Conjugate Hydrogen-transfer Reactions

Cascades Initiated by Conjugate Hydrogen-transfer Reaction... 

Scheme 7.46 Cycle-specific catalysis in several tandem processes initiated by conjugate hydrogen-transfer reaction.

The asymmetric organocatalytic enantioselective conjugate hydrogen transfer reaction is clearly inspired by the mode of action in biological processes, in which reductions are accomplished by enzymes using hydride reduction cofactors like NADH. 

The chemoselectivity in the hydrogen transfer reaction is the same already observed in H2 addition conditions in the presence of C11/AI2O3. Thus, the conjugated enone is selectively hydrogenated while the saturated keto-group remains unchanged. Also regioselectivity is the same and the olefinic bond is reduced before the carbonylic one. 

Upon UV irradiation in hydrocarbon solution, the hexacarbonyls of chromium, molybdenum, and tungsten react differently with conjugated dienes like 1,3-butadiene (la), ( )-l,3-pentadiene (lb), 2-methyl-1,3-butadiene (lc), ( , )-2,4-hexadiene (Id), ( )-2-methyl-l,3-pentadiene (le), 2-ethyl-1,3-butadiene (If), or 1,3-cyclohexadiene (Ig). Chromium hexacarbonyl (2) yields, with the acyclic dienes la-lf, tetracarbonyl-r/2-dienechromium(0) complexes (3a-3f) in a smooth reaction (8-10). With 1,3-cyclohexadiene, in addition to 3g, dicarbonylbis(>/4-l,3-cyclohexadiene)chromium(0) (4g) is obtained [Eqs. (7) and (8)j. During chromatography on silica gel, the 1,3-cyclohexadiene complex 3g dismutates readily to [Cr(CO)6] and 4g [Eq. (9)]. Under the same conditions with 2 1,3-cyclopentadiene (lh) yields, in a hydrogen-transfer reaction, the stable dicarbonyl- / 5-cyclopentadienyl-r/ 3-cyclopent-enylchromium (5) (11-13) [Eq. (10)]. 

A number of hydrogen-transfer reactions involving carbonyl groups are known in organic chemistry however, these are for the most part limited to liquid-phase, homogeneously catalyzed systems. In this paper there is described a vapor-phase surface-catalyzed reaction which like the liquid-phase aluminum alkoxide catalyzed reductions of Meerwein-Ponndorf-Verley (J) will selectively reduce a carbonylic group in conjugation with a carbon-carbon double bond. 

Scheme 7.44 Cascade conjugate hydrogen transfer/intramolecular Michael reaction and application to the total synthesis of (+ )-ricciocarpin A.

The possible reaction mechanism for a cascade olefination-hydrogenation reaction is illustrated in Scheme 1.21. First, the reaction of proline with ciis-isomer 67 generates the iminium cation 68, which reacts with electrophile 64 via a Mannich-type reaction to generate Mannich product 69. A retro-Mannich or base-induced elimination reaction of amine 69 would furnish active olefin 70. The subsequent hydrogen-transfer reaction is dependent on the electronic nature of the in situ-generated conjugated system or, more precisely, the HOMO-LUMO gap of reactants 65 and 70. 

Any anion of a weak acid, including the anions of polyprotic acids, is a weak base. The acid-base properties of monoanions of polyprotic acids are complicated, however, because the monoanion is simultaneously the conjugate base of the parent acid and an acid in its own right. For example, hydrogen carbonate anions undergo two proton-transfer reactions with water ... 

The hydrogen transfer from different secondary alcohols to a steroidic conjugated enone and a saturated ketone in the presence of CU/AI2O3 has been investigated. The stereochemical pathway of the reaction has been studied and the results are compared with those obtained by conventional molecular hydrogen addition in the presence of the same catalyst. 

This observation can be used to derive a possible reaction mechanism for the hydrogen transfer process. We assume that the first step is the dehydrogenation of the alcoholic group, followed by isomerization of the unsaturated ketone to the conjugated one ... 

Chemoselective reduction of conjugated enones to allylic alcohols via hydrogen transfer from propan-2-ol over metal oxides is investigated in vapour phase conditions. The unique ability of Mgo to reduce exclusively carbonyl group is observed. However, because of the high basicity of MgO side reactions are present. It is shown that by doping the Mgo catalyst with HC1 a significant decrease of its basicity occurs and consequently side reactions are minimized. 

Reduction of ketones and aldehydes by hydrogen transfer from alcohols is catalyzed by a variety of oxides [7,10]. For example, alumina catalysts turned out to be active in this reaction both in the gas-solid [11,12] and liquid-solid conditions with the alcohol preadsorbed on the catalyst [13], Also zeolites [14] and hydroxyapatite [15] have been employed in this reaction. However, a,/9 conjugated ketones resulted to be quite resistant to the reduction and poor yields of allylic alcohols or only saturated ketones could be obtained [10-13]. 

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