Shielding substituents

The importance of the o-hydroxyl moiety of the 4-benzyl-shielding group of R,R-BOX/o-HOBn-Cu(OTf)2 complex was indicated when enantioselectivities were compared between the following two reactions. Thus, the enantioselectivity observed in the reaction of O-benzylhydroxylamine with l-crotonoyl-3-phenyl-2-imi-dazolidinone catalyzed by this catalyst was 85% ee, while that observed in a similar reaction catalyzed by J ,J -BOX/Bn.Cu(OTf)2 having no hydroxyl moiety was much lower (71% ee). In these reactions, the same mode of chirality was induced (Scheme 7.46). We believe the free hydroxyl groups can weakly coordinate to the copper(II) ion to hinder the free rotation of the benzyl-shielding substituent across the C(4)-CH2 bond. This conformational lock would either make the coordination of acceptor molecules to the metallic center of catalyst easy or increase the efficiency of chiral shielding of the coordinated acceptor molecules. 

The latter procedure was used in syntheses of stable nitrile oxides such as P,P-diphenylacrylonitrile oxide and 2,6-diphenylbenzonitrile oxide (22), a series of functionally substituted 2,6-dimethylbenzonitrile oxides (29), as well as 2,4,6-triethylbenzene-l,3-dicarbonitrile oxide (29), stable bis(nitrile oxides) of a novel structure 6, in which two benzene rings, bearing hindered fulmido groups are connected with a bridge (30), tetrachloroisophthalo- and terephthalonitrile oxides (31). Stable o-sullamoylbenzonitrile oxides with only one shielding substituent were also prepared using NaOCl/NaOH in a two-phase system (20, 32). 

The results indicate that the formation of long-lived trimethyl substituted silyl cations, in the presence of aromatic solvents, as claimed by Lambert et al.95 is not feasible under these conditions. Persistent silicenium ions require sterically more shielding substituents at silicon or hypercoordinative stabilization.96 98 13C and 29Si NMR chemical shifts were calculated for a series of disilylated arenium ions 85 using density functional theory (DFT). The calculations predict consistently the unsaturated carbon atoms to be too deshielded by 8-15 ppm. Applying an empirical correction, the deviation between experiment and theory was reduced to -0.4 to 9 ppm, and the 13C NMR chemical shift of the highly diagnostic cipso is reproduced by the calculations (Ad = -3.8 to 2.7 ppm).99... 

The pyrones and thiinones show general 13C NMR spectral characteristics similar to the pyridones which reflect charge distributions in the heterocyclic rings. Thus, carbon atoms a or y to the heteroatom are deshielded relative to benzene, while those (3 are shielded. Substituent effects are in general as expected, although fewer detailed studies have been carried out in this area with the oxygen and sulfur heterocycles than with the azines. Chemical shift data for representative compounds are given in Scheme 10. 

The reason for this unexpected stereochemistry is that the tetrahedral attack of the radical is shielded by the methyl- and the L substituents in the A-strain conformation to such a degree that a reaction after rotation to a conformation where hydrogen is the shielding substituent is energetically favored. Thus, the main product is formed from the less stable but more reactive conformer. This is a case, described by the Curtin-Hammett principle, where the transition states and not the ground states govern the stereoselectivity of the reaction [20]. 

Another fluorine-containing compound used for this purpose is a-cyano-a-fluoro-p-tolylacetic acid (CFTA). The structure of this compound is shown in Figure 80, and it is used for secondary alcohols ( H NMR) and amines ( F NMR see Section 3.4.5.1). The procedure requires the preparation of the esters from the two enantiomers of CFTA and measurement of the value (5(5) - 5(i )) for the substituents (Li/ L2) of the alcohol. The assignment is based on the fact that, in the ester derived from (S)-CFTA, substituent Li is shielded by the fluorophenyl group whereas in the (i -CFTA ester, the shielded substituent is L2 (see Figure 83). 

