### Water - Moderately good nucleophile (not as good as hydroxide) - Weak electrophilic character - Brønsted acid with pKa = 15.7 ### Sodium Amide (Na$^{+}$NH$_{2}^{-}$) - Powerful Brønsted base (pKa of conjugate acid NH$_{3}$ = 33) - Strong nucleophilic character ### Metal Acetylides - Carbon (EN = 2.5) is not very electronegative and does not tolerate a full negative charge well - Alkynes are relatively acidic (pKa = ca. 25), however, due to sp "orbital electronegativity" - Metal acetylides (e.g., Met = Li, Na, MgX) exhibit strong nucleophilic character - Sodium acetylides are more reactive than lithium acetylides due to greater electropositive character of sodium compared to lithium ### Metal Alkoxides (e.g., NaOEt) - Moderately strong Brønsted base (pKa of conjugate acid 16-19) - Stronger base than NH$_{3}$ and amines, similar to hydroxide - Strong nucleophilic character (greater than ROH!) - Nucleophilic character suppressed if R is sterically bulky (e.g., KOt-Bu) ### Ammonia (NH$_{3}$) - Moderately strong Brønsted base (pKa of conjugate acid NH$_{4}^{+}$ is 9.4) - Stronger base than H$_{2}$O, weaker than OH$^{-}$ (pKa of their conjugate acids: -1.7 and 15.7) - Strong nucleophilic character (greater than H$_{2}$O!) - Weak Brønsted acid (pKa to form amide anion (NH$_{2}^{-}$) is ca. 38) ### Sodium Azide (NaN$_{3}$) - Strong nucleophilic character (highly polarizable anion) - Delocalized negative charge shared equally at terminal nitrogen atoms - Weak Brønsted base (pKa of hydrazoic acid HN$_{3}$ is 4.6) ### Amines (e.g., RNH$_{2}$, R$_{2}$NH) - Moderately strong Brønsted base (pKa of conjugate acid RNH$_{3}^{+}$ is 9-12) - Stronger base than H$_{2}$O, weaker than OH$^{-}$ (pKa of their conjugate acids is -1.7 and 15.7) - Strong nucleophilic character (greater than H$_{2}$O since N is less electronegative) - Very weak Brønsted acid (pKa to form amide anion (RNH$^{-}$) is ca. 38) - Weak electrophile (not much δ+ character on carbon of C-N bond) - Not subject to nucleophilic attack since amide anion (NH$_{2}^{-}$) is a very poor leaving group ### n-Butyllithium - Very polarized σ bond (carbon EN = 2.5, lithium 1.0) with significant carbanionic (δ-) character at carbon bonded to lithium - "Unactivated" carbons (sp$^{3}$ and sp$^{2}$) do not tolerate negative charge character well - Extremely powerful nucleophile, reacts with wide range of weak to strong electrophiles - Extremely high Brønsted basicity - pKa of butane is ca. 50 - Deprotonates weak acids including wide range of compounds with O-H and N-H bonds - Reacts rapidly and vigorously with H$_{2}$O, CO$_{2}$, and O$_{2}$ in atmosphere ### Thiols and Thiolates - Thiols (pKa 10-12) are more acidic than alcohols (pKa 16-19) - Thiols can be deprotonated by strong bases (NaOH, NaH) to form thiolate anions - Thiols (and thiolate anions) are very polarizable - Thiols (and thiolate anions) are very strong nucleophiles especially in protic solvents ### Lithium Aluminum Hydride (LiAlH$_{4}$) - Polarized Al-H bonds from Al (Pauling EN 1.5) to more electronegative H (EN 2.1) - AlH$_{4}^{-}$ has formal negative charge on Al (but Al is actually electron deficient!) - Excess electrons actually distributed at four hydrogen atoms - Behaves as a soluble equivalent of hydride anion (use THF or Et$_{2}$O) - Reacts as nucleophilic equivalent of hydride anion with even weakly electrophilic species - Highly basic and reacts even violently with moderate acids like water and alcohols ### Grignard Reagents (R-Mg-X) - Very polarized σ bond (carbon EN = 2.5, magnesium 1.2) with significant carbanionic (δ-) character at carbon bonded to magnesium - Extremely powerful nucleophile, reacts with wide range of weak to strong electrophiles - Extremely high Brønsted basicity - pKa of butane is ca. 50 - Deprotonates weak acids including wide range of compounds with O-H and N-H bonds - Reacts rapidly and vigorously with H$_{2}$O, CO$_{2}$, and O$_{2}$ in atmosphere ### Enolates - Highly polarized covalent oxygen-metal bond in organic solvents (e.g., THF) - Strong nucleophiles with negative charge character on both oxygen and carbon - Reactivity as nucleophiles is related to pKa of conjugate acids - Ambident nucleophiles, react at oxygen with very reactive electrophiles (e.g., acyl chlorides, Me$_{3}$SiCl - will not be studied in 5.12) - Ambident nucleophiles, react at carbon with most carbon electrophiles (e.g., alkyl halides, carbonyl compounds) ### Sodium Cyanide (NaCN) - Strong nucleophilic character (highly polarizable anion) - Moderate Brønsted base (pKa of HCN is 9.1) - Small anion, not as sensitive to steric shielding of electrophilic sites ### Sodium Borohydride (NaBH$_{4}$) - Polarized B-H bonds from B (Pauling EN 2.0) to more electronegative H (EN 2.1), but not polarized as much as Al-H bonds in LAH - BH$_{4}^{-}$ has formal negative charge on B (but B is actually electron deficient!) - Excess electrons actually distributed at four hydrogen atoms - Behaves as a soluble equivalent of hydride anion - Reacts as nucleophilic equivalent of hydride anion with moderately electrophilic species (but less nucleophilic than LiAlH$_{4}$) - Less basic than LAH and reacts slowly with water and alcohols, so they can be used as solvents ### Sodium Cyanoborohydride (NaBH$_{3}$CN) - Polarized B-H bonds from B (Pauling EN 2.0) to more electronegative H (EN 2.1) (but not polarized as much as Al-H bonds in LiAlH$_{4}$) - BH$_{3}$CN$^{-}$ has formal negative charge on B (but B is actually electron deficient!) - Excess electrons actually distributed at 3 H atoms, H atoms have significant δ- character - Electron-withdrawing cyano group reduces excess electron density on hydrogens - Behaves as a soluble equivalent of hydride anion - Reacts as nucleophilic equivalent of hydride anion with electrophilic species but is less nucleophilic than NaBH$_{4}$ and LAH (reacts with iminium ions but not carbonyls if pH > 5) - Less basic than NaBH$_{4}$ and reacts slowly with water even under mildly acidic conditions