Carbonyl groups, reduction

Thus, reduction of the bicyclic derivatives 25 (RR = CH2 RR = CH=C(Ph)) affords the corresponding 26a-type products, while hydrogenation of 2-ethoxy-3-acetylpyridine gives, along with the carbonyl group reduction product, the imine isomer 26b (R = Me, R = Et). These results were explained by the so-called internal strain effect, e.g., by steric repulsion between the nitrogen and oxygen lone pair in rotationally restricted bicyclic derivatives or between the 2 and 3 substituents. 

Figure 19.7 Mechanism of carbonyl-group reduction by nucleophilic addition of "hydride ion" from NaBH4 or LiAIH4.

The Meerwein-Ponndorf-Verley reaction is a classic method for ketone/ aldehyde carbonyl group reduction, which involves at least 1 equivalent of aluminum alkoxide as a promoter. In this reaction, the hydrogen is transferred from isopropanol to the ketone/aldehyde substrate, so the reaction can also be referred to as a transfer hydrogenation reaction. 

Derivatization of carbonyl groups (reduction or formation of N,N-dimethyl-hydrazones or oximes)... 

Unsaturated ketones of all kinds can be converted to saturated ketones, to unsaturated alcohols, to saturated alcohols, to alkenes and to alkanes. If the double bond is conjugated with the carbonyl group reduction usually takes place more readily and may give, in addition to the above products, e-diketones formed by coupling at j -carbons. 

Figure 17 (a) Crown ether based cytochrome P4S0 model (b) alcohol dehydrogenase model (c) proposed transition state in carbonyl group reduction by 1,4-dihydropyridine-containing crown ethers... 

Inasmuch as flavins can accommodate two electrons but possess a relatively stable one-electron intermediate, an obvious question which can be asked of any flavin-mediated two electron redox reaction is whether or not the mechanism includes the radical species on a direct line between reactants and products. The mere observation of semiquinones in a reaction mixture is not sufficient evidence for their intermediacy, due to the existence of side reactions such as comproportionation (F -I- FH2 2 FH-) which can generate radicals rapidly. Bruice has discussed this question from a physical-organic point of view and concluded that there must exist a competition between one-electron and two-electron processes and that the actual mechanism should be determined mainly by the free energy of formation of substrate radical and the nucleophilicity of the substrate. Bruice has analyzed a variety of systems which he feels should proceed via one-electron mechanisms among these are quinone and carbonyl group reduction by FH2... 

Borane ). This reagent is commercially available or prepared by hydroboration of (-)-a-pinene (16) with 9-BBN (17).10 The stereoselectivity of carbonyl group reduction with (S)-Alpine Borane is explained via six-membered transition state 18. 

The above described total synthesis features the first enantiodivergent approach to (+)- and (—)-scopadulcic acid A. The central transformations are the stereoselective carbonyl group reduction with (S)-Alpine Borane , the use of enolization stereoselection to dictate which enantiomer is produced, and the palladium-catalyzed bis-Heck cyclization which occurs with complete stereo- and regiocontrol to establish the scopadulan scaffold. 

In 1979, Pelletier and co-workers reported (203) a method for selective reduction of the oxazolidine ring of C20-diterpenoid alkaloids in the presence of a ketone or an a,/ -unsaturated carbonyl group. Reduction of atisinone (225) with sodium cyanoborohydride at pH 6-7 at room temperature furnished dihydroatisinone (441) in almost quantitative yield. They generalized this reduction method by using various alkaloid derivatives containing either an a,/l-unsaturated ketone or a simple ketone moiety. 

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. 10.23. Asymmetric carbonyl group reduction with the Noyori reagent Note that the chirality of the reducing agent resides in the ligand but that the aluminum atom is not a stereocenter.

The stereoselectivities of the carbonyl group reductions with Alpine-Borane (Figure 10.24) or with Brown s chloroborane (Figure 10.25) are explained as shown in the for-... 

Fig. 10.24. Asymmetric carbonyl group reduction with Alpine-Borane (preparation Figure 3.27 for the "parachute-like" notation of the 9-BBN part of this reagent see Figure 3.21). The hydrogen atom that is in the cis-position to the boron atom (which applies to both ft- and /T-H) and that after removal of the reducing agent leaves behind a tri- instead of a disubstituted C=C double bond (which applies to ft-, but not / -H) is transferred as a hydride equivalent. In regard to the reduction product depicted in the top row, the designation S of the configuration relates to the aryl-substituted and R to the Rtert-substituted propargylic alcohol.

Fig. 10.25. Asymmetric carbonyl group reduction with diisopinocampheylchloroborane [Brown s chloroborane, (IPC)2BCL]. Concerning the reduction product depicted in the top row, the designation 5 of the configuration relates to the aryl-substituted and R to the Rttrt-substituted propargylic alcohol.

Fig. 10.26. Catalytic asymmetric carbonyl group reduction according to Corey and Itsuno.

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.

Fig. 8.18. Asymmetric carbonyl group reduction with the Noyori reagent.

Although borane appears superficially similar to borohydride, it is not an ion and that makes all the difference to its reactivity. Whereas borohydride reacts best with the most electrophilic carbonyl groups, borane s reactivity is dominated by its desire to accept an electron pair into its empty p orbital. In the context of carbonyl group reductions, this means that it reduces electron-rich carbonyl groups fastest. The carbonyl groups of acyl chlorides and esters are relatively electron-poor (Cl and OR are very electronegative) borane will not touch acyl chlorides and reduces esters only slowly. But it will reduce amides. 

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