Over-reduction to alcohol

The reaction tolerates ketone, chloride, internal C=C bonds, esters, nitriles, and ether functional groups. Given that the DIBAL-H reduction of acid derivatives often suffers from over-reduction to alcohols, these catalytic procedures are of synthetic value for laboratory-scale syntheses. However, it is likely that the requirement for excess (tBuCO)20 will prevent this reaction from ever being used in commercial production. 

C. Side Reactions in Reductions 1. Over-Reduction to Alcohol... 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

The main difficulties connected with this hydrogenation arise from over-reduction to the alcohol, which is a yield loss per se... 

One of the more difficult partial reductions to accomplish is the conversion of a carboxylic acid derivative to an aldehyde without over-reduction to the alcohol. Aldehydes are inherently more reactive than acids or esters so the challenge is to stop the reduction at the aldehyde stage. Several approaches have been used to achieve this objective. One is to replace some of the hydrogens in a group III hydride with more bulky groups, thus modifying reactivity by steric factors. Lithium tr i - / - b u to x y a I u m i n u m hydride is an example of this approach.42 Sodium tri-t-butoxyaluminum hydride can also be used to reduce acyl chlorides to aldehydes without over-reduction to the alcohol.43 The excellent solubility of sodium bis(2-methoxyethoxy)aluminum hydride makes it a useful reagent for selective... 

Reduction of acid chlorides to aldehydes One of the most useful synthetic transformations in organic synthesis is the conversion of an acid chloride to the corresponding aldehyde without over-reduction to the alcohol. Until recently, this type of selective reduction was difficult to accomplish and was most frequently effected by catalytic hydrogenation (the Rosenmund reduction section 6.4.1). However, in the past few years, several novel reducing agents have been developed to accomplish the desired transformation. Among the reagents that are available for the partial reduction of acyl chlorides to aldehydes are bis(triphenylphosphine)cuprous borohydride , sodium or lithium tri-terf-butoxyaluminium hydride, complex copper cyanotrihydridoborate salts °, anionic iron carbonyl complexes and tri-n-butyltin hydride in the presence of tetrakis(triphenylphosphine)palladium(0). ... 

The synthesis of aldehydes by the Sommclet reaction, the Rosenmund reduction and the Stephens reaction all involve the conversion of a group already present in the molecule. The Rosenmund reduction (Scheme 6.7) is the catalytic hydrogenation of a benzoyl chloride in the presence of a catalyst poison, quinoline/sulfur, which prevents over-reduction to the alcohol. In the Stephens reaction (Scheme 6.7), a nitrile group is reduced by tin(II) chloride and hydrochloric acid to an imine salt, which is then hydrolysed. 

The Jamison group reported that a cryogenically controlled microreactor setup enabled diisobutylaluminum hydride (DIBALH) reduction of esters to give corresponding aldehydes in high yield and superior selectivity (trace amount of over-reduction products alcohol) within a few seconds of reaction time [28]. They extended their work to combine three highly exothermic reactions in a single... 

Specific enol equivalents will be needed for both synthons (61) and (66), Since (61) is to give a double bond but (66) is to give an alcohol, the logical choices are a Wittig reagent - actually (67) - for (61) and a Reformatsky reagent for (66). The ester to aldehyde conversion (65 63) Is easiest by over-reduction and re-... 

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

If the two Oads species are not scavenged, then the reaction will stop. This is the case, for instance, of NO decomposition on Cu/ZSM-5 [25], Adsorbed oxygen species have to be scavenged either by an activated form of the initial HC reductant, such as QH O , (alcohol, aldehyde, etc.) or by the initial HC if their total oxidation is simultaneous with NO decomposition-reduction to N2. These oxygenates and/or HC suffer a total oxidation to C0/C02 and H20, regenerating the active site this is the principle of catalysis. Once the active site is recovered, the reaction continues to turn over. This is the catalytic cycle . 

Arylalkyl ketones (80) are reduced to alcohols over the pH range of 7 to 12 (approx.) 73>. The reduction probably involves the following sequence of steps ... 

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