Reduction

Alkali/Alkaline metals as reducing agents

Alkali metals (Li, Na, K) are powerful stoichiometric reductants capable of reducing aromatic rings/heterocycles (Birch reduction) and esters to primary alcohols (Bouveault-Blanc reduction). Hazardous handling requirements and scalability limitations have driven the field toward alternatives such as metal hydrides (NaBH₄, LiAlH₄) for ester reductions and electrochemical methods for aromatic reductions. Alkaline earth metals such as calcium have also shown similar performance for use in reductive applications when alkali metals are not suitable. 

Hydrides as reducing agents

Metal hydrides

Metal hydrides including sodium hydride (NaH), potassium hydride (KH), and lithium hydride (LiH) are strong, non-nucleophilic bases and reducing agents essential for generating enolates, alkoxides, and other reactive intermediates through deprotonation and hydride transfer. Lithium aluminum hydride (LiAlH₄) is one of the most powerful and broadly applicable hydride reductants, capable of reducing esters, amides, carboxylic acids, and nitriles that are otherwise resistant to milder hydride sources.  Aluminum-based reagents like DIBAL-H and Red-Al^® extend this reactivity further by offering precise control over partial reductions, while tin hydrides such as tributyltin hydride (Bu₃SnH) operate through a distinct radical chain mechanism uniquely suited for radical dehalogenations, deoxygenations, and cyclization reactions.

Borohydrides

Borohydrides are a versatile and widely used class of hydride-based reducing agents characterized by the delivery of nucleophilic hydride from a boron center to electrophilic substrates such as aldehydes, ketones, imines, and iminium ions. Sodium borohydride (NaBH₄) is the most employed member of this class, valued for its mild reactivity, operational simplicity, and compatibility with protic solvents. Lithium aminoborohydride (LAB) reagents represent an important advancement over LiAlH₄, offering enhanced reactivity and improved safety. Sterically hindered and electronically modified borohydrides, including L-/N-/K-Selectride^®, provide enhanced stereoselectivity and chemoselectivity by controlling the facial approach of hydride to prochiral carbonyl centers. Specialized derivatives such as sodium cyanoborohydride (NaBH₃CN) and sodium triacetoxyborohydride (NaBH(OAc)₃) further expand the utility of this class by enabling selective reductive amination under mild, functional-group-tolerant conditions. Borohydrides can also act as strong reducing agents, such as Super-Hydride^® (lithium triethylborohydride), a stronger reducing agent than sodium borohydride and lithium aluminum hydride. 

Boranes as reducing agents

Borane reducing agents, including 9-BBN, catecholborane and borane Lewis-adducts such as BH₃·THF and BH₃·SMe₂ are hydride sources that are commonly used to add across unsaturated bonds (hydroboration). These reagents are particularly valued for reducing functional groups (carboxylic acids, amides, esters) that resist conventional nucleophilic hydride reagents like NaBH₄. The steric bulk of modified boranes such as 9-BBN further enables high regioselectivity and enantioselectivity, allowing chemists to selectively reduce one functional group in the presence of another or achieve asymmetric reductions using chiral borane catalysts. Notable reactions are Corey–Bakshi–Shibata reduction and Midland Alpine–Borane^® reduction. 

Silanes as reducing agents

Silanes, such as triethylsilane (Et₃SiH), deliver hydride through a Si–H bond and are used in combination with Lewis or Brønsted acid catalysts to reduce carbocations, iminium ions, and carbonyl compounds via ionic hydrosilylation. Their low toxicity, ease of handling, and functional group tolerance make them particularly attractive as safer alternatives to metal hydride reagents in both laboratory and industrial scale reductions. 

Phosphines as reducing agents

Phosphine-based reducing agents, such as triphenylphosphine (PPh₃) and tris(2-carboxyethyl)phosphine (TCEP), function by donating a lone pair of electrons to electrophilic substrates, with the formation of a strong P=O bond serving as the thermodynamic driving force. They are widely used in peptide synthesis for selective disulfide bond reduction and in reactions such as the Staudinger reduction and Mitsunobu reaction in broader organic synthesis. 

Thiols as reducing agents

Thiol-based reducing agents, such as dithiothreitol (DTT) and β-mercaptoethanol (BME), reduce disulfide bonds through a nucleophilic thiol-disulfide exchange mechanism and are indispensable in peptide and protein chemistry for maintaining cysteine residues in their free thiol form. However, their strong odor, pH sensitivity, and potential interference with downstream assays have led to increasing preference for phosphine-based alternatives like TCEP in modern workflows.