From reduction of aldehydes and ketones

From reduction of aldehydes and ketones Using aluminum-based reagents Diisobutylaluminum hydride-Tin(II) chloride-(S)-l-[l-Methyl-2-pyrrolidinyl] methylpiperidine, 116... 

Alcohols, From reduction of aldehydes and ketones (Continued)... 

The carbonyl reductases catalyze reduction of aldehydes and ketones by reduced pyridine nucleotides (NADH and/or NADPH). As mentioned earlier, alcohol dehydrogenase can perform this function in the presence of a high ratio of NADH to NAD+. Other enzymes capable of carbonyl reduction include the aldehyde and ketone reductases. The aldehyde and ketone reductases have a ubiquitous species distribution, with the enzymes present in organisms ranging from bacteria to vertebrates. The mammalian carbonyl reductases have been extensively reviewed (101). 

Much emphasis has been placed on the selectivity of quaternary ammonium borohydrides in their reduction of aldehydes and ketones [18-20]. Predictably, steric factors are important, as are mesomeric electronic effects in the case of 4-substituted benzaldehydes. However, comparison of the relative merits of the use of tetraethyl-ammonium, or tetra-n-butylammonium borohydride in dichloromethane, and of sodium borohydride in isopropanol, has shown that, in the competitive reduction of benzaldehyde and acetophenone, each system preferentially reduces the aldehyde and that the ratio of benzyl alcohol to 1-phenylethanol is invariably ca. 4 1 [18-20], Thus, the only advantage in the use of the ammonium salts would appear to facilitate the use of non-hydroxylic solvents. In all reductions, the use of the more lipophilic tetra-n-butylammonium salt is to be preferred and the only advantage in using the tetraethylammonium salt is its ready removal from the reaction mixture by dissolution in water. 

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

The reduction of aldehydes and ketones is carried out very easily. The carbonyl compound and aluminum isopropoxide, prepared from aluminum and isopropyl alcohol, are heated in boiling isopropyl alcohol solution with provision for slow distillation until no more acetone is formed. The general equation may be represented as follows. 

The time required for a reduction varies greatly with the particular aldehyde or ketone the aldehydes are usually more reactive. Quinone and cyclohexanone are reduced completely in a few minutes camphor requires twelve to twenty-four hours. The rate of reduction also depends upon the amount of reducing agent used. The length of time required for a reaction, however, usually has little effect on the final yield, since removal of the acetone which is formed ensures complete reduction in any event. Reduction of aldehydes and ketones has been carried out successfully with quantities ranging from a few milligrams to more than 500 g. 

The relatively inexpensive and safe sodium borohydride (NaBH4) has been extensively used as a reducing agent because of its compatibility with protic solvents. Varma and coworkers reported a method for the expeditious reduction of aldehydes and ketones that used alumina-supported NaBH4 and proceeded in the solid state accelerated by microwave irradiation (Scheme 7) [50]. The chemoselectivity was apparent from the reduction of frarcs-cinnamaldehyde to afford cinnamyl alcohol. 

The Meerwein-Pondorff-Verley (MPV) reduction of aldehydes and ketones to the corresponding alcohols [61] is another example of a long-standing technology. The reaction mechanism involves coordination of the alcohol reagent, usually isopropanol, and the ketone substrate to the aluminum center, followed by hydride transfer from the alcohol to the carbonyl group. In principle, the re-... 

The McMurry coupling is most useful for the intramolecular reduction of aldehydes and ketones to form cycloalkenes with ring size varying from 3 to 36. The medium and large rings are usually formed with the -configuration . 

The formation of alcohols by the reduction of aldehydes and ketones, carboxylic acids, esters and epoxides is summarized in Scheme 2.9. The change in the strength of the reducing agents, from the relatively mild sodium borohydride to the vigorous lithium aluminium hydride, reflects the difference in the electron deficiency of the carbonyl group which is being reduced. 

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. 

Figure 14. Plot of logfcobs for the acid-catalyzed reduction of aldehydes and ketones by AcrH2 in the presence of HCIO4 (2.7 x 10 M) in MeCN at 333 K vs. logfcet for the acid-catalyzed electron transfer from [Ru(bpy),il + to the same series of substrates in the presence of HCIO4 (2.0 M) at 298 K. Numbers refer to the aldehydes and ketones (1, acetaldehyde 2, propionaldehyde 3, butyraldehyde ...

Reduction of aldehydes and ketones with hydride leads to the formation of alcohols. The hydride ion can be derived from a number of reagents. 

The water-soluble iridium(III) complex, [IrCp (H20)3]2+ (Cp = p5-C5Me5) was found a suitable catalyst precursor for reduction of aldehydes and ketones by hydrogen transfer from aqueous formate [254], Under the conditions of Scheme 3.34 turnover frequencies in the range of 0.3-4.3 h-1 were determined. Of the several water-soluble substrates the cyclic cyclopropanecarboxaldehyde reacted faster than the straight-chain butyraldehyde, and aldehydes were in general more reactive than the only simple ketone studied (2-butanone). While glyoxylic acid was reduced fast, pyruvic acid did not react at all. 

This section describes the stereochemistry of mechanistically related reductions of aldehydes and ketones by hydride transfer from a sp3 carbon atom that is located ft to a metal atom (M). The following general scheme describes the reaction ... 

Indeed, by immobilization of optically active a- or )0-amino alcohols on cross-linked polystyrenes as in 6a-d, utilization of chiral borane complexes becomes feasible. These functionalized polymers were incorporated into simple columns and enantioselective reductions of aldehydes and ketones were performed. Thus, reduction of acetophenone with a borane complex prepared from 6d yielded optically active (-)-l-phenyl-2-propanol in high optical yield (>99% ee) [31]. In addition, the flow system also served for continuous regeneration of the immobilized complex. Injection of borane and valerophenone into the column, which was loaded with polymer 6a, was followed by collection of fractions every 30 min. The individual batches of collected 1-phenylpentanol were analyzed and the enantiomeric excess was determined to be 87,93, and 91% for three batches [32]. 

Reduction of aldehydes and ketones allylic alcohols from a, 3-unsaturated aldehydes and ketones alcohols from carboxylic acid chlorides amines from aliphatic azides.21 ... 

Alcohols can also be produced from aldehydes and ketones via Grignard reagents. Other methods to synthesize alcohols include the reduction of aldehydes and ketones. These reactions will be discussed in Chapter 22. 

---