In this way, substituent Li is shielded by the phenyl group in the ap conformer and substituent L2 is shielded in the sp conformer in the case of BPG amides (see Figure 113a). Conversely, substituent L2 is shielded in the ap conformer and substituent Li is shielded in the sp conformer in (S)-BPG amides (see Figure 113b). Because the ap population is larger than the sp population, Li is the most shielded substituent in (i -BPG amides and L2 is the most shielded substituent in (S)-BPG amides. 

From a theoretical standpoint, the different esterification shifts observed for the shielded and non-shielded substituents are explained on the basis of the conformational composition and structure of the 9-AMA esters (see Figure 46 in Section 3.1.3). In the (i -9-AMA ester of the alcohol of Figure 46, substituent Li is located under the shielding cone of the anthryl ring of the reagent in the sp conformer, whereas in conformer ap, it is not shielded. The reverse holds for substituent L2 (shielded in the minor conformer ap and unaffected in sp) and, as a result, when one compares the spectrum of an alcohol in Figure 182a with that of its (i -9-AMA derivative. 

A 2-methylthio substituent decreases the basicity of thiazole pK = 2.52) by 0.6 pK unit (269). The usual bathochromic shift associated with this substituent in other heterocycles is also found for the thiazole ring (41 nm) (56). The ring protons of thiazole are shielded by this substituent the NMR spectrum of 2-methylthiothiazole is (internal TMS, solvent acetone) 3.32 (S-Me) 7.3 (C -H) 6.95 (Cj-H) (56, 270). Typical NMR spectra of 2-thioalkylthiazoles are given in Ref. 266. 

The decreased shielding caused by electronegative substituents is primarily an inductive effect and like other inductive effects falls off rapidly as the number of bonds between the substituent and the proton increases Compare the chemical shifts of the pro tons m propane and 1 mtropropane... 

In deuterochloroform, pyrazine shows a single proton resonance at S 8.59 (72CPB2204). Vo, Vm and Vp values between pyrazine ring protons obtained from a number of pyrazine derivatives are 2.5-3, 1.1-1.4 and 0 Hz respectively, and these values do not appear to be affected by the nature of the ring substituents. Some substituent shielding parameters are shown in Table 1. 

Table 1 Substituent Shielding Parameters in Substituted Pyrazines ...

Substituent effects (substituent increments) tabulated in more detail in the literature demonstrate that C chemical shifts of individual carbon nuclei in alkenes and aromatic as well as heteroaromatic compounds can be predicted approximately by means of mesomeric effects (resonance effects). Thus, an electron donor substituent D [D = OC//j, SC//j, N(C//j)2] attached to a C=C double bond shields the (l-C atom and the -proton (+M effect, smaller shift), whereas the a-position is deshielded (larger shift) as a result of substituent electronegativity (-/ effect). 

The reversed polarity of the double bond is induced by a n electron-accepting substituent A (A = C=0, C=N, NO2) the carbon and proton in the p-position are deshielded (-A/effect, larger shifts). These substituents have analogous effects on the C atoms of aromatic and heteroaromatic rings. An electron donor D (see above) attached to the benzene ring deshields the (substituted) a-C atom (-/ effect). In contrast, in the ortho and para positions (or comparable positions in heteroaromatic rings) it causes a shielding +M effect, smaller H and C shifts), whereas the meta positions remain almost unaffected. 

The methoxy group is a +M substituent, and so shields ortho protons and C atoms in ortho positions the protons at 5 = 6.67 and 6.79 reflect this shielding. The carbonyl group as a -M substituent deshields ortho protons, and is ortho to the proton at <5// = 7.97. With the additional doublebond equivalent for a ring, 6-methoxytetralin-l-one (E) results. 

The preference for endo attack in 7,7-dimethylnorbomene is certainly steric in origin, with the 7-methyl substituent shielding the exo direction of approach. The origin of the preferred exo-attack in norbomene is more subject to discussion. A purely steric explanation views the endo hydrogens at C—5 and C—6 as sterically shieldihg the endo approach. There probably is also a major torsional effect Comparison of the exo and endo modes of reproach shows that greater torsional strain develops in the endo mode of... 

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