Hydrogen vinylic

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Depending on the substituents of l,6-enynes, their cyclization leads to 1.2-dialkylidene derivatives (or a 1.3-diene system). For example, cyclization of the 1,6-enyne 50 affords the 1.3-diene system 51[33-35]. Furthermore, the 1.6-enyne 53, which has a terminal alkene, undergoes cyclization with a shift of vinylic hydrogen to generate the 1,3-diene system 54. The carbapenem skeleton 56 has been synthesized based on the cyclization of the functionalized 1,6-enyne 55[36], Similarly, the cyclization of the 1,7-enyne 57 gives a si -mem-bered ring 58 with the 1,3-diene system. 

Figure 13 20 there are two other vinylic protons Assuming that the coupling constant between the two geminal protons in ArCH=CH2 is 2 Hz and the vicinal coupling constants are 12 Hz (cis) and 16 Hz (trans) describe the splitting pattern for each of these other two vinylic hydrogens... 

The NMR spectrum of the syn isomer shows evidence of a diamagnetic ring current, based on both the relatively low-field position of the vinylic hydrogens and the upfield shift of the methylene hydrogens. The anti isomer shows much less pronounced shifts. The X-ray crystal structure of the syn isomer shows a moderate level of bond alternation, ranging ftom 1.36 to 1.45 A (Fig. 9.4A). In the anti isomer, bond alternation is more pronounced, vith the double bond in the center ring being essentially a localized double bond (Fig. 9.4B). 

During the course of base-catalyzed exchange in O-deuterated alcohols, the vinylic hydrogen in the a position to the ketone is replaced by deuterium, in addition to the hydrogens activated by enolization. Thus, under these conditions the exchange of androst-l-en-3-one (16, R = H) gives a trideuterio derivative (18) instead of the expected 4,4-d2 analog (16, R = D). " (For other examples see compounds 13, 19, 21, 23, 26 and 27.) Incorporation of this deuterium is due to rapidly reversible alcohol addition (16 -+17) and elimination (17 18) which competes with the enolization step. " ... 

Subsbtuting vinylic hydrogen in a,P-unsaturated carbonyl compounds with vinylic fluonne does not affect their dienophilic character negatively Indeed, 3,3-difluoroacrylic acid is more reactive toward furan than its nonfluonnated counterpart [95] (equation 81) Consistent with this observation is the fact that tctrafluorobenzoquinone forms only a bis-Diels-Alder adduct m 68% yield in its reaction with cyclopentadiene at room temperature [96, 97 ... 

Malhotra et al. (5pyrrolidine enamine of 3-methyl-cyclohexanone, prepared under equilibrating conditions, is a 3 7 mixture of A and A isomers (67 and 68) on the basis of NMR spectral data. The preponderance of the A isomer in the mixture was attributed to strain between the equatorial methyl group and the vinylic hydrogen atom... 

Interestingly the pyrrolidine enamine of 3-t-butylcyclohexanone (41) consists of a 3 2 mixture of A and A isomers (79 and 80). The preference for the A isomer in this case is due to the relief of two of the four skew butane interactions, which are present in the isomer. The A isomer, owever, contains two additional interactions, i.e., one modified skew utane interaction 0.4 kcal/mole (42) and one interaction between c C-2 vinylic hydrogen atom and the ethyl portion of the t-butyl group hich is pointed toward it. 

Oxidative cleavage of an alkene with Klvln04 gives a carboxylic acid if the alkene has at least one vinylic hydrogen (Section 7.9). 

Stames el al.I7 have provided support for the above mechanism (Scheme 6.29) by determining the unsaturated chain ends (112) in low conversion PVAc by l3C NMR. They were able to distinguish (112) from chain ends that might have been formed if transfer involved abstraction of a vinylic hydrogen. The number of unsaturated chain ends (112) was found to equate with the number of -CH OAc ends suggesting that most chains arc formed by transfer to monomer. Stames et a . 13 also found an isotope effect k kD of 2.0 for the abstraction reaction with CTTpCHOiCCD as monomer. This result is consistent with the mechanism shown in Scheme 6.28 but is contrary to an earlier finding.174... 

Aldehydes, ketones, and carboxylic acids containing a hydrogens can be sulfo-nated with sulfur trioxide. The mechanism is presumably similar to that of 12-4. Sulfonation has also been accomplished at vinylic hydrogen. 

Alkenes. When the substrate molecule contains a double bond, treatment with chlorine or bromine usually leads to addition rather than substitution. However, for other radicals (and even for chlorine or bromine atoms when they do abstract a hydrogen) the position of attack is perfectly clear. Vinylic hydrogens are practically never abstracted, and allylic hydrogens are greatly preferred to other positions of the moleeule. Allylic hydrogen abstraction from a cyclic alkenes is usually faster than abstraction from an acyclic alkene. ... 

The trans cinnamic acid and phenyl propiolic acid data involve fits of essentially the same precision at o-, m-, and p- positions (SD =. 05 . 02). However, the RMS of these sets is quite low, and consequently, / values of. 200 prevail. The interpretation of these results is therefore uncertain. To the extent that the results of Table VII are meaningful, it is of particular interest that Kj =p°Ip =. 68 for the phenyl propiolic acid, whereas for the tram cinnamic acids, K° = 1.02. These results suggest that in contrast to the ortho substituted benzoic acids, the lines of field forces in the ortho substituted phenyl propiolic acids do (partly at least) penetrate regions of hi dielectric solvent. The results for the tram cinnamic acids would then indicate some (but not complete) exclusion of solvent resulting from the presence of the vinyl hydrogens. These interesting results from the application of eq. (1) clearly need to be confirmed by additional studies. 

The vinyl + hydrogen atom reaction is a rich example of competition between abstraction and addition-elimination pathways... 

In the above spectrum, the vinylic hydrogen appears as a pentet at 8 6.14 with a three-bond F—H coupling constant of 9 Hz the allylic... 

As a typical example, Fig. 1 shows the H NMR NOE difference spectra of the monomer 3, 1-phenyl-7,7-dihexyl-8,8-dimethyl-7,8-disilabicyclo[2.2.2]octa-2,5-diene. Irradiation of the methyl peak on silicon of the major isomer enhanced the peak intensities of the methyne (H and two vinylic hydrogens (Hb). The fact clearly indicates that the major isomer has the structure 3a. The isomer ration (7.8/1) was calculated from the relative area of methyl peaks. In a similar way, structures and isomer ratios were determined for all the monomers. Table 1 lists the results. Apparently, the ratio of the isomers a/b increased with increasing steric bulkiness of the alkyl substituents on the dichlorodisilanes, reaching to 96/4 for the di(2-methylpropyl)dimethyl-substituted derivative 5. 

From the electronic populations on the vinylic hydrogens, the acidity of vinylic C—H was estimated to be higher in cyclopropenone than in cyclopropene (0.684 e/ 0.776 e). This agrees with kinetic measurements of the H-D-exchange at n-propyl cyclopropenone23 which showed an acidity of the vinylic C—H even higher than that of the acetylenic C—H in the reference compound propargyl alcohol. 

In monomethyl and mono n-propyl cyclopropenones, the down-field shifts of CH3 and ck-CH2 groups as well as the CH2 (a/ ) separation (0.94 ppm) are somewhat larger than in the dialkyl case, but only to about 50% of the relative displacement of vinylic hydrogens (distance vinyl-H (200) versus vinyl-H (210) taken as a reference (3.70 ppm)). 

---