Chemoselective reduction of keton

Very recently, a spectacular improvement in carbonyl reduction chemistry was achieved by Noyori, Ohkuma, and co-workers (Scheme 2-47). They demonstrated that the three-components reduction system, BINAP (15)-Ru(II), 1,2-diamine and KOH is crucial for the chemoselective reduction of ketone carbonyls with H2 in the presence of olefinic units. The extremely efficient reaction conditions [Ru(II) catalyst, 0.5 mol% H2, 1 8 atm 28 "C i-PrOH-toluene] render the reduction quite practical, bringing about almost quantitative yields as well as absolute che-... 

Thus, chemoselective reductions of ketones have been achieved in the absence of solvent 5. In general these reactions are performed at room temperature using 40-100% excess Alpine-Borane and typical ketones are reduced in 7-14 days. 

Aluminum chloride hexahydrate An efficient and versatile reagent in organic synthesis (reductive cleavage of2,l-benzisoxazoles and isoxazo-hdines, chemoselective reduction of ketones and of C=C bonds in a,P-unsaturated carbonyl compounds, deoxygenation of N-oxides, dehydration) 13ARK(1)243. 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

A stereochemical issue of great importance presents itself here. In the chemoselective reduction of the two ketone carbonyls at C-5 and C-8 in 6, the addition of hydride takes place on the same side... 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

Yu J-Q, Wu H-C, Ramarao C, Spencer JB, Ley SV 2003) Transfer hydrogenation using recyclable polyurea-encapsulated palladium efficient and chemoselective reduction of aryl ketones. J Chem Soc Chem Commun 678-679... 

This was the first example of catalytic chemoselective reduction of a,/ -unsatu-rated ketones to allylic alcohols by hydrogen transfer and, unusually, did not require the use of a basic co-catalyst. 

Chemoselective reduction of aldehydes.1 Aldehydes can be reduced in the presence of ketones by 1 with 98-100% chemoselectivity. This chemoselectivity is the highest reported for this 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.

The Cp2TiCl/H20 combination can also be used for the chemoselective reduction of aromatic ketones. The reaction discriminates between ketones and alkenes, between ketones and esters and, remarkably, between conjugated and non-conjugated ketones [80]. There is strong evidence that this reduction proceeds via ketyl-type radicals, which are finally reduced by H-atom transfer from 42 [81]. Under dry conditions, titanium-promoted ketyl radicals from aromatic ketones can be used for intermolecular and intramolecular cross-coupling of ketones [82], Thus, depending on whether water is added or not, complementary and versatile synthetic procedure protocols are available. 

Chemoselective reductions. The reactivity of NaBH4 can be decreased by use of a lower temperature or by a mixed solvent such as methanol or ethanolic methylene chloride. This simple strategy can be used to effect selective reduction of ketones in the presence of enones,1 and of aldehydes in the presence of ketones. ... 

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.

Dichloroindium hydride (Cl2InH), generated by the reaction of InCl3 with tributyltin hydride, is also successfully used for the reduction of carbonyl compounds and for the debromination of alkyl bromides.366 This reductant has features such as the chemoselective reduction of functionalized benzaldehydes, chelation-controlled reduction of benzoin methyl ether, and 1,4-reduction of chalcone. The stable carbene and tertiary phosphine adducts of indium trihydride, InH3 CN(Mes)CH=CHN(Mes) and InH3 P(c-G6H11)3, reduce ketones to alcohols (Equation (90)).367... 

Catalytic hydrogenation reduces the imine (as the protonated iminium ion) but not the ketone from which it is formed. This chemoselectivity (reduction of iminium ions but not ketones) is also displayed by sodium cyanoborohydride and we can add NaCNBH3 to complete our table of reactivity, if we insert imines at the left-hand end. 

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. 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

The reactivity of boranes is dominated by the desire to accept an electron pair into the empty p-orbital. Therefore boranes reduce electron-rich carbonyl groups fastest. In the context of carboxylic acid reduction a triacylborate 35 is formed first. Compared to, for example, ketones, esters are less electrophilic because of conjugation between the carbonyl group and the lone pair of the sp -hybridized oxygen atom. However, in the case of boron esters such as 35, the oxygen next to the boron has to share its lone pair between the carbonyl group and the empty p-orbital of the boron. This fact makes them considerably more reactive than normal esters and allows the chemoselective reduction of carboxylic acids in the presence of esters or acyl chlorides. 

The facile reduction of the -COOH group by BHj THF or BH3 SMej has been employed for chemoselective reductions of the carboxyl group in the presence of ester or lactone functionalities using a stoichiometric quantity of the borane. The carbonyl group in triacylboranes resembles the reactivity of an aldehyde or a ketone more than of an ester (ester resonance) due to electron delocalization from the acyl oxygen into the p orbital of boron. 

Some amino alcohols react with borane to generate oxazaborolidines, which have been mainly used in asymmetric reduction of ketones (Section 3.2.3) and imines (Section 3.3.1) [NNl, S3]. In addition, they can also perform some chemoselective reductions [IWl]. 

Esters are much less sensitive than ketones to Zn(BH4)2 or cyanoborohydrides [PSl], and the selective reduction of the ketone groups of a- and P-ketoesters can be accomplished without problems (Section 3.2.4). Moreover, Zn(BH4)2 in DME under sonication reduces acetates or cyclohexanecarboxylates while benzoates are left untouched [R3]. The chemoselective reduction of the acetate residue of 3.163 can be performed under these conditions (Figure 3.55). 

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