Aldol hydrogen-mediated

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

Scheme 4 syn-Diastereoselective intermolecular hydrogen-mediated aldol coupling employing cationic Rh catalysts ligated by tri-2-furylphosphine... 

Scheme 6 Complementary regioselectivities in direct aldol couplings of 2-butanone and corresponding hydrogen-mediated reductive aldol couplings of MVK...

Scheme 18 Hydrogen-mediated reductive aldol reaction...

Table 22.2 Catalytic hydrogen-mediated reductive aldol cyclization of keto-enones.

Table 22.3 Use of phenyl vinyl ketone (PVK) in intermolecular hydrogen-mediated reductive aldol coupling.

Thus far, the use of acrylates and related acyl derivatives as nucleophilic partners in hydrogen-mediated reductive aldol coupling has been unsuccessful due to competitive conventional hydrogenation. Although the mechanistic basis of these results remains unclear, it may be speculated that for acrylates and struc-... 

Jung, C.-K., Krische, M. J. (2006). Asymmetric induction in hydrogen-mediated reductive aldol additions to a-amino aldehydes catalyzed by rhodium Iniramoleeular hydrogen-bonding. Jonmal of the American Chemical Society, 128,17051-17056. 

A possible mechanism for the P-alkylation of secondary alcohols with primary alcohols catalyzed by a 1/base system is illustrated in Scheme 5.28. The first step of the reaction involves oxidation of the primary and secondary alcohols to aldehydes and ketones, accompanied by the transitory generation of a hydrido iridium species. A base-mediated cross-aldol condensation then occurs to give an a,P-unsaturated ketone. Finally, successive transfer hydrogenation of the C=C and C=0 double bonds of the a,P-unsaturated ketone by the hydrido iridium species occurs to give the product. 

Momiyama and Yamamoto have recently demonstrated that acid cocatalysts can even influence the outcome of enamine-mediated reactions [63]. In their studies of the acid-catalyzed O- and A-nitroso aldol reaction, they found that the nature of the acid catalyst dictates the regioselectivity of the reaction between preformed enamine species A carboxylic acid catalyst promoted the 0-nitroso aldol reaction whereas a hydrogen bonding catalyst catalyzed the formation of an A-adduct, both in high enantioselectivities(Scheme 10). 

When DHAP-dependent aldolases are used as catalyst of the aldol reaction, a phosphorylated azido or amino polyhydroxyketone is obtained. The phosphate may be cleaved enzymatically or reductively cleaved under the hydrogenation conditions of the next step in which the azide is reduced to the amine. Intramolecular imine formation occurs spontaneously when the azide is reduced. The intramolecular reductive amination is the second key step of the aldolase-mediated synthesis of iminocyclitols. In general, delivery of hydrogen onto five- and six-membered ring imines occurs from the face opposite to the C4 hydroxyl group. 

Heteroatom-substituted carbohydrates are efficiently assembled by the enzymatic aldol condensation of DHAP with an appropriately appended aldehyde. Iminocyclitols that are inhibitors of glycosidases, such as deoxynojirimycin and deoxymannojirimycin, are simply prepared by condensation of azo-substituted aldehydes under the FDP protocol followed by dephosphorylation and palladium mediated reductive animation (Scheme 5.18a).39 In addition a number of polyhydroxylated pyrrolidines that are efficient glucosidase inhibitors have been synthesized by this chemo-enzymatic strategy (Scheme 5.18 ).1" 30,40 If the palladium mediated hydrogenation is done in the presence of hydrochloric acid, an amino-sugar intermediate is formed as its hydrochloride salt. Treatment with base then forms polyhydroxylated imines, instead of iminocyclitols (Scheme 5.19).41... 

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