Chemoselective carbonyl group reduction

Fig. 10.7. Chemoselective carbonyl group reductions, II. A chemoselective reduction of the less hindered ketone takes place on the left side, and a chemoselective reduction of the more strongly hindered ketone takes place on the right side.

Fig. 10.8. Chemoselective carbonyl group reductions, III. Reduction of a saturated ketone in the presence of an unsaturated ketone (left) and reduction of an unsaturated ketone in the presence of a saturated ketone (right).

Fig. 8.2. Chemoselective carbonyl group reductions I. On the left side a chemoselective reduction of the aldehyde takes place, whereas on the right side a chemoselective reduction of the ketone is shown.

Reductions. Carbonyl group reduction is achieved with Mg-FeCl3-6H20 in aq DMF at room temperature. For chemoselective reduction of aldehydes, the combination of Mg-SnCl2 2H20 in THF suffices. ... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

Inherent in the reduction of asymmetrically substituted cyclic imides is the problem of regiose-lectivity. Imides, in which one carbonyl group is part of a (thio)carbamate or urea function, usually show complete chemoselectivity for reduction of the other carbonyl group, indicated with an arrow. 

The chemoselectivity of the ozonolysis is all right because ozone attacks the most electron-rich double bond, that is the one furthest from the carbonyl group in (17, R=H). Reductive work-up is again needed after the ozonolysis,... 

Reduction of carbon-carbon double bond Microalgae easily reduce carbon-carbon double bonds in enone. Usually, the reduction of carbonyl group and carbon-carbon double bond proceeds concomitantly to afford the mixture of corresponding saturated ketone, saturated alcohol, and unsaturated alcohol because a whole cell of microalgae has two types of reductases to reduce carbonyl and olefinic groups. The use of isolated reductase, which reduces carbon-carbon double bond chemoselectively, can produce saturated ketones selectively. 

The Noyori reduction of various diketo esters in this series was very dependent upon the amount of add present in the reaction. Without the presence of a stoichiometric amount of add, the rate of reduction as well as the selectivity in the reduction dropped off. At higher pressures, the chemoselectivity of the reduction was poor resulting in die reduction of both alkene groups. Further, the carbonyl at C5 was never reduced under these reaction conditions but was absolutely necessary for the reduction of the C3 carbonyl. When C5 was in the alcohol oxidation state, no reduction was seen. A. Balog, unpublished results. 

In polyfunctional molecules, the elec-trophore with the least negative reduction potential is selectively cleaved [164]. A bromine atom at a carbon atom a to a carbonyl group is fairly easily reducible therefore, cpe at the potential in which this C— Br bond is reduced proceeds highly chemoselectively (Fig. 35) [164]. 

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. 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

In a bifunctional compound, if a reagent reacts with one functional group preferentially, even though the other is apparently susceptible to the reaction conditions, the reaction is said to be chemoselective. Two illustrative examples are the reduction of a carbonyl group in the presence of a cyano, nitro or alkoxycarbonyl group (Section 5.4.1, p. 519 see also Metal hydrides, Section 4.2.49, p. 445) and the acylation of an aromatic amino group in the presence of a phenolic group (Section 6.9.3, p. 984). 

Finally, this catalyst system was applied to the chemoselective, diastereose-lective, and enantioselective reduction of racemic 2-alkyl-l,3-diketones [57]. Scheme 11 shows examples of this transformation catalyzed by (R,R)-15. To minimize the effects of uncatalyzed reduction, four portions of 0.1 equivalents of modified borohydride with THFA and ethanol (i.e., total 0.4 equiv) were successively added to the substrate solution at -20°C. The selectivity of the carbonyl group at the benzylic position over the simple aliphatic carbonyl function (in... 

We shall use this synthesis as a basis for discussion on chemoselectivity in reductions. In the first step, sodium borohydride leaves the black carbonyl group of the ester untouched while it reduces the ketone (in yellow) in the last step, lithium aluminium hydride reduces the ester (in black). These chemoselectivities are typical of these two most commonly used reducing agents borohydride can usually be relied upon to reduce an aldehyde or a ketone in the presence of an ester, while lithium aluminium hydride will reduce almost any carbonyl group. 

Treatment of particular fully conjugated heterocyclic enaminediones with NaBH4 resulted in a chemoselective reduction of the keto carbonyl group, followed by a stereoselective reduction of the carbon-carbon double bond135 (Scheme 100). Catalytic hydrogenation allowed a complete reduction of the second carbonyl group. 

The presently available wide selection of complex hydrides greatly simplifies the problem of control over the chemoselectivity of reduction in polyfunctional compounds. For example, a 1,2-reduction of the carbonyl group in a,/S-... 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

Hydrostannation of carbonyl compounds with tributyltin hydride is promoted by radical initiation and Lewis or protic acid catalysis.The activation of the carbonyl group by the acidic species allows the weakly nucleophilic tin hydride to react via a polar mechanism. Silica gel was a suitable catalyst allowing chemoselective reduction of carbonyl groups under conditions that left many functional groups unchanged. Tributyltin triflate generated in situ from the tin hydride and triflic acid was a particularly efficient catalyst for the reduction of aldehydes and ketones with tributyltin hydride in benzene or 1,2-di-chloromethane at room temperature. Esters and ketals were not affected under these conditions and certain aldehydes were reduced selectively in preference to ketones. 

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