### Hydrogen - Very strong, non-polar bond (H-H BDE = 104 kcal/mol) - Very weak Brønsted acid (pKa = 35-40) - Behavior: expected to be neither a nucleophile or electrophile - Reacts with certain transition metals in "insertion" reactions (e.g., Pd + H-H → H-Pd-H) ### Potassium tert-Butoxide (KOt-Bu) - Strong Brønsted base (pKa of conjugate acid t-BuOH is only 19) - Weak nucleophilic character due to steric shielding of oxygen ### DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene) - Planar amidine moiety with amide-like π delocalization - Strong Brønsted base (protonated at C=N nitrogen) (pKa of conjugate acid = 13.5) - Weak nucleophilic character (steric shielding of nitrogen) - Very weak electrophilic character at ring junction carbon ### Sodium Hydride (NaH) - Strong Brønsted base (pKa of conjugate acid H$_{2}$ is 35-40) - Weak nucleophilic character - Insoluble in organic solvents; reactions take place on solid surface ### Ethers - Simple ethers have no protons with significant acidity - Ethers are very weak Brønsted bases (pKa of conjugate acid is ca. -3) - Ethers are moderate Lewis bases (recall complexes with strong Lewis acids) - α carbons have some δ+ character due to inductive electron withdrawal in C-O bond - α carbons are thus weakly electrophilic but ethers do not undergo nucleophilic substitution because alkoxy anions are very poor leaving groups ### Dimethyl Sulfoxide (DMSO) - Very high dipole moment (4.0 D) and high dielectric constant (47) - Very weak Brønsted acid (pKa ca. 35) - Dipolar structure with tetrahedral geometry at sulfur which has lone pair - Weak Lewis acid and weak electrophile; δ+ sulfur is shielded by methyl groups - Lewis basic oxygen good at solvating cations and δ+ species ### Ethylene Ketals - Very weak Brønsted bases (pKa of conjugate acids is ca. -5), similar to ethers - Very weak nucleophilicity, similar to ethers - Weak electrophilicity (alkoxides are poor leaving groups) - Hydrolyzed in aqueous strong acid (e.g., HCl, H$_{2}$SO$_{4}$) to generate ketone or aldehyde - Stable to most reducing agents (e.g., H$_{2}$, LiAlH$_{4}$, Na) and oxidizing agents (if non-acidic) ### Amides (RCONH$_{2}$, RCONHR, RCONR$_{2}$) - Moderately electrophilic carbonyl group; less electrophilic than esters due to greater delocalization - Weak Brønsted base pKaH ca. -1, protonated on oxygen (pKaH of amines RNH$_{3}^{+}$ is 9-12) - Weak nucleophile, generally reacts on oxygen (note structure of resonance hybrid) - Weak Brønsted acid pKa ca. 15, comparable to H$_{2}$O, ROH (pKa of amines is ca. 35-38) - Four-membered cyclic amides (β-lactams) are more electrophilic than acyclic amides ### Lithium Diisopropylamide (LDA, LiN(i-Pr)$_{2}$) - Very strong Brønsted base (pKa of conjugate acid R$_{2}$NH is ca. 35) - Weak nucleophilic character due to steric shielding of nitrogen - Reactions with electrophiles (R-X, carbonyl groups) slow - Soluble in THF even at -78 °C ### Benzenoid Aromatic Compounds - Strong, non-polar C-C and C-H σ bonds - Negligible electrophilic character (unless strongly electron-withdrawing substituents) - Relatively weak acidity (pKa 40-45) - Polarizable π electrons - moderate nucleophilic character - Less nucleophilic compared to alkenes and non-aromatic polyenes since electrophilic attack disrupts aromaticity - Requires especially strong electrophiles for addition to π system