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Monday 22 December 2014

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FIG. 1 is a gHMBC spectrum of the borylation products of 4-chlorobenzonitrile. BELOW
 







FIG. 2 is a gHMBC spectrum of the borylation products of 4-bromobenzonitrile.
 






FIG. 3 is a gHMBC spectrum of the borylation product of 4-iodobenzonitrile.


 





FIG. 4 is a gHMBC spectrum of the borylation products of 4-methoxybenzonitrile.
FIG. 5 is a gHMBC spectrum of the borylation products of 4-thiomethylbenzonitrile.
FIG. 6 is a gHMBC spectrum of the borylation product of 4-dimethylaminobenzonitrile.
FIG. 7 is a gHMBC spectrum of the borylation product of methyl 4-cyanobenzoate.
FIG. 8 is a gHMBC spectrum of the borylation product of 4′-cyanoacetanilide.
FIG. 9 is a gHMBC spectrum of the borylation products of 1,5-dimethyl-2-pyrrolecarbonitrile.
FIG. 10 is a gHMBC spectrum of the borylation products of 5-methyl-2-furonitrile.



Regioisomer Assignment by NMR Spectroscopy:

From gHMBC NMR experiments, the two regioisomers for the borylation of 4-substituted benzonitriles can be distinguished unambiguously as in FIGS. 1 to 10. In isomer A, carbon atoms represented as C1 and C4 on the benzene ring, as well as C7 (nitrile carbon) are the three quaternary carbon atoms in the 100-170 ppm region (quaternary carbon C3 is typically not observed due to broadening from and coupling with boron). These three quaternary carbon atoms should show cross peaks due to long range H—C couplings (3JC-H), which can be observed using gHMBC spectroscopy. In the gHMBC spectrum, carbon atoms C1 and C7 should show one cross peak each to proton Hc, whereas carbon atom C4 should show two cross peaks to protons Ha and Hb. Therefore the resulting number of cross peaks for C1, C4, and C7 should be 1, 2, and 1, respectively.
In Isomer B, carbon atoms represented as C1′, C4′, on the benzene ring, as well as C7′ (nitrile carbon) are the three quaternary carbon atoms in the 100-170 ppm region (quaternary carbon C2′ is typically not observed due to broadening from and coupling with boron). These three quaternary carbon atoms should show cross peaks due to long range H—C couplings (3JC-H). In the gHMBC spectrum, carbon atoms C1′ and C7′ should show two cross peaks each, to protons Hd and He, whereas carbon atom C4′ should show only one cross peak to proton Hf. Therefore the resulting number of cross peaks for C1′, C4′, and C7′ should be 2, 1, and 2, respectively. Hence isomers A and B can be unambiguously assigned from gHMBC data.
For isomer A, with proton Hc unambiguously assigned by gHMBC, Ha and Hb can be assigned from their multiplicities. Proton Ha appears as a doublet, coupled to proton Hb with J≈2-3 Hz. Proton Hb appears as a doublet of doublets due to coupling to protons Ha and Hc. Carbon atoms C2, C6, and C5 were then assigned from the correlations in the gHMQC spectra. Carbon atom C7 (nitrile carbon) usually appears around δ 119. Depending on the substituent, carbon atom C1 was usually found shifted downfield around δ 130-170 (except in 4-iodobenzonitrile for which it appears around δ 100). Carbon atom C4 is shifted upfield, and was usually found around δ 100-115. Similarly, all the carbons of isomer B can be assigned.
In the five membered heterocycles, the 4JH-H coupling was used together with gHMBC and NOESY1D spectroscopy to identify the major isomer. Regioisomers in the fluorine containing benzonitriles were assigned by 13C spectroscopy (with the help of the fact that the boron bearing carbon is not observed due to broadening from and coupling with boron). In the case of 1,3-dicyanobenzene, 1H NMR spectroscopy was employed to assign the major and minor isomers.
Experimental Details and Spectroscopic Data EXAMPLE 1 Borylation of 4-fluorobenzonitrile
General procedure A was applied to 4-fluorobenzonitrile (242 mg, 2 mmol) and HBPin (73 μL, 64 mg, 0.5 mmol) with a reaction time of 8 h. The ratio of the two isomers in the crude reaction mixture by GC was 11:89. Kugelrohr distillation furnished a mixture of the two isomeric borylated products (88.5 mg, 72%) as a white solid. The ratio of the two isomers in the isolated product by GC was 8:92. 13C NMR spectroscopy was used to assign the major isomer as 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboryl)benzonitrile. 1H NMR (CDCl3, 500 MHz): δ (major isomer) 8.04 (dd, 4JH-F=5.4 Hz, J=2.2 Hz, 1H, Hd), 7.7 (ddd, J=8.5, 2.2 Hz, 4JH-F=4.9 Hz, 1H, He), 7.1 (t, J=8.5 Hz, 1H, Hf), 1.32 (br s, 12H), (minor isomer) 7.67 (dd, J=8.8 Hz, 4JH-F=4.9 Hz, 1H, Hc), 7.52 (dd, 3JH-F=8.5 Hz, J=2.9 Hz, 1H, Ha), 7.17 (dt, J=8.3, 2.9 Hz, 1H, Hb) 1.34 (br s, 12H); 13C NMR {1H} (CDCl3, 125 MHz): δ (major isomer) 169.0 (d, 1JC-F=261.3 Hz, C1′), 141.6 (d, 3JC-F=9.6 Hz, C3′), 137.0 (d, 3JC-F=10.5 Hz, C5′), 117.9 (nitrile C7′), 116.7 (d, 2JC-F=25.6 Hz, C6′), 108.2 (d, 4JC-F=3.8 Hz, C4′), 84.5 (C8′), 24.7 (C9′), (minor isomer) 164.2 (d, 1JC-F=257.1 Hz, C1), 135.9 (d, 3JC-F=8.8 Hz, C5), 122.8 (d, 2JC-F=21.0 Hz, C2), 118.5 (d, 2JC-F=22.2 Hz, C6), 118.1 (nitrile C7), 113.1 (C4), 85.1 (C8), 24.7 (C9); 11B NMR (CDCl3, 96 MHz): δ 29.92; 19F NMR (CDCl3, 282 MHz): δ (major isomer) −92.62 (m), (minor isomer) −104.84 (m); FT-IR (neat): 3076, 2982, 2934, 2231, 1608, 1487, 1429, 1412, 1373, 1350, 1236, 1143, 1070, 964, 852, 835, 571 cm−1; LRMS (% rel. int.): m/e (major isomer) 247 M+ (26), 232 (100), 205 (12), 188 (20), (minor isomer) 247 M+ (29), 232 (97), 206 (100), 189 (74), 148 (97), 121 (25); Anal. Cacld for C13H15BFNO2: C, 63.20; H, 6.12; N, 5.67. Found: C, 63.52; H, 6.20; N, 5.56. HRMS Calcd for C13H15BFNO2: 247.1180. Found: 247.1171.





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