Enol carbonates, hydrogenation

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

HYDROGENATION OF ENOL CARBONATES AND 4-MKTIIYI. KNK-N-ACYI OYA/.OI IPINONK USING [Rh((R)-BiNAP)l COMPLEXES... 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

Carbonyl-containing molecules, such as 1, with an a-carbon-hydrogen C(25p )-H(li) hybridized bond can exist as an enol tautomer 2, and their relative proportions depend on the relative stability of each tautomeric component (Scheme i)"4-i20 p j. saturated carbonyl-containing molecules, like 1, the amount of enol content 2 is quite low (<1% ... 

Another problem in comparing CP/MAS spectra to liquid-state spectra is that there may be a difference between the chemical shift of a given group in the liquid state and that in the solid state. This is particularly pronounced in the case of j8-ketones where Imashiro et al. (1982) found that the chemical shift of the carbonyl and enol carbons in a CP/MAS spectrum may be as much as 20 ppm downfield from the corresponding shift measured in DMSO solution. They attributed this to strong intermolecular hydrogen bonding in the solid. 

Muzart and coworkers have succeeded in a catalytic asymmetric protonation of enol compounds generated by palladium-induced cleavage of 3-ketoesters or enol carbonates under nearly neutral conditions [47,48]. Among the various optically active amino alcohols tested, (-i-)-e do-2-hydroxy-endo-3-aminoborn-ane (25) was effective as a chiral catalyst for the enantioselective reaction. Treatment of the P-ketoester of 2-methyl-1-indanone 58 with a catalytic amount of the amino alcohol 25 (0.3 equiv) and 5% Pd on charcoal (0.025 equiv) under bubbling of hydrogen at 21 °C gave the (P)-enriched product 59 with 60% ee... 

Several cyclic enol ethers are intramolccularly cyclopropanated using rhodium(II) acetate as a highly effective catalyst 1 7. When the connecting chain becomes too long (n = 2, 3, 4), carbon-hydrogen insertion of the carbenoid competes with the intramolecular [2 + 1] cycloaddition. However, when R is methyl and n is 2 or 3, cyclopropane formation is again the dominant... 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

It is only in these two conformations that the orbital of the developing carbon —hydrogen bond overlaps with the remainder of the enolate 7i-system. The trans transition state 2 is generally more stable than the ci.i transition state 3, and therefore the trims-prod net is usually found as the major product, as illustrated with the reduction of octalone 443. 

In most enzyme systems, enolate intermediates are stabilized by metal ion complexation. Although few good numbers are available, it appears that metal ion complexation of the oxygen of the keto and enol forms can increase the acidity of an adjacent carbon-hydrogen bond by four to six orders of magnitude. For example, complexation with lowers the ipK at C-3 of oxaloacetate from 13 to 9 (76), and a similar shift is seen with pyruvate (75). Enolates of a-keto acids can be effectively stabilized by metal complexation. For example, in the cases of pyruvic acid and oxaloacetic acid, both the keto oxygen and one of the carboxyl oxygens coordinate to the metal (Scheme 11). 

To provide support for this assignment, we examined the IR and NMR spectra of several species derived from the lithium enolate 4 (Scheme 20.5, Table 20.1). The C chemical shift at C2, along with the one-bond C2 carbon-hydrogen conpling constant (Jce)> provides a distinction between the oxygen-metallated strnctnre and the two carbon-metallated structures, whereas the C chemical... 

The first step in this scheme is a Michael addition of the nucleophile to the j5-carbon of the alkynyliodonium salt to give the ylide 102. Loss of iodobenzene from 102 gives alkylidenecarbene 103, which rearranges to alkyne 104 in the absence of external traps. This mechanism is experimentally supported by the isolation of cyclic by-products 108 besides the major products, the alkynyl esters 107 in the reaction of alkynyliodonium salt 105 with nucleophiles (equation 67). These cyclic enol ethers are the result of the insertion of the intermediate carbene 106 into the tertiary-8-carbon-hydrogen bond. 

Because the polarity of carbon-hydrogen bond is very small and exhibits very low acidity, very strong bases are required for such reactions. However, C-H bonds adjacent to substituents such as carbonyl or cyano groups are stabiUzed by resonance/induction and are more acidic. Nitrogen bases have been used effectively in these reactions to minimize the nucleophihc addition that can compete with proton removal when an organometallic compound such as n-butyllithium is used as the base. For example, methyl ketones react with Hthium diisopropylamide (LDA) to form the enolate ion (Eq. (3.4)), and even more sterically hindered amides have been used. The enolate anion is a strong base and a good nucleophile ... 

---