1C2-N3C3 | N1C3-N3C2 |
2a+3a | −0.22 (−0.05, −0.17) | −0.05 (−0.05,0.00) | – | – |
2b+3a | −0.91 (−0.20, −0.71) | −0.05 (−0.17,0.12) | – | – |
1a+3a | −0.51 (−0.48, −0.04) | −0.60 (−0.04, −0.56) | 0.30 (−0.04,0.34) | 0.34 (0.38, −0.04) |
1b+3b | −0.34 (-0.10, −0.24) | −0.35 (−0.26, −0.10) | −0.29 (−0.26, −0.04) | −0.28 (−0.04, −0.24) |
1b+3c | −0.019(−0.007, −0.012) | −0.018(−0.011, −0.007) | −0.025 (−0.011, −0.013) | −0.024 (−0.012, −0.012) |
Reaction | Isomer | R1a (Å) | R3b (Å) | <R> c (Å) | Δ d (Å) | N1-N̂2-N3 (°) | C1-Ĉ2-C3 (°) |
---|---|---|---|---|---|---|---|
2a+3a | N1C1-N3C2 | 2.33 | 2.12 | 2.22 | 0.21 | 139.9 | 147.3 |
N1C2-N3C1 | 2.17 | 2.20 | 2.18 | –0.03 | 137.1 | 151.5 | |
2b+3a | N1C1-N3C2 | 2.12 | 2.15 | 2.14 | –0.03 | 141.0 | 146.3 |
N1C2-N3C1 | 2.12 | 2.06 | 2.09 | 0.07 | 140.2 | 145.4 | |
1a+3a | N1C1-N3C2 | 2.21 | 1.99 | 2.10 | 0.22 | 139.2 | 151.8 |
N1C2-N3C1 | 2.00 | 2.24 | 2.12 | –0.24 | 140.9 | 149.8 | |
N1C2-N3C3 | 2.13 | 2.12 | 2.13 | 0.01 | 139.2 | 154.9 | |
N1C3-N3C2 | 2.17 | 2.09 | 2.13 | 0.08 | 139.5 | 154.4 | |
1b+3b | N1C1-N3C2 | 2.14 | 2.09 | 2.11 | 0.05 | 140.1 | 150.4 |
N1C2-N3C1 | 2.15 | 2.13 | 2.14 | 0.03 | 143.2 | 146.3 | |
N1C2-N3C3 | 2.23 | 1.94 | 2.09 | 0.29 | 140.2 | 152.3 | |
N1C3-N3C2 | 1.92 | 2.33 | 2.12 | –0.41 | 140.5 | 153.9 | |
1b+3c | N1C1-N3C2 | 2.13 | 2.13 | 2.13 | 0.00 | 140.3 | 153.9 |
N1C2-N3C1 | 2.21 | 1.95 | 2.08 | 0.26 | 138.7 | 151.0 | |
N1C2-N3C3 | 1.95 | 2.27 | 2.11 | –0.33 | 141.7 | 147.3 | |
N1C3-N3C2 | 2.14 | 2.09 | 2.11 | 0.05 | 139.2 | 152.0 |
δEdist (kJ/mol) | |||||
---|---|---|---|---|---|
Reaction | Isomer | δEint (kJ/mol) | Total | Azide | Allene |
2a+3a | N1C1-N3C2 | 0 | 0 | 0 | 0 |
N1C2-N3C1 | 4.4 | 4.8 | 11.6 | –6.8 | |
2b+3a | N1C1-N3C2 | 0 | 0 | 0 | 0 |
N1C2-N3C1 | –2.7 | 27.7 | 22.5 | 5.3 | |
1a+3a | N1C1-N3C2 | –1.1 | 2.5 | 9.8 | –7.3 |
N1C2-N3C1 | 0 | 0 | 0 | 0 | |
N1C2-N3C3 | 11.9 | –8.1 | 3.8 | –11.9 | |
N1C3-N3C2 | 15.6 | –10.2 | 3.8 | –13.9 | |
1b+3b | N1C1-N3C2 | 13.4 | 1.2 | 18.0 | –16.8 |
N1C2-N3C1 | 0 | 0 | 0 | 0 | |
N1C2-N3C3 | 25.4 | –22.4 | 12.7 | –35.1 | |
N1C3-N3C2 | 43.0 | –39.0 | 9.9 | –49.0 | |
1b+3c | N1C1-N3C2 | 15.5 | –1.2 | 13.8 | –15.0 |
N1C2-N3C1 | 0 | 0 | 0 | 0 | |
N1C2-N3C3 | 24.9 | –23.0 | 7.2 | –30.2 | |
N1C3-N3C2 | 46.1 | –44.9 | 2.5 | –47.3 |
M08-HX | ωB97X-D | B3LYP | Exp | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Reaction | Isomer | δΔH‡ (kJ/mol) | Y (%) | δΔH‡ (kJ/mol) | Y (%) | δΔH‡ (kJ/mol) | Y (%) | Y (%) | ||||
2a+3a | N1C1-N3C2 | 0 | 96 | 0 | 97 | 0.0 | 99 | 100 | ||||
N1C2-N3C1 | 9.5 | 4 | 10.0 | 3 | 13.7 | 1 | 0 | |||||
2b+3a | N1C1-N3C2 | 0 | 100 | 0.0 | 100 | 0.0 | 100 | 89 | ||||
N1C2-N3C1 | 24.9 | 0 | 22.9 | 0 | 22.3 | 0 | 11 | |||||
1a+3a | N1C1-N3C2 | 2.0 | 27 | 2.4 | 24 | 1.6 | 24 | 10 | ||||
N1C2-N3C1 | 0.0 | 54 | 0 | 56 | 3.6 | 12 | 90 | |||||
N1C2-N3C3 | 4.1 | 13 | 4.1 | 13 | 2.0 | 21 | 0 | |||||
N1C3-N3C2 | 6.1 | 7 | 6.5 | 6 | 0 | 43 | 0 | |||||
1b+3b | N1C1-N3C2 | 15.7 | 0 | 19.5 | 0 | 19.7 | 0 | 0 | ||||
N1C2-N3C1 | 0 | 66 | 3.9 | 17 | 19.4 | 0 | 100 | |||||
N1C2-N3C3 | 2.8 | 25 | 0 | 69 | 6.0 | 10 | 0 | |||||
N1C3-N3C2 | 5.6 | 9 | 4.4 | 14 | 0 | 90 | 0 | |||||
1b+3c | N1C1-N3C2 | 15.4 | 0 | 19.6 | 0 | 23.5 | 0 | 0 | ||||
N1C2-N3C1 | 0 | 51 | 5.4 | 8 | 28.1 | 0 | 0 | |||||
N1C2-N3C3 | 1.6 | 28 | 0 | 58 | 8.8 | 4 | 100 | |||||
N1C3-N3C2 | 2.6 | 20 | 1.5 | 34 | 0 | 96 | 0 |
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Molteni, G.; Ponti, A. The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity? Molecules 2021, 26, 928. https://doi.org/10.3390/molecules26040928
Molteni G, Ponti A. The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity? Molecules. 2021; 26(4):928. https://doi.org/10.3390/molecules26040928
Chicago/Turabian StyleMolteni, Giorgio, and Alessandro Ponti. 2021. "The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity?" Molecules 26, no. 4: 928. https://doi.org/10.3390/molecules26040928