the carbonyl oxygen. Lithium is smaller and more electrophilic than sodium, so it coordinates much more strongly and activates the carbonyl more. Metals that can have multiple charges (such as Mg, Al, and Zn) form cations with high charge density, and are therefore also stronger activators than Na+. Second, the central metal can influence a reducing agent’s strength. Aluminum is larger than boron, so it bonds more weakly to hydrides, which are more free to attack; aluminum hydrides are therefore better reducers than borohydrides. A third factor, sterics, is what makes certain substituted hydrides (hydrides in which one or more hydrides are replaced by substituents) much weaker reducers than other metal hydrides: sodium triacetoxyborohydride (NaBH(OAc)3), for instance, can be used to selectively reduce aldehydes, and leave the less reactive ketones unreacted. Finally, substituents can have other effects on a reducing agent’s reactivity: acetoxy groups hinder the reducing power of NaBH(OAc)3 not only through steric bulk but also because they are electron-withdrawing. Cyano groups also hinder reducing agents, while electron-donating groups such as alkyl groups can improve them, such as in superhydride (lithium triethylborohydride), which is a strong enough nucleophile to prevent undesired rearrangements during reduction. Because of these substituent effects, NaBH3CN is a very poor reducer at moderate pH (>4), so it prefers reductive amination to carbonyl reduction, as shown below: The relatively weak reducer sodium borohydride is typically used for reducing ketones and aldehydes because unlike lithium aluminum hydride, it tolerates many functional groups (nitro group, nitrile, ester) and can be used with water or ethanol as solvents. Lithium aluminum hydride and other strong reducers such as diisobutylaluminium hydride, L-selectride, diborane, diazene, and aluminum hydride can also reduce aldehydes and ketones, but are disfavored because they are hazardous and violently reactive. However, these compounds are useful for reducing carboxylic acids and esters to alcohols, since sodium borohydride is not powerful enough to do so. The following table illustrates which carbonyl functional groups can be reduced by which reducing agents (some of these reagents vary in efficacy depending on reaction conditions): Carboxylic acid derivatives to aldehydes Using metal hydrides Forming aldehydes from carboxylic acid derivatives is often a challenge, because weaker reducing agents (NaBH4) are incapable of reducing esters and carboxylic acids, which are relatively stable, and stronger reducing agents (LiAlH4) immediately reduce the formed aldehyde to an alcohol. Since acid chlorides are less stable than aldehydes and ketones, they