Methine/methylene/methyl

The method shows selectivity between diastereotropic methylene C-H bonds, permitting enantioselective construction. The C-H insertion proceeds with retention of configuration and the order of reactivity of the C-H sites was found to be methine>methylene>methyl. Interestingly, allylic and benzylic C-H were found to be less reactive than aliphatic C-H. These results are presumably being due to a delicate balance between steric and electronic effects [92]. 

Figure 21 Expansion of the aliphatic region of the HSQC-1,1-ADEQUATE spectrum of the CDK-2 inhibitor dinaciclib (48). The connectivity network is traced out for the 2-(P-hydroxyethyljpiperidine moiety contained in the structure. Methylene resonances are inverted and plotted in grey methine and methyl resonances have positive intensity and are plotted in black.

Of the multitude of ID 13C NMR experiments that can be performed, the two most common experiments are a simple broadband proton-decoupled 13C reference spectrum, and a distortionless enhancement polarization transfer (DEPT) sequence of experiments [29]. The latter, through addition and subtraction of data subsets, allows the presentation of the data as a series of edited experiments containing only methine, methylene and methyl resonances as separate subspectra. Quaternary carbons are excluded in the DEPT experiment and can only be observed in the 13C reference spectrum or by using another editing sequence such as APT [30]. The individual DEPT subspectra for CH, CH2 and CH3 resonances of santonin (4) are presented in Fig. 10.9. 

Fig. 10.9. Multiplicity edited DEPT traces for the methine, methylene and methyl resonances of santonin (4). Quaternary carbons are excluded in the DEPT experiment and must be observed in the 13C reference spectrum or through the use of another multiplicity editing experiment such as APT.

Fig. 10.15. Pulse sequence for the multiplicity-edited gradient HSQC experiment. Heteronuclear single quantum coherence is created by the first INEPT step within the pulse sequence, followed by the evolution period, t . Following evolution, the heteronuclear single quantum coherence is reconverted to observable proton magnetization by the reverse INEPT step. The simultaneous 180° XH and 13C pulses flanked by the delays, A = l/2( 1 edits magnetization inverting signals for methylene resonances, while leaving methine and methyl signals with positive phase (Fig. 16A). Eliminating this pulse sequence element affords a heteronuclear shift correlation experiment in which all resonances have the same phase (Fig. 16B).

Using strychnine (1) as a model compound, a pair of HSQC spectra are shown in Fig. 10.16. The top panel shows the HSQC spectrum of strychnine without multiplicity editing. All resonances have positive phase. The pulse sequence used is that shown in Fig. 10.15 with the pulse sequence operator enclosed in the box eliminated. In contrast, the multiplicity-edited variant of the experiment is shown in the bottom panel. The pulse sequence operator is comprised of a pair of 180° pulses simultaneously applied to both H and 13C. These pulses are flanked by the delays, A = l/2(xJcii), which invert the magnetization for the methylene signals (red contours in Fig. 10.16B), while leaving methine and methyl resonances (positive phase, black contours) unaffected. Other less commonly used direct heteronuclear shift correlation experiments have been described in the literature [47]. 

Figure 13.6 is the proton-decoupled carbon-13 NMR distortionless enhancement of polarization transfer (DEPT) spectra of poly(methyl-l-pentene) [29]. This experiment, after data manipulation, separates the methine, methylene, and... 

DEPT Spectra Identifying Quaternary, Methine, Methylene and Methyl Carbons... 

DEPT 90 is rarely used, as it is less differentiating, with all methine, methylene and methyl signals being positive. 

Woessner47 has also treated the case of a methyl group attached to an axially symmetric ellipsoid, whereas Levy et al.66 derived equations for the methyl internal rotation superposed on a fully anisotropic motion. The effect of anisotropic reorientation can dramatically alter the relationship between rigidly held methine, methylene, and methyl C—H vectors. Deviation from the ratio T,(CH)/ T,(CH3) = 3 can be considerable, depending on the relative orientation of C—H vectors with respect to the principal diffusion axes. 

The other experiment worth mentioning, which, by the way, is also obsolete, is the attached proton test or APT. This experiment is based on the different magnitudes of Tl—13C coupling for methine, methylene, and methyl groups. By adjusting certain delays in the pulse sequence (not given), quaternary and methylene carbons could be phased up, and methine and methyl carbons could be phased down. Since phase is arbitrary, this order could be reversed. This ability of distinguishing... 

Figure 5 18 Spectral editing of the 75.6 MHz C spectruni of the trisaccharide gentamycin by the DEPT sequence. The bottom spectrum contains resonances of all carbons with attached protons, and the ascending spectra are respectively of the methine, methylene, and methyl carbons. (Courtesy of Bruker Instruments, Inc.)...

The spectra shown in this problem provide relatively routine practice. In the DEPT spectra, the methine and methyl carbons give positive peaks and methylene carbons negative peaks at the top. Only methine carbons are in the middle, and a full spectrum of all carbons is at the bottom. The H spectra were recorded at 300 MHz and the spectra at 75 MHz. The spectra are as follows ... 

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