Carbon compound protonation

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

Available carbon and proton data are also provided for these compounds in the same scheme. 

Proton and Carbon Spectra. Proton and carbon NMR data, including 31P chemical shift and P—C coupling constants for the above compounds are given in Scheme 3.27. 

Carbon and Proton NMR Spectra of Trifluorovinyl Compounds. Scheme 6.31 provides the carbon and proton NMR data for a few trifluorovinyl compounds. 

Another example which probably comes into this category is provided by the anions of the interesting spirans (III) where M = C or Si 29). For the Carbon compound the sum of the proton coupling constants in the e.s.r. spectrum of the monoanion is 21 gauss while for the Silicon com-... 

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

Compounds with a low HOMO and LUMO (Figure 5.5b) tend to be stable to selfreaction but are chemically reactive as Lewis acids and electrophiles. The lower the LUMO, the more reactive. Carbocations, with LUMO near a, are the most powerful acids and electrophiles, followed by boranes and some metal cations. Where the LUMO is the a of an H—X bond, the compound will be a Lowry-Bronsted acid (proton donor). A Lowry-Bronsted acid is a special case of a Lewis acid. Where the LUMO is the cr of a C—X bond, the compound will tend to be subject to nucleophilic substitution. Alkyl halides and other carbon compounds with good leaving groups are examples of this group. Where the LUMO is the n of a C=X bond, the compound will tend to be subject to nucleophilic addition. Carbonyls, imines, and nitriles exemplify this group. 

Fig. 3.14. Ranges of one-bond carbon-13-proton coupling constants for sp3, sp2, and sp carbons (dotted rectangles) and linear correlation between JCH and carbon s character of comparable compounds (coupling constants from Ref. [115]). The empirical relation is. /CH 500 s (Hz).

The main source of conformational information for biopolymers are the easy-to-obtain chemical shifts that can be translated into dihedral restraints. In addition, for fully 13C labeled compounds, proton-driven spin diffusion between carbons [72] can be used to measure quantitatively distances between carbons. The CHHC experiment is the equivalent of the NOESY in solution that measures distances between protons by detecting the resonances of the attached carbons. While both techniques, proton-driven spin diffusion and CHHC experiment [73], allow for some variation in the distance as determined from cross-peak integrals, REDOR [74] experiments in selective labeled compounds measure very accurate distances by direct observation of the oscillation of a signal by the dipolar coupling. While the latter technique provides very accurate distances, it provides only one piece of information per sample. Therefore, the more powerful techniques proton-driven spin diffusion and CHHC have taken over when it comes to structure determination by ss-NMR of fully labeled ligands. 

An important point about quaternary carbons requires comment. Until now, we have had no direct correlations for carbons without protons, nor have we been able to see through heteroatoms such as oxygen, nitrogen, sulfur, etc. Both the two- and three-bond coupling correlations of HMBC provide us with both types of critical information. For example, C-4 of caryophyllene oxide at 59.1 ppm has no attached protons, and so far it has only appeared in the l3C spectrum of the compound, and we know that it is quaternary... 

The halonium structure 17 was also attributed107 to protonated bromo- and chloromethane, in agreement with theoretical predictions105,106. However, in these two ions an additional interaction (stronger for the bromo than for the chloro compound) is present between the hydrogen bonded to the halogen and the carbon atom107. Protonated iodomethane, on the contrary, structurally resembles protonated methane with the proton bonded to the carbon atom. These conclusions are supported by both MI and CID data for protonated and deuterated halomethanes and by thermochemical data. 

Another possibility of a second reaction step following the protonation of the carbonyl compound is the abstraction of a carbon-bonded proton by a base, as it occurs in the enolization of a ketone (see Sect. 3.1). 

As with the reduction of carbon) compounds discussed in the previous section, wc ll defer a detailed treatment of the mechanism of Grignard reactions until Chapter 19. For the moment, it s sufficient to note that Grignard reagents ad as nucleophilic carbon anions, or carlnm ums ( R ), and that the addition of a Grignard reagent to a carbonyl compound is analogous to the addition of hydride ion. The intermediate is an alkoxide ion, which is protonated by addition of in a second step. 

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