Chemoselective carbonyl group

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.

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 combination of thionation by Lawesson s reagent [98] of oxoenamino-ketones 96 with normal electron-demand Diels-Alder reaction of conjugated aldehydes allows a variety of thiopyrans 97 to be synthesized by a regio-selective and chemoselective one-pot methodology [99] (Equation 2.28). Thionation occurred at the more electrophilic ketonic carbonyl group. O O... 

It turned out that the Friedel-Crafts reaction and the chlorination can be done in the same pot. The vhlorination needs to be chemoselective as reaction on -.he methyl group or next to the carbonyl group could ccur. Lewis acid catalysis Is the answer. 

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,... 

This is nearly a Diels-Alder adduct and removal of the extra CHg group gives a Dlels-Alder adduct (2). The reaction must be chemoselective addition of CH2N2 to one carbonyl group only of (2). This is most easily achieved from the anhydride (3). 

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 chemoselectivity of Schwartz s reagent (1) toward alkynes, alkenes, nitriles, and carbonyl groups, and thus its general functional group compatibility, can be modulated. However, it is important to keep in mind that the presence of functional groups may have regiochemical consequences on the hydrozirconation reaction. 

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]. 

It is worthwhile emphasising here that the observed chemoselectivity is due to the fact that enolethers are better electrophiles than the free carbonyl groups. In fact, the ketoacetal 15, obtained by chromatography, is an equilibrium 60 40 mixture of methyl epimers at C(4) in which the desired a-epimer 5 is the predominant isomer. However, the pure compound 5. could be obtained in good yields by recrystallisation from hexane (m.p. 117-118 °C) and re-equilibration-crystallisation recycling of the remaining mixmre 15 in the mother liquor. 

The less hindered peripheric secondary hydroxyl group of the key intermediate 28 was chemoselectively tosylated (29), submitted to an internal Wharton-Grob fragmentation (30). After attack on the carbonyl group (3i) with methyllithium and activation of the secondary alcohol as the corresponding tosylate, the resulting... 

The excellent chemoselectivity achieved with catalyst 153r may be attributed to its steric properties the bulky 3,3 -silyl substituents (R = SiPhj) ensure an effective shielding of the carbonyl group and thus prevent 1,2-addition. In the presence of catalyst 153r (5 mol%), the reaction of A-methylindoles 151 and p,y-unsaturated a-ketoesters 152 furnished the 1,4-addition products 155 in moderate to good yields and enantioselectivities (43-88%, 80-92% ee) (Scheme 64). 

In continuation of our efforts to explore the utility of the SAMP/RAMP hydra-zone methodology, we developed the first asymmetric synthesis of a-phosphino ketones via formation of a carbon-phosphorus bond in the a-position to the carbonyl group [70]. The key step of this asymmetric C—P bond formation is the electrophilic phosphinylation of the ketone SAMP hydrazone 87, giving rise to the borane-adduct of the phosphino hydrazone 88 with excellent diastereoselectiv-ity (de = 95-98%). Since these phosphane-borane adducts are stable with respect to oxidation, the chemoselective cleavage of the chiral auxiliary by ozonolysis leading to the a-phosphino ketones (R)-89 could be accomplished with virtually no racemization. Using RAMP as a chiral auxiliary, the synthesis of the enantiomer (S)-89 was possible (Scheme 1.1.25). 

